Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility.

Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.

The Cryoprotective Effect of an Antifreeze Collagen Peptide Complex Obtained by Enzymatic Glycosylation on Tilapia.

Antifreeze peptides have become effective antifreeze agents for frozen products, but their low quantity of active ingredients and high cost limit large-scale application. This study used the glycosylation of fish collagen peptides with glucosamine hydrochloride catalyzed by transglutaminase to obtain a transglutaminase-catalyzed glycosylation product (TGP) and investigate its antifreeze effect on tilapia. Compared with the blank group, the freshness (pH value of 6.31, TVB-N value of 21.7 mg/100 g, whiteness of 46.28), textural properties (especially hardness and elasticity), and rheological properties of the TGP groups were significantly improved. In addition, the protein structures of the samples were investigated using UV absorption and fluorescence spectroscopy. The results showed that the tertiary structure of the TGP groups changed to form a dense polymer. Therefore, this approach can reduce the denaturation and decomposition of muscle fibers and proteins in fish meat more effectively and has a better protective effect on muscle structure and protein aggregation, improving the stability of fish meat. This study reveals an innovative method for generating antifreeze peptides by enzymatic glycosylation, and glycosylated fish collagen peptide products can be used as new and effective green antifreeze agents in frozen foods.

Gut microbiota and therapy for obesity and type 2 diabetes.

There has been a major increase in Type 2 diabetes and obesity in many countries, and this will lead to a global public health crisis, which not only impacts on the quality of life of individuals well but also places a substantial burden on healthcare systems and economies. Obesity is linked to not only to type 2 diabetes but also cardiovascular diseases, musculoskeletal disorders, and certain cancers, also resulting in increased medical costs and diminished quality of life. A number of studies have linked changes in gut in obesity development. Dysbiosis, a deleterious change in gut microbiota composition, leads to altered intestinal permeability, associated with obesity and Type 2 diabetes. Many factors affect the homeostasis of gut microbiota, including diet, genetics, circadian rhythms, medication, probiotics, and antibiotics. In addition, bariatric surgery induces changes in gut microbiota that contributes to the metabolic benefits observed post-surgery. Current obesity management strategies encompass dietary interventions, exercise, pharmacotherapy, and bariatric surgery, with emerging treatments including microbiota-altering approaches showing promising efficacy. While pharmacotherapy has demonstrated significant advancements in recent years, bariatric surgery remains one of the most effective treatments for sustainable weight loss. However, access to this is generally limited to those living with severe obesity. This underscores the need for non-surgical interventions, particularly for adolescents and mildly obese patients. In this comprehensive review, we assess longitudinal alterations in gut microbiota composition and functionality resulting from the two currently most effective anti-obesity treatments: pharmacotherapy and bariatric surgery. Additionally, we highlight the functions of gut microbiota, focusing on specific bacteria, their metabolites, and strategies for modulating gut microbiota to prevent and treat obesity. This review aims to provide insights into the evolving landscape of obesity management and the potential of microbiota-based approaches in addressing this pressing global health challenge.

The effect of deviations in sintering temperature on the translucency and color of multi-layered zirconia.

OBJECT: This study aimed to investigate the changes in the translucency and color of four different multi-layered zirconia materials when the sintering temperature were inaccurate. MATERIALS AND METHODS: Two hundred zirconia samples (11 × 11 × 1.0 mm) of four multi-layered zirconia, Upcera TT-GT (UG), Upcera TT-ML (UM), Cercon xt ML (CX), and Lava Esthetic (LE), were divided into five subgroups according to the sintering temperature: L1 (5% lower temperature), L2 (2.5% lower temperature), R (recommended sintering temperature), H2 (2.5% higher temperature), H1 (5% higher temperature). After sintering, color coordinates were measured. Then the translucency parameter (TP) values, and the color differences (between the inaccurate sintering temperature and the recommended temperature) of each zirconia specimen were calculated. Statistical analysis was performed by using three-way ANOVA tests, the one-way ANOVA, and Tukey's post hoc test. RESULTS: Three-way ANOVA results showed that material type, sintering temperature, specimen section, and their interactions significantly influenced the TP values (except for the interactions of specimen section and sintering temperature) (P < .05). TP values of zirconia specimens were significantly different in the inaccurate sintering temperatures (P < .05), except for the cervical and body sections of UG group (P > .05). Compared with recommended sintering temperature, higher sintering temperature caused higher TP values for CX, but lower for LE. Three-way ANOVA results showed that material type, sintering temperature, and their interactions significantly influenced the ∆E00 values (P < .05). There were no significant differences in ∆E00 values of UM and CX groups at different inaccurate sintering temperatures, and were clinical imperception (except for UM-L1) (∆E00 < 1.25). ∆E00 values of all zirconia specimens showed clinically acceptable (∆E00 < 2.23). CONCLUSION: The deviations in sintering temperature significantly influenced the translucency and color of tested multi-layered zirconia. The trends of translucency in the multi-layered zirconia depended on material type and the color changes of all zirconia materials were clinically acceptable at inaccurate sintering temperatures.

