Available Potential Energy Research Articles

Is Amazon deforestation decreasing the number of thunderstorms over South America?

AbstractLightning activity has been predicted to increase with global warming, though estimates of lightning sensitivity to a change of temperature vary widely. Since lightning is a small‐scale process, it must be represented by parametrizations in climate models. This article uses large‐scale meteorological parameters tied to thunderstorm generation to improve existing empirical models that simulate regional thunderstorm behaviour. The response of the number of thunderstorms (as presented here) to climate change is rarely analysed in global studies. This study focuses on Tropical America, and uses the ERA5 higher‐resolution reanalysis data (ERA5) to develop our empirical model. Thunderstorm data were taken from the World Wide Lightning Location Network (WWLLN) and processed using the clustering algorithm developed by Mezuman et al. (2014). The two meteorological parameters that correlated best with thunderstorm clusters in Tropical America were specific humidity (SH) and convective available potential energy (CAPE). The resulting empirical model was run from 1979 to 2019 using ERA5 reanalysis data as input. This approach approximates the long‐term trends in the behaviour of thunderstorms in the regions, in the absence of a complete historical lightning record. To our surprise, Tropical American thunderstorms exhibited a negative trend over this period, with an 8% decrease in thunderstorm clusters since the 1980s even with a rise of 1 K in temperature over the same period. The regions of largest decreases in thunderstorm activity align well with estimates of deforestation. We estimate that for every 1 Tg C lost due to deforestation, there is a 10% decrease in thunderstorm number.

Spatial and temporal distribution of HCHO and its pollution sources based on satellite remote sensing: a case study of the Yangtze River Economic Belt

Abstract In recent years, with the acceleration of industrialization and the expansion of urban scale, air pollution including formaldehyde (HCHO) becomes more and more serious. In order to study HCHO pollution in the Yangtze River Economic Belt (YEB), the temporal and spatial evolution of atmospheric HCHO and its influencing factors were analyzed by using the Ozone Monitoring Instrument (OMI) during 2012–2021. The results showed that the concentration of YEB HCHO column was unevenly distributed, with high values concentrated in Anhui, Jiangsu, Yunnan and Hubei provinces. During the past 10 years, the concentration of YEB HCHO column varied between 10.28 and 17.19 × 1015 molec cm−2, and the lowest concentration of HCHO column was 13.16 × 1015 molec cm−2 in 2015. However, it reached the peak value in 2018 (14.93 × 1015 molec cm−2). In natural sources, normalized vegetation index (NDVI) and leaf area index (LAI) had greater influence on YEB HCHO, and the correlation was −0.91 ∼ 0.97 and −0.9 ∼ 0.95, respectively. The positive correlation area between HCHO and Mean annual temperature (MAT) reached 93%. The contribution of high-intensity human activity areas to HCHO cannot be underestimated. Industrial and civil sources have great influence on HCHO. In addition, the potential source of HCHO in Shanghai is affected by local emission sources, trans-regional potential sources, northwest air mass and ocean airflow.

Ultrasound and x-ray examination at lung edema of domestic cat

The aim: This study aims to determine the diagnostic value of lung ultrasound compared with radiography for respiratory distress in cats.
 Materials and methods: The database of the veterinary center was analyzed. 130 animals diagnosed with pulmonary edema were selected. The lungs of sick cats were examined ultrasonographically; The line was counted in 4 anatomical sections on each hemithorax. A site was evaluated as positive when > 3 "B-lines" were detected. Animal treatment protocols were studied to clarify the final diagnosis (reference standard), and the sensitivity and specificity of lung ultrasound and chest X-ray for the diagnosis of pulmonary edema were calculated.
 Result: Cats with a final diagnosis of cardiogenic pulmonary edema had a greater number of positive areas on ultrasound than those, in which respiratory distress was caused by non-cardiogenic pulmonary edema. The overall sensitivity and specificity of US for the diagnosis of pulmonary edema were 87 % and 89 %, respectively, and these values were similar to those of chest radiography (85 % and 86 %, respectively). The use of ultrasound led to a false diagnosis of cardiogenic pulmonary edema (ie, a false-positive result) in animals with diffuse interstitial or alveolar changes.
 Conclusions: Ultrasound examination of the lungs in cats with respiratory distress syndrome is a promising diagnostic method. Emergency diagnosis of pulmonary edema in cats is difficult, especially in patients with severe shortness of breath, and limits the diagnostic evaluation. Chest x-rays are considered the standard diagnostic test, but the results are sometimes ambiguous and the process of obtaining the x-rays can increase respiratory distress in the animal.
 According to the results of the study, it was established, that ultrasound examination of the lungs can be used to differentiate the causes of shortness of breath (cardiogenic and non-cardiogenic) with sufficiently high sensitivity and specificity and less influence of the iatrogenic factor on the development of respiratory distress in cats, compared to chest radiography

Cold Surge Effect on Vertical Profile Atmosphere over Meteorological Station of Ranai Natuna: Case Study Asian Winter Monsoon 2019/2020

