Functional Damage Research Articles

Energy restriction inhibits β-catenin ubiquitination to improve ischemic stroke injury via USP18/SKP2 axis.

Ischemic stroke (IS) remains a global health issue because of its great disability and mortality. Energy restriction (ER) has been justified to perform an inhibitory role in cerebral injury caused by IS. This research was purposed to inquire the potential molecular mechanism of ER in IS. To verify the function of ER in the animal and cell models of IS, rats were subjected to intermittent fasting (IF) and middle cerebral artery occlusion/reperfusion (MCAO/R) surgery and HAPI cells were treated with oxygen-glucose deprivation and reoxygenation (OGD/R) and 2-deoxyglucose (2-DG). It was disclosed that IF mitigated brain damage and inflammation in MCAO/R rats. Likewise, ER inhibited OGD/R-evoked microglial activation and inflammatory response. Of note, ubiquitin specific protease 18 (USP18) was uncovered to be the most significantly upregulated in MCAO/R rats receiving IF compared to free-feeding MCAO/R rats. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot verified that ER led to the promotion of USP18 expression. Moreover, downregulation of USP18 neutralized the meliorative effects of ER on OGD/R-treated HAPI cells. Functionally, USP18 restrained β-catenin ubiquitination to enhance its expression. In addition, our results manifested that S-phase kinase associated protein 2 (SKP2) contributed to degradation of β-catenin and USP18 abolished the role of SKP2 in β-catenin ubiquitination. Knockout of USP18 eliminated the protective effects of IF on MCAO/R rats, while SKP2 exacerbated brain damage and inflammation by decreasing β-catenin expression after IF. In summary, we validated that ER-induced USP18 exerts a suppressive function in IS damage through SKP2-mediated β-catenin ubiquitination.

Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy

ObjectivesAmong all the diabetes complications brought on by persistent inflammation is diabetic kidney disease (DKD). One essential method of the inflammatory response's programmed cell death is anthrax. One of the main causes of diabetic renal disease progression in a high-glycemic environment is the lysis of renal resident cells.MethodThis investigation sought to determine whether Astragaloside IV (AS-IV)'s anti-pyroptosis action provides a protective function for the kidneys. For 12 weeks, db/db mice received 40 mg/kg of AS-IV by transgastric gavage. To validate the possible in vitro mechanism, mouse podocytes were cultivated for additional experiments.ResultsIn vitro, AS-IV led to a significant reduction in blood urea nitrogen (BUN), urine albumen-to-creatinine ratio (UACR), serum creatinine (CREA), and hyperglycemia in db/db mice and lessen the pathological alterations in the kidney. Moreover, pyrin structural domain of the NLR family pyrin domain containing 3 (NLRP3), cleaved-caspase-1, gasdermin D (GSDMD), IL-18, and IL-1β were down-expressed and podocyte markers podocin and nphs1 were up-regulated following AS-IV intervention. By silencing GSDMD, we demonstrated in vitro that HG-stimulated podocytes undergo pyroptosis. We also discovered that AS-IV can mitigate this pyroptosis. To confirm that AS-IV prevented the NLRP3 inflammasome from activating, the NLRP3 inhibitor CY-09 was employed. It was also discovered that AS-IV prevents the expression of TXNIP and NLRP3 as well as their interaction. GSDMD expression was significantly downregulated following TXNIP-siRNA treatment, whereas GSDMD expression was upregulated in TXNIP overexpression cells; this upregulation could be undone with AS-IV.ConclusionsThe anti-pyroptosis effect of AS-IV via the TXNIP-NLRP3-GSDMD axis improves the renal function and podocyte damage of db/db mice and delays the onset of DKD, according to in vivo and in vitro experimental data.

Temporal Effects of Hypoxia Exposure at High Altitudes on Compensatory Brain Function: Evidence from Functional Connectivity of Resting-State EEG Brain Networks.

