Levels Of Precursors Research Articles

Ozone production over arid regions: insights into meteorological and chemical drivers

Arid urban areas are pivotal in the global landscape, and their air quality issues are highlighted by the complexities of tropospheric ozone production. Here, we use recent satellite observations from TROPOMI and a longer record of data from OMI to investigate the levels of ozone precursors (NO2 and CH2O) in 12 major cities in arid regions. Using a space-based CH2O/NO2 indicator, we identified the dominant chemical regime influencing ozone formation, revealing a clear temporal trend that aligns with previously reported economic trajectories as well as variation in emission control strategies implemented in these cities. Our results show that, NO2 concentrations decreased in cities with proactive regulatory policies, such as Madrid and Los Angeles in semi-arid and arid regions. A contrasting increase was observed in rapidly developing cities within arid and hyper-arid regions, such as Tehran and Cairo, where emission controls are less strict. An increase in CH2O levels was also apparent, requiring more attention to VOCs control. Furthermore, our analysis clearly shows that the interactions between ozone production and climatic factors such as temperature exhibit a nonlinear relationship, especially in arid climates. These findings highlight the importance of emission reduction strategies that consider the meteorological and chemical drivers of dry regions, particularly in light of the rising global aridity.

Method for rock fracture prediction and early warning: Insight from fusion of multi-physics field information

Understanding the precursors leading to rock fracture is crucial for ensuring safety in mining and geotechnical engineering projects. To effectively discern these precursors, a collaborative monitoring approach that integrates multiple sources of information is imperative. This paper considered a rock multi-parameter monitoring loading system, incorporating infrared radiation and acoustic emission monitoring technologies to simultaneously track the rock fracture process. The study delves into the spatiotemporal evolution patterns of infrared radiation and acoustic emission in rock under loading. Utilizing stress, cumulative acoustic emission count, and average infrared radiation temperature (AIRT), the paper establishes a comprehensive evaluation model termed “acoustic-thermal-stress” fusion information, employing principal component analysis (PCA). The research reveals that the sensitivity to rock sample damage response follows the sequence of cumulative acoustic emission count, AIRT, and stress. Furthermore, a novel method for identifying rock fracture precursors is proposed, based on the first derivative of the comprehensive evaluation model. This method addresses the limitations of single physical field information, enhancing the robustness of monitoring data. It determines the average stress level of fracture precursors to be 0.77σmax. Subsequently, the study defines the probability function of rock damage during loading and fracture, enabling the realization of probability-based warnings for rock fracture. This approach introduces a new perspective on rock fracture prediction, significantly contributing to safety monitoring and warning systems in mine safety and geotechnical engineering. The findings of this research hold paramount engineering significance, offering valuable insights for enhancing safety measures in such projects.

Special bakery products - Acrylamide formation and bread quality are influenced by potato addition

Especially high levels of asparagine, like those present in potatoes, combined with reducing sugars, lead to increased acrylamide formation. As the influence of potato addition on acrylamide and baking quality in breads has not been examined yet, we aimed to investigate this area and prepared breads with potato flakes (7.5–22.5 g/100 g flour) at different moisture levels as a common mitigation approach (56.5–79.1 g/100 g flour). Analyses included reducing sugars (HPAEC–PAD), asparagine (HPLC) in dough, acrylamide (HPLC-MS/MS) in crumbs and crusts and baking quality measures (dimensions, baking yield, specific volume, lightness, browning index, firmness, crumb and crust moisture, crust-to-crumb ratio, crust thickness, pore analysis). High acrylamide concentrations were measured in crusts, reaching 292.3 ± 16.2 μg/kg, or 91.8 ± 5.3 μg/kg in bread. Significant (p < 0.001) linear correlations were identified between crust acrylamide and asparagine (r = 0.97), glucose (r = 0.85) and maltose (r = 0.92) in doughs, and also potato flakes addition (r = 0.95), surface browning index (r = 0.90) and bread lightness (r = −0.97). Summarizing, potato flakes addition led to higher precursor levels, while water addition influenced the reaction kinetics. Both parameters affected the quality of the bread significantly.

Synbiotic Bacillus megaterium DSM 32963 and n-3 PUFA Salt Composition Elevates Pro-Resolving Lipid Mediator Levels in Healthy Subjects: A Randomized Controlled Study.