During the Asian Winter season, which spans from November to February, the phenomenon of cold surge often occurs, leading to increased convective activity over the western Indonesian Maritime Continent. The location of Natuna Island, situated in the southern part of the South China Sea, is of particular importance for studying cold surges due to their propagation over this area. In this study, the vertical structure of the atmosphere was analyzed using radiosonde observation data collected at the Meteorological Station of Ranai Natuna. The analysis focused on physical parameters such as air temperature and relative humidity, atmospheric kinematics including wind direction and speed, as well as atmospheric thermodynamic parameters such as Lifting Condensation Level (LCL), Level of Free Convection (LFC), Equilibrium Level (EL), Convective Available Potential Energy (CAPE), and Convective Inhibition (CIN). The results indicate that during the passage of a cold surge, air temperature (T) tends to be higher in the lower troposphere, including at the surface, but lower in the middle and upper troposphere. Relative humidity (RH) also tends to be higher during cold surges, with a significant increase in the middle and upper troposphere. In the lower troposphere, the wind direction shifts from east to northeast at a higher speed compared to when a cold surge is absent. Furthermore, the LCL and LFC heights are elevated during the presence of a cold surge, while the EL height shows an insignificant decrease. It is worth noting that intense rainfall occurs, particularly when the cold surge is more pronounced, even though the values of CAPE and CIN do not change significantly.

Carboniferous marine deposits of the Tontal section suggest that no Protoprecordillera existed along the Western Gondwana margin

We present new palaeontological and stratigraphic data from a poorly known section located in the Tontal Range, Argentina, whose importance is key to defining the character of a hypothetical Carboniferous mountain chain, the Protoprecordillera. The Tontal Range composed the core of the hypothetical Protoprecordillera, also called the Tontal arch. The section described here comprises Mississippian and Pennsylvanian marine and mixed marine–terrestrial units that were deposited within a proglacial (non-fjord) environment. A new correlating scheme of Tontal section units is brought based on new biostratigraphic data plus the recent development of a stratigraphic order of Carboniferous units cropping out only 15 km away. The lowermost unit in the Tontal section is Del Ratón Formation conglomerate, which passes upwards into glaciomarine shales correlated with the El Planchón Formation that bears marine bivalves and palynomorphs suggesting a Serpukhovian (Upper Mississippian) age. El Planchón is overlain by the barren Churupatí Formation, with lower units of shallow marine, fan-deltaic conglomerate, passing to fluvial redbeds. The overlying Del Salto Formation has intense intraformational folding due to slumping at its base, and consists of sandstone, organic-rich shale, and shelf carbonate, the latter containing marine invertebrates and palynomorphs that suggest a Bashkirian (Lower Pennsylvanian) age. The Tontal section represents a marginal position within a previously defined strike-slip basin (Milana and Di Pasquo, 2019) that was active during most of the Carboniferous. It was deposited in a shallow marine shelf beside a hummocky coastal landscape, the erosion of which provided rounded gravels deposited in Gilbert-type deltas with associated slumps. We found no indication this area hosted any kind of glaciers, and most of the time it was below sea level. These observations, along with the lack of any mountain-side complex or any alpine-valley glacio-related depositional features remain at this, or any neighbouring sections; suggest that there was no Protoprecordillera mountain chain. Correlation with nearby sections also suggests this margin was not influenced by any prominent topographic highs during the depositional time of the Tontal section (upper Mississipian to Pennsylvanian), but rather that this area was located near sea level, potentially with emergent and positive areas along both margins of the strike-slip basin that allowed preservation of the oldest Carboniferous units of this region. On the other hand, the tendency for generalised subsidence during the Upper Carboniferous over most of the Precordillera, may respond to the development of a volcanic arc westwards over the present Cordillera, associated with the activation of a subduction zone in the present-day Chile, turning most of the area into retroarc basins.

Effects of Consuming Ounce-Equivalent Portions of Animal- vs. Plant-Based Protein Foods, as Defined by the Dietary Guidelines for Americans on Essential Amino Acids Bioavailability in Young and Older Adults: Two Cross-Over Randomized Controlled Trials.

The Dietary Guidelines for Americans (DGA) recommends consuming a variety of "Protein Foods" based on "ounce-equivalent" (oz-eq) portions. No study has assessed the same oz-eq portions of animal- vs. plant-based protein foods on essential amino acid (EAA) bioavailability for protein anabolism in young and older adults. We assessed the effects of consuming two oz-eq portions of pork, eggs, black beans, and almonds on postprandial EAA bioavailability in young and older adults. We conducted two investigator-blinded, randomized crossover trials in young (n = 30; mean age ± SD: 26.0 ± 4.9 y) and older adults (n = 25; mean age ± SD: 64.2 ± 6.6 y). Participants completed four testing sessions where they consumed a standardized meal with two oz-eq of either unprocessed lean pork, whole eggs, black beans, or sliced almonds. Blood samples were taken at baseline and 30, 60, 120, 180, 240, and 300 min postprandially. Plasma EAA bioavailability was based on postprandial integrated positive areas under the curve. Participant age did not affect EAA bioavailability among the four protein foods tested. Two oz-eq portions of pork (7.36 g EAA) and eggs (5.38 g EAA) resulted in greater EAA bioavailability than black beans (3.02 g EAA) and almonds (1.85 g EAA) in young and older adults, separately or combined (p < 0.0001 for all). Pork resulted in greater EAA bioavailability than eggs in young adults (p < 0.0001), older adults (p = 0.0007), and combined (p < 0.0001). There were no differences in EAA bioavailability between black beans and almonds. The same "oz-eq" portions of animal- and plant-based protein foods do not provide equivalent EAA content and postprandial bioavailability for protein anabolism in young and older adults.

