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Abstract Circadian clock serves as a regulator of gastrointestinal health, and the disruption of circadian rhythm may trigger the dysregulation of the intestinal barrier functions. This study investigated the effectiveness of capsaicin (CAP) in mitigating intestinal barrier dysfunction induced by circadian disruption in male SPF C57BL/6J mice. Our findings indicated that CAP supplementation attenuated abnormal weight gain, alterations in serum lipid levels, and misalignment in hepatic and colonic circadian clock gene expressions in mice caused by constant darkness (CD) treatment. The restoration of the intestinal barrier integrity was also observed through the increase in mucosal thickness and goblet cell numbers. Both the diversity and the circadian rhythm of gut microbiota were improved in CAP‐treated group. Correlation analysis indicated that CAP could modulate the gut microbiota by affecting intestinal barrier function and systemic metabolism in CD‐treated mice. These results highlight the potential of CAP as a functional food component in maintaining the intestinal barrier homeostasis through regulating gut microbiota.

Abstract Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we described the changes in various immune cells during bone metastasis and discussed their related mechanisms. Osteoblasts, adipocytes, and other non‐immune cells closely related to bone metastasis were also included. This review also summarized the existing treatment methods and potential therapeutic targets, and provided insights for future studies of cancer bone metastasis.

BackgroundHeavy metals may play an important role in environmental risk factors associated disorders of activities of daily living (ADL) in older adults. ObjectiveTo investigate the associations between plasma levels of six heavy metals (zinc, arsenic, cadmium, lead, manganese, and copper) and ADL disorders in older adults. MethodsA cross-sectional survey was conducted from 2018 to 2019 among 1412 rural elderly people in Gongcheng Yao Autonomous County, Guangxi Zhuang Autonomous Region. The plasma metal concentrations were detected by inductively coupled plasma mass spectrometry (ICP-MS), and subsequently classified into three groups (T1-T3) based on tertiles, with the T1 group as the reference. The samples were assessed for ADL disorders using the ADL scale. Logistic regression and restricted cubic spline model (RCS) were used to estimate the odds ratio (OR) and 95% confidence interval (CI) to assess the associations between heavy metals and the prevalence of reporting ADL disorders. ResultsThe mean age of the study population was (68.52 ± 5.92) years, 825 (58.4%) female and 587 (41.6%) male. Of these, 372 (26.34%) subjects reported ADL disorders, and most of them were female (74.30%). The results of logistic regression showed that the participants in the cadmium T2 group (0.15-0.25 µg·L−1) had a higher risk of ADL disorders compared to the T1 group (≤0.15 μg·L−1) (OR=1.552, 95%CI: 1.086, 2.134). After stratification by sex, the relative risk of ADL disorders was lower in the plasma copper T3 group (>1019.58 µg·L−1) compared to the T1 group (≤868.12 μg·L−1) in men (OR=0.481, 95%CI: 0.232, 0.998). The relative risk of ADL disorders was higher in the plasma cadmium T2 group (0.15-0.25 µg·L−1) compared to the T1 group (≤0.15 μg·L−1) in women (OR=1.758, 95%CI: 1.182, 2.616). The RCS results showed that the risk of ADL disorders in men was nonlinearly associated with copper (Pnonlinear=0.011, Poverall

Abstract Chemotherapy is one of the conventional treatments for cancer in clinical practice. However, poor delivery efficiency, systemic toxicity, and the lack of pharmacokinetic monitoring during treatment are the critical limitations of current chemotherapy. Herein, we reported a brand-new antitumor drug delivery strategy that harnesses an optical fiber endoscopically therapeutic probe. The fiber probe carries photosensitizers in the fiber core and antitumor agents on the fiber surface mediated by a temperature-responsive hydrogel film, giving rise to an activable photothermal-chemotherapy that orchestrates the localized hyperthermia and thermal-stimuli drug release to the tumor lesion. Furthermore, the dynamical drug release and in-situ temperature can be real-time supervised through the built-in fiber sensors, including the reflective Mach–Zehnder interferometer and fiber Bragg grating, to visualize the therapy process and thus improve the safety of treatment. Compared with conventional methods, the fiber-optic drug delivery can adequately take advantage of the chemotherapeutics through collaboratively recruiting the photoheating-mediated enhanced permeability and the hydrogel particle-assisted high drug retention, shedding new light on a “central-to-peripheral” drug pervasion and retention mechanism to destroy tumors completely. The fiber-optic chemotherapy strategy incorporates precise drug delivery, accurate controllability of drug release, high drug permeability and retention in tumor, low off-target rate, and real-time drug release and temperature feedback, performing a straightforward and precise photothermal-chemotherapy pathway. More than that, the proposed strategy holds tremendous promise to provide a revolutionized on-demand drug delivery platform for the highly efficient evaluation and screening of antitumor pharmaceuticals.