Beneficial health effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) are partly attributed to specialized pro-resolving mediators (SPMs), which promote inflammation resolution. Strategies to improve n-3 PUFA conversion to SPMs may, therefore, be useful to treat or prevent chronic inflammatory disorders. Here, we explored a synbiotic strategy to increase circulating SPM precursor levels. Healthy participants (n = 72) received either SynΩ3 (250 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) lysine salts; two billion CFU Bacillus megaterium; n = 23), placebo (n = 24), or fish oil (300 mg EPA plus DHA; N = 25) capsules daily for 28 days in a randomized, double-blind placebo-controlled parallel 3-group design. Biomarkers were assessed at baseline and after 2 and 28 days of intervention. The primary analysis involved the comparison between SynΩ3 and placebo. In addition, SynΩ3 was compared to fish oil. The synbiotic SynΩ3 comprising Bacillus megaterium DSM 32963 and n-3 PUFA salts significantly increased circulating SPM precursor levels, including 18-hydroxy-eicosapentaenoic acid (18-HEPE) plus 5-HEPE, which was not achieved to this extent by fish oil with a similar n-3 PUFA content. Omega-3 indices were increased slightly by both SynΩ3 and fish oil. These findings suggest reconsidering conventional n-3 PUFA supplementation and testing the effectiveness of SynΩ3 particularly in conditions related to inflammation.

Efficacy of catheter ablation for atrial fibrillation in heart failure: a meta-analysis of randomized controlled trials.

The study aims to evaluate whether rhythm control by catheter ablation is superior to medical therapy for the patients with atrial fibrillation (AF) and heart failure (HF). The literatures were searched by using PubMed, Cochrane Library, Embase, and Web of Science databases up to 12 October 2023. The randomized controlled trials (RCTs) comparing rhythm control using catheter ablation vs. medical therapy in AF patients with HF were pooled. The primary outcomes included all-cause mortality, HF re-hospitalization, and stroke, and the secondary outcomes included left ventricular ejection fraction (LVEF), atrial tachyarrythmia recurrence, quality of life (Minnesota Living with Heart Failure Questionnaire score, MLHFQ score), 6min walking distance (6MWD), the level of N-terminal B-type natriuretic peptide precursor (NT-proBNP), and adverse events. Nine RCTs involving in 2293 patients met the inclusion criteria. Compared with medical therapy, catheter ablation reduced all-cause mortality [10.07% (121/1201) vs. 15.26% (175/1147), risk ratio (RR):0.60, 95% confidence interval (CI): 0.48-0.74, P<0.00001, I2=0%] and the rate of HF re-hospitalization (RR: 0.65, P=0.02, 95% CI: 0.45 to 0.94, I2=74%), but had no obvious difference in incidence of stroke (RR: 0.67, P=0.27, 95% CI: 0.32 to 1.38, I2=0%). Catheter ablation enhanced LVEF [mean difference (MD), 6.26%, P<0.00001, I2=89%], reduced AT recurrence (RR: 0.37, P<0.00001, 95% CI: 0.26 to 0.52, I2=89%), improved the quality of life (MLHFQ score) (MD: -6.83, P=0.003, I2=67%), elevated 6MWD (MD: 15.92, P=0.006, I2=76%), and diminished the level NT-proBNP (MD: -44.19, P<0.00001, I2=75%), but had no significant difference in adverse events [25.81% (310/1201) vs. 30.25% (347/1147), RR: 0.81, 95% CI: 0.65-1.01, P=0.06, I2=55%]. Catheter ablation as rhythm control strategy substantially enhances the survival rate, reduces HF re-hospitalization, increases the rate of sinus rhythm maintenance, improves the left ventricular function and the quality of life for AF patients with HF, and has similar safety, compared with medical therapy. The rhythm control by catheter ablation may be a better strategy for the AF patients with HF.

Sex Steroid Levels in Women With Hypopituitarism: A Case-controlled Observational Study.

Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped. To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay. Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started GH replacement in 1995 to 2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol, and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone, and estradiol showed similar patterns. Women with HH and ACTH deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency. This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study, and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement.