Convection-parameterized and convection-permitting modelling of heavy precipitation in decadal simulations of the greater Alpine region with COSMO-CLM

Abstract. Heavy precipitation is a challenging phenomenon with high impact on human lives and infrastructure, and thus a better modelling of its characteristics can improve understanding and simulation at climate timescales. The achievement of convection-permitting modelling (CPM) resolutions (Δx&lt;4 km) has brought relevant advancements in its representation. However, further research is needed on how the very high resolution and switching-off of the convection parameterization affects the representation of processes related to heavy precipitation. In this study, we evaluate reanalysis-driven simulations for the greater Alpine area over the period 2000–2015 and assess the differences in representing heavy precipitation and other model variables in a CPM setup with a grid size of 3 km and a regional climate model (RCM) setup at 25 km resolution using the COSMO-CLM model. We validate our simulations against high-resolution observations (E-OBS (ENSEMBLES observations), HYRAS (Hydrometeorologische Rasterdatensätze), MSWEP (Multi-Source Weighted-Ensemble Precipitation), and UWYO (University of Wyoming)). The study presents a revisited version of the precipitation severity index (PSI) for severe event detection, which is a useful method to detect severe events and is flexible for prioritizing long-lasting events and episodes affecting typically drier areas. Furthermore, we use principal component analysis (PCA) to obtain the main modes of heavy precipitation variance and the associated synoptic weather types (WTs). The PCA showed that four WTs suffice to explain the synoptic situations associated with heavy precipitation in winter, due to stationary fronts and zonal flow regimes. Whereas in summer, five WTs are needed to classify the majority of heavy precipitation events. They are associated with upper-level elongated troughs over western Europe, sometimes evolving into cutoff lows, or with winter-like situations of strong zonal circulation. The results indicate that CPM represents higher precipitation intensities, better rank correlation, better hit rates for extremes detection, and an improved representation of heavy precipitation amount and structure for selected events compared to RCM. However, CPM overestimates grid point precipitation rates, which agrees with findings in past literature. CPM systematically represents more precipitation at the mountain tops. However, the RCMs may show large intensities in other regions. Integrated water vapour and equivalent potential temperature at 850 hPa are systematically larger in RCM compared to CPM in heavy precipitation situations (up to 2 mm and 3 K, respectively) due to wetter mid-level conditions and an intensified latent heat flux over the sea. At the ground level, CPM emits more latent heat than RCM over land (15 W m−2), bringing larger specific humidity north of the Alps (1 g kg−1) and higher CAPE (convective available potential energy) values (100 J kg−1). RCM, on the contrary simulates a wetter surface level over Italy and the Mediterranean Sea. Surface temperatures in RCM are up to 2 ∘C higher in RCM than in CPM. This causes outgoing longwave radiation to be larger in RCM compared to CPM over those areas (10 W m−2). Our analysis emphasizes the improvements of CPM for heavy precipitation modelling and highlights the differences against RCM that should be considered when using COSMO-CLM climate simulations.

P-408 The ovarian tissues outside of the radiation field could be damaged by radiation-induced abscopal effects in mice: an experimental study.

Abstract Study question Could irradiation-induced abscopal effects (RIAEs) induce structural and functional damage in the distal ovary in female mice, and what is its mechanism? Summary answer The RIAEs can induce an inflammatory reaction and inhibit the growth and development of ovarian follicles in mice leading to a decrease in ovarian reserve. What is known already The irradiated tumor could induce cell and tissue injury in the organs distant from the radiation site, referred to as the radiation-induced abscopal effects (RIAEs). Many pieces of research have shown out-of-field tumor regression effects of radiation therapy. However, RIAEs is a double-edged sword and may cause serious side effects on normal tissues. Premature ovarian insufficiency (POI) is one of the main side effects of radiotherapy, but the relationship between RIAE and POI has not been clarified. Study design, size, duration C57BL/6J mice were used to establish a RIAEs model by irradiating the thorax and the abdomens were shielded. Sixteen C57BL/6J female mice were randomly allocated to sham and experimental groups (n = 8/group) according to the presence or absence of irradiation with an 8 Gy X-ray on the local area of the chest every day for three days. After irradiation for twenty-one days, The effect and possible mechanism of RIAEs on non-irradiated ovarian were discussed. Participants/materials, setting, methods After irradiation, the estrous cyclicity, serum steroid hormones, and pro-inflammatory factors were compared between groups. Furthermore, RNA-seq was used to detect the expression of transcriptional levels in ovarian tissues in both groups. The differentially expressed genes (DEGs) were screened and analyzed by gene ontology-biological process (GO_BP) between irradiated and sham groups. The expression and localization of spermatogenesis-and oogenesis-specific basic helix-loop-helix-containing protein 1(SOHLH1) and neutrophil elastase (NE) in ovarian tissues were detected by immunohistochemistry(IHC). Main results and the role of chance Compared with mice in the sham group, the irradiation group had disordered estrous cycles, reduced primordial follicles (P&amp;lt;0.001)] and growing follicles (P&amp;lt;0.001), significantly increased atretic follicles (P&amp;lt;0.001). Levels of serum estradiol [(70.28 ± 5.27) pmol/L] and AMH [(104.00±6.98) ng/L] in the irradiation group were significantly lower than those in the sham group [estradiol (97.58±7.25) pmol/L, P=0.016; AMH [(129.70±8.39) ng/mL, P=0.046], but FSH levels in the irradiation group were not significantly different from those in the sham group (P=0.996). Compared with the sham group, Serum levels of TNF-α [(488.30±36.20) ng/L vs. (31.61±12.89) ng/L, P&amp;lt;0.001] and IL-1β [(62.37±2.50) ng/L vs. (52.75±2.06) ng/L, P=0.018)] in the irradiation group were significantly increased. Serum levels of IL-6 in the irradiation group were also increased compared with the sham group, but the difference was not statistically significant (P=0.301). The results of GO_BP analysis showed that down-regulated DGEs were mainly involved in the process of follicular development, and up-regulated DGEs were involved in the inflammation process. The IHC results showed that the positive expression area of SOHLH1 in the irradiation group was significantly lower than in the sham group (P=0.005). In comparison, the positive expression area of NE was significantly higher than that of the Sham group(P=0.024). Limitations, reasons for caution This study was performed using a short, 3-day irradiation treatment condition. Therefore, the results need to be cautiously interpreted concerning radiation-associated chronic toxicity. Moreover, further studies in mouse tumor models are required to determine the clinical relevance of the role of RIAE. Wider implications of the findings Although the precise molecular mechanisms of these distal effects on the genital system are still unclear, the current discovery might pave the way for establishing novel fertility preservation protocols. The research offers hope to women with POI related to cancer therapy through the modulation of abscopal effects associated with radiotherapy. Trial registration number not applicable