Abstract Purpose We aimed to develop and evaluate a new diagnostic method, the 'chicken-wing muscle up test', to improve the accuracy of diagnosis of glenolabral articular disruption (GLAD) lesions compared to currently used clinical tests for injuries to the labrum. Methods Preoperative evaluations were conducted on 85 patients undergoing arthroscopic surgery at a single center between July 2021 to July 2022. The diagnostic performance of the preoperative clinical examinations (chicken-wing muscle up test, O'Brien test, crank test, and O'Driscoll test) were validated against the findings of arthroscopic examinations. Results 12 of the 85 patients in this study had arthroscopically confirmed GLAD lesions. The chicken-wing muscle up test demonstrated significantly higher sensitivity (83.33%) for GLAD lesions than the O'Brien test (33.33%), but not the crank test (50.00%) or O'Driscoll test (25.00%), and significantly higher specificity (95.89%) than the O'Brien test (75.34%), crank test (82.19%), and O'Driscoll test (71.23%). The chicken-wing muscle up test had the largest area under the receiver operating characteristic curve (AUC = 0.896, P 0.05; crank test AUC = 0.661, P > 0.05; O'Brien test AUC = 0.481, P > 0.05), indicating significantly better diagnostic efficacy for GLAD lesions than the other three tests. Conclusions The chicken-wing muscle up test is a reliable diagnostic method that improves the accuracy of diagnosis of GLAD lesions.

Abstract Background IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. Case presentation : A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz’s disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. Conclusion Mikulicz’s disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.

Abstract In the clinical application of intravascular optical coherence tomography (IVOCT), it is necessary to flush opaque blood during image acquisition. However, there are no specific standards for how to perform low-dose but effective flushing. In this study, computational fluid dynamics (CFD) and optical models were integrated to numerically simulate the complete process of IVOCT, which includes blood flushing with normal saline followed by image acquisition. Moreover, an intermittent injection scheme was proposed, and its advantages over the conventionally adopted scheme of continuous injection were verified. The results show that intermittent injection can significantly reduce the dosage of normal saline (reduced by 44.4%) with only a slight sacrifice of image quality (reduced by 8.7%, but still acceptable). The developed model and key findings in this work can help surgeons practice optimized IVOCT operations and potentially lead to improved designs of the IVOCT equipment.

Objective To investigate the relationship between sleep duration and myopia among primary school students in minority regions of Southwest China.Methods The school-based, cross-sectional study was conducted from October 2020 to January 2021. All participants underwent a comprehensive ocular examination and completed a questionnaire on demographic characteristics, ophthalmological history and major environmental factors for myopia. Spherical equivalent (SE) and ocular biometric parameters were measured after cycloplegia, with myopia being defined as SE ≤−0.5 D (Diopter). Multivariate regression models were used to examine the association of sleep duration with myopia, SE and axial length (AL).Results A total of 857 students from grades 2 to 4 were included in the analysis, of which 63.6% were myopic and 62.0% belonged to ethnic minorities. Boys had a slightly higher prevalence of myopia compared with girls (66.7% vs 60.6%, p=0.06). Myopic students had longer AL, deeper anterior chamber depth and thinner central corneal thickness compared with non-myopic students (all p

Green tides caused by Ulva prolifera occur annually in the Yellow Sea of China, and the massive amount of biomass decomposing during the demise stage of this green tide has deleterious ecological effects. Although microorganisms are considered key factors influencing algal bloom demise, an understanding of the microbial-algae interactions within the phycospheric microenvironment during this process is still lacking. Here, we focused on the variations in phycospheric microbial communities during the late stage of the green tide in three typically affected areas of the Yellow Sea via metagenomic sequencing analysis. In total, 16.9 million reads obtained from 18 metagenome samples were incorporated into the assembled contigs (13.4 Gbp). The phycosphere microbial community composition and diversity changed visibly during the demise of U. prolifera. The abundances of algae-lysing bacteria, Flavobacteriaceae at the family level and Alteromonas, Maribacter, and Vibrio at the genus level increased significantly in the phycosphere. In addition, the levels of glycoside hydrolases (GHs) and polysaccharide lyases (PLs) enzymes, which decompose U. prolifera polysaccharides in the phycosphere, were greater. Therefore, the degradation of algal polysaccharides can increase the efficiency of carbon metabolism pathways in the phycospheric microenvironment. Most of the genes detected in the phycosphere, especially norC, nrfA, and nasA, were associated with nitrogen metabolism pathways and showed dynamics related to the demise of the large amount of organic matter released by a green tide. Therefore, the demise of green tide algae may affect the potential carbon and nitrogen cycles of the phycospheric microenvironment by driving changes in the structure and diversity of microbial communities. Our research provides a novel perspective to better understand the ecological impact of U. prolifera during the green tide demise stage.