Ren, Hong, Xi-Yue Yang, Rui Su, HaiLin Ma, and Hao Li. Temporal Effects of Hypoxia Exposure at High Altitudes on Compensatory Brain Function: Evidence from Functional Connectivity of Resting-State EEG Brain Networks. High Alt Med Biol. 00:00-00, 2024. Background: The aim of this study was to investigate the effects of prolonged exposure to hypobaric hypoxia at high altitude on changes in brain function measured by electroencephalography (EEG), focusing specifically on the resting-state brain network functional connectivity and compensatory adaptations in brain function among individuals with varying durations of high altitude residency. Methods: In study I, 64 participants were divided into high-altitude group (HG) and low-altitude group (LG). Ninety-six long-term migrants residing at an altitude of 3,650 m were recruited for studyII and categorized into three groups based on their duration of stay at high altitude: group A (1-2 years), group B (8-10 years), and group C (18-20 years). Resting-state EEG data were collected from each participant, and functional connectivity analysis was conducted using Phase Locking Value. Results: Study I showed that participants with HG had stronger functional connectivity in the occipital lobe than those with LG (p < 0.05). The study II findings indicate that there were significant differences in functional connectivity strength among the frontal and occipital lobes in groups A, B, and C across the α, β, δ, and θ frequency bands. Specifically, the functional connectivity strength of the frontal lobe was significantly higher in group A compared with group B, and in group B compared with group C (p < 0.05). Additionally, the functional connectivity of the occipital lobe was significantly higher in group C compared with group B, and in group B compared with group A (p < 0.05). Conclusions: The consistent results of the whole frequency band suggest that the individual's occipital lobe function is enhanced to compensate for the damage of frontal lobe function, so as to better adapt to the extreme environment at high altitude.

The experience of bilateral lung retransplantation after prolonged extracorporeal oxygenation

Background. Transplantation is the only effective method of helping patients with irreversible damage of the lung function when the possibilities of other treatment methods have been exhausted. At the same time, a chronic graft rejection is the main cause of the loss of the donor organ function in the long-term period, developing in more than 50% of patients within 5 years after surgery. Given irreversible lung damage with loss of lung functions, the only effective treatment method for this patient population is retransplantation, which is associated with high risks of complications and a long rehabilitation of the patient in the postoperative period.Objective. Demonstration of the first Russian experience of bilateral lung retransplantation in a patient after a longterm extracorporeal oxygenation.Results. The article presents the description of the first experience of bilateral lung retransplantation in Russia performed in a patient with a chronic rejection 4.5 years after the primary transplantation performed for end-stage lung lesions in non-langerhans cell histiocytosis. In the 96-day period of waiting for a donor organ, the patient's gas-exchange lung function was compensated by using veno-venous extracorporeal membrane oxygenation.Conclusions. Retransplantation is an effective method of treatment for patients with irreversibly damaged lung function, but still remains an operation associated with high risks of complications and unfavorable outcome.

Research on Damage Assessment Method for Reinforced Concrete T-Girder Bridges Under Munitions Strikes

As a transportation hub, the girder bridge is often an important target for both sides in combat, and it is very important for wartime decision-making and subsequent fire planning to carry out assessment on the effect of the damage to the bridge after the fight. The use of images for target damage assessment is more secure and efficient compared with the traditional method of manual inspection. However, the current image-based damage assessment of girder bridges has the problems of neglecting the damage to bridge piers and the poor stability of the damage features. To address these issues, this paper proposes a functional damage assessment method for beam bridges after being hit by ammunition based on visible light images. This method decomposes the girder bridge into two main sub-targets (the abutment and deck), analyzes its functional characteristics, designs the residual bearing capacity of the bridge and the number of passable lanes in the damage features, proposes an algorithm for conversion from image features to damage features and a fusion algorithm for the damage features, and establishes the rules for the evaluation of the damage level accordingly. The MATLAB experiment verifies that the method is able to extract the residual bearing capacity and the number of passable lanes from the image of the post-fighting girder bridge and to obtain the damage assessment results, which provides a new method for the assessment of the effect of damage to girder bridges.

Vanadium exposure and kidney markers in a pediatric population: a cross-sectional study.

Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed. A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin-creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders. Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile. Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.

Distinguishing short-term and long-term climate impacts in damage functions

Abstract Climate change presents substantial challenges to global economic stability, with damage functions widely applied to evaluate its potential impacts. However, differing assumptions within damage functions lead to significant variability in estimated climate damages, with limited quantitative investigation into the reasons for these discrepancies. This study addresses this gap by distinguishing between short-term and long-term climate impacts in damage assessments, using the Dynamic Integrated Climate-Economy (DICE) model as a case study, alongside other assessments. Short-term impacts capture immediate economic disruptions, whereas long-term impacts encompass enduring effects on economic growth, such as reductions in capital stock. The results demonstrate that accounting for long-term impacts increases estimated damages by approximately 30% in the DICE model. Comparative analysis across multiple models reveals that different treatments of short-term and long-term climate impacts contribute significantly to variations in projected economic damages. This study emphasizes the urgent need for future damage functions to clarify both long-term and short-term climate damages to inform robust climate policies.