A quantitative analysis of causes for increasing ozone pollution in Shanghai during the 2022 lockdown and implications for control policy

Ground-level ozone (O3) pollution is a major air quality issue in densely populated urban areas. Despite a significant decline in human activities in the megacity Shanghai from March 28 to May 31, 2022, ground-level measurements indicate a rise in maximum daily average 8-h (MDA8) O3 concentrations in comparison to the corresponding period in 2021. There is a need for quantitative analysis to identify the reasons behind this increasing O3 concentration. We analyzed ground measurements of O3 and its precursors and meteorological parameters made in Shanghai, using random-forest (RF) model and chemical box model to elucidate the roles of meteorological and chemical factors in influencing O3 concentrations. Across urban, suburban, semi-rural, and coastal sites, the urban center of Shanghai experienced the largest decreases in the concentrations of nitrogen oxides (NOx; 53%) and volatile organic compounds (VOCs; 52%), with the most notable rise in MDA8 O3 concentrations (16%). RF modeling indicates that meteorological factors reduced MDA8 O3 concentrations by a marginal 3%, whereas a decline in anthropogenic emissions resulted in a 17% increase in MDA8 O3 concentrations. Chemical box modeling at the Pudong urban site indicates that while the decline in VOCs reduced O3 production by 42%, this was negated by a reduction in NOx from traffic emissions, which enhanced O3 production by 51%, resulting in an increase in O3 production overall. Despite a halving in precursor levels, Shanghai's urban centre remains predominately under VOC-limited conditions throughout the study period, with high NO2 levels from the petrochemical industry and traffic emissions. Joint control of anthropogenic VOCs (AVOCs) and NOx, with a ratio greater than 1.29, could help avoid exacerbation of O3 pollution and reduce NO2 pollution. Our findings emphasize the necessity of reducing industrial emissions along with ongoing green transportation strategies for alleviating O3 pollution in megacities like Shanghai.

Monocytes and Fibrinogen as Biomarkers in Type 2 Diabetes Mellitus

Background: In the diagnosis of diabetic foot, in addition to the inflammatory biomarkers that have been widely interested and used, for example procalcitonin, C-reactive protein (CRP), ESR, leukocyte count, neutrophil count, Fibrinogen and Monocytes are considered as biomarkers in this study. possible. Methods: A prospective study was designed to examine the utility of fibrinogen and monocytes in estimating disease severity in patients with DFU (Diabetic Foot Ulcer). The severity of DFU was assessed using the Wagner criteria distinguishing between patients with diabetic foot without ulcer (WDFU) and with non-infected diabetic foot ulcer (NIDFU) or with infected ulcer (IDFU). In this study the AA also wanted to correlate HbA1c to the concentration of Fibrinogen and the appearance of DFU, as well as the level of lymphocytes and monocyte precursors of macrophages in the evolution of ulcerated and non-ulcerated diabetic feet. Results: Mean blood fibrinogen values were significantly higher in patients with DFU grade ≧2 compared to those with DFU grade ≤1 (424.4±138.8 mg/dL versus 395.3±130.0 mg/dL; p=0.091). Fibrinogen values were correlated with CRP levels, neutrophils, ESR and leukocyte count. Monocytes presented a significant difference between non-diabetic patients with ulcer and without ulcer (0.41 vs 0.29 k/L; p=0.000) and between the diabetic without ulcer (WDFU) and non-diabetic without ulcer (NDWU) groups (0.39 vs 0.29 k/L; p=0.000). The Procalcitonin (PCT) value was &lt;0.5 ng/dl, therefore it had no diagnostic significance. Only 1% of the values found were higher than 0.5 with an average of 1.04 ng/dl (range: 0.52-2.5). Conclusions: Neither monocytes nor HbA1c can be considered biomarkers for the risk of ulcer formation in the diabetic foot, but only as biomarkers of type 2 Diabetes Mellitus. Differently, fibrinogenemia, its pre/post intervention ratio, the  angle and the k value of thromboelastography (TEG), have a clinical significance on the risk of onset and development of ulcerated diabetic foot. The cut-off for ulcer formation for both the pre/post intervention ratio of fibrinogenemia and monocythemia is 1.10, with a sensitivity of 84.1% and a specificity of 24.5% for fibrinogen and 93.8% and 14.8% for monocytes.