IntroductionScorias spongiosa is an edible fungus.MethodsIn this study, a nontargeted metabonomic analysis was conducted on the fruiting bodies of this fungus at five growth stages, and the differences in metabolites and the related metabolic pathways during growth and development were analysed.ResultsThis study revealed that the five growth stages of S. spongiosa fruiting bodies were associated with 15 pathways. These 15 metabolic pathways are speculated to play important roles in the growth of S. spongiosa fruiting bodies. Eleven bioactive substances were identified among the differentially expressed compounds. The content of six bioactive substances was highest at the S1 growth stage among all the growth stages. The metabolites related to sugar metabolism were enriched in three main pathways: pentose and gluconate interconversions, the pentose phosphate pathway, and the citrate cycle (TCA cycle).DiscussionThese results suggested that the S1 growth stage can be selected as the harvest period of S. spongiosa in fruiting bodies to retain most of the bioactive substances. Pentose and gluconate interconversions, the pentose phosphate pathway, and the TCA cycle are related to changes in polysaccharide content during the growth of S. spongiosa fruiting bodies.

BackgroundPeripartum respiratory complications are a major reason for pregnant women’s admission to the ICU, even endangers the maternal life. This bibliometric analysis was designed to elucidate the spectrum of diseases and risk factors for various respiratory complications during the peripartum period, as well as the future research directions in this field.MethodsRelevant publications were downloaded from the Web of Science Core Collection on November 1, 2023. CiteSpace was utilized for conducting the scientometric study.ResultsA total of 2,331 articles and reviews on respiratory complications during pregnancy published between 2004 and 2023 were retrieved, comprising 87,244 co-cited references, originating from 568 institutions across 104 countries/regions. The United States emerged as the leading country in this domain, with Harvard University standing out as the most actively engaged institution. Bibliometric analysis reveals that the current research hotspots include “COVID-19 pandemic,” “venous thromboembolism,” “respiratory distress syndrome” and “cardiovascular diseases.” Meanwhile, “venous thromboembolism,” cytokine storm” and supportive management such as “extracorporeal membrane oxygenation” might represent potential future research directions.ConclusionOver the past two decades, research on respiratory system complications in pregnancy has continually evolved. This study contributes to enabling researchers in the related field to understand future research hotspots and trends, providing information on potential collaborators, institutions, countries, and citation references.

Abstract For lithium‐sulfur batteries (Li‐S batteries), a high‐content electrolyte typically can exacerbate the shuttle effect, while a lean electrolyte may lead to decreased Li‐ion conductivity and reduced catalytic conversion efficiency, so achieving an appropriate electrolyte‐to‐sulfur ratio (E/S ratio) is essential for improving the battery cycling efficiency. A quasi‐solid electrolyte (COF‐SH@PVDF‐HFP) with strong adsorption and high catalytic conversion was constructed for in situ covalent organic framework (COF) growth on highly polarized polyvinylidene fluoride‐hexafluoropropylene (PVDF‐HFP) fibers. COF‐SH@PVDF‐HFP enables efficient Li‐ion conductivity with low‐content liquid electrolyte and effectively suppresses the shuttle effect. The results based on in situ Fourier‐transform infrared, in situ Raman, UV–Vis, X‐ray photoelectron, and density functional theory calculations confirmed the high catalytic conversion of COF‐SH layer containing sulfhydryl and imine groups for the lithium polysulfides. Lithium plating/stripping tests based on Li/COF‐SH@PVDF‐HFP/Li show excellent lithium compatibility (5 mAh cm−2 for 1400 h). The assembled Li‐S battery exhibits excellent rate (2 C 688.7 mAh g−1) and cycle performance (at 2 C of 568.8 mAh g−1 with a capacity retention of 77.3% after 800 cycles). This is the first report to improve the cycling stability of quasi‐solid‐state Li‐S batteries by reducing both the E/S ratio and the designing strategy of sulfhydryl‐functionalized COF for quasi‐solid electrolytes. This process opens up the possibility of the high performance of solid‐state Li‐S batteries.

BackgroundUnilateral or bilateral anterolateral thoracotomy May lead to severe acute pain in lung transplantation (LTx). Although serratus anterior plane block (SAPB) is apparently effective for pain control after open thoracic surgery, there remains a lack of evidence for the application of SAPB for postoperative analgesia after LTx.ObjectiveIn this case series pilot study, we describe the feasibility of continuous SAPB after lung transplantation and provide a preliminary investigation of its safety and efficacy.MethodsAfter chest incisions closure was complete, all patients underwent ultrasound-guided SAPB with catheter insertion. Numerical rating scale (NRS), additional opioid consumption, time to endotracheal tube removal, ICU length of stay, and catheter-related adverse events were followed up and recorded for each patient within 1 week after the procedure.ResultsA total of 14 patients who received LTx at this center from August 2023 to November 2023 were included. All patients received anterolateral approaches, and 10 (71.4%) of them underwent bilateral LTx. The duration of catheter placement was 2 (2–3) days, and the Resting NRS during catheter placement was equal to or less than 4. A total of 11 patients (78.6%) were supported by extracorporeal membrane oxygenation (ECMO) in LTx, whereas 8 patients (57.1%) removed the tracheal tube on the first day after LTx. Intensive care unit (ICU) stay was 5 (3–6) days, with tracheal intubation retained for 1 (1–2) days, and only one patient was reintubated. The morphine equivalent dose (MED) in the first week after LTx was 11.95 mg, and no catheter-related adverse events were detected.LimitationsWe did not assess the sensory loss plane due to the retrospective design. In addition, differences in catheter placement time May lead to bias in pain assessment.ConclusionAlthough continuous SAPB May be a safe and effective fascial block technique for relieving acute pain after LTx, it should be confirmed by high-quality clinical studies.

