The APSES Transcription Factor SsStuA Regulating Cell Wall Integrity Is Essential for Sclerotia Formation and Pathogenicity in Sclerotinia sclerotiorum.

APSES (Asm1p, Phd1p, Sok2p, Efg1p, and StuAp) family transcription factors play crucial roles in various biological processes of fungi, however, their functional characterization in phytopathogenic fungi is limited. In this study, we explored the role of SsStuA, a typical APSES transcription factor, in the regulation of cell wall integrity (CWI), sclerotia formation and pathogenicity of Sclerotinia sclerotiorum, which is a globally important plant pathogenic fungus. A deficiency of SsStuA led to abnormal phosphorylation level of SsSmk3, the key gene SsAGM1 for UDP-GlcNAc synthesis was unable to respond to cell wall stress, and decreased tolerance to tebuconazole. In addition, ΔSsStuA was unable to form sclerotia but produced more compound appressoria. Nevertheless, the virulence of ΔSsStuA was significantly reduced due to the deficiency of the invasive hyphal growth and increased susceptibility to hydrogen peroxide. We also revealed that SsStuA could bind to the promoter of catalase family genes which regulate the expression of catalase genes. Furthermore, the level of reactive oxygen species (ROS) accumulation was found to be increased in ΔSsStuA. In summary, SsStuA, as a core transcription factor involved in the CWI pathway and ROS response, is required for vegetative growth, sclerotia formation, fungicide tolerance and the full virulence of S. sclerotiorum.

Arachidonic acid released by PIK3CA mutant tumor cells triggers malignant transformation of colonic epithelium by inducing chromatin remodeling.

Key gene mutations are essential for colorectal cancer (CRC) development; however, how the mutated tumor cells impact the surrounding normal cells to promote tumor progression has not been well defined. Here, we report that PIK3CA mutant tumor cells transmit oncogenic signals and result in malignant transformation of intestinal epithelial cells (IECs) via paracrine exosomal arachidonic acid (AA)-induced H3K4 trimethylation. Mechanistically, PIK3CA mutations sustain SGK3-FBW7-mediated stability of the cPLA2 protein, leading to the synthetic increase in AA, which is transported through exosome and accumulated in IECs. Transferred AA directly binds Menin and strengthens the interactions of Menin and MLL1/2 methyltransferase. Finally, the combination of VTP50469, an inhibitor of the Menin-MLL interaction, and alpelisib synergistically represses PDX tumors harboring PIK3CA mutations. Together, these findings unveil the metabolic link between PIK3CA mutant tumor cells and the IECs, highlighting AA as the potential target for the treatment of patients with CRC harboring PIK3CA mutations.

Exposure to heavy metals and trace elements among pregnant women with twins: levels and association with twin growth discordance.

Background: Twin growth discordance is one of the leading causes of perinatal mortality in twin pregnancies. Whether prenatal exposure to heavy metals and trace elements is associated with twin growth discordance has not been studied yet. Objective: To evaluate the prenatal level of heavy metals and trace elements in twin pregnancy and its relationship with twin growth discordance. Methods: This study involving 60 twin pairs and their mothers was conducted in Zhejiang Province, China, in 2020-2021. The concentration of heavy metals and trace elements in maternal blood, umbilical cord, and placenta were collected at delivery and measured by inductively coupled plasma tandem mass spectrometer. The association of prenatal level with twin growth discordance was evaluated using conditional logistic regression. Results: High levels of heavy metal elements (thallium in maternal blood and umbilical cord blood of larger twins, vanadium in the placenta of larger twins) and trace elements (iodine in the placenta of larger twins) during pregnancy, as well as low levels of heavy metal elements (strontium in the umbilical cord blood of larger twins, strontium and chromium in the umbilical cord blood of smaller twins, strontium in the placenta of larger twins, molybdenum and lead in the placenta of smaller twins and difference of molybdenum in the placenta of twins), are associated with intertwin birthweight discordance. Univariate regression analyses showed a significant effect of gestational age at delivery and eleven trace element data on intertwin birthweight discordance. Multivariable logistic regression analysis with transformed variables as dichotomous risk factors combined with baseline demographic characteristics showed Tl in maternal blood as an independent risk factor. The model constructed by combining Tl in maternal blood (OR = 54.833, 95% CI, 3.839-83.156) with the gestational week (OR = 0.618, 95% CI, 0.463-0.824) had good predictive power for intertwin birthweight discordance (AUC = 0.871). The sensitivity analysis results indicate that the effect of maternal blood thallium on intertwin birthweight discordance is stable and reliable. Conclusion: To our knowledge, ours is the first case-control study to investigate the association between elevated maternal thallium levels before delivery and twin growth discordance.