609-P: Postprandial GLP-1 Response to Two Diabetes-Specific Formulas Compared with Instant Oatmeal in Adults With Type 2 Diabetes

Diabetes specific formulas (DSFs) are designed with an optimized macronutrient profile as a meal or snack replacement to meet the nutritional needs of people with diabetes while helping to manage blood glucose response. Macronutrients found in DSFs have been shown to promote glucagon-like peptide-1 (GLP-1) secretion, a key hormone involved in regulating incretin response to manage blood glucose levels during the postprandial period. We tested the postprandial GLP-1 response in two randomized, controlled crossover studies in adults with T2D with two DSFs (DSF-1; Study 1, DSF-2; Study 2) varying in macronutrient composition compared to isocaloric instant oatmeal (IOM). In each study, participants were randomly allocated to receive IOM or the study DSF on two test days separated by 4 - 14 days. Total GLP-1 concentration was measured at baseline, 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption. Outcome parameters included adjusted peak GLP-1 concentration, and positive area under the curve (pAUC) over 0 - 240 minutes for each participant. Respectively, Study 1 and Study 2 included 26 (n = 15 males, n = 11 females; mean age = 63.6 ± 1.4 years; mean BMI = 30.0 ± 0.9) and 22 (n = 14 males, n = 8 females; mean age = 64.6 ± 2.0 years; BMI = 32.8 ± 0.9) completed participants. Median (1st and 3rd quartile) adjusted peak GLP-1 concentration was significantly higher for DSF-1 (9.2 (6.4, 16.5) pmol/L vs. 3.7 (2.5, 9.0) pmol/L; p = 0.012) and DSF-2 (10.8 (7.5, 20.0) pmol/L vs. 6.3 (4.3, 9.4) pmol/L; p &amp;lt; 0.001) compared to IOM. DSFs significantly increased pAUC for GLP-1 response (DSF-1: 901 (410, 1091) vs. IOM: 177 (47, 421); p &amp;lt;0.001 and DSF-2: 1122 (682, 1820) vs. IOM: 403 (183, 778); p &amp;lt; 0.001) by 410% and 178%, respectively. As part of a diabetes management plan, DSFs can serve as a convenient tool to meet nutritional needs while improving GLP-1 response to help manage blood glucose. Disclosure S.Thomas: Employee; Abbott Nutrition. B.Besecker: Employee; Abbott Nutrition, Stock/Shareholder; Abbott Nutrition. Y.Choe: Employee; Abbott Nutrition.

Barotropic and Nonlinear Decay of the Wintertime Baroclinic Wave Packets over the North Pacific: Energetics Analysis

Abstract Based on daily data from the Japanese 55-year Reanalysis (JRA-55) covering the winters (NDJFM) from 1958 to 2018, this study examines the growth and decay mechanisms of the baroclinic wave packet (BWP) inferred from regression analysis over the North Pacific. Day-to-day kinetic energy (KE) and available potential energy (APE) budget analysis suggest that BWP is driven mainly by baroclinic energy conversion (CPB), barotropic energy conversion (CKB), and the nonlinear term (CKE). CPB acts as a predominant APE source for BWP. Part of CPB acts to overcome the APE loss caused by transient eddy flux and most of it acts as a dominant KE source to drive BWP throughout its lifespan. CKB acts as a KE source before day −1, and as a major KE sink to damp BWP afterward, in which the north–south gradient of the climatological meridional flow plays a key role. Similarly, CKE acts as a KE source before day 0 and as a major KE sink afterward. The damping effect of CKE comes mainly from the scale interaction through the advection of high-frequency meridional momentum by the low-frequency zonal flow. It turns out that the vertical geopotential flux divergence also plays an active role in the dynamical coupling of different vertical BWP parts. There is persistent geopotential flux transfer from the middle-tropospheric layer into the lower- and upper-tropospheric layers, which serves as a major KE source to drive the BWP anomalies for the two layers and a major KE sink for the middle-tropospheric layer where the baroclinic energy conversion is the strongest. Significance Statement Previous studies indicate that baroclinic waves tend to organize into wave packets and are driven by the baroclinic instability. This study finds that the baroclinic waves decay mainly through the barotropic energy conversion and nonlinear processes. The results also indicate that the vertical geopotential flux divergence plays an active role in the dynamical coupling of the BWP anomalies in different layers of the troposphere. It is therefore very important to improve the representations of the climatological-mean flow, wave–mean flow interaction, and wave–wave interaction between high- and low-frequency waves in the midlatitudes, as well as the process of vertical transfer of the geopotential flux in numerical models for a better prediction of weather and climate variability in the extratropic regions.