Associations of serum albumin and dietary protein intake with all-cause mortality in community-dwelling older adults at risk of sarcopenia.

Objective: The Asian Working Group for Sarcopenia 2019 consensus emphasized nutritional assessment and intervention for community-dwelling older people with sarcopenia status. This study aimed to examine the association of serum albumin and dietary protein intake (DPI) with all-cause mortality among older adults at risk of sarcopenia. Methods: We enrolled 1763 older adults at risk of sarcopenia in the Chinese Longitudinal Healthy Longevity Survey (2012-2018) using calf circumference and handgrip strength. Serum albumin concentrations were measured using bromocresol green methods, and DPI frequency was evaluated using a semi-quantitative questionnaire at baseline. Cox proportional hazards models were used to explore the association of serum albumin and DPI with all-cause mortality. Results: During 5606.3 person-years of follow-up (median: 3.28 years), 802 older people died. After adjusting for socio-demographics, health behaviors, and clinical characteristics, we observed an inverse linear association between serum albumin and all-cause mortality (Pnon-linear = 0.429). Participants with low albumin levels (<40.0 g/L) had a 43 % higher risk of mortality than their counterparts (hazard ratio (HR) = 1.43, 95 % confidence interval (CI) = 1.22-1.66). There was no significant association between DPI and mortality (Ps > 0.05). Moreover, the association between low albumin and all-cause mortality remained significant in the lower DPI subgroup (HR = 1.47, 95 % CI = 1.18-1.85), but was not significant in the high DPI subgroup (HR = 1.15, 95 % CI = 0.92-1.39). Conclusions: Serum albumin levels are inversely associated with all-cause mortality in community-based older adults at risk of sarcopenia. Sufficient dietary protein consumption may attenuate the effect of low serum albumin on increased mortality and potential mechanisms for the interaction warrant further exploration.

Lipopolysaccharide modification enhances the inhibitory effect of clodronate liposomes on hepatic fibrosis by depletion of macrophages and hepatic stellate cells.

Hepatic fibrosis is a complex chronic liver disease in which both macrophages and hepatic stellate cells (HSCs) play important roles. Many studies have shown that clodronate liposomes (CLD-lipos) effectively deplete macrophages. However, no liposomes have been developed that target both HSCs and macrophages. This study aimed to evaluate the therapeutic efficacy of lipopolysaccharide-coupled clodronate liposomes (LPS-CLD-lipos) and the effects of liposomes size on hepatic fibrosis. Three rat models of hepatic fibrosis were established in vivo; diethylnitrosamine (DEN), bile duct ligation (BDL), and carbon tetrachloride (CCl4). Hematoxylin and eosin staining and serological liver function indices were used to analyze pathological liver damage. Masson's trichrome and Sirius red staining were used to evaluate the effect of liposomes on liver collagen fibers. The hydroxyproline content in liver tissues was determined. In vitro cell counting kit-8 (CCK-8) and immunofluorescence assays were used to further explore the effects of LPS modification and liposomes size on the killing of macrophages and HSCs. Both in vitro and in vivo experiments showed that 200 nm LPS-CLD-lipos significantly inhibited hepatic fibrosis and the abnormal deposition of collagen fibers in the liver and improved the related indicators of liver function. Further results showed that 200 nm LPS-CLD-lipos increased the clearance of macrophages and induced apoptosis of hepatic stellate cells, significantly. The present study demonstrated that 200 nm LPS-CLD-lipos could significantly inhibit hepatic fibrosis and improve liver function-related indices and this study may provide novel ideas and directions for hepatic fibrosis treatment.

Repurposing diacerein to suppress colorectal cancer growth by inhibiting the DCLK1/STAT3 signaling pathway.