Porous α-Fe2O3 Hollow Rods/Reduced Graphene Oxide Composites Templated by MoO3 Nanobelts for High-Performance Supercapacitor Applications.

Porous α-Fe2O3 hollow rods/reduced graphene oxide (α-Fe2O3 HR/RGO) composites with unique morphological characteristics and a high surface area are prepared through a template strategy, which was systematically studied and found to have outstanding supercapacitive properties. When served as active material in a three-electrode setup, the optimized α-Fe2O3 HR/RGO-30, comprised 76.5 wt% α-Fe2O3 and 23.2 wt% RGO, was able to offer the largest specific capacitance of 426.3 F g-1, an excellent rate capability as well as satisfactory cycle life with capacitance retention of 87.7% and Coulombic efficiency of 98.9% after continuously charging/discharging at 10 A g-1 for beyond 10,000 cycles. Such electrochemical behaviors of the α-Fe2O3 HR/RGO-30 electrode can rival or even surpass those of many Fe2O3-based electrodes documented in the previous literature. Later, a symmetric supercapacitor cell of α-Fe2O3 HR/RGO-30//α-Fe2O3 HR/RGO-30 was fabricated. The assembled device offers the maximum energy density of 18.7 Wh kg-1, and also exhibits commendable rate capability, and features stable cycling durability (with capacitance retention of 83.2% together with a Coulombic efficiency of 99.3% after 10,000-cycle charge/discharge at 5 A g-1). These notable electrochemical performances enable the α-Fe2O3 HR/RGO-30 composite to be a high-potential material for advanced energy storage systems.

Poly-(lactic acid) composite films comprising carvacrol and cellulose nanocrystal-zinc oxide with synergistic antibacterial effects.

Herein, carvacrol (CRV) and modified cellulose nanocrystal-zinc oxide (CNC-ZnO) were incorporated into a poly (lactic acid) (PLA) matrix to prepare a PLA-based composite film using a simple solution casting method to achieve antimicrobial effects for application in antimicrobial food packaging. Compared with films obtained from neat PLA, the PLA@CRV20%@CNC-ZnO3% composite film shows better performance in terms of mechanical properties, ultraviolet (UV) blocking, and antimicrobial effects. The PLA composites containing CRV and 3 wt% CNC-ZnO blends exhibit improved tensile strength (21.8 MPa) and elongation at break (403.1 %) as well as excellent UV resistance. In particular, CRV and the CNC-ZnO hybrid endow the obtained PLA composite films with a synergistic antibacterial effect, resulting in good antibacterial properties for microbes, such as Escherichia coli, Staphylococcus aureus and Aspergillus niger. The diameters of the inhibition zone of the PLA@CRV20%@CNC-ZnO3% composite films against E. coli, S. aureus, and A. niger were 4.9, 5.0, and 3.4 cm, respectively. Appling the PLA@CRV20%@CNC-ZnO3% composite film as an antibacterial food packaging material, the storage period for strawberries was considerably extended. This study provides a theoretical basis for developing new organic/inorganic composite antimicrobial film materials from PLA.

Effect of hornification on the isolation of anionic cellulose nanofibrils from Kraft pulp via maleic anhydride esterification.

Cellulose nanofibrils (CNF) isolation based on a catalyst-free maleic anhydride esterification has proven to be effective, however, the effects of pulp hornification on CNF isolation by this strategy have yet to be explored, which could present significant impacts for CNF isolation. Herein, dried northern bleached softwood Kraft pulp (D-NBSK) and never-dried northern bleached softwood Kraft pulp (ND-NBSK) were selected as the substrates. After esterification with maleic anhydride (MA), the esterified ND-NBSK pulp (E-ND) shows a significantly smaller size and more fragmented structure than the esterified D-NBSK pulp (E-D). Meanwhile, higher degree of esterification can be realized for the never dried pulp as compared to the dried pulp, which is corroborated by the significantly stronger characteristic peaks of CO (1720 cm-1) and -COO- (1575 cm-1) from the FTIR spectra and the higher surface charge content (0.86 ± 0.04 mmol/g vs. 0.55 ± 0.05 mmol/g). A comparison of the characteristics of the resulting CNF similarly demonstrated the negative impact of hornification. Overall, this work indicates that hornification tends to reduce the accessibility of chemical reagents to the pulp, leading to insufficient deconstruction. Such negative impact of hornification should be considered when performing nanocellulose isolation, especially when using pulp as feedstock.