ПРОГНОСТИЧЕСКАЯ МОДЕЛЬ ВЕРОЯТНОСТИ УВЕЛИЧЕНИЯ СТАДИИ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ ПОСЛЕ ВИРУСНОЙ ПНЕВМОНИИ, ВЫЗВАННОЙ SARS-COV-2

Abstract. Introduction. An alarming aspect and area of study are represented by the COVID-19 consequences. Arterial hypertension is one of the most frequently reported comorbid pathologies in patients with severe-course COVID-19 requiring the patient’s hospitalization. Given the similarity of some pathogenetic mechanisms underlying arterial hypertension and COVID-19, there is no doubt about their interinfluence. One of the common pathogenetic links of arterial hypertension and COVID-19 is endothelial dysfunction. Objective: To develop a prognostic model of the probability of an increase in the stage of arterial hypertension in 6 months after viral pneumonia caused by SARS-COV-2. Material and Methods: The study included 45 patients with a confirmed diagnosis of COVID-19 (virus identified) with arterial hypertension. This group of patients was dynamically monitored for 6 months after discharge from the hospital. The duration of inpatient treatment was 14 [10-16] bed days. The level of biomarkers of endothelial dysfunction - endothelin-1 and the N-terminal precursor of natriuretic peptide C-type was determined in blood serum by enzyme immunoassay. The dynamics of the levels of these biomarkers during the hospital stay is regarded as positive with a decrease in the level of more than 10% and as insufficient – with an increase, unchanged values or a decrease to 10% inclusive. Results and discussion. The final prognostic model included: the level of the N-terminal precursor of natriuretic peptide C-type upon admission to the hospital and the dynamics of its level in the hospital. The model was statistically significant (p=0,028). Based on the values of regression coefficients, the level of the N-terminal precursor of natriuretic peptide C-type has a direct relationship with the probability of an increase in the stage of arterial hypertension after 6 months in patients with arterial hypertension after viral pneumonia caused by SARS-COV-2. An increase in the level of the N-terminal precursor of natriuretic peptide C-type by 1 pg/ml upon admission increases the risk of an increase in the stage of arterial hypertension by 1,3 times. The absence of positive dynamics of the level of the N-terminal precursor of natriuretic peptide C-type during inpatient treatment increases the likelihood of an increase in the stage of arterial hypertension by 19,6 times. The diagnostic sensitivity of the developed prognostic model was 86,7%, diagnostic specificity – 80,0%, diagnostic efficiency – 84,4%. Conclusions: The prognostic model developed by us, including as a predictor the level of the N-terminal precursor of natriuretic peptide C-type at admission and its dynamics in the hospital, can be used to individually predict an increase in the stage of arterial hypertension within 6 months after viral pneumonia caused by SARS-COV-2.

B-cell lymphoma-2 phosphorylation at Ser70 site-related autophagy mediates puerarin-inhibited the apoptosis of MC3T3-E1 cells during osteoblastogenesis.

To explore the relationship between autophagy and apoptosis regulated by puerarin during osteoblastogenesis. In this study, the effects of puerarin on the autophagic activity and apoptosis level of osteoblast precursors (MC3T3-E1 cells) was observed. Subsequently, the roles of puerarin on B-cell lymphoma-2 (Bcl-2) phosphorylation at different sites in osteoblast precursors were observed. The effect of puerarin on the interaction between Bcl-2 and autophagy regulatory molecule or pro-apoptotic molecule was also investigated using Co-immunoprecipitation assays. In addition, the effect of puerarin on mitochondrial membrane potential of osteoblast precursors was also identified by mitochondrial membrane potential fluorescence probe assays. Our results showed that puerarin can promote the autophagic activity and apoptosis level of MC3T3-E1 cells. In addition, puerarin promoted Bcl-2 phosphorylation at Ser70 site, and the dissociation of Bcl-2-Beclin1 complex. Moreover, puerarin could enhance the binding of Bcl-2-Bcl-2-Associated X (Bax) complex in MC3T3-E1 cells. Furthermore, puerarin increased the mitochondrial membrane potential of MC3T3-E1 cells. Therefore, puerarin promotes Beclin1 into autophagy flux through Bcl-2 phosphorylation at Ser70, thereby enhancing autophagy of osteoblast precursors, which mediates its anti-apoptotic role during osteoblastogenesis. Furthermore, the dissociation of Bcl-2-Beclin1 complex is conducive to the binding of Bcl-2-Bax complex, which resists the apoptosis of osteoblast precursors viathe increased mitochondrial membrane potential.