Abstract Background Although physician-pharmacist collaborative clinics for diabetes management have been shown to be effective and cost-effective worldwide, there is limited understanding of the factors that influence their sustainable implementation. This study aims to identify the associated factors and provide sustainability strategy to better implement physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers in China. Methods A sample of 43 participants were participated in face-to-face, in-depth, semi-structured interviews. Consolidated Framework for Implementation Research was used to identify facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers, and to explore discriminating factors between low and high implementation units. A sustainable strategy repository based on dynamic sustainability framework was established to inform further implementation. Results This study demonstrated that clear recognition of intervention benefits, urgent needs of patients, adaptive and tailored plan, highly collaborative teamwork and leadership support were the major facilitators, while the major barriers included process complexity, large number and poor health literacy of patients in primary areas, inappropriate staffing arrangements, weak financial incentives and inadequate staff competencies. Six constructs were identified to distinguish between high and low implementation units. Sixteen strategies were developed to foster the implementation of physician-pharmacist collaborative clinics, targeting Intervention, Practice setting, and Ecological system. Conclusion This qualitative study demonstrated facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers and developed theory-based strategies for further promotion, which has the potential to improve the management of diabetes and other chronic diseases in under-resourced areas.

Abstract Chronic pain after lung transplantation (LTx) can substantially reduce quality of life (QoL), yet current consensus guidelines say little about how to prevent or manage it. Research on pain after LTx has tended to focus on acute rather than chronic pain, and it has not extensively examined the factors associated with onset or resolution of chronic pain, which differ from factors influencing chronic pain after general thoracic surgery. This narrative review explores what is known about the epidemiology and risk factors of chronic pain after LTx, as well as effective ways to treat or prevent it. The review identifies key questions and issues that should be the focus of future research.

In order to address the issue of high development of hard overlying rock water-conducting fracture zones in deep coal mining and achieve water-preserved coal mining by reducing the height of water-conducting fracture zones, a new method is proposed in this study, which combines the techniques of pre-fracturing and weakening of hard main controlling overlying strata. This study comprehensively investigates the modification effect of pre-fracturing and weakening of hard main controlling overlying strata through laboratory experiments, theoretical analysis, and numerical simulation. The control mechanisms of different weakening layers on water-conducting fracture zones are elaborated and validated through field measurements. The results demonstrate that pre-existing fractures can induce the rock mass to shift its failure mode from intact rock fracturing to tension-shear failure controlled by pre-existing fractures, leading to a reduction in the severity of rock mass failure. The weakening effect of pre-existing fractures on the hard rock mass is revealed, and the damage variables coupled with stress and fractures are calculated. The relationship between the degree of weakening and the transformation of rock properties is qualitatively analyzed. It is found that the energy storage capacity of the rock mass is reduced while the dissipation capacity is enhanced after the modification. Numerical simulations are conducted to evaluate the control effect of different weakening layers on water-conducting fracture zones. By comparing the dynamic evolution of overlying rock failure modes, fracture counts, and failure heights, it is observed that the “saddle-shaped” failure mode gradually weakens with the increase of weakening layer height, and the evolution trend of fracture counts follows a pattern of “slow increase-sudden increase”. The dynamic evolution of failure height for unweakened and moderately to highly weakened overlying strata approximately exhibits an “S” shape, while the moderately weakened overlying strata exhibit a “semi-ejection” shape. Based on the analysis of the characteristics of failure in hard rock layers at different positions, the mechanisms of controlling the development of water-conducting fracture zones by different pre-fracturing weakening layers are revealed. Furthermore, using the borehole measurement method, the development height of the “two zones” under the condition of top plate fracturing in Mengcun mine is obtained. It is observed that the fracture extraction ratio is reduced under the condition of pre-fracturing weakening, thus preliminarily validating the inhibitory effect of top plate pre-fracturing weakening on the development of water-conducting fracture zones.It provides theoretical and scientific basis for coupling disaster prevention and control, water resources and ecological protection。

Abstract It is important to study the bacteria that cause endometritis to identify effective therapeutic drugs for dairy cows. In this study, 20% oxytetracycline was used to treat Holstein cows (n = 6) with severe endometritis. Additional 10 Holstein cows (5 for healthy cows, 5 for cows with mild endometritis) were also selected. At the same time, changes in bacterial communities were monitored by high-throughput sequencing. The results show that Escherichia coli, Staphylococcus aureus and other common pathogenic bacteria could be detected by traditional methods in cows both with and without endometritis. However, 16S sequencing results show that changes in the abundance of these bacteria were not significant. Endometritis is often caused by mixed infections in the uterus. Oxytetracycline did not completely remove existing bacteria. However, oxytetracycline could effectively inhibit endometritis and had a significant inhibitory effect on the genera Bacteroides, Trueperella, Peptoniphilus, Parvimonas, Porphyromonas, and Fusobacterium but had no significant inhibitory effect on the bacterial genera Marinospirillum, Erysipelothrix, and Enteractinococcus. During oxytetracycline treatment, the cell motility, endocrine system, exogenous system, glycan biosynthesis and metabolism, lipid metabolism, metabolism of terpenoids, polyketides, cofactors and vitamins, signal transduction, and transport and catabolism pathways were affected.