Double cortin-like kinase 1 (DCLK1) exhibits high expression levels across various cancers, notably in human colorectal cancer (CRC). Diacerein, a clinically approved interleukin (IL)-1ß inhibitor for osteoarthritis treatment, was evaluated for its impact on CRC proliferation and migration, alongside its underlying mechanisms, through both in vitro and in vivo analyses. The study employed MTT assay, colony formation, wound healing, transwell assays, flow cytometry, and Hoechst 33342 staining to assess cell proliferation, migration, and apoptosis. Additionally, proteome microarray assay and western blotting analyses were conducted to elucidate diacerein's specific mechanism of action. Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo. Through high-throughput proteomics microarray and molecular docking studies, we identified that diacerein directly interacts with DCLK1. Mechanistically, the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed. Furthermore, diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets, including MCL-1, VEGF, and survivin, thereby inhibiting CRC progression in a mouse model, thereby inhibiting CRC progression in a mouse model.

Pectin: Health-promoting properties as a natural galectin-3 inhibitor.

Galectin-3 has a variety of important pathophysiological significance in the human body. Much evidence shows that the abnormal expression of galectin-3 is related to the formation and development of many diseases. Pectin is mostly obtained from processed citrus fruits and apples and is a known natural inhibitor of galactin-3. A large number of peels produced each year are discarded, and it is necessary to recycle some of the economically valuable active compounds in these by-products to reduce resource waste and environmental pollution. By binding with galectin-3, pectin can directly reduce the expression level of galectin-3 on the one hand, and regulate the expression level of cytokines by regulating certain signaling pathways on the other hand, to achieve the effect of treating diseases. This paper begins by presenting an overview of the basic structure of pectin, subsequently followed by a description of the structure of galectin-3 and its detrimental impact on human health when expressed abnormally. The health effects of pectin as a galectin-3 inhibitor were then summarized from the perspectives of anticancer, anti-inflammatory, ameliorating fibrotic diseases, and anti-diabetes. Finally, the challenges and prospects of future research on pectin are presented, which provide important references for expanding the application of pectin in the pharmaceutical industry or developing functional dietary supplements.

Autoantibodes to GP210 are a metric for UDCA responses in primary biliary cholangitis.

Objectives: Antibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear. Materials and methods: Using the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296-386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients. Results: In our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.ß = 0.35, P = 0.003) and gamma-glutamyltransferase (GGT) (st.ß = 0.23, P = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease. Conclusions: Our study reflects that quantitative changes of anti-gp210 antibody are indicative of UDCA responses. There is a great need for newer metrics in PBC and we suggest that a more detailed and longer study of these unique ANAs is warranted.

Integrated Optimization of Structure and Control for Fast Steering Mirrors.

This study concerns the problem of integrated optimization of structure and control based on a fast steering mirror, aiming to achieve simultaneous optimization of the mechanical structure and control system. The traditional research and development path of the fast steering mirror involves a lengthy process from the initial design to the final physical manufacture. In the prior process, it was necessary to produce physical prototypes for repeated debugging and iterative optimization to achieve design requirements, but this approach consumes a significant amount of time and cost. To expedite this process and reduce unnecessary experimental costs, this study proposes an integrated optimization of structure and control (IOSC) method. With the use of IOSC, it is possible to achieve simultaneous optimization of structure and control. Specifically, the use of non-dominated sorting genetic algorithm II (NSGA-II) obtains globally optimal controller parameters and mechanical structure parameters under certain performance indices. This achieves an effective balance between the resonance frequency generated by the system and the working bandwidth, providing a high-precision reference for the research and development of fast steering mirrors.

Prospects of yam (Dioscorea) polysaccharides: Structural features, bioactivities and applications.

Yam (Dioscorea) is a tuber crop cultivated for food security, revenue, and medicinal purposes. It has been used to treat diabetes, asthma, diarrhea, and other diseases. The main active ingredients in yam, polysaccharides, are regarded to be the important reason for its widespread applications. Now, a comprehensive review of research developments of yam polysaccharides (YPs) was presented to explore their prospects. We outlined the structural characteristics, biological activities, structure-activity relationships, and potential applications. Around 13 neutral components and 17 acidic components were separated. They exhibited various bioactivities, including immunomodulatory, hypoglycemic, hypolipidemic, antioxidant, gastrointestinal protective, anti-fatigue, and senile disease treatment activities, as well as prebiotic effect. Structure-activity relationships illustrated that unique structural properties, chemical modifications, and carried biopolymers could influence the bioactivities of YPs. The potential applications in medicine, food, and other fields have also been summarized.

Effect of ceramic type and thickness on the masking ability of chairside machinable all-ceramic crowns.