TP53 mitigates cisplatin resistance in non-small cell lung cancer by mediating the effects of resistant cell-derived exosome mir-424-5p.

Background: Cisplatin (DDP) is the principal agent used for chemotherapy in patients with non-small cell lung cancer (NSCLC). Nevertheless, DDP resistance is an essential cause for a worse prognosis of patient. Therefore, this study proposes to discover features of miR-424-5p in DDP resistance of NSCLC. Method: After exogenous modulation of miR-424-5p expression, A549 cell activity was measured using CCK-8 and flow cytometry. A549/DDP and A549/DDP-associated subcutaneous tumor model were constructed to investigate the effect of miR-424-5p on DDP resistance in NSCLC in vivo. TargetScan and JASPAR databases predicted the potential molecular mechanism of miR-424-5p. A549-and A549/DDP-derived exosomes were isolated and characterized using a transmission electron microscope and nanoparticle tracking analysis. Result: Overexpression of miR-424-5p facilitated proliferation and DDP resistance in A549 cells, and knockdown of miR-424-5p did the opposite. Knockdown of miR-424-5p enhanced DDP restriction on tumor weight and volume. Moreover, SOCS5 and SOCS56 (SOCS5/6) were downstream targets of miR-424-5p. miR-424-5p down-regulated SOCS5/6 expression to activate JAK2/STAT3 and PI3K/AKT pathways. Notably, tumor protein p53 (TP53) is a transcription factor for the miR-424-5p host gene, as confirmed by the dual-luciferase reporter gene. Cellular and animal experiments indicated that TP53 limited the regulatory function of miR-424-5p on NSCLC growth, DDP resistance, and related molecules. Interestingly, miR-424-5p was markedly enriched in A549/DDP cell-derived exosomes than in A549 cell-derived exosomes, and TP53 down-regulated miR-424-5p expression in A549/DDP cell-derived exosomes. Conclusion: DDP-resistant cell-derived exosome miR-424-5p contributes to NSCLC growth and DDP resistance by targeting SOCS5 and SOCS6 to activate JAK2/STAT3 and PI3K/AKT pathways, which are blocked by TP53.

Development of PEG-mediated genetic transformation and gene editing system of Bryum argenteum as an abiotic stress tolerance model plant.

KEY MESSAGE: To establish a sterile culture system and protoplast regeneration system for Bryum argenteum, and to establish and apply CRISPR/Cas9 system in Bryum argenteum. Bryum argenteum is a fascinating, cosmopolitan, and versatile moss species that thrives in various disturbed environments. Because of its comprehensive tolerance to the desiccation, high UV and extreme temperatures, it is emerging as a model moss for studying the molecular mechanisms underlying plant responses to abiotic stresses. However, the lack of basic tools such as gene transformation and targeted genome modification has hindered the understanding of the molecular mechanisms underlying the survival of B. argenteum in different environments. Here, we reported the protonema of B. argenteum can survive up to 95.4% water loss. In addition, the genome size of B. argenteum is approximately 313 Mb by kmer analysis, which is smaller than the previously reported 700 Mb. We also developed a simple method for protonema induction and an efficient protoplast isolation and regeneration protocol for B. argenteum. Furthermore, we established a PEG-mediated protoplast transient transfection and stable transformation system for B. argenteum. Two homologues of ABI3(ABA-INSENSITIVE 3) gene were successfully cloned from B. argenteum. To further investigate the function of the ABI3 gene in B. argenteum, we used the CRISPR/Cas9 genetic editing system to target the BaABI3A and BaABI3B gene in B. argenteum protoplasts. This resulted in mutagenesis at the target in about 2-5% of the regenerated plants. The isolated abi3a and abi3b mutants exhibited increased sensitivity to desiccation, suggesting that BaABI3A and BaABI3B play redundant roles in desiccation stress. Overall, our results provide a rapid and simple approach for molecular genetics in B. argenteum. This study contributes to a better understanding of the molecular mechanisms of plant adaptation to extreme environmental.