#5664 PERITONEAL DIFFUSE PODOPLANIN EXPRESSION IS ASSOCIATED WITH SEVERE ARTERIOLOPATHY IN CHILDREN ON PERITONEAL DIALYSIS

Abstract Background and Aims Podoplanin is a transmembrane glycoprotein binding chemokines and modulating inflammatory reactions. In healthy peritoneum, it is expressed in mesothelial cells and in lymphatic endothelium, expression beyond these structures (diffuse podoplanin staining, DPS) has been observed in adult patients with encapsulating peritoneal sclerosis (EPS). Method Parietal peritoneal tissues from 71 children on PD fluids with low glucose degradation product (GDP) content underwent digital histomorphometry. DPS and pathomechanisms of peritoneal membrane transformation and vasculopathy were hierarchically clustered. A panel of 13 peritoneal cell markers was selected and tissue sections were stained with metal conjugated antibodies and acquired using imaging mass cytometry (IMC; Hyperion Imaging System®). After single-cell segmentation, spillover correction, and normalization, cell types were identified using manual gating to train a random forest classifier for final cell type identifications using published workflows. Single-cell analysis was used to characterize peritoneal cells with positive podoplanin signals. Results DPS was present in 22% of the PD patients, all devoid of any clinical, radiological or histological feature of EPS. DPS positive patients were younger, had higher dialytic glucose exposure (median 103 vs. 154 g/m²/day, p = 0.002), and lower peritoneal arteriolar lumen to vessel (L/V) ratio, i.e. exhibited more arteriolar lumen narrowing. PD duration [median 20 (14.5, 48) months] and peritonitis incidence were similar as in non-DPS patients. In multivariable analysis, glucose exposure, PD duration, epithelial-to-mesenchymal transformed (EMT) cells and lower patient body surface area (BSA) independently predicted the presence of DPS. DPS and lower mesothelial surface coverage predicted lower arteriolar L/V ratio. In subgroups matched for BSA, PD duration and dialytic glucose exposure, DPS patients had a lower L/V ratio, (0.44 ± 0.13 vs. 0.31 ± 0.18, p = 0.003) and higher submesothelial CD45 leucocyte, CD68 macrophage and EMT cell count. Submesothelial lipopolysaccharide and hyaluronic acid receptor CD44 were increased in DPS positive patients, hyaluronan synthase 1 and 2 were similar. Among DPS positive patients, DPS intensity grade was higher in those with history of bacterial or fungal peritonitis (7 out of 15). Two patients had three and four peritonitis episodes respectively, their DPS pattern did not differ from patients with history of only one peritonitis episode. Hierarchical clustering demonstrated highest similarity of DPS positive areas with CD68 positive areas. In IMC analysis of DPS positive areas, highest podoplanin signals were derived from M2 classified macrophages (CD68+CD163+) and fibroblastic cells [αSMA positive/non-endothelial/non-macrophage (αSMA+PROX1-CD31-CD68-CD163-)], signals derived from M1 classified macrophages (CD68+CD163-) were lowest. Conclusion Peritoneal DPS in pediatric patients on low-GDP PD is associated with lower BSA, higher dialytic glucose exposure, history of infectious peritonitis and peritoneal inflammatory and EMT cell invasion, and predicts obliterating peritoneal vasculopathy. We identified M2 macrophages as major source of extra-lymphatic peritoneal podoplanin accumulation, suggesting their role in severe peritoneal transformation.