OBJECTIVES: This study aimed to evaluate the influence of ceramic type and thickness on the masking ability and final aesthetic effects of chairside machinable all-ceramic crowns. METHODS: Six kinds from three types chairside machinable ceramic materials (IPS e.max CAD HT/MT/LT, IPS Empress LT, and VITA Suprinity HT/T) in shade A2 were fabricated to slice specimens into 1.0, 1.5, and 2.0 mm-thick sections (n=10). The color parameters of the specimens against black and white tiles and four resin substrates (A2, A4, B3, and C4 shade) were measured with a spectrophotometer. The translucency parameter (TP) was calculated using color parameters measured over standard white and black backgrounds. The color differences (ΔE) were calculated between there substrate shades (A4, B3, C4 ) and A2 shade (control group). Two-way analysis of variance (ANOVA) was performed on the TP values. The two va-riables were ceramic type and ceramic thickness. Three-way ANOVA was used to determine the effects of ceramic materials, ceramic thickness, and substrate shades on the ΔE values, followed by Tukey test for multiple comparisons (α=0.05). RESULTS: Ceramic type, ceramic thickness, and substrate shade significantly affected the ΔE values (P<0.001). The L* and b* values of the specimens increased with increasing ceramic thickness, except in substrate A2, whereas the ΔE values decreased. The color difference of all 1.0 mm-thick specimens or all specimens over the substrates C4 shade exceeded the clinically acceptable threshold (ΔE>3.3). CONCLUSIONS: The masking ability of chairside machinable all-ceramic crowns is influenced by ceramic type and thickness, and ceramic material. The thickness of ceramic less than 2.0 mm cannot mask the gray shade abutment.

Heat-Resistant Inbred Lines Coordinate the Heat Response Gene Expression Remarkably in Maize (Zea mays L.).

High temperatures are increasingly becoming a prominent environmental factor accelerating the adverse influence on the growth and development of maize (Zea mays L.). Therefore, it is critical to identify the key genes and pathways related to heat stress (HS) tolerance in maize. Great challenges have been faced in dissecting genetic mechanisms and uncovering master genes for HS tolerance. Here, Z58D showed more thermotolerance than AF171 at the seedling stage with a lower wilted leaf rate and H2O2 accumulation under HS conditions. Transcriptomic analysis identified 3006 differentially expressed genes (DEGs) in AF171 and 4273 DEGs in Z58D under HS treatments, respectively. Subsequently, GO enrichment analysis showed that commonly upregulated genes in AF171 and Z58D were significantly enriched in the following biological processes, including protein folding, response to heat, response to temperature stimulus and response to hydrogen peroxide. Moreover, the comparison between the two inbred lines under HS showed that response to heat and response to temperature stimulus were significantly over-represented for the 1234 upregulated genes in Z58D. Furthermore, more commonly upregulated genes exhibited higher expression levels in Z58D than AF171. In addition, maize inbred CIMBL55 was verified to be more tolerant than B73, and more commonly upregulated genes also showed higher expression levels in CIMBL55 than B73 under HS. These consistent results indicate that heat-resistant inbred lines may coordinate the remarkable expression of genes in order to recover from HS. Additionally, 35 DEGs were conserved among five inbred lines via comparative transcriptomic analysis. Most of them were more pronounced in Z58D than AF171 at the expression levels. These candidate genes may confer thermotolerance in maize.

Predictive impact of sarcopenia in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: A retrospective study.