Single-cell analysis with childhood and adult systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE), a heterogeneous and chronic autoimmune disease, exhibit unique changes in the complex composition and transcriptional signatures of peripheral blood mononuclear cells (PBMCs). While the mechanism of pathogenesis for both childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) remains unclear, cSLE patients are considered more unpredictable and dangerous than aSLE patients. In this study, we analysed single-cell RNA sequencing data (scRNA-seq) to profile the PBMC clusters of cSLE/aSLE patients and matched healthy donors and compared the PBMC composition and transcriptional variations between the two groups. Our analysis revealed that the PBMC composition and transcriptional variations in cSLE patients were similar to those in aSLE patients. Comparative single-cell transcriptome analysis between healthy donors and SLE patients revealed IFITM3, ISG15, IFI16 and LY6E as potential therapeutic targets for both aSLE and cSLE patients. Additionally, we observed that the percentage of pre-B cells (CD34-) was increased in cSLE patients, while the percentage of neutrophil cells was upregulated in aSLE patients. Notably, we found decreased expression of TPM2 in cSLE patients, and similarly, TMEM150B, IQSEC2, CHN2, LRP8 and USP46 were significantly downregulated in neutrophil cells from aSLE patients. Overall, our study highlights the differences in complex PBMC composition and transcriptional profiles between cSLE and aSLE patients, providing potential biomarkers that could aid in diagnosing SLE.

Advances in ionogels for proton-exchange membranes.

To ensure the long-term performance of proton-exchange membrane fuel cells (PEMFCs), proton-exchange membranes (PEMs) have stringent requirements at high temperatures and humidities, as they may lose proton carriers. This issue poses a serious challenge to maintaining their proton conductivity and mechanical performance throughout their service life. Ionogels are ionic liquids (ILs) hybridized with another component (such as organic, inorganic, or organic-inorganic hybrid skeleton). This design is used to maintain the desirable properties of ILs (negligible vapor pressure, thermal stability, and non-flammability), as well as a high ionic conductivity and wide electrochemical stability window with low outflow. Ionogels have opened new routes for designing solid-electrolyte membranes, especially PEMs. This paper reviews recent research progress of ionogels in proton-exchange membranes, focusing on their electrochemical properties and proton transport mechanisms.

Alkoxy-Functionalized Hydroxamate/Zinc Metal-Organic Frameworks and the Effects of Substituents and Acid Addition on Their Structures.

Single crystals of alkoxy-functionalized hydroxamate/zinc metal-organic frameworks (MOFs) were obtained by fixating the hydroxamate moiety via intramolecular hydrogen bonding. The resulting MOF structures depend on the steric demand of the alkoxy groups, whereby the incorporation of bulky isopropyl groups affords porous hydroxamate/zinc MOFs. The topological structures of the isopropyl-substituted MOFs could be controlled by adding acid.

Developing Prussian blue/wood-derived biochar catalyst for persistent organic pollutant degradation: Preparation, characterization, and mechanism.

Biomass-derived biochar shows broad promise for persistent organic pollutants (POPs) degradation and thus establishes a more sustainable homestead. However, effective catalytic performance is still challenging. Herein, an efficient catalyst (Prussian blue decorated wood-derived biochar, PBB) was constructed by introducing Prussian blue (PB) into wood-based biochar to activate peroxymonosulfate (PMS) for removing POPs. After anchoring of PB, the degradation performance of biochar was enhanced (degradation efficiency of methylene blue (MB, 20 mg/L) increased from 52% of biochar to 95% of PBB within 60 min). The PBB presents effective MB degradation performance with a wide pH value (3.0 < pH < 11.0) or co-existing diverse anions (Cl-, NO3-, H2PO4-, and HCO3-). Electron paramagnetic resonance (EPR) analysis as well as electrochemical tests confirmed that the non-radical pathway (1O2) is the key to biochar activation of PMS, but by restricting PB into the biochar, the radical pathway (SO4•- and •OH), the non-radical pathway (1O2), and direct electron transfer can work together to activate PMS. In addition, the degradation efficiency could remain about 80% after five-time cyclic tests. This work elucidates the role of PB nanoparticles in enhancing biochar catalysts, which can inspire the development of a carbon-neutralized, cost-effective, and effective strategy for POPs removal.