Optical Microangiography and Progressive Retinal Nerve Fiber Layer Loss in Primary Angle-closure Glaucoma

Precis Younger patient age (coefficient: 0.10, P=0.04) and greater peak IOP during follow-up (coefficient: -0.14, P=0.03), but not baseline optical microangiography parameters, were significantly associated with a faster rate of RNFL loss in mild-moderate PACG. Purpose: To evaluate the association between optical microangiography (OMAG) measurements and progressive retinal nerve fiber layer (RNFL) loss in primary angle-closure glaucoma (PACG). Methods: In a prospective study, 45 eyes of 30 PACG patients (86 hemifields) with mild to moderate functional damage were longitudinally studied for at least 2 years and with a minimum of 3 optical coherence tomography (OCT) examinations. OMAG imaging was performed at the baseline visit. Effect of clinical parameters (age, gender, presence of systemic diseases, central corneal thickness, mean, peak and fluctuation of intraocular pressure during follow-up), baseline hemifield mean deviation (MD) and baseline OMAG (quadrant peripapillary and macular perfusion density [PD]) on the rate of RNFL change was evaluated using linear mixed models. Results: Average (±SD) hemifield MD, RNFL thickness, peripapillary PD and macular PD of the analyzed quadrants at baseline were -6.0±3.4 dB, 89±21 µm, 40.1±3.5% and 29.6±10.3%, respectively. Rate of quadrant RNFL change was -2.5±1.7 µm/year. Multivariate mixed models showed that younger patient age (coefficient: 0.10, P=0.04) and higher peak IOP during follow-up (coefficient: -0.14, P=0.03) were significantly associated with a faster rate of RNFL loss. Conclusions: Younger patient age and greater peak IOP during follow-up were significantly associated with a faster rate of RNFL loss in PACG patients with mild to moderate severity of functional damage. None of the OMAG parameters at baseline were associated with RNFL thinning suggesting a limited role of OCTA imaging in predicting structural progression in mild-moderate PACG.

Lysosphingolipids in ceramide-deficient skin lipid models.

Ceramides are key components of the skin's permeability barrier. In atopic dermatitis, pathological hydrolysis of ceramide precursors - glucosylceramides and sphingomyelin - into lysosphingolipids, specifically glucosylsphingosine (GS) and sphingosine-phosphorylcholine (SPC), and free fatty acids (FFAs) has been proposed to contribute to impaired skin barrier function. This study investigated whether replacing ceramides with lysosphingolipids and FFAs in skin lipid barrier models would exacerbate barrier dysfunction. When applied topically to human stratum corneum sheets, SPC and GS increased water loss, decreased electrical impedance and slightly disordered lipid chains. In lipid models containing isolated human stratum corneum ceramides, reducing ceramides by ≥30% significantly increased permeability to four markers, likely due to loss of long-periodicity phase (LPP) lamellae and phase separation within the lipid matrix, as revealed by X-ray diffraction and infrared spectroscopy. However, when the missing ceramides were replaced by lysosphingolipids and FFAs, no further increase in permeability was observed. Conversely, these molecules partially mitigated the negative effects of ceramide deficiency, particularly with 5-10% SPC, which reduced permeability even compared to control with "healthy" lipid composition. These findings suggest that while ceramide deficiency is a key factor in skin barrier dysfunction, the presence of lysosphingolipids and FFAs does not aggravate lipid structural or functional damage, but may provide partial compensation, raising further questions about the behaviour of lyso(sphingo)lipids in rigid multilamellar lipid environments, such as the stratum corneum, that warrant further investigation.

Mincle Maintains M1 Polarization of Macrophages and Contributes to Renal Aging Through the Syk/NF-κB Pathway.