#4359 LOSS OF GASDERMIN D LEADS TO AN EXACERBATION OF KIDNEY DAMAGE IN NEPHROCALCINOSIS-RELATED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Gasdermin D (GSDMD) is a membrane-targeting and pore-forming protein that is primarily expressed in immune cells. In the proinflammatory cell death process known as pyroptosis, cleaved GSDMD plays a crucial role through cell membrane pore formation, leading to the release of proinflammatory cytokines and membrane rapture. Despite this, the majority of GSDMD's other physiological functions remain to be elucidated. Previous reports have implicated GSDMD in the pathogenesis of kidney disease, utilizing some acute kidney injury (AKI) animal models and a few chronic kidney disease (CKD) animal models. However, it remains uncertain if GSDMD contributes to the pathogenesis of nephrocalcinosis-related CKD. Therefore, this study aimed to investigate the role of GSDMD in in this context. Method In our study, 8-week-old GSDMD-knockout (KO) mice and wildtype (WT) mice received an oxalate-rich diet (50 μmol/g sodium oxalate) for three weeks. All mice were sacrificed on day 21 and kidneys were harvested after the sacrifice. Plasma and urine samples were collected at different time points before the sacrifice. The glomerular filtration rate (GFR) was measured on day 0 and day 20 to assess kidney excretion function. Histological analysis was performed using Periodic Acid-Schiff (PAS) staining to assess renal injury, Sirius Red staining to check renal fibrosis, Pizzolato staining to evaluate calcium crystal deposition, F4/80 staining to evaluate the infiltration of macrophages, TUNEL staining to check for cell death, RIPK3 and phosphorylated MLKL (pMLKL) staining to detecting necroptosis. And GSDMD staining was also performed to examine the expression of GSDMD in the kidney. Results Pizzolato staining showed no differences in calcium crystal deposition between WT mice and KO mice. GFR was decreased in both WT mice and KO mice after the oxalate-rich diet (day 0 WT: 199.5±40.1 μl/min vs KO 175.0±44.8 μl/min, day 20 WT: 156.5±37.9 μl/min vs KO: 73.0±48.1 μl/min), and ΔGFR was much greater in KO mice (WT: −22.4±26.5% vs KO: −59.4±19.3%). The level of blood urea nitrogen was significantly higher in KO mice (WT: 41.9±3.90 mg/dl vs KO: 58.7±22.5 mg/dl) in accordance with the result of the GFR. PAS staining revealed more severe kidney injury in KO mice, and Sirius Red staining indicated a higher degree of renal fibrosis in KO mice. Furthermore, F4/80 staining showed greater infiltration of macrophages in KO mice. Although TUNEL staining showed no significant differences in positive cells between WT and KO, KO mice showed greater positive areas implicating more necroptosis in RIPK3 and pMLKL staining. GSDMD staining revealed that injured tubular cells during the chronic phase express GSDMD (Fig. 1). In in vitro experiments, we evaluated the functionality of macrophages such as phagocytic ability and migratory ability using bone marrow-derived macrophages (BMDMs), but we didn't find any significant disparities between BMDMs from WT mice and those from KO mice. Conclusion Genetic deletion of GSDMD resulted in more severe kidney injury, macrophage infiltration and fibrosis in mice with nephrocalcinosis-related CKD. Our results suggest a potential role for pyroptosis, especially GSDMD, in contributing to renal tubular cell necroptosis, a process downstream of calcium-oxalate crystal formation and deposition, in the progression of nephrocalcinosis-related CKD, similar to previous reports in mouse models of AKI.

Dynamical analysis of multi-scale interaction during the “21·7” persistent rainstorm in Henan

This study explored the multiscale dynamical processes and energy contributions to the “21∙7” torrential rainfall event (TRE), which hit Zhengzhou on July 20, 2021. Using a localized, instantaneous energetics diagnostic tool: the multiscale window transform (MWT) and MWT-based energy and vorticity analysis (MS-EVA), three scales fields: basic-flow fields (>64 days), intraseasonal oscillation fields (8–64 days) and synoptic-scale-eddy fields (<8 days) were obtained. An inverted trough over “21∙7” TRE area on the scale of 8–64 days and a mesoscale high in front of Typhoon In-Fa (2021) on the scale of <8 days were identified by the MWT. There was persistent energy conversion from available potential energy (APE) to kinetic energy (KE) represented by the buoyancy term in the last 12 h and throughout the occurrence of the exceptional rainstorm. Latent heating was an important source of APE 12 h prior to the rainstorm. In addition to buoyancy conversion, a downscale energy cascade process of KE (barotropic instability) above 500 hPa was another source of KE prior to the rainstorm. During the rainstorm's occurrence, the downscale energy cascade process of APE (baroclinic instability) at middle levels was the major source of APE. KE decreased significantly owing to eddy dissipation and diffusion at middle levels and the divergence of KE fluxes at low levels. The work done by the pressure gradient force was negligible for KE.

Dietary Iron Restriction Protects against Aneurysm Rupture in a Mouse Model of Intracranial Aneurysm

Introduction: Iron accumulation in vessel walls induces oxidative stress and inflammation, which can cause cerebrovascular damage, vascular wall degeneration, and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture. Methods: Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet (n = 23) or a normal diet (n = 25). Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination. Results: The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%; p < 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2′-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (p < 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2′-deoxyguanosine in both normal diet and iron-restricted diet mouse aneurysms. Conclusions: These findings suggest that iron is involved in intracranial aneurysm rupture via vascular inflammation and oxidative stress. Dietary iron restriction may have a promising role in preventing intracranial aneurysm rupture.

Industrial tourism as an effective direction of urban regeneration (analysis of Kryvyi Rih practice)

Formulation of the problem. The world is constantly moving towards the post-industrial phase of development of society, and if the majority of civilized Western countries have decided on their place and role, the cities of Ukraine are just beginning to outline their future landmarks. This is especially true for the future of single-industry cities, the number of which in Ukraine is quite large. Kryvyi Rih is the largest city with exclusively industrial specialization, performing administrative functions only at the local level and having a scientific sector almost completely focused on the needs of the industrial complex. For the last 10 years, managers and scientists have been actively thinking about the problem of diversifying the city's economy and changing its image, and this is reflected in the Marketing Strategy for the city development. Industrial tourism is one of the key tasks of the Strategy. The promising character of the chosen direction of activities is confirmed by the practice of European countries, which are guidelines for development for us. This is due to the fact that not only individual cities, but also entire regions of Great Britain, Germany, France, Poland, the Czech Republic have a wide experience in regeneration of former industrial territories and further popularization of successful practices through industrial tourism. Methods. The research is based on the system approach and the dialectical method of cognition. The key scientific results are obtained using a complex of general scientific methods, namely: analysis and synthesis, abstraction, theoretical generalization. The historical method enables determining significant moments for development of this tourist destination. With the help of these methods, industrial tourism is considered in its internal and external relations entirety. The simulation method enables presenting the organizational model of this tourist destination at the local level. Comparative-geographical and statistical analysis methods allow assessment of the state and dynamics of tourism development in Kryvorizhzhia (Kryvyi Rih region). Based on the method of observation and analysis, the most visited objects of industrial tourism in Kryvyi Rih are systematized and their base map is created. The study aims to analyze best practices of implementing theoretical developments concerning establishment of industrial tourism in Kryvorizhzhia so that Ukrainian cities with similar resources can factor in all positive areas and minimize shortcomings. Results. The theoretical foundations of industrial tourism establishment are analyzed and this definition is outlined. The practice of Kryvyi Rih concerning integrated development of industrial tourism as a direction of further regeneration of the city, which is pioneering for our country, is revealed, the results obtained are analyzed and available shortcomings are identified. Scientific novelty and practical significance. An organizational model of industrial tourism has been developed, which demonstrates the relationship between the resource of the territory and the management mechanism for introducing tourist activities in order to create a tourist product and bring it to the tourist.