Single-cell disulfidptosis regulator patterns guide intercellular communication of tumor microenvironment that contribute to kidney renal clear cell carcinoma progression and immunotherapy.

Background: Disulfidptosis, an emerging type of programmed cell death, plays a pivotal role in various cancer types, notably impacting the progression of kidney renal clear cell carcinoma (KIRC) through the tumor microenvironment (TME). However, the specific involvement of disulfidptosis within the TME remains elusive. Methods: Analyzing 41,784 single cells obtained from seven samples of KIRC through single-cell RNA sequencing (scRNA-seq), this study employed nonnegative matrix factorization (NMF) to assess 24 disulfidptosis regulators. Pseudotime analysis, intercellular communication mapping, determination of transcription factor activities (TFs), and metabolic profiling of the TME subgroup in KIRC were conducted using Monocle, CellChat, SCENIC, and scMetabolism. Additionally, public cohorts were utilized to predict prognosis and immune responses within the TME subgroup of KIRC. Results: Through NMF clustering and differential expression marker genes, fibroblasts, macrophages, monocytes, T cells, and B cells were categorized into four to six distinct subgroups. Furthermore, this investigation revealed the correlation between disulfidptosis regulatory factors and the biological traits, as well as the pseudotime trajectories of TME subgroups. Notably, disulfidptosis-mediated TME subgroups (DSTN+CD4T-C1 and FLNA+CD4T-C2) demonstrated significant prognostic value and immune responses in patients with KIRC. Multiple immunohistochemistry (mIHC) assays identified marker expression within both cell clusters. Moreover, CellChat analysis unveiled diverse and extensive interactions between disulfidptosis-mediated TME subgroups and tumor epithelial cells, highlighting the TNFSF12-TNFRSF12A ligand-receptor pair as mediators between DSTN+CD4T-C1, FLNA+CD4T-C2, and epithelial cells. Conclusion: Our study sheds light on the role of disulfidptosis-mediated intercellular communication in regulating the biological characteristics of the TME. These findings offer valuable insights for patients with KIRC, potentially guiding personalized immunotherapy approaches.

miR-19b-3p regulated by estrogen controls lipid synthesis through targeting MSMO1 and ELOVL5 in LMH cells.

miR-19b-3p is reported to undertake various biological role, while its function and action mechanism in chicken hepatic lipid metabolism is unclear. Conservation analysis and tissue expression pattern of miR-19b-3p and its target gene were evaluated, respectively. Dual luciferase reporter system and Western blot technologies were adopted to validate miR-19b-3p target gene. Overexpression and knockdown assays were done to explore the biological functions of miR-19b-3p and target gene in Leghorn Male Hepatoma cell line (LMH). Regulatory approaches of estrogen on miR-19b-3p and target gene expressions are analyzed through site-directed mutation combined with estrogen receptors antagonist treatment assays. The results showed that chicken miR-19b-3p mature sequences are highly conserved among Capra hircus, Columba livia, Rattus norvegicus, Mus musculus, Cricetulus griseus, Danio rerio, Danio novaehollandiae, Orycodylus porosus, Crocodylus porosus, Gadus morhua, and widely expressed in lung, ovary, spleen, duodenum, kidney, heart, liver, leg muscle, and pectoral muscle tissues. miR-19b-3p could significantly increase intracellular triglyceride (TG) content and decrease intracellular cholesterol (TC) content via targeting methylsterol monooxygenase 1 (MSMO1) and elongase of very long chain fatty acids 5 (ELOVL5), which are highly conserved among species, in both mRNA and protein levels. Estrogen could inhibit miR-19b-3p expression, but directly promoted MSMO1 transcription via estrogen receptor α (ERα) and indirectly regulated ELOVL5 expression at the transcription level. Meanwhile, estrogen could also upregulate MSMO1 and ELOVL5 expression through inhibiting miR-19b-3p expression at the post-transcription level. Taken together, these results highlight the role and regulatory mechanism of miR-19b-3p in hepatic lipid metabolism in chicken, and might produce useful comparative information for human obesity studies and biomedical research.