Kidney is a classic organ undergoing senescence, and chronic inflammation has an important effect in cellular senescence. Mincle has been shown to be vital for maintaining the M1 phenotype of macrophages, but its role in regulating renal aging has yet to be explored. Young (2 months of age) and old (24 months of age) mice were used to analyze the changes of kidney damage during natural aging. Mice were subcutaneously injected with D-galactose (D-gal) to establish a renal aging model, and miR-6948-3p mimic and Mincle siRNA were administered via the tail vein every 3 days. Aged kidney and experimental aging kidney were characterized by decreased renal function and structural damage, and upregulated expression of senescence-related proteins and SPAP components. The ratio of M1 macrophages was increased in the aged kidney, and Mincle accumulated in the aged kidney macrophages. Administration of miR-6948-3p mimic or Mincle siRNA alleviated D-gal-induced renal senescence. LPS was used to induce M1 polarization of bone marrow-derived macrophages, and a coculture system of M1 macrophages and mouse renal tubular epithelial cells (TCMK-1) was established. Mincle was upregulated in LPS-induced M1 macrophages in vitro, and silencing Mincle in M1 macrophages attenuated M1 macrophage-induced TCMK-1 cell senescence. Mechanistically, Mincle was regulated by miR-6948-3p and maintained the M1 phenotype of macrophages through the Syk/NF-κB pathway. In conclusion, Mincle, posttranscriptionally suppressed by miR-6948-3p, modulated renal senescence by maintaining the phenotype of M1 macrophages through the Syk/NF-κB pathway.

Tempol mitigates inflammation, oxidative stress, and histopathological alterations of cadmium-induced parotid gland injury in rats

Cadmium (Cd) is a potent environmental pollutant that causes functional and structural damage to the salivary glands. Tempol (TEM) has powerful antioxidant activity that can potentially preserve organ function. Aims: This study was designed to investigate the protective effects of TEM on Cd-induced toxicity in rat parotid salivary glands. Materials and methods: Twenty-four adult Wistar male rats were randomly assigned to four equal groups: control, TEM (27.5 g/100 ml), Cd (0.6 g/100 ml), and TEM plus Cd (at the same doses). All treatments were dissolved in distilled water and administered subcutaneously four times a week for four weeks. Parotid gland tissues were isolated and subjected to molecular and histo-biochemical assessments. Key findings: TEM exerted a prophylactic effect against Cd-induced toxicity in the parotid glands by controlling inflammation through the downregulation of toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B/ interleukin-1 beta mRNA expression, upregulation of aquaporin-5 mRNA expression, improvement of the oxidant/antioxidant status in the parotid gland, mitigation of endoplasmic reticulum stress, and repair of the associated histological and ultrastructural abnormalities. Significance: TEM protects against Cd-induced toxicity in the parotid glands of rats, attributable at least in part to its anti-inflammatory and antioxidant properties, as well as its ability to inhibit ER stress and facilitate glandular repair. However, the protective effects of TEM did not reach the levels observed in the control group. TEM could be a promising clinical candidate for protecting the salivary glands, particularly in high-risk groups such as workers exposed to Cd and cigarette smokers.

Saudi Awareness of Chronic Kidney Disease Risk Factors

Background: Complex disorder CKD involves excessive fluid and waste buildup in the circulation, causing structural or functional damage to the kidneys. This article used general Saudi population data to assess public understanding of chronic kidney disease risk factor among adults. Methodology: The present study is a cross-sectional investigation that included a sample of 1111 participants from the Kingdom of Saudi Arabia, all of whom were above the age of eighteen and represented both genders. The data was analyzed utilizing Microsoft Excel and SPSS software. The findings of this study encompassed a total of 1111 participants, with 67.9% identifying as females and 32.1% as males. A total of 23.7% of the participants indicated that they had a family member who had been diagnosed with renal illness. Among this group, 51% reported that the affected family member belonged to the first-class category. A majority of respondents (71.6%) indicated possessing a moderate level of knowledge, while a smaller proportion (17.5%) reported having little knowledge. Conversely, only 11% of participants claimed to possess a high level of knowledge. A total of 44.9% of participants indicated a moderate attitude, while 39.9% reported a low attitude score. Only 15.2% of respondents reported a high attitude score. Conclusion: Based on the present research, it was determined that the participants exhibited a commendable comprehension of chronic kidney diseases (CKDs), with findings aligning with previous investigations conducted in Saudi Arabia and surpassing those from diverse nations. Furthermore, the participants in our research had a favorable disposition towards chronic kidney diseases (CKDs), aligning with findings from previous studies.