The effectiveness of hardware CPAP therapy in heart failure with preserved left ventricular ejection fraction and obstructive sleep apnea syndrome

Aim. To evaluate the effectiveness of hardware Continuous Positive Airway Pressure therapy (CPAP therapy) and its likely predictors in patients with heart failure with preserved ejection fraction (HFpEF) associated with obstructive sleep apnea syndrome (OSAS).&#x0D; Materials and methods. The study involved 207 men with HFpEF and OSAS (apnea/hypopnea index 15 per hour) who did not initially have ischemic disease and other structural heart pathology. At inclusion in the study, polysomnography and echocardiography were performed with an assessment of diastolic function and global longitudinal deformation of the left ventricular myocardium, as well as a 6-minute walk test (6MWT) and the level of the brain natriuretic peptide precursor (NT-proBNP) in the blood was determined. 80 patients received hardware CPAP the rapy, 127 patients made up the control group. After 12 months, 6MWT was repeated, NT-proBNP was determined, and clinical outcomes were assessed retrospectively.&#x0D; Results. The CPAP group had 16% fewer hospitalizations (p=0.011 [95% confidence interval – CI 4.29]) and showed a trend towards an increase in the 6MWT distance (p=0.065). To assess the likely predictors of the effectiveness of CPAP therapy, a subgroup of “responders” was identified, characterized by an increase in the distance according to the 6MWT, a decrease in the level of NT-proBNP, and the absence of adverse clinical events during the observation period. There were significant differences between responders and non-responders in apnea/hypopnea index (p=0.01 [95% CI -10.6; -2.5]), global longitudinal deformation of the left ventricular myocardium (p=0.05 [95% CI -4.7; 0]), diastolic function E/A (p=0.02 [95% CI -0.1; 0]).&#x0D; Conclusion. CPAP therapy improves clinical outcomes and functional status in patients with OSAS-associated HFpEF. The predictive model built using the identified efficacy predictors can be used to develop a personalized treatment algorithm for this cohort of patients.

An Engineered Microbial Consortium Provides Precursors for Fengycin Production by Bacillus subtilis.

Fengycin has great potential for applications in biological control because of its biosafety and degradability. In this study, the addition of exogenous precursors increased fengycin production by Bacillus subtilis. Corynebacterium glutamicum was engineered to produce high levels of precursors (Thr, Pro, Val, and Ile) to promote the biosynthesis of fengycin. Furthermore, recombinant C. glutamicum and Yarrowia lipolytica providing amino acid and fatty acid precursors were co-cultured to improve fengycin production by B. subtilis in a three-strain artificial consortium, in which fengycin production was 2100 mg·L-1. In addition, fengycin production by the consortium in a 5 L bioreactor reached 3290 mg·L-1. Fengycin had a significant antifungal effect on Rhizoctonia solani, which illustrates its potential as a food preservative. Taken together, this work provides a new strategy for improving fengycin production by a microbial consortium and metabolic engineering.

Analysis of Influencing Factors of Ozone Pollution Difference Between Chengdu and Chongqing in August 2022

In August 2022, Chengdu and Chongqing showed significant differences in ozone (O3) pollution. Chengdu had O3 pollution days for 20 days, whereas Chongqing had no O3 pollution days. In this study, we analyzed the influencing factors of this difference from the emission level of precursors and meteorological conditions. The results showed that:① the total mixing ratio of 52 VOCs (volatile organic compounds) (including 26 alkanes, 16 aromatics, and 10 alkenes) in Chengdu (18.8×10-9) was 2.8 times that of Chongqing (6.6×10-9), and the total O3 formation potential (OFP) (51.2×10-9) was 2.0 times that of Chongqing (25.0×10-9). The·OH radical loss rate (L·OH) (3.9 s-1) was 1.7 times that of Chongqing (2.3 s-1). The top three OFP in Chengdu were ethylene, m/p-xylene, and isoprene, and those in Chongqing were isoprene, ethylene, and propylene. The contribution rate of alkenes to O3 in Chongqing was 60.7%, whereas the OFP of alkenes and aromatics in Chengdu were 1.6 times and 2.9 times that in Chongqing. In conclusion, the total mixing ratio of VOCs, atmospheric photochemical activity, and O3 formation potential of Chengdu were higher than those of Chongqing. ② Isoprene was ranked first place in L·OH in both Chengdu and Chongqing, indicating that the contribution of biogenic sources to O3 pollution in August was significant. However, the biogenic source emission activity was in response to temperature. From August 14 to 24, the high temperature in Chongqing (38.3℃) decreased biogenic source emission activity, whereas the temperature in Chengdu (34.9℃) increased the biogenic sources emission activity. ③ The horizontal and vertical atmospheric diffusion conditions of Chongqing were better than those of Chengdu, and Chengdu was affected by regional pollution transmission.