The Snf5-Hsf1 transcription module synergistically regulates stress responses and pathogenicity by maintaining ROS homeostasis in Sclerotinia sclerotiorum.

The SWI/SNF complex is guided to the promoters of designated genes by its co-operator to activate transcription in a timely and appropriate manner to govern development, pathogenesis, and stress responses in fungi. Nevertheless, knowledge of the complexes and their co-operator in phytopathogenic fungi is still fragmented. We demonstrate that the heat shock transcription factor SsHsf1 guides the SWI/SNF complex to promoters of heat shock protein (hsp) genes and antioxidant enzyme genes using biochemistry and pharmacology. This is accomplished through direct interaction with the complex subunit SsSnf5 under heat shock and oxidative stress. This results in the activation of their transcription and mediates histone displacement to maintain reactive oxygen species (ROS) homeostasis. Genetic results demonstrate that the transcription module formed by SsSnf5 and SsHsf1 is responsible for regulating morphogenesis, stress tolerance, and pathogenicity in Sclerotinia sclerotiorum, especially by directly activating the transcription of hsp genes and antioxidant enzyme genes counteracting plant-derived ROS. Furthermore, we show that stress-induced phosphorylation of SsSnf5 is necessary for the formation of the transcription module. This study establishes that the SWI/SNF complex and its co-operator cooperatively regulate the transcription of hsp genes and antioxidant enzyme genes to respond to host and environmental stress in the devastating phytopathogenic fungi.

Three new cadinene-type sesquiterpenoids from the aerial parts of Ageratina adenophora.

Three new cadinene sesquiterpenoids 1-3, were isolated from the aerial sections of Ageratina adenophora using various chromatographic techniques. Their structures were characterised by comprehensive spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The cytotoxic activity of new compounds 1-3 were evaluated by testing in vitro tumour growth inhibitory rate against five human tumour cell lines, HL-60, A-549, SMMC-7721, MDA-MB-231, and SW480.

The risk factors for miscarriage of viable intrauterine pregnancies in patients with heterotopic pregnancy after surgical intervention.

To summarize the clinical characteristics and explore the risk factors for miscarriage of a viable intrauterine pregnancy following surgical intervention in patients with heterotopic pregnancy (HP). A total of 106 women diagnosed with HP that underwent surgical intervention in the Women's Hospital School of Medicine Zhejiang University between January 2014 and December 2021 were included in this retrospective study. They were divided into a miscarriage group (n = 13) and an ongoing pregnancy group (n = 93) according to the outcomes of the HP within 2 weeks after surgery. Data regarding clinical characteristics, surgical conditions, postoperative recovery, and complications were collected and compared between the groups. Logistic multivariate analysis was performed to explore the risk factors for miscarriage in patients with HP within 2 weeks of surgical intervention. Among the 106 women with HP, 80 had tubal HP, 8 had cornual HP, and 18 had interstitial HP. Eighty-seven (82.1%) patients developed clinical symptoms that manifested primarily as abnormal vaginal bleeding and/or abdominal pain, whereas 19 (17.9%) patients had no clinical symptoms. The mean gestational age on the day of surgery was 7.2 weeks (inter-quartile range, 6.4-8.3). The miscarriage rate within 2 weeks of surgical intervention was 12.3% in patients with HP. Compared to the ongoing pregnancy group, the miscarriage group had a higher body mass index, earlier gestational age at treatment, and higher volume of hemoperitoneum (P < .05 for all). Logistic multivariate analysis indicated that the women with a hemoperitoneum volume > 200 mL had significantly higher risk of miscarriage after adjusting covariates [OR (odds ratio) = 5.285, 95% CI (confidence interval) (1.152-24.238), P < .05]. Hemoperitoneum volume was independently associated with miscarriage of viable intrauterine pregnancies in patients with HP within 2 weeks of surgical intervention.

Association between allergic rhinitis and hypertension risk: A bidirectional 2-sample mendelian randomization study.