Effects of milk powder fortified with red ginseng extracts on the skin barrier function and immunity of middle-aged women

This study investigated the effects of a nutritional milk composition containing red ginseng extract (MCCRG) on the skin barrier function and immunity of middle-aged women. Fifty women (aged, 25 to 45) consumed MCCRG orally for 56 days. Evaluations of skin phenotype, facial bacterial microbiome, immune system function, and clinical diagnoses were conducted. The results indicated that MCCRG significantly improved skin hydration, firmness, elasticity, and glossiness. Furthermore, MCCRG also reduced TEWL and wrinkles and enhanced skin barrier integrity. Additionally, high IgG levels and improved CD4+/CD8+ ratios due to MCCRG consumption increased facial microbiota diversity and immune function. Clinical diagnoses provided supplementary evidence for the efficacy of MCCRG. The findings of this study demonstrated that MCCRG, through nutritional support, enhanced both skin barrier and immune system functions. This study offers substantial evidence of the innovative therapeutic effects of nutritional support on skin barrier damage and immune function.

Plasma metabolic profile reveals signatures of maternal health during gestational hypertension and preeclampsia without and with severe features.

Preeclampsia, a pregnancy-specific syndrome, poses substantial risks to maternal and neonatal health, particularly in cases with severe features. Our study focuses on evaluating the impact of low molecular weight metabolites on the intricate mechanisms and pathways involved in the pathophysiology of preeclampsia when severe features are present. We aim to pinpoint the distinct metabolomic profile in maternal plasma during pregnancies affected by hypertensive disorders and to correlate the metabolite levels with the clinical characteristics of the study cohort. A total of 173 plasma samples were collected, comprising 36 healthy pregnant women (HP), 52 patients with gestational hypertension (GH), 43 with preeclampsia without (PE-), and 42 with severe features (PE+). Nuclear magnetic resonance spectroscopy and metabolite identification were conducted to establish the metabolomic profiles. Univariate and chemometric analyses were conducted using MetaboAnalyst, and correlations were performed using GraphPad Prism. Our study unveils distinct metabolomic profiles differentiating HP women, patients featuring GH, and patients with PE-and PE+. Our analysis highlights an increase in acetate, N,N-dimethylglycine, glutamine, alanine, valine, and creatine levels in the PE+ group compared to the HP and GH groups. The PE+ group exhibited higher concentrations of N,N-dimethylglycine, glutamine, alanine, and valine compared to the PE-group. Moreover, elevated levels of specific metabolites, including N,N-dimethylglycine, alanine, and valine, were associated with increased blood pressure, worse obstetric outcomes, and poorer end-organ function, particularly renal and hepatic damage. Metabolomic analysis of PE+ individuals indicates heightened disturbances in nitrogen metabolism, methionine, and urea cycles. Additionally, the exacerbated metabolic disturbance may have disclosed renal impairment and hepatic dysfunction, evidenced by elevated levels of creatine and alanine. These findings not only contribute novel insights but also provide a more comprehensive understanding of the pathophysiological mechanisms at play in cases of PE+.

Antitumor effects of plasma‑activated solution on a murine melanoma model in vivo and in vitro.

Melanoma is a common malignant skin tumor with highly invasive features and a high metastasis rate that can be difficult to treat clinically. Large-scale resection of primary cutaneous melanoma is often used to avoid postoperative recurrence. For advanced patients, radiotherapy, targeted therapy and immunotherapy are often needed. Low-temperature plasma has been proved to have significant antitumor effects on a variety of cancer cell lines cultured in vitro. The main limitation of direct low-temperature plasma treatment is that it has weak penetration ability and can only treat superficial lesions. In recent years, research on low-temperature plasma-activated solution has revealed that it also have good antitumor effects and low-temperature plasma penetration depth problems can be solved by local injection. The present study revealed that low-temperature plasma-activated phosphate buffer solution exhibited good antitumor effects and biosafety against melanoma in vitro and in vivo. It demonstrated that low-temperature plasma-activated solution has antitumor effects due to its regulation of intracellular redox, destruction of mitochondrial function and DNA damage. In vivo experiments demonstrated that treatment with low-temperature plasma-activated solution not only exhibited antitumor effects but also caused no significant damage to hematopoietic function or liver and kidney functions in mice. All these results demonstrated that low-temperature plasma-activated solution represent a promising antitumor treatment strategy.