Selection of a Digitalis purpurea Cell Line with Improved Bioconversion Capacity of Hydroquinone into Arbutin.

This study aimed to investigate the biotransformation capabilities of a hydroquinone-tolerant Digitalis purpurea cell line (DpHQ) for bioconverting hydroquinone (HQ) into arbutin, a compound with significant therapeutic and cosmetic applications. The research evaluated the influence of various HQ concentrations, feeding protocols, and carbon sources on arbutin bioconversion yield. By using HPLC-MS for the quantification of arbutin in biomass and medium, the study revealed that higher precursor (HQ) concentration led to a more pronounced growth inhibition under single dosing than sequential dosing. At lower sugar (3%) and precursor (4 mM HQ) levels, arbutin predominantly remained within the cells, whereas higher sugar (6%) and HQ (5-6 mM) levels promoted its release into the medium. Arbutin production ranged from 591 mg/L under single dosing to 3049 mg/L with sequential dosing, with the highest yield being achieved with 5 mM HQ in divided doses and 6% glucose. This study holds novelty for being the first to demonstrate the DpHQ's tolerance to high concentrations of HQ and its efficient capabilities to bioconvert HQ to arbutin, indicating that D. purpurea is equipped with the enzymes required for this process. These aspects highlight its potential as a biotechnological source for arbutin synthesis.

Shaping immune landscape of colorectal cancer by cholesterol metabolites.

Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer-immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.

Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study.

The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

A metabolomics perspective reveals the mechanism of the uric acid-lowering effect of Prunus salicina Lindl. cv. "furong" polyphenols in hypoxanthine and potassium oxybate-induced hyperuricemic mice.

The incidence of hyperuricemia (HUA) shows a gradually increasing trend towards affecting younger individuals, and it can significantly harm the overall health status of the body. Based on a metabolomics perspective, this study reveals the mechanism of the uric acid-lowering action of Prunus salicina Lindl. cv. "furong" polyphenols (PSLP) on a hyperuricemia mouse model induced by hypoxanthine and potassium oxybutyrate. The results demonstrate that PSLP comprise an effective treatment strategy for reducing the levels of serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) in HUA mice (p < 0.05), wherein the maximum decrease rates are up to 44.50%, 29.46%, and 32.95%, respectively. PSLP are observed to exert a pronounced inhibitory effect on the activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the livers of HUA mice, with reductions of up to 16.36% and 20.13%, respectively. These findings illustrate that PSLP exert a significant uric acid-lowering effect. Subsequent metabolomic analysis of mouse serum identified 28 potential biomarkers for hyperuricemia, whose levels were markedly diminished by PSLP. This process involved alterations in purine, glycine, the pentose phosphate pathway, and galactose metabolism. Twenty-eight potential biomarkers were identified for hyperuricemia by subsequent metabolomic analysis of mouse serum, whose levels were markedly reversed by PSLP intervention. The regulation of HUA by PSLP involved alterations in purine metabolism, glycerolipid metabolism, the pentose phosphate pathway, and galactose metabolism. The mechanism of PSLP ameliorated hyperuricemia might be attributed to reduction of the level of the uric acid precursor ribose-5-phosphate in the pentose phosphate pathway, the inhibition of the activities of uric acid synthase XOD and ADA in purine metabolism, and reduction of the synthesis of the end product uric acid. This study provides a theoretical basis for the development of functional foods based on PSLP, which can potentially reduce uric acid levels.

Cytochrome P450 VvCYP76F14 dominates the production of wine bouquet precursors in wine grapes.