Background: Sarcopenia, characterised by an ongoing loss of skeletal muscle mass and reduced strength and function, is frequently observed in patients with non-small cell lung cancer (NSCLC). However, the relationship between sarcopenia and the prognosis of NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. This aimed to assess whether sarcopenia is an independent prognostic factor for survival in patients with advanced NSCLC receiving ICIs. Methods: For this retrospective cohort study, we analysed the medical records of patients attending our hospital aged 18-75 years who were newly diagnosed with stage IIIB to stage IV NSCLC, and who had received ICIs as first- or second-line therapy between May 2019 and April 2022. The skeletal muscle index (SMI) was calculated from computed tomography (CT) images and relevant clinical characteristics within 4 weeks of initiating treatment and used to diagnose sarcopenia status. The Kaplan-Meier method and log-rank test were used to calculate and compare patients' progression-free survival (PFS). Cox proportional hazard regression was used to examine the associations between sarcopenia and survival outcomes. The chi-square test was used to compare treatment response outcomes, such as the objective response rate (ORR), disease control rate (DCR), and immunotherapy-related adverse events (irAEs), between individuals with and without sarcopenia. Additionally, the Student's t-test was utilised to compare SMI values between patients by their objective response (OR) and disease control (DC). Finally, the Mann-Whitney U test was used to compare nutritional and inflammatory indicators between the sarcopenia groups. Results: The study enrolled 70 patients, of whom 34 (48.6%) were diagnosed with sarcopenia. The median PFS of patients with and without sarcopenia was 7.5 vs. 13.4 months, respectively (p = 0.006). The proportional hazards regression analysis showed sarcopenia to be an independent prognostic factor for shorter PFS (hazard ratio (HR): 0.504, 95% CI: 0.265-0.962, p = 0.038). Using chi square tests, we found significant differences in the ORR (20.59% vs. 58.33%, p = 0.001) and occurrence of any irAEs (44.1% vs. 22.2%, p = 0.028) between the sarcopenia and the non-sarcopenia groups, respectively. The Student's t-test showed a significant difference in SMI between the ORR group and the non-ORR group (49.99 ± 7.00 vs. 42.98 ± 2.18 cm2/m2, p = 0.0015). While the sarcopenia group were with significantly a lower CD4+/CD8+ ratios and a higher C-reactive protein (CRP) level (p = 0.026, p = 0.011, respectively). Conclusions: This study found that sarcopenia is a significant predictor of a poor prognosis for patients with advanced NSCLC receiving ICIs. Multiple inflammatory and immune functions related to prognosis also differ by sarcopenia status.

Preparation and characterization of a novel humanized collagen III with repeated fragments of Gly300-Asp329.

Recombinant human collagens have attracted intensive interest in the past two decades, demonstrating considerable potential in medicine, tissue engineering, and cosmetics. Several humanized recombinant collagens have been produced, exhibiting similar characteristics as the native species. To get insight into the structural and bioactive properties of different parts of collagen, in this study, the segment of Gly300-Asp329 of type III collagen was first adopted and repeated 18 times to prepare a novel recombinant collagen (named rhCLA). RhCLA was successfully expressed in E. coli, and a convenient separation procedure was established through reasonably combining alkaline precipitation and acid precipitation, yielding crude rhCLA with a purity exceeding 90%. Additionally, a polishing purification step utilizing cation exchange chromatography was developed, achieving rhCLA purity surpassing 98% and an overall recovery of approximately 120 mg/L culture. Simultaneously, the contents of endotoxin, nucleic acids, and host proteins were reduced to extremely low levels. This fragmented type III collagen displayed a triple-helical structure and gel-forming capability at low temperatures. Distinct fibrous morphology was also observed through TEM analysis. In cell experiments, rhCLA exhibited excellent biocompatibility and cell adhesion properties. These results provide valuable insights for functional studies of type III collagen and a reference approach for the large-scale production of recombinant collagens.

Global fungal-host interactome mapping identifies host targets of candidalysin.

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Regulatory RNAs in Bacillus subtilis: A review on regulatory mechanism and applications in synthetic biology.

Bacteria exhibit a rich repertoire of RNA molecules that intricately regulate gene expression at multiple hierarchical levels, including small RNAs (sRNAs), riboswitches, and antisense RNAs. Notably, the majority of these regulatory RNAs lack or have limited protein-coding capacity but play pivotal roles in orchestrating gene expression by modulating transcription, post-transcription or translation processes. Leveraging and redesigning these regulatory RNA elements have emerged as pivotal strategies in the domains of metabolic engineering and synthetic biology. While previous investigations predominantly focused on delineating the roles of regulatory RNA in Gram-negative bacterial models such as Escherichia coli and Salmonella enterica, this review aims to summarize the mechanisms and functionalities of endogenous regulatory RNAs inherent to typical Gram-positive bacteria, notably Bacillus subtilis. Furthermore, we explore the engineering and practical applications of these regulatory RNA elements in the arena of synthetic biology, employing B. subtilis as a foundational chassis.

The Antioxidant Salidroside Ameliorates the Quality of Postovulatory Aged Oocyte and Embryo Development in Mice.