Exacerbated ischemic brain damage in type 2 diabetes via methylglyoxal-mediated miR-148a-3p decline.

Although microvascular dysfunction is a widespread phenomenon in type 2 diabetes (T2D) and is recognized as a main cause of T2D-aggravated ischemic stroke injury, the underlying mechanisms by which T2D-mediated exacerbation of cerebral damage after ischemic stroke is still largely uncharacterized. Here, we found that methylglyoxal-mediated miR-148a-3p decline can trigger blood-brain barrier dysfunction, thereby exacerbating cerebrovascular injury in diabetic stroke. Using T2D models generated with streptozotocin plus a high-fat diet or db/db mice, and then inducing focal ischemic stroke through middle cerebral artery occlusion and reperfusion (MCAO/R), we established a diabetic stroke mouse model. RNA-sequencing was applied to identify the differentially expressed miRNAs in peri-cerebral infarction of diabetic stroke mice. RT-qPCR confirmed the potential miRNA in the plasma of ischemic stroke patients with or without T2D. Fluorescence in situ hybridization was used to image the localization of the miRNA. Brain pathology was analyzed using magnetic resonance imaging, laser-Doppler flowmetry, and transmission electron microscope in diabetic stroke mice. Immunofluorescence and immunoblotting were performed to elucidate the molecular mechanisms. miR-148a-3p level was downregulated in the peri-infarct cortex of stroke mice and this downregulation was even more enhanced in diabetic stroke mice. A similar decrease in miR-148a-3p expression was also confirmed in the plasma of ischemic stroke patients with T2D compared to patients with ischemic stroke only. This miR-148a-3p downregulation intensified the severity of BBB damage, infarct size, and neurological function impairment caused by stroke. Notably, the reduction in miR-148a-3p levels was primarily triggered by methylglyoxal, a toxic byproduct of glucose metabolism commonly associated with T2D. Furthermore, methylglyoxal somewhat replicated the influence of T2D in exacerbating BBB damage and increasing infarct size caused by ischemia. Mechanistically, we found that downregulation of miR-148a-3p de-repressed SMAD2 and activated matrix metalloproteinase 9 signaling pathway, promoting blood-brain barrier impairment, and exacerbating thecerebral ischemic injury. Blood-brain barrier damage caused by methylglyoxal-mediated miR-148a-3p downregulation may provide a novel target for the therapeutic intervention for the treatment of stroke patients with diabetes.

Progress in the mechanism of functional dyspepsia: roles of mitochondrial autophagy in duodenal abnormalities.

Mitochondria are the main source of energy for cellular activity. Their functional damage or deficiency leads to cellular deterioration, which in turn triggers autophagic reactions. Taking mitochondrial autophagy as a starting point, the present review explored the mechanisms of duodenal abnormalities in detail, including mucosal barrier damage, release of inflammatory factors, and disruption of intracellular signal transduction. We summarized the key roles of mitochondrial autophagy in the abnormal development of the duodenum and examined the in-depth physiological and pathological mechanisms involved, providing a comprehensive theoretical basis for understanding the pathogenesis of functional dyspepsia. At present, it has been confirmed that an increase in the eosinophil count and mast cell degranulation in the duodenum can trigger visceral hypersensitive reactions and cause gastrointestinal motility disorders. In the future, it is necessary to continue exploring the molecular mechanisms and signaling pathways of mitochondrial autophagy in duodenal abnormalities. A deeper understanding of mitochondrial autophagy provides important references for developing treatment strategies for functional dyspepsia, thereby improving clinical efficacy and patient quality of life.

Numerical analysis and simulation of a quasistatic frictional bilateral contact problem with damage, long-term memory and wear

We present a mathematical model describing the equilibrium of a viscoelastic body with long-term memory in frictional contact with a sliding foundation. The process is quasistatic, and material damage resulting from excessive stress or strain is captured by a damage function. We assume the material is inhomogeneous, leading to multiple contact boundary conditions. The contact interface is partitioned into two segments: One part takes into account the wear of the contact surface, utilizing Archard's law. Here, contact is modeled with a normal compliance condition with unilateral constraints, coupled with a sliding version of Coulomb's law of dry friction. In the other part, contact is modeled with a nonmonotone condition involving normal compliance and a subdifferential frictional boundary condition. Variational formulation of the model is governed by a coupled system consisting of a variational–hemivariational inequality for the displacement field, a parabolic variational inequality for the damage field and an integral equation for the wear function. We study a fully discrete scheme for numerical approximation with an error estimation of the solution to this problem. Optimal error estimates for the linear finite element method are derived, followed by numerical simulations illustrating the behavior of the model.