Concordance among the three commercially available PD-L1 assays for esophageal squamous cell carcinoma.

4058 Background: Immune checkpoint inhibitors are now standard-of-care for patients with esophageal squamous cell carcinoma (ESCC). The predictive significance of PD-L1 expression in ESCC has been investigated by different antibodies, scoring algorithms and cutoff values in several phase III trials. However, it remains controversial whether PD-L1 is a predictive biomarker for response to PD-1/PD-L1 blockade. Evaluating the concordance of the commercially available PD-L1 assays is essential to understand the discrepancy in the ESCC clinical trials, and helpful to further investigate the predictive value of PD-L1 expression. Methods: 145 archival tumor samples were obtained from 131 patients with ESCC (stage I-IV) at National Taiwan University Hospital. Formalin-fixed, paraffin-embedded archival tumor samples were assessed by three commercially available PD-L1 assays: VENTANA SP263, Dako 22C3 and Dako 28-8 assays. Assays were performed in a College of American Pathologists accredited central laboratory and scored for PD-L1 staining by using multiple metrics including tumor cell score (TC), immune cell score (IC) and combined positive score (CPS) or tumor area percentage (TAP). Analytical concordance was calculated pairwise between assays using the Spearman (ρ) rank correlation coefficient. Classification concordance, including agreement between clinically relevant scoring algorithms, was investigated using positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement (OPA) at multiple cutoff values to assess the overlap between populations by using different assays. Results: SP263, 22C3 and 28-8 assays showed good analytical correlation for TC staining (Spearman’s rank correlation coefficient 0.8–0.9). Correlation was lower for IC (Spearman’s rank correlation coefficient 0.59-0.61). There was moderate overlap between populations identified by SP263 and 28-8 or 22C3 based on CPS or TAP algorithm at multiple cutoff values. OPAs for these 3 assays ranged from 68%–88% at various matched algorithms. The SP263 and 22C3 PD-L1 assays appeared relatively more sensitive, assigning a higher proportion of patients as PD-L1 positive or high, compared to 28-8 assay. When using assay-specific clinically relevant algorithm, moderate classification agreement was seen for SP263 versus 22C3 or 28-8. Differences were observed between patient populations with tumor classified as PD-L1 high versus PD-L1 low/negative using CPS≥10, TAP≥10% and TC≥1%. The PPA between 22C3 CPS≥10 and SP263 TAP≥10 or 28-8 CPS≥10 or 28-8 TC≥1% were 75%, 57% and 68% respectively. Conclusions: This study is the first dataset to compare various PD-L1 assays in ESCC. Differences in classification of patients with PD-L1 high versus low/negative using clinically relevant algorithms suggest that caution should be taken when comparing data across the trials.

Internal Expansion Preconditioning of Recipient Site Increases Fat Graft Retention by Enriching Stem Cell Pool and Inducing Browning in Rats.

Fat grafting has an unsatisfactory retention rate for breast reconstruction because of poor recipient conditions. The contribution of the recipient site to fat grafts is unknown. In this study, the authors hypothesize that tissue expansion could improve fat graft retention by preconditioning the recipient fat pad. Overexpansion was achieved using 10-mL cylindrical soft-tissue expanders implanted beneath the left inguinal fat flaps of 16 Sprague-Dawley rats (weighing 250 to 300 g), whose contralateral parts were implanted with a silicone sheet as a control. After 7 days of expansion, the implants were removed and both inguinal fat flaps received 1 mL of fat grafts from eight donor rats. Fluorescent dye-labeled mesenchymal stromal cells were injected into rats and tracked in vivo by fluorescence imaging. Transplanted adipose tissue was harvested at 4 and 10 weeks ( n = 8 per time point). After 7 days of expansion, OCT4 + ( P = 0.0002) and Ki67 + ( P = 0.0004) areas were increased with up-regulated expression of CXCL12 in recipient adipose flaps. An increasing number of CM-DiI-positive mesenchymal stromal cells were observed in the expanded fat pad. At 10 weeks after fat grafting, retention rate, measured using the Archimedes principle, was much higher in the expanded group than in the nonexpanded group (0.3019 ± 0.0680 versus 0.1066 ± 0.0402; P = 0.0005). Histologic and transcriptional analyses revealed that angiogenesis was enhanced, and macrophage infiltration was decreased in the expanded group. Internal expansion preconditioning increased circulating stem cells into the recipient fat pad and contributed to improved fat graft retention. Patients who have limited soft tissue after mastectomy are encouraged to undergo fat grafting. Then, an internal expander could be placed beneath the transferred fat. After internal expansion preconditioning of the recipient site, fat grafting could be performed again for soft-tissue volumization.