Postovulatory aging is known to impair the oocyte quality and embryo development due to oxidative stress in many different animal models, which reduces the success rate or pregnancy rate in human assisted reproductive technology (ART) and livestock timed artificial insemination (TAI), respectively. Salidroside (SAL), a phenylpropanoid glycoside, has been shown to exert antioxidant and antitumor effects. This study aimed to investigate whether SAL supplementation could delay the postovulatory oocyte aging process by alleviating oxidative stress. Here, we show that SAL supplementation decreases the malformation rate and recovers mitochondrial dysfunction including mitochondrial distribution, mitochondrial membrane potential (ΔΨ) and ATP content in aged oocytes. In addition, SAL treatment alleviates postovulatory aging-caused oxidative stress such as higher reactive oxygen species (ROS) level, lower glutathione (GSH) content and a reduced expression of antioxidant-related genes. Moreover, the cytoplasmic calcium ([Ca2+]c) and mitochondrial calcium ([Ca2+]mt) of SAL-treated oocytes return to normal levels. Notably, SAL suppresses the aging-induced DNA damage, early apoptosis and improves spindle assembly in aged oocytes, ultimately elevating the embryo developmental rates and embryo quality. Finally, the RNA-seq and confirmatory experience showed that SAL promotes protective autophagy in aged oocytes by activating the MAPK pathway. Taken together, our research suggests that supplementing SAL is an effective and feasible method for preventing postovulatory aging and preserving the oocyte quality, which potentially contributes to improving the successful rate of ART or TAI.

Influence of loneliness burden on cardio-cerebral vascular disease among the Chinese older adult: a national cohort study.

Background: Adverse psychosocial factors play an important role in cardio-cerebral vascular disease (CCVD). The aim of this study was to evaluate the impact of the cumulative burden of loneliness on the risk of CCVD in the Chinese older adult. Methods: A total of 6,181 Chinese older adult over the age of 62 in the monitoring survey of the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) were included in this study. The loneliness cumulative burden (scored by cumulative degree) was weighted by the loneliness score for two consecutive years (2017-2018) and divided into low- and high-burden groups. The outcome was defined as the incidence of CCVD 1 year later (2018-2019). A multivariate logistic regression model was used to examine the relationship between the cumulative burden of loneliness and the new onset of CCVD. Results: Among participants, 18.9% had a higher cumulative burden of loneliness, and 11.5% had a CCVD incidence within 1 year. After multivariate adjustment, the risk of developing CCVD in the high-burden group was approximately 37% higher than that in the low-burden group (OR 1.373, 95%CI 1.096-1.721; p = 0.006). Similar results were obtained when calculating the burden based on cumulative time. Longitudinal change in loneliness was not significantly associated with an increased risk of CCVD. A higher cumulative burden of loneliness may predict a higher risk of developing CCVD in older adult individuals aged 62-72 years or in those with diabetes. Conclusion: The cumulative burden of loneliness can be used to assess the risk of new-onset CCVD in the older adult in the short term.

Risk model for predicting mortality in patients with necrotizing soft tissue infections in the intensive care unit.

BACKGROUND: The goal of this study is to look into the factors that lead to death in patients with necrotizing soft tissue infections（NSTIs） in the intensive care unit and create a mortality risk model. METHODS: The clinical data of 106 patients with necrotizing soft tissue infections admitted to intensive care unit(ICU) of the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2021 were retrospectively analyzed. Univariate analysis and multivariate analysis were performed to evaluate the risk factors impacting patient mortality. The regression coefficient in binary logistic regression analysis was converted into the item score in the model, and then the model score of each patient was calculated. Finally, an ROC curve was constructed to evaluate the efficiency of the model for predicting mortality. Thirteen patients with NSTIs admitted to ICU between January 2022 and November 2022 were used to validate the model. RESULTS: The death group had 44 patients, while the survival group had 62 patients. The overall mortality was 41.5%. Binary logistic regression analysis showed that risk factors for mortality were age≥ 60 years(OR:4.419; 95%CI:1.093-17.862; P = 0.037), creatinine ≥ 132µmol/L(OR:11.166; 95%CI:2.234-55.816; P = 0.003), creatine kinase ≥ 1104 U/L(OR:4.019; 95%CI:1.134-14.250; P = 0.031), prothrombin time ≥ 24.4 s(OR:11.589; 95%CI:2.510-53.506; P = 0.002), and invasive mechanical ventilation (OR:17.404; 95%CI:4.586-66.052; P＜0.000). The AUC of the model for predicting mortality was 0.940 (95% CI:0.894-0.986). When the cut-off value for the model was 4 points, the sensitivity was 95.5% and the specificity was 83.9%. CONCLUSION: The death risk model in this study for NSTIs patients in the intensive care unit shows high sensitivity and specificity. Patients with a score of ≥ 4 points have a higher risk of mortality.