In wine grape, the multi-functional cytochrome P450 enzyme VvCYP76F14 sequentially catalyzes the formation of linalool-derived compounds, including (E)-8-hydroxylinalool, (E)-8-oxolinalool, and (E)-8-carboxylinalool, which are crucial precursors for the wine bouquet. However, molecular basis towards VvCYP76F14 in regulating the wine bouquet precursor production remain unknown. In this study, both wine bouquet precursor contents and catalytic activities of VvCYP76F14s varied among the three different wine bouquet type varieties. Subcellular localization analysis revealed that VvCYP76F14s are predominantly localized in the endoplasmic reticulum. Notably, a maltose-binding protein (MBP) fusion-tag was added to each of the three VvCYP76F14 proteins in the Escherichia coli expression system, significantly induced the concentration of the MBP-VvCYP76F14 fusion proteins. Site-directed mutation of 4 amino acid residues (I120L, L298V, E378G, and T389A) in VvCYP76F14 resulted in a significant decrease in VvCYP76F14 enzymatic activities, respectively. Furthermore, the transient expression of VvCYP76F14 cloned from 'Yanniang No.2' significantly increased the levels of (E)-8-hydroxylinalool, 8-oxolinalool, and (E)-8-carboxylinalool compounds in the transformed 'Yanniang No.2', 'Italian Riesling', and 'Marselan' berries, respectively. In conclusion, VvCYP76F14 dominates the production of wine bouquet precursors and could be a fingerprint marker for screening superior hybrid offspring with desired levels of wine bouquet precursors.

Cloning, tissue specificity and regulation of expression of genes of four key enzymes related to long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis by ambient salinity during embryogenesis in the marine teleost Siganus guttatus.

The rabbitfish Siganus canaliculatus was the first marine teleost reported to possess long-chain polyunsaturated fatty acid (LC-PUFA) biosynthetic ability, and the related molecular mechanisms have been well clarified. Here, we investigated the LC-PUFA biosynthesis capability of the congeneric rabbitfish S. guttatus. First, cDNAs of genes for four key enzymes related to LC-PUFA biosynthesis, namely Δ6Δ5 fatty acyl desaturase (fads2) (1335 bp; 445 aa), Δ4 fads2 (1335 bp; 445 aa), and elongation of very long chain fatty acid proteins (elovl5) (873 bp; 291 aa) and elovl4 (906 bp; 302 aa) were cloned from the liver of S. guttatus. The Δ6Δ5 fads2, Δ4 fads2 and elovl5 genes showed high expression in brain, liver, spleen, gallbladder, and intestine but relatively low expression in eye, whereas the elovl4 gene showed specific and high expression in eye. During embryogenesis, mRNA expression of Δ4 fads2 and elovl4 was detected from 8 h post-fertilization (hpf) and then maintained a high level to 24 hpf, while mRNA expression of Δ6Δ5 fads2 and elovl5 reached a peak at 14 hpf but then declined. In addition, ambient salinity (32 ppt and 20 ppt) exerted some regulatory influence on the expression of the four genes during embryogenesis. The levels of C18 PUFA precursors and, especially, PUFA and DHA of the embryos, decreased from 17 hpf to 24 hpf. These results suggested that S. guttatus, similar to the congeneric S. canaliculatus, would have capability for LC-PUFA biosynthesis, which is still not activated at the fertilized egg stage.

Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a.

The oncogenic role of long intergenic noncoding RNA for IGF2BP2 stability (LINRIS) has been reported in colorectal cancer. This research aimed to study its potential involvement in gastric cancer (GC). In this study, paired GC and non-tumor tissues were obtained from 64 GC patients, and the levels of LINRIS, mature microRNA-34a (miR-34a), and miR-34a precursor in these tissues were measured with RT-qPCR. Linear regression was used to analyze their correlations. The role of LINRIS overexpression and siRNA silencing in regulating the maturation of miR-34a was analyzed by RT-qPCR. Cell apoptosis was studied with flow cytometry. It was observed that LINRIS was overexpressed in GC and showed a negative correlation with mature miR-34a, but not miR-34a precursor. In GC cells, LINRIS siRNA silencing upregulated mature miR-34a level, but not miR-34a precursor level. LINRIS overexpression downregulated miR-34a level. Cell apoptosis analysis showed that LINRIS siRNA silencing and miR-34a overexpression promoted GC cell apoptosis and suppressed cell migration and invasion, while LINRIS overexpression suppressed cell apoptosis and enhanced cell migration and invasion. In addition, the effect of LINRIS overexpression was reversed by miR-34a overexpression. Therefore, LINRIS siRNA silencing in GC may promote cell apoptosis by promoting miR-34a maturation.