Photomechaelectric Nanogenerators with Different Photoisomers and Dipole Units for Harvesting UV Light Energy.

To date, transforming environmental energy into electricity through a non-mechanical way is challenging. Herein, a series of photomechaelectric (PME) polyurethanes containing azobenzene-based photoisomer units and ionic liquid-based dipole units are synthesized, and corresponding PME nanogenerators (PME-NGs) to harvest electricity are fabricated. The dependence of the output performance of PME-NGs on the structure of the polyurethane is evaluated. The results show that the UV light energy can directly transduce into alternating-current (AC) electricity by PME-NGs via a non-mechanical way. The optimal open-circuit voltage and short-circuit current of PME-NGs under UV illumination reach 17.4 V and 696 µA, respectively. After rectification, the AC electricity can be further transformed into direct-current (DC) electricity and stored in a capacitor to serve as a power system to actuate typical microelectronics. The output performance of PME-NGs is closely related to the hard segment content of the PME polyurethane and the radius of counter anions in the dipole units. Kelvin probe force microscopy is used to confirm the existence of the PME effect and the detailed mechanism about the generation of AC electricity in PME-NGs is proposed, referring to the back and forth drift of induced electrons on the two electrodes in contact with the PME polyurethanes.

CTRP6 alleviates endometrial fibrosis by regulating Smad3 pathway in intrauterine adhesion†.

Intrauterine adhesion (IUA) is manifestations of endometrial fibrosis and excessive extracellular matrix deposition. C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog which has been reported to modulate the fibrosis process of several diseases; however, the endometrial fibrosis function of CTRP6 remains unknown. Our study aimed to assess the role of CTRP6 in endometrial fibrosis and further explore the underlying mechanism. Here, we found that the expression of CTRP6 was downregulated in the endometrial tissues of IUA. In vitro experiments demonstrated the reduced level of CTRP6 in facilitated transforming growth factor-ß1 (TGF-ß1)-induced human endometrial stromal cells (HESCs). In addition, CTRP6 inhibited the expression of α-smooth muscle actin (α-SMA) and collagen I in TGF-ß1-treated HESCs. Mechanistically, CTRP6 activated the AMP-activated protein kinase (AMPK) and protein kinase B (AKT) pathway in HESCs, and AMPK inhibitor (AraA) or PI3K inhibitor (LY294002) pretreatment abolished the protective effect of CTRP6 on TGF-ß1-induced fibrosis. CTRP6 markedly decreased TGF-ß1-induced Smad3 phosphorylation and nuclear translocation, and AMPK or AKT inhibition reversed these effects. Notably, CTRP6-overexpressing treatment alleviated the fibrosis of endometrium in vivo. Therefore, CTRP6 ameliorates endometrial fibrosis, among which AMPK and AKT are essential for the anti-fibrotic effect of CTRP6 via the Smad3 pathway. Taken together, CTRP6 may be a potential therapeutic target for the treatment of intrauterine adhesion.

The application of endoscopic purse-string suture in refractory non-variceal gastrointestinal bleeding:a multicenter study (with video).

BACKGROUND AND AIMS: Non-variceal gastrointestinal bleeding is a common medical emergency. Endoscopic hemostasis is recommended and some patients experienced rebleeding after conventional endoscopic hemostasis. Originally, the purse-string suture (PSS) was employed for lesion closure during endoscopic mucosal resection (EMR). We aimed to learn whether endoscopic PSS is effective in controlling the refractory bleeding. METHODS: We retrospectively collected data of patients who underwent endoscopic PSS for refractory non-variceal gastrointestinal bleeding from 3 hospitals. Clinical success was defined as no recurrent bleeding, and patients were discharged according to medical advice. RESULTS: From October 2017 to May 2024, 36 patients who received PSS treatments were included. 83.3% (30/36) of patients achieved clinical success. In refractory upper gastrointestinal bleeding, the clinical success rate was 81.25% (26/32), and it was 100% (4/4) in lower gastrointestinal bleeding. CONCLUSION: The endoscopic PSS is effective in treating refractory non-variceal gastrointestinal bleeding.

Ultra-high PDCR(>109) of vacuum-UV photodetector based on Al-doped Ga2O3microbelts.

Al-doped Ga2O3 microbelts with widths ranging from 20 to 154 µm and lengths up to 2 mm were grown using carbothermal reduction. Based on these ultra-wide microbelts, single-microbelt (37µm wide) and double-microbelts(38 µm/42 µm wide) metal-semiconductor-metal (MSM) photoconductive ultraviolet (UV) detectors PDs were fabricated and their optoelectronic performances were investigated at Vacuum-UV (VUV) wavelengths of 185 nm. Under irradiation of 185 nm, the Al-doped Ga2O3 PD has a very-high photocurrent (Iph) of 192.07 µA and extremely low dark current (Id) of 156 fA at 10 V, and presents a ultra-high light-to-dark current ratio(PDCR) of 1.23× 10^9. The responsivity(R), external quantum efficiency (EQE), and detectivity (D*) of the double-microbelts detector device were 1920 A/W, 9.36× 10^5 %, and 8.6× 10^16 Jones, respectively. Since the bandgap of the Al-doped microbelts becomes wider, and the fabricated detector has weaker sensitivity to radiation in the 254/365 nm wavelengths. Compared with the 254nm and 365nm UV cases, the devices under 185 nm VUV show the excellent high selectivity ratios of 1.47× 10^6 and 1.7× 10^7, respectively. This paper should provide a new insight on the VUV photodetectors utilizing Ga2O3 microbelts. .

Interplay of Systemic Immune-Inflammation Index and Serum Klotho Levels: Unveiling a New Dimension in Rheumatoid Arthritis Pathology.

Aim: The association between the systemic immune-inflammation index (SII) and serum Klotho concentrations (pg/ml) in patients with rheumatoid arthritis (RA) has not been elucidated. The purpose of this study was to clarify the relationship between the SII and serum Klotho concentrations in RA patients. Methods: All data come from the National Health and Nutrition Examination Survey (NHANES) database in the United States, which included 982 RA patients (age range: 40 to 79 years). The measurement data of the SII and serum Klotho are all from the NHANES mobile examination centre. We constructed a multivariate linear regression model to evaluate the association between the SII and serum Klotho levels in RA patients and conducted a subgroup analysis to test the stability of the statistical results. Results: Multivariate linear regression results indicated a negative linear relationship between the SII and serum Klotho concentrations in RA patients (ß = -6.33, 95% CI [confidence interval]: -10.15 to -2.53). Compared to the quartile 1 group, the quartile 4 group was associated with significantly lower (P<0.001) serum Klotho concentrations (ß = -120.93, 95% CI: -174.84 to -67.02). Compared with the quartile 1 group, with the increase in the SII, the ß value showed a decreasing trend (P trend < 0.001). The subgroup analysis showed that none of the covariates affected the stability of these results (all P for interaction ≥ 0.05). Conclusion: There is a significant negative linear association between the SII and serum Klotho concentrations in RA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in RA patients, and Klotho may be a potential anti-inflammatory target for RA treatment.

Bibliometric analysis of research on spinal cord and sacral neuromodulation in spinal cord injury.

STUDY DESIGN: Qualitative studies. OBJECTIVES: Spinal cord injury (SCI) is one of the most devastating injuries to the central nervous system that places a major burden on society. Neuromodulation technology involving spinal cord stimulation (SCS) and sacral nerve modulation (SNM) is a promising technique for patients with SCI. However, there has been no bibliometric analysis of research in this field to date. SETTING: Not applicable. METHODS: Systematic analyses of countries, institutions, authors, journals, co-cited documents, keywords, genes and diseases were performed. Related gene and disease data from the citexs platform were also reviewed. A total of 7437 articles on SCS and SNM in SCI were retrieved from the Web of Science database. The search time was limited to 1985-01-01 to 2022-12-31. RESULTS: We identified a significant increase in research output on SCS and SNM in SCI in recent years, with a concentrated period of high publication activity. Multiple publications were identified on neuropathic pain, electronic stimulation, TNF, BDNF and STAT3 gene expression, indicating that complications and potential therapeutic strategies for SCI are a key focus in the field. CONCLUSION: Our study provides insights that may help to advance scientific research and potentially improve outcomes in patients with SCI.

Enhanced Predefined-Time Control for Spacecraft Attitude Tracking: A Dynamic Predictive Approach.

This study presents a predefined-time control strategy for rigid spacecraft, employing dynamic predictive techniques to achieve robust and precise attitude tracking within predefined time constraints. Advanced predictive algorithms are used to effectively mitigate system uncertainties and environmental disturbances. The main contributions of this work are introducing adaptive global optimization for period updates, which relaxes the original restrictive conditions; ensuring easier parameter adjustments in predefined-time control, providing a nonconservative upper bound on system stability; and developing a continuous, robust control law through terminal sliding mode control and predictive methods. Extensive simulations confirm the control scheme reduces attitude tracking errors to less than 0.01 degrees at steady state, demonstrating the effectiveness of the proposed control strategy.

Mechanical strength changes of combustible municipal solid waste components during their early pyrolysis stage and mechanism analysis.

Implementation of municipal solid waste (MSW) source segregation leads to a more convenient recycle of combustible MSW components. Textiles, plastics and papers are commonly available combustible components in MSW. Their shredding is conducive to resources recovery. But these components usually have high tensile strengths and are difficult to shred. To understand their mechanical strength changes in their early pyrolysis stage will help to address this problem. In this study, a universal electronic testing machine was used to determine the breaking strengths of the materials including cotton towel, polyethylene glycol terephthalate (PET), ivory board (IB), kraft paper (KP) and wool scarf in the temperature range of 30-250°C under N2 atmosphere, and the mechanisms of their strength changes were explored. The reaction force field molecular dynamics (ReaxFF-MD) simulation was used to explain the decomposition behaviours of different sugar groups of hemicellulose in cotton and paper and the change of van der Waals energy of wool during their early pyrolysis stages. The results showed that breaking strengths of all the combustible MSW components reduced as the temperature increased. The breaking strength of PET was found to have the highest descent rate with increasing temperature, then the descent rates of wool and cotton came as the second and third, respectively. Compared with cotton, the breaking strengths of KP and IB decreased more slowly. As the temperature increased, the breaking strength of cotton reduced mainly due to the decomposition of the glucuronic acid in hemicellulose, and the reduction was characterized by CO2 release. The breaking strength reduction of PET was caused by its molecular chain being relaxed. The breaking strength reduction of wool was firstly caused by the decrease in the van der Waals energy between its molecules, and then caused by molecular chain breaking. In addition, in order to understand the influence of material size on the breaking strength change during thermal treatment, the breaking strengths of cotton yarn bundles were correlated with their yarn number and temperature. This study lays the foundation for understanding changes in mechanical strengths of combustible MSW components during their early pyrolysis stage.

Detection of pediatric obstructive sleep apnea using a multilayer perceptron model based on single-channel oxygen saturation or clinical features.

PURPOSE: This study was performed to develop and evaluate a method of detecting pediatric obstructive sleep apnea (OSA) using a multilayer perceptron (MLP) model based on single-channel nocturnal oxygen saturation (SpO2) with or without clinical data. METHODS: Polysomnography data for 888 children with OSA and 417 unaffected children were included. An MLP model was proposed based on the features obtained from SpO2 and combined features of SpO2 and clinical data to screen symptomatic children for OSA. The performance of the overall classification was evaluated with the receiver operating characteristics curve and the metrics of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and accuracy. RESULTS: The sensitivity, specificity, PPV, NPV, LR+, LR-, and accuracy of the MLP model for SpO2 of an obstructive apnea-hypopnea index (OAHI) cutoff value of 1, 5, and 10 were 0.62-0.96, 0.11-0.97, 0.70-0.81, 0.55-0.93, 1.08-21.0, 0.39-0.39, and 0.69-0.91, respectively. The area under the receiver operating characteristics curve of an OAHI cutoff value of 1, 5, and 10 was 0.720, 0.842, and 0.922, respectively. After adding the clinical data of age, sex, body mass index, weight category, adenoid grade, or tonsil scale, the performance of the MLP model was basically at the same level as only single-channel SpO2. CONCLUSIONS: Application of this MLP model using single-channel SpO2 in children with snoring has high accuracy in the diagnosis of moderate to severe OSA but a poor effect in the diagnosis of mild OSA. The combination of clinical data did not significantly improve the diagnostic performance of the MLP model.

Association between serum uric acid, hyperuricemia and periodontitis: a cross-sectional study using NHANES data.

OBJECTIVES: Diabetes and other metabolic diseases have been linked to the development of periodontitis, but little research has been done to determine whether serum uric acid (SUA) levels and hyperuricemia play a role. This study aimed to investigate the relationship between SUA, hyperuricemia, and periodontitis. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, we created a nationally representative data set. We used multivariable logistic regression models to assess the relationship between SUA, hyperuricemia, and periodontitis and presented odds ratios (OR) in women and men, respectively. RESULTS: In women, adjusted multivariable regression models showed that SUA (4.1-4.3mg/dl) was associated with higher odds of periodontitis (OR = 1.43; 95% confidence interval (CI):1.0 ~ 2.03, p = 0.047) with SUA (≤ 3.3mg/dl) as reference. The risk of periodontitis tended to increase slightly but insignificantly with increasing SUA levels, and the adverse effects occurred only when SUA increased to a certain level, and then reached a plateau. In men, the adjusted OR values for SUA (4.9-5.2mg/dl), SUA (5.3-5.5mg/dl), SUA (5.9-6.2mg/dl), and SUA (6.3-6.5mg/dl) were 0.66 (95% CI: 0.45 ~ 0.96, p = 0.029), 0.58 (95% CI: 0.40 ~ 0.85, p = 0.006), 0.67(95% CI: 0.47 ~ 0.97, p = 0.035), and 0.67 (95% CI: 0.45 ~ 0.99, p = 0.043), respectively, with SUA (≤ 4.3mg/dl) as reference. The elevated SUA levels are protective against periodontitis, but there is a range within which the risk of periodontitis decreases, followed by a non-significant tendency to increase. CONCLUSIONS: The levels of SUA that are linked to the risk of periodontitis. Future prospective longitudinal studies and strategies are required to further confirm whether controlled SUA treatment is an effective adjunct to systematic periodontal therapy and whether SUA can be used as a diagnostic biomarker to assess the risk or progression of periodontitis.

Irisin reduces the abnormal reproductive and metabolic phenotypes of PCOS by regulating the activity of brown adipose tissue in mice†.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women, with clinical manifestations of anovulation and hyperandrogenaemia. The treatment of PCOS mainly focuses on improving clinical symptoms, such as insulin sensitivity or menstrual disorder, through drug treatment. However, due to the pathogenesis diversity of PCOS, there is still a lack of effective treatment in clinics. Metabolic disorder is the key factor in the occurrence of PCOS. Brown adipose tissue (BAT) is a special adipose tissue in the human body that can participate in metabolic balance by improving heat production. BAT has been demonstrated to be an important substance involved in the metabolic disorder of PCOS. Although increasing evidence indicates that BAT transplantation can improve the symptoms of PCOS, it is difficult to achieve BAT transplantation at present due to technical limitations. Stimulation of BAT activation by exogenous substances may be an effective alternative therapy for PCOS. In this study, we investigated the effects of Irisin on dehydroepiandrosterone (DHEA)-induced PCOS in mice and evaluated the effect of Irisin on serum hormone levels and changes in body temperature, body weight, and ovarian morphology. In our study, we found that Irisin can enhance the thermogenesis and insulin sensitivity of PCOS mice by activating the function of BAT. In addition, Irisin treatment can correct the menstrual cycle of PCOS mice, improve the serum steroid hormone disorder status, and reduce the formation of ovarian cystic follicles. In conclusion, our results showed that Irisin treatment significantly improved the metabolic disorder of PCOS and may provide a new and alternative therapy for the treatment of this pathology.

A Megabirnavirus Alleviates the Pathogenicity of Fusarium pseudograminearum to Wheat.

Fusarium pseudograminearum is a phytopathogen that causes wheat crown rot disease worldwide. Fusarium pseudograminearum megabirnavirus 1 (FpgMBV1) was isolated from the hypovirulent strain FC136-2A of F. pseudograminearum as a novel double-stranded RNA mycovirus belonging to the family Megabirnaviridae. Here we examined the effects of FpgMBV1 on colony morphology and pathogenicity of F. pseudograminearum. Through hyphal tip culture, we obtained virus-free progeny of strain FC136-2A, referred to as FC136-2A-V-. FpgMBV1 was transferred horizontally to another virus-free strain, WZ-8A-HygR-V-. The progeny obtained through horizontal transfer was referred to as WZ-8A-HygR-V+. Colony morphology was similar between the FpgMBV1-positive and -negative strains. The ability to penetrate cellophane in vitro was lost, and pathogenicity on wheat plants was reduced significantly in the FpgMBV1-positive strains relative to the FpgMBV1-negative strains. Microscopic observations showed a 6-h delay in the formation of appressoria-like structures in FC136-2A relative to FC136-2A-V-. Mycelium extension was significantly longer in wheat coleoptiles infected by WZ-8A-HygR-V- than in that infected by WZ-8A-HygR-V+ at 12 and 20 h after inoculation (hai). In addition, expression of five genes that encode cell wall-degrading enzymes differed significantly between FpgMBV1-positive and -negative strains at 12 and 20 hai during early infection of wheat cells by conidia. This study provides evidence for the hypovirulence effect of FpgMBV1 on F. pseudograminearum and suggests that the underlying mechanism involves unsuccessful early infection and perhaps cell wall degradation.

Cd and pb Co-Pollution Increased Ecological Risk and Changed Rhizosphere Characteristics of Arabidopsis Thaliana During Phytoremediation.

Previous studies have reported that co-contamination can result in more complex effects on the phytoremediation efficiency of plants relative to those of a single pollutant. However, the effect of co-contamination on plant rhizosphere characteristics has rarely been revealed. This study was carried out to assess the changes in soil pH, the content and fractionation of dissolved organic matter (DOM), and the metal solubility in the rhizosphere of Arabidopsis thaliana when treated with Cd and Pb simultaneously. The results showed that co-contamination increased the concentrations of DOM by 24.8% and 30.9% in the rhizosphere soil of A. thaliana relative to individual Cd or Pb pollution, respectively. At the end of the experiment, co-contamination significantly decreased the initial soil pH from 6.6 ± 0.3 to 5.5 ± 0.4, whereas a decrease was not observed under Pb pollution alone. Variations in soil pH and DOM can change the fractions of the two metals in the rhizosphere soil of A. thaliana. DOM in co-contaminated soil showed a higher Cd (1.05 mg L-1) and Pb (0.75 mg L-1) extraction ability relative to that in the Cd-polluted (0.89 mg Cd L-1 and 0.59 mg Pb L-1) or Pb-polluted (0.68 mg Cd L-1 and 0.63 mg Pb L-1) soils. The soluble Cd content in the co-contaminated (0.44 mg L-1) soil was significantly lower than that in the Cd-polluted (0.71 mg L-1) soil because A. thaliana is a Cd accumulator, whereas the soluble Pb content showed the opposite trend (47.0 mg L-1 vs. 37.4 mg L-1) because the species is a Pb excluder. Therefore, A. thaliana in co-contaminated soil would pose a leaching risk for the non-hyperaccumulated metals, thereby increasing the potential ecological risk during the phytoremediation process.

Impact of chronic intermittent hypoxia on the long non-coding RNA and mRNA expression profiles in myocardial infarction.

Chronic intermittent hypoxia (CIH) is the primary feature of obstructive sleep apnoea (OSA), a crucial risk factor for cardiovascular diseases. Long non-coding RNAs (lncRNAs) in myocardial infarction (MI) pathogenesis have drawn considerable attention. However, whether CIH participates in the modulation of lncRNA profiles during MI is yet unclear. To investigate the influence of CIH on MI, cardiac damage was assessed by histology and echocardiography, and lncRNA and mRNA integrated microarrays were screened. MI mouse model showed myocardial hypertrophy, aggravated inflammation and fibrosis, and compromised left ventricle function under CIH. Compared with normoxia, 644 lncRNAs and 1084 differentially expressed mRNAs were identified following CIH for 4 weeks, whereas 1482 lncRNAs and 990 mRNAs were altered at 8 weeks. Strikingly, reoxygenation after CIH markedly affected 1759 lncRNAs and 778 mRNAs. Of these, 11 lncRNAs modulated by CIH were restored after reoxygenation and were validated by qPCR. The GO terms and KEGG pathways of genes varied significantly by CIH. lncRNA-mRNA correlation further showed that lncRNAs, NONMMUT032513 and NONMMUT074571 were positively correlated with ZEB1 and negatively correlated with Cmbl. The current results demonstrated a causal correlation between CIH and lncRNA alternations during MI, suggesting that lncRNAs might be responsible for MI aggravation under CIH.

TAK1-AMPK Pathway in Macrophages Regulates Hypothyroid Atherosclerosis.

PURPOSE: Hypothyroidism (HT) is associated with accelerated atherosclerosis (AS). The efficacy of traditional strategies of hypothyroid AS remains controversial. Here, we aimed to deepen the understanding of the HT-induced acceleration of AS, to decrease the residual risk of coronary artery disease (CAD) and to find a new therapeutic target. METHODS: We collected peripheral venous blood samples from 20 patients and divided them into 4 groups, namely, the normal group, the HT group, the CAD group and the HT + CAD group. Then we performed mRNA microarray analysis and bioinformatics analysis to screen the differentially expressed genes and pathways, and we also conducted validations on ApoE knockout mice models and Raw264.7 cell models. RESULTS: In short, (1) in the analysis between the CAD group and the HT + CAD group, we found a total of 1218 differentially expressed genes, 11 upregulated pathways and 40 downregulated pathways. (2) We validated that patients with HT and CAD had a significantly decreased expression of MAP3K7 (encoding transforming growth factor-ß-activated kinase 1, TAK1) gene than normal subjects. (3) In animal and cell experiments, we found the decreased expression of TAK1 and the reduced phosphorylation of AMP-activated protein kinase (AMPK) under the hypothyroid and atherosclerotic condition. (4) Changes in the expressions of TAK1 may affect the progression of AS. CONCLUSION: Taken together, these data suggest that the accelerated AS in hypothyroid patients may be due to the suppression of TAK1-AMPK pathway in macrophages. This new finding may become a novel therapeutic target in hypothyroid AS.

A fluorinated chitosan-based QuEChERS method for simultaneous determination of 20 organophosphorus pesticide residues in ginseng using GC-MS/MS.

In this study, a new fluorinated methacrylamide (MACF) was synthesized and evaluated as an adsorbent in the dispersive solid-phase extraction for the effective determination and extraction of 20 organophosphorus pesticides (OPPs) from ginseng samples using the QuEChERS (quick, easy, cheap, effective, rugged, safe) method coupled with GC-MS/MS. The properties of MACF were characterized using Fourier-transform infrared spectroscopy, elemental analysis, and high-resolution 19 F NMR. MACF, chitosan, primary and secondary amine, octadecylsilane, graphitized carbon black, Z-Sep, Z-Sep+ , and EMR-Lipid were compared in terms of extraction efficiency. The best results were obtained when MACF was used. Matrix-matched calibration was employed for quantification. All the OPPs exhibited good linearity (r2 > 0.9969) with the concentration at their respective concentration ranges. The limits of detection were 1.5-3.0 µg/kg, and the limits of quantification were 5.0-10.0 µg/kg. The trueness of the 20 pesticides at four spiked levels ranged from 86.1 to 111.1%, and the relative standard deviation was less than 11.3%. The modified QuEChERS method using MACF as the adsorbent was sensitive, reliable, and cost-effective and could be used for the determination of 20 OPP residues in ginseng.

Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy.

Cancer metastasis is the leading cause of cancer-related death. Circulating tumor cells (CTCs) are shed into the bloodstream from either primary or metastatic tumors during an intermediate stage of metastasis. In recent years, immunotherapy has also become an important focus of cancer research. Thus, to study the relationship between CTCs and immunotherapy is extremely necessary and valuable to improve the treatment of cancer. In this review, based on the advancements of CTC isolation technologies, we mainly discuss the clinical applications of CTCs in cancer immunotherapy and the related immune mechanisms of CTC formation. In order to fully understand CTC formation, sufficiently and completely understood molecular mechanism based on the different immune cells is critical. This understanding is a promising avenue for the development of effective immunotherapeutic strategies targeting CTCs.

Transcriptomics Analysis of the Chinese Pear Pathotype of Alternaria alternata Gives Insights into Novel Mechanisms of HSAF Antifungal Activities.

Alternaria alternata (Fries) Keissler is a lethal pear pathogen that causes leaf black spot disease of pear in Southern China. Heat-stable activity factor (HSAF) is a polycyclic tetramate macrolactam (PTM) produced by Lysobacter enzymogenes and many other microbes with a broad-spectrum antifungal activity against many filamentous fungi. In this study, we evaluated the antifungal effect of HSAF against A. alternata and proposed its antifungal mechanism in A. alternata. We report that HSAF inhibited the mycelial growth of A. alternata in a dose-dependent manner. Transcriptomics analysis revealed that HSAF treatment resulted in an expression alteration of a wide range of genes, with 3729 genes being up-regulated, and 3640 genes being down-regulated. Furthermore, we observed that HSAF treatment disrupted multiple signaling networks and essential cellular metabolisms in A. alternata, including the AMPK signaling pathway, sphingolipid metabolism and signaling pathway, carbon metabolism and the TCA (tricarboxylic acid) cycle, cell cycle, nitrogen metabolism, cell wall synthesis and a key hub protein phosphatase 2A (PP2A). These observations suggest that HSAF breaches metabolism networks and ultimately induces increased thickness of the cell wall and apoptosis in A. alternata. The improved understanding of the antifungal mechanism of HSAF against filamentous fungi will aid in the future identification of the direct interaction target of HSAF and development of HSAF as a novel bio-fungicide.

Novel Fluorescein-Based Fluorescent Probe for Detecting H2S and Its Real Applications in Blood Plasma and Biological Imaging.

A broad-spectrum fluorescent probe, which can be applied to monitoring H2S in various biological systems, has been rationally designed and synthesized. This specific probe was applied to localize the endogenous H2S in living Raw264.7 macrophage cells, HepG2 cells, and H9C2 cells. At the same time, the probe has successfully visualized CBS- and CSE-induced endogenous H2S production and monitored CBS and CSE activity in H9C2 cells. This probe could serve as a powerful molecular imaging tool to further explore the physiological function and the molecular mechanisms of endogenous H2S in living animal systems.

Diabetic peripheral neuropathy and glycemic variability assessed by continuous glucose monitoring: A systematic review and meta-analysis.

Continuous glucose monitoring (CGM)-derived metrics have been used to accurately assess glycemic variability (GV) to facilitate management of diabetes mellitus, yet their relationship with diabetic peripheral neuropathy (DPN) is not fully understood. We performed a systematic review and meta-analysis to evaluate the association between GV metrics and the risk of developing DPN. Nine studies totaling 3,649 patients with type 1 and type 2 diabetes mellitus were included. A significant association was found between increased GV, as indicated by metrics including standard deviation (SD) with OR and 95% CI of 2.58 (1.45-4.57), mean amplitude of glycemic excursions (MAGE) with OR and 95% CI of 1.90 (1.01-3.58), mean of daily difference (MODD) with OR and 95% CI of 2.88 (2.17-3.81) and the incidence of DPN. Our findings support a link between higher GV and an increased risk of DPN in patients with diabetes. These findings highlight the potential of GV metrics as indicators for the development of DPN, advocating for their inclusion in diabetes management strategies to potentially mitigate neuropathy risk. Longitudinal studies with longer observation periods and larger sample sizes are necessary to validate these associations across diverse populations.