Evaluation of hippocampal arylalkylamine N-acetyltransferase activity in amyloid-β neurotoxicity.

Arylalkylamine N-acetyltransferase (AANAT), a rate-limiting enzyme in melatonin synthesis, is present in extra-pineal tissues such as the hippocampus. The hippocampal AANAT activity in amyloid β (Aβ) neurotoxicity has not been exactly defined. Adult male rats received bilateral intra-CA1 Aβ administration. The hippocampus tissue sampling was performed 2, 12, and 24 h after Aβ injection in the morning and night. The inflammation was monitored using tumor necrosis factor-alpha (TNF-α) immunohistochemistry. The AANAT enzyme activity and melatonin levels were measured using western blotting and high-performance liquid chromatography. The sampling in the morning vs night showed no significant differences in the AANAT activity. The Aβ increased the area of TNF-α positive staining 24 h after injection, which indicated the induction of an inflammatory context. It was accompanied by a significant reduction in AANAT activity and hippocampal melatonin. A reverse correlation was also detected between TNF-α and AANAT activity in the 24-h group. The TNF-α positive area was significantly increased in the 24-h group as compared to the 12-h group. Data showed that inflammatory processes began 12 h after the Aβ injection and augmented 24 h later. In the second experiment, the impact of Aβ injection on hippocampus AANAT activity was examined in the pinealectomized (PIN×) animals. The PIN× per se did not affect the hippocampal AANAT and melatonin levels. However, there was a significant decrease in hippocampal melatonin in the PIN×+Aβ group. The findings suggest the accompanying hippocampal inflammatory context and AANAT enzyme activity reduction in early stages after Aβ administration. Understanding the underlying mechanism of the decreased AANAT activity may suggest new treatment strategies.

A comparative study of the therapeutic effect of bone marrow mesenchymal stem cells versus insulin on mandibular dento-alveolar complex collagen formation and beta-catenin expression in experimentally induced type I diabetes

ObjectiveTo assess and compare the therapeutic effect of bone marrow mesenchymal stem cells (BM-MSCs) versus insulin on mandibular dento-alveolar complex collagen formation and beta-catenin (β-catenin) expression in experimentally induced type I diabetes in albino rat. DesignTwenty-eight male albino rats were equally divided as follows; Group I: was composed of rats which received no drug. The remaining rats were administrated a single streptozotocin (STZ) (40 mg/kg) intra-peritoneal injection. After affirmation of diabetes induction, the rats were divided into: Group II: Diabetic rats were given no treatment. Group III: Diabetic rats received a single BM-MSCs intravenous injection (1x106 cells). Group IV: Diabetic rats were given a daily insulin subcutaneous injection (5 IU/kg). After 28 days, mandibles were processed and stained by Hematoxylin & Eosin (H&E), Masson’s trichrome and anti-β-catenin antibody. A statistical analysis was performed to measure positive area% of Masson’s trichrome and β-catenin. ResultsDento-alveolar complex tissues and cells of Group II showed destructive changes histologically, while Groups III and IV demonstrated improved histological features. Group II presented almost old collagen in all dento-alveolar complex tissues, and nearly negative β-catenin expression. Groups III and IV revealed a newly formed collagen intermingled with very few areas of old collagen, and both groups showed positive β-catenin immunoreactivity. Statistically, Groups III and IV represented the highest mean values of Masson’s trichrome area% and β-catenin area%, while Group II reported the lowest mean. ConclusionsStreptozotocin has a destructive effect on the dento-alveolar complex structure and function. BM-MSCs and insulin show regenerative capacity in STZ-affected periodontal tissues, and statistically, they increase collagen formation and β-catenin expression.

Identification and prediction of climate factors based on factor analysis and a grey prediction model in China.

Identifying and predicting the impacts of climate change are crucial for various purposes, such as maintaining biodiversity, agricultural production, ecological security, and environmental conservation in different regions. In this paper, we used the surface pressure (SP), surface temperature (ST), 2-m air temperature (AT), 2-m dewpoint temperature (DT), 10-m wind speed (WS), precipitation (PRE), relative humidity (RH), actual evapotranspiration (ETa), potential evapotranspiration (ETP), total solar radiation (TRs), net solar radiation (NRs), UV intensity (UVI), sunshine duration (SD), convective available potential energy (CAPE) as factors in our climate modeling. The spatiotemporal distribution characteristics of the climate factors were analyzed and identified based on historical data for China from 1950 to 2020 using factor analysis and a grey model (GM (1,1)), and their future change characteristics were predicted. The results show that there is a strong correlation between climate factors. ST, AT, DT, PRE, RH, and ETa are the main factors that have the potential to cause heavy rain, thunderstorms, and other severe weather. Meanwhile, PRE, RH, TRs, NRs, UVI, and SD are among the major factors linked to climate change. Specifically, SP, ST, AT, and WS are among the minor factors in most areas. The top ten provinces in terms of combined factor scores are Heilongjiang, Neimenggu, Qinghai, Beijing, Shandong, Xizang, Shanxi, Tianjin, Guangdong, and Henan. The trend of climate factors in China is expected to remain relatively stable over the next 30years, with a noteworthy decrease observed in CAPE compared to the past 71years. Our findings can help to better mitigate the risks associated with climate change and enhance resilience; they also provide a scientific basis for environmental, ecological, and agricultural systems to cope with climate change.