Inhibiting NLRP3 Inflammasome Activation to Alleviate Retinal Inflammation and Protect the Optic Nerve of OPTN(E50K)Mice.

OPTN (E50K) mutation is one of the significant pathogenic mutations in normal tension glaucoma (NTG). The molecular mechanism of NTG optic nerve injury is complex and diverse; its key mechanism is still unclear. The NLR family pyrin domain containing (NLRP3) inflammasome plays an essential role in the occurrence and development of inflammation. There is no report on whether NLRP3 inflammasome activation plays a crucial role in NTG optic nerve injury. Here, we explored the role of retinal inflammatory cascade reaction triggered by NLRP3 inflammasome activation in OPTN (E50K) mutated NTG optic nerve injury. This research may provide innovative strategies for effectively treating NTG optic nerve injury caused by OPTN (E50K) mutation. The R28 cell was constructed by AAV2 transfection, named GFP-R28, WT-R28, and E50K-R28 groups. Western blot, qPCR, and immunofluorescence were performed to measure the expression levels of the neurotrophic factors, the senescence indicators, the NLRP3-related indicators, the expression of the glial cell markers, and the inflammatory cytokines. Further, observe the changes in the above indicators in the WT-R28 and E50K-R28 groups after treatment with MCC950. Next, we compared the expression of neurotrophic factors and senescence indicators, NLRP3-related indicators, glial cell markers, and inflammatory factors between young and old WT and OPTN (E50K) mice. We examined the visual function of mice on days 1, 4 and 7. Furthermore, we observed the retinal morphology and the expression of neurotrophic factors and senescence indicators, NLRP3-related indicators, glial cell markers, and inflammatory factors between all groups were measured. We found that OPTN (E50K) mutations lead to NLRP3 inflammasome activation. The OPTN (E50K) mutant groups showed an inflammatory cascade, including glial cell activation and release of proinflammatory factors, leading to retinal structural and functional impairment in mice.MCC950 effectively inhibited the activation of the NLRP3 inflammasome and alleviated the retinal inflammatory cascade caused by the OPTN (E50K) mutation, ultimately improving visual function and retinal damage in mice. OPTN (E50K) mutation induces the activation of the NLRP3 inflammasome, which leads to a retinal inflammatory cascade. MCC950 can inhibit the activation of the NLRP3 inflammasome and retinal inflammatory cascade, improving visual function in OPTN (E50K) mutation mice.

Comprehensive evaluation of UV inactivation of E. coli using multiple gene targets and real-time quantitative PCR

UV disinfection is extensively used for wastewater disinfection and disinfection efficiency is commonly monitored using culture-based enumeration of E. coli. While culture-independent real-time quantitative polymerase chain reaction (qPCR) based methods are attractive due to faster turnaround and easier application, previous attempts with qPCR to monitor disinfection have been unsuccessful. In this study, the effect of UV irradiation on a pure E. coli culture was examined in collimated beam (CB) experiments and monitored using both a culturing technique and DNA damage quantified using both short amplicon (SA; <∼200 bp) qPCR and longer amplicon (LA; ∼500-bp) qPCR. The results, covering a UV dose range of 0 - 20 mJ/cm2 commonly used for wastewater disinfection, indicate a correlation between DNA gene damage quantified by both SA- and LA-qPCR and the decline in E. coli observed through culture-based methods. This demonstrates the potential of qPCR to serve as rapid alternative for monitoring wastewater disinfection efficacy. Furthermore, LA-qPCR was observed to be more sensitive than SA-qPCR. The results using LA-qPCR also revealed that UV exposure caused widespread and indiscriminate damage to E. coli’s genome, which is considered critical for its function and survival. The combined effect of UV on E. coli’s ability to function, grow or repair damage is suggested as the reason for the decline in culturability observed.