Abstract Background Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. Methods A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan–Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. Results Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120–134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p

All-solid-state lithium batteries (ASSLB) utilizing solid polymer electrolytes (SPEs) are attractive due to the enhanced safety and processability. However, operation of the cells usually requires elevated temperatures to overcome the low ionic conductivity or high interfacial resistance issue. Through this study, we identify that grain boundaries within SPE exist and play a crucial role on Li-ion transport and cell performance. Accordingly, a direct hot-press activation approach was proposed and demonstrated significant reduction of boundary resistance within the SPE, leading to a fourfold increase in room temperature (r.t.) ionic conductivity. The detailed morphological and structural study suggest a pressure-induced amorphization mechanism for the activation of room-temperature SPE. Through this facile activation procedure, all solid-state LiFeO4 (LFP)|SPE|Li cells demonstrate improved performance for both high specific capacity and stable cycling at r.t.

The guar gum/borax-based hydrogel system was employed to rapidly consolidate waste construction slurry to form porous soft solid, which could effectively mitigate the impact of waste construction slurry on the environment. The adsorbability of porous soft solid on methylene blue from cationic dye wastewater was studied to explore new utilization way in the paper. For the methylene blue solution with the pH of 8 and concentration of 30 mg·L−1, when the dosage of porous soft solid was 0.15 g·mL−1, the adsorption equilibrium was reached at 32 h, and the removal rate of methylene blue by the porous soft solid was up to 82.96 %. The X-ray diffraction and Fourier Transform Infrared Spectroscopy analysis indicated that both the hydrogel and clay particles in the porous soft solid were involved in the adsorption of methylene blue. The pseudo first-order kinetic equation and the Weber-Morris intraparticle diffusion equation can be used to describe the adsorption process on methylene blue by the porous soft solid.

As an important component of the glomerular filtration membrane, the state of the podocytes is closely related to kidney function, they are also key cells involved in aging and play a central role in the damage caused by renal aging. Therefore, understanding the aging process of podocytes will allow us to understand their susceptibility to injury and identify targeted protective mechanisms. In fact, the process of physiological aging itself can induce podocyte senescence. Pathological stresses, such as oxidative stress, mitochondrial damage, secretion of senescence-associated secretory phenotype, reduced autophagy, oncogene activation, altered transcription factors, DNA damage response, and other factors, play a crucial role in inducing premature senescence and accelerating aging. Senescence-associated-β-galactosidase (SA-β-gal) is a marker of aging, and β-hydroxybutyric acid treatment can reduce SA-β-gal activity to alleviate cellular senescence and damage. In addition, CCAAT/enhancer-binding protein-α, transforming growth factor-β signaling, glycogen synthase kinase-3β, cycle-dependent kinase, programmed cell death protein 1, and plasminogen activator inhibitor-1 are closely related to aging. The absence or elevation of these factors can affect aging through different mechanisms. Podocyte injury is not an independent process, and injured podocytes interact with the surrounding epithelial cells or other kidney cells to mediate the injury or loss of podocytes. In this review, we discuss the manifestations, molecular mechanisms, biomarkers, and therapeutic drugs for podocyte senescence. We included elamipretide, lithium, calorie restriction, rapamycin; and emerging treatment strategies, such as gene and immune therapies. More importantly, we summarize how podocyte interact with other kidney cells.

Objectives Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are at risk for hyperkalemia (HK), associated with cardiac arrhythmia and sudden death. Data on the burden of HK and management techniques among HD patients in China are still scarce. This study assessed the treatment modalities, recurrence, and prevalence of HK in Chinese HD patients.Methods In this prospective cohort study conducted from May 2021 to July 2022, patients aged ≥18 years who had ESRD and were on HD were enrolled from 15 centers in China (up to 6 months).Results Overall, 600 patients were enrolled. At the baseline visit, mean (± standard deviation) urea reduction ratio was 68.0% ± 9.70 and Kt/V was 1.45 ± 0.496. Over 6 months, 453 (75.5%) patients experienced HK, of whom 356 (78.6%) recurred. Within 1, 2, 3, 4, 5, and 6 months, 203 (44.8%), 262 (57.8%), 300 (66.2%), 326 (72.0%), 347 (76.6%), and 356 (78.6%) patients had at least one HK recurrence event, respectively. The proportions of patients with ≥1, 2, 3, 4, 5, or 6 HK recurrence events were 356 (78.6%), 306 (67.5%), 250 (55.2%), 208 (45.9%), 161 (35.5%), and 110 (24.3%), respectively. Among the 453 patients who experienced HK, only 24 (5.3%) were treated with potassium binders: seven (1.5%) with sodium polystyrene sulfonate, 13 (2.9%) with calcium polystyrene sulfonate, and six (1.3%) with sodium zirconium cyclosilicate.Conclusion Since HK is a chronic illness, long-term care is necessary. Patients on HD should have effective potassium management on non-dialysis days, yet our real-world population rarely used potassium binders.Trial registration ClinicalTrials.gov Identifier NCT04799067