Previous studies have suggested a potential association between allergic rhinitis (AR) and hypertension, but the genetic basis remains unclear. In this study, we aimed to explore the genetic correlation and potential causal association between AR and hypertension. Using a large-scale genome-wide association study (GWAS) public database, we conducted meticulous screening to acquire the most up-to-date GWAS data on single nucleotide polymorphisms (SNPs) relevant to AR and hypertension, with a significance threshold of P < 5 × 10-8. Then, we investigated the causal association between AR and hypertension through mendelian randomization (MR) analysis. We also performed reverse MR analysis to assess the possibility of reverse causality. Sensitivity analyses encompassed various factors, including horizontal pleiotropy, heterogeneity testing, and stepwise exclusion sensitivity checks. To investigate the causal relationship between AR and hypertension, we utilize the odds ratio (OR) and 95% confidence interval (CI) as our evaluative metric. This study leveraged a database comprising 112583 samples for AR and 461880 samples for hypertension. After meticulous screening, we identified 32 SNPs as instrumental variables. By employing the aforementioned 2-sample Mendelian randomization approaches, the estimated causal effects showed striking concordance. A discernible causal association between AR and hypertension was found using the IVW method (OR = 0.91, 95% CI: 0.86-0.98, P = .008), with horizontal pleiotropy and heterogeneity tests supporting the validity of our MR study. MR-Egger regression findings provided reassurance against bias stemming from genetic pleiotropy (intercept = -0.0006802, P = .6947). Interestingly, "leave-one-out" analysis yielded no evidence of nonspecific SNP influences, further consolidating our findings. Moreover, our reverse MR analysis yielded no indication of reverse causality from hypertension to AR, effectively discounting any influence from the latter on the former. Our study found evidence of a causal association between AR and hypertension in individuals of European ancestry. It demonstrated that AR reduced the risk of hypertension, suggesting a protective effect on hypertension due to the negative correlation with AR.

The Role and Application of the AMPK-Sirtuins Network in Cellular Senescence.

Aging and related diseases significantly affect the health and happiness index around the world. Cellular senescence is the basis of physiological aging and is closely related to various senile diseases. AMP-activated protein kinase (AMPK) is associated with both the regulation of cellular energy metabolism and the regulation of cellular senescence. Another set of proteins, sirtuins, has also been demonstrated to play an important role in cell senescence. However, it is not clear how AMPK and sirtuins coordinate to regulate cellular senescence. Herein, we summarized the role of AMPK and sirtuins in regulating metabolism, repairing DNA damage, and even prolonging human life. We have provided a detailed explanation of the clinical trials relating to the AMPK and sirtuins involved in aging. Systematically analyzing individual senescence genes and developing functional reference notes will aid in understanding the potential mechanisms underlying aging and identify therapeutic targets for both anti-aging interventions and age-related illnesses.

A survey of bloodborne occupational exposure protection behavior among qualified Chinese midwives: A cross-sectional study.

Background: Bloodborne occupational exposure is a major public health concern of the China Health Commission, especially among midwives who are at high risk among healthcare workers. Knowledge of occupational exposure and appropriate protective behaviors play important roles in reducing occupational exposure. The purpose of this study was to understand the knowledge and level of protection against bloodborne occupational exposure among midwives in China. Methods: This was a multi-center, cross-sectional study. Midwives from hospitals that are members of Infectious Disease Nursing Committee of Chinese Nursing Association were selected as survey participants from February 2019 to February 2022 using a judged sampling method. Data were collected by using a self-developed questionnaire for Chinese midwives to report their current knowledge and behavior related to bloodborne occupational exposure protection. Results: A total of 2850 questionnaires were distributed and 2742 valid questionnaires were obtained, resulting in an effective rate of 96.21 %. Midwives scored 2742 (6.495 ± 1.529) points for their knowledge about bloodborne occupational exposure protection, with the level and type of hospital being independent factors affecting the midwives' knowledge of bloodborne occupational exposure protection (χ2 = 27.284, P = 0.038; χ2 = 28.374, P = 0.000). Of the midwives, 1460 were qualified for bloodborne occupational exposure protection behavior, with a qualified rate of 53.25 %. Working years (χ2 = 9.372, P = 0.002) and working hours (χ2 = 13.933, P = 0.000) were also the independent factors for bloodborne occupational exposure protective behavior in midwives. Conclusion: Chinese midwives possess relatively good knowledge of bloodborne exposure protection against bloodborne infectious diseases, but their behavioral level is not optimistic. Improvements to both knowledge and behavioral level of bloodborne occupational exposure protection are necessary.