Dry eye disease (DED) is a common eye disease in clinical practice. The crucial pathogenesis of DED is that hyperosmolarity activates oxidative stress signaling pathways in corneal epithelial and immune cells and, thus, produces inflammatory molecules. The complex pathological changes in the dry eye still need to be elucidated to facilitate treatment. In this study, we found that astaxanthin (AST) can protect against DED through the SLC7A11/GPX4 pathway. After treatment with AST, the SLC7A11/GPX4 pathway was positively activated in DED both in vivo and in vitro, accompanied by enhanced autophagy and decreased ferroptosis. In hyperosmolarity-induced DED corneal epithelial cells, AST increased the expression of ferritin to promote iron storage and reduce Fe2+ overload. It increased glutathione (GSH) and GPX4, scavenged reactive oxygen species (ROS) and lipid peroxide, and rescued the mitochondrial structure to prevent ferroptosis. Furthermore, inhibition of ferroptosis by ferrostatin-1 (Fer-1), iron chelator deferoxamine mesylate (DFO), or AST could activate healthy autophagic flux. In addition, in a dry eye mouse model, AST upregulated SLC7A11 and GPX4 and inhibited ferroptosis. To summarize, we found that AST can ameliorate DED by reinforcing the SLC7A11/GPX4 pathway, which mainly affects oxidative stress, autophagy, and ferroptosis processes.

Pain sensitivity varies depending on both the state and age of an individual. For example, chronic pain is more common in older individuals, but the underlying mechanisms remain unknown. This study revealed that 18-month-old mice (aged) experienced more severe and long-lasting allodynia and hyperalgesia in the chronic constriction injury (CCI)-induced pain state compared to 2-month-old mice. Interestingly, the aged mice had a higher baseline mechanical pain threshold than the adult mice. The expression of spinal receptor-active modification protein 1 (RAMP1), as a key component and regulator of the calcitonin gene-related peptide (CGRP) receptor for nociceptive transmission from the periphery to the spinal cord, was reduced in the physiological state but significantly increased after CCI in the aged mice compared to the adult mice. Moreover, when RAMP1 was knocked down using shRNA, the pain sensitivity of adult mice decreased significantly, and CCI-induced allodynia in aged mice was reduced. These findings suggest that spinal RAMP1 is involved in regulating pain sensitivity in a state- and age-dependent manner. Additionally, interfering with RAMP1 could be a promising strategy for alleviating chronic pain in older individuals.

Introduction: Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is widely used for sedation and anesthesia in patients undergoing hepatectomy. However, the effect of DEX on autophagic flux and liver regeneration remains unclear. Objectives: This study aimed to determine the role of DEX in hepatocyte autophagic flux and liver regeneration after PHx. Methods: In mice, DEX was intraperitoneally injected 5 min before and 6 h after PHx. In vitro, DEX was co-incubated with culture medium for 24 h. Autophagic flux was detected by LC3-II and SQSTM1 expression levels in primary mouse hepatocytes and the proportion of red puncta in AML-12 cells transfected with FUGW-PK-hLC3 plasmid. Liver regeneration was assessed by cyclinD1 expression, Edu incorporation, H&E staining, ki67 immunostaining and liver/body ratios. Bafilomycin A1, si-GSK3β and Flag-tagged GSK3β, α2-ADR antagonist, GSK3β inhibitor, AKT inhibitor were used to identify the role of GSK3β in DEX-mediated autophagic flux and hepatocyte proliferation. Results: Pre- and post-operative DEX treatment promoted liver regeneration after PHx, showing 12 h earlier than in DEX-untreated mice, accompanied by facilitated autophagic flux, which was completely abolished by bafilomycin A1 or α2-ADR antagonist. The suppression of GSK3β activity by SB216763 and si-GSK3β enhanced the effect of DEX on autophagic flux and liver regeneration, which was abolished by AKT inhibitor. Conclusion: Pre- and post-operative administration of DEX facilitates autophagic flux, leading to enhanced liver regeneration after partial hepatectomy through suppression of GSK3β activity in an α2-ADR-dependent manner.

Previous studies have shown that major depressive disorder (MDD) patients exhibit structural and functional impairments, but few studies have investigated changes in higher-order coupling between structure and function. Here, we systematically investigated the effect of MDD on higher-order coupling between structural connectivity (SC) and functional connectivity (FC). Each brain region was mapped into embedding vector by the node2vec algorithm. We used support vector machine (SVM) with the brain region embedding vector to distinguish MDD patients from health controls (HCs) and identify the most discriminative brain regions. Our study revealed that MDD patients had decreased higher-order coupling in connections between the most discriminative brain regions and local connections in rich-club organization and increased higher-order coupling in connections between the ventral attentional network and limbic network compared with HCs. Interestingly, transcriptome-neuroimaging association analysis demonstrated the correlations between regional rSC-FC coupling variations between MDD patients and HCs and α/β-hydrolase domain-containing 6 (ABHD6), β 1,3-N-acetylglucosaminyltransferase-9(β3GNT9), transmembrane protein 45B (TMEM45B), the correlation between regional dSC-FC coupling variations and retinoic acid early transcript 1E antisense RNA 1(RAET1E-AS1), and the correlations between regional iSC-FC coupling variations and ABHD6, β3GNT9, katanin-like 2 protein (KATNAL2). In addition, correlation analysis with neurotransmitter receptor/transporter maps found that the rSC-FC and iSC-FC coupling variations were both correlated with neuroendocrine transporter (NET) expression, and the dSC-FC coupling variations were correlated with metabotropic glutamate receptor 5 (mGluR5). Further mediation analysis explored the relationship between genes, neurotransmitter receptor/transporter and MDD related higher-order coupling variations. These findings indicate that specific genetic and molecular factors underpin the observed disparities in higher-order SC-FC coupling between MDD patients and HCs. Our study confirmed that higher-order coupling between SC and FC plays an important role in diagnosing MDD. The identification of new biological evidence for MDD etiology holds promise for the development of innovative antidepressant therapies.

Engineering cementitious composites (ECC) is an innovative high performance engineering structural material with high ductility, high toughness, and unique multiple cracking characteristics. Currently, most of the fibers used in ECC are expensive Kuraray PVA fibers produced in Japan. More and more researchers are using Polyethylene (PE) fibers made in China with low cost, high strength and high elastic modulus to replace Kuraray PVA fibers. However, the finer diameter and hydrophobicity make it difficult for the PE fibers to be distributed in the matrix evenly. In addition, most research currently focuses on the static performance of PE-ECC, with limited research on its dynamic performance. In this study, PE-ECC with different fiber contents was prepared with a high-power, high-speed mixer. Compressive tests, tensile tests and split Hopkinson pressure bar (SHPB) impact compression tests on the specimens were conducted to study their static and dynamic performance. The results indicated that increasing the fiber content can improve the mechanical properties of PE-ECC when the fiber volume fraction is low. Further increasing the volume fraction of fibers will affect the uniform distribution of fibers, leading to a decrease in the mechanical properties of PE-ECC and an increase in the discreteness of test results. Considering the difficulty of fiber dispersion and mechanical properties, it is recommended that the content of PE fibers should not exceed 2.25%. The research results of this paper may provide a reference for the promotion and application of PE-ECC, especially in the field of collision protection.

Abstract Background Due to its enormous biomass, Antarctic krill (Euphausia superba) plays a crucial role in the Antarctic Ocean ecosystem. In recent years, Antarctic krill has found extensive application in aquaculture, emerging as a sustainable source of aquafeed with ideal nutritional profiles. However, a comprehensive study focused on the detailed effects of dietary Antarctic krill on aquaculture animals, especially farmed marine fishes, is yet to be demonstrated. Results In this study, a comparative experiment was performed using juvenile P. leopardus, fed with diets supplemented with Antarctic krill (the krill group) or without Antarctic krill (the control group). Histological observation revealed that dietary Antarctic krill could reduce lipid accumulation in the liver while the intestine exhibited no obvious changes. Enzyme activity measurements demonstrated that dietary Antarctic krill had an inhibitory effect on oxidative stress in both the intestine and the liver. By comparative transcriptome analysis, a total of 1,597 and 1,161 differentially expressed genes (DEGs) were identified in the intestine and liver, respectively. Functional analysis of the DEGs showed multiple enriched terms significantly related to cholesterol metabolism, antioxidants, and immunity. Furthermore, the expression profiles of representative DEGs, such as dhcr7, apoa4, sc5d, and scarf1, were validated by qRT-PCR and fluorescence in situ hybridization. Finally, a comparative transcriptome analysis was performed to demonstrate the biased effects of dietary Antarctic krill and astaxanthin on the liver of P. leopardus. Conclusions Our study demonstrated that dietary Antarctic krill could reduce lipid accumulation in the liver of P. leopardus, enhance antioxidant capacities in both the intestine and liver, and exhibit molecular-level improvements in lipid metabolism, immunity, and antioxidants. It will contribute to understanding the protective effects of Antarctic krill in P. leopardus and provide insights into aquaculture nutritional strategies.

Turnout is the key equipment for realizing the turnback of subway trains. Frequent movements and environmental changes often lead to abnormal increases in resistance during turnout conversion, resulting in jamming failures that directly affect traffic safety and efficiency. In order to effectively foresee the risk of failure during operation and minimize the adverse effects of failure, a real-time turnout jamming failure prewarning method is proposed. Firstly, a weighted grey prediction machine using PSO for weight optimization (PSO-WGPM) is proposed to predict the short-term action load index, and the predicted index series is used to characterize the future changes in the resistance state of the turnout; Secondly, the predicted index and the generated index are cascaded into a risk identification index series, and a multi-dimensional hybrid prewarning feature set with time continuity are constructed by time-domain characteristics and overload statistical characteristics of the risk identification index series; Then, the prewarning feature set is fed into the learning vector quantization(LVQ) network for prewarning discrimination, and an ensemble learning based on a hybrid voting strategy is designed to obtain the final prewarning result, in order to fit the learning environment of unbalanced small-scale samples; After giving an prewarning, the occurrence time range of jamming failure is inferred based on the overload rate of the predicted index series. The experimental results show that: the proposed method can improve the prewarning success rate and effectively control false alarms, with good correctness; it can infer the range time of fault occurrence, achieving prewarning accuracy; the prewarning calculation time is much shorter than the failure advance time, meeting the timeliness requirements for applications.

Abstract Background Mesothelin (MSLN) has been implicated in cancer migration, invasion, and prognosis, making it a potential tumor marker. However, the precise role of MSLN in the migration and invasion of malignant pleural mesothelioma (MPM) remains elusive, and effective noninvasive methods for assessing MSLN status are currently lacking. In this study, we focused on MSLN expression and elucidated the underlying mechanisms by which MSLN regulates migration and invasion in MPM. Building upon this knowledge, we developed an MRI nanoprobe that targets MSLN to assess its status in vitro and in vivo by comparing T2 signal intensity and T2 values on magnetic resonance imaging examinations. This nanoprobe combines the anatomical information obtained from MRI with biological information obtained from MSLN for comprehensive evaluation of MPM. Results Notably, we observed that MSLN expression in the epithelial type of MPM was higher and increased continuously with tumor growth than that in other types. In addition, MSLN upregulation promoted N-cadherin, matrix metalloproteinase-7, and MMP9 expression and resulted in higher migration/invasion ability and shorter survival. We synthesized MSLN-targeted nanoprobes (Fe3O4@SiO2-PEG-MSLN, FSPM) to assess MSLN expression by comparing the T2 signal intensity and T2 value of different cell lines and mice after 14, 28, and 42 days of modeling. Remarkably, MSLN-targeted nanoprobes demonstrated excellent targeting capabilities. In vitro studies revealed a pronounced reduction in T2 signal intensity and T2 values of the epithelial type as the probe concentration increased. In addition, in vivo experiments demonstrated a gradual decline in these parameters over time, particularly in the epithelial type as compared to the biphasic type, corresponding to the dynamic expression patterns of MSLN during different growth stages. Conclusion Our comprehensive research succeeded in confirming the regulatory mechanisms by which MSLN influences migration and invasion. Moreover, we introduced a promising method for monitoring MSLN expression that may help in facilitating the early detection, histological subtype identification, and assessment of migration, invasion, and prognosis in MPM.

To expand the application of nobiletin (NOB) in semi-solid functional foods, bovine serum albumin (BSA)/carboxymethyl inulin (CMI) complexes-stabilized Pickering emulsion (BCPE) (φoil = 60%, v/v) was fabricated, and the swallowing index and bioavailability of the NOB-loaded Pickering emulsion was evaluated. Confocal laser scanning microscope (CLSM) and cryo-scanning electron microscopy (cryo-SEM) images revealed that BSA/CMI complexes attached to the oil–water interface. NOB-loaded BCPE exhibited a viscoelastic and shear-thinning behavior. Fork drip test results suggested that the textural value of unloaded and NOB-loaded emulsions was International Dysphagia Diet Standardisation Initiative Level 4, which could be swallowed directly without chewing. The in vitro lipolysis model suggested that NOB had a faster digestive profile and a higher bioaccessibility in the BCPE than in the oil suspension. The in vivo rat model revealed that the oral bioavailability of NOB was increased by 2.07 folds in BCPE compared to its bioavailability in unformulated oil. Moreover, BCPE led to a higher plasma concentration of the major demethylated metabolite of NOB (4′-demethylnobiletin) than the unformulated oil. Accordingly, BCPE enhanced the oral bioavailability of NOB by improving bioaccessibility, absorption, and biotransformation.

Abstract Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end‐stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the “gut‐kidney axis,” therefore, although clinical intervention to modulate the “gut‐kidney axis” imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non‐absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD‐triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain‐containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor‐β (TGF‐β) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4‐regulated TGF‐β pathway.

Abstract Background Echocardiography (ECHO) and cardiac magnetic resonance imaging (MRI) are used to observe changes in the left ventricular structure in patients with breast and gastric cancer after 6 cycles of chemotherapy. Based on the observed values, we aimed to evaluate the cardiotoxicity of anthracyclines in cancer patients and to analyze the consistency of the two examination methods in assessing left ventricular function after chemotherapy. Methods From January 2020 to January 2022, the data of 80 patients with malignant tumors who received anthracycline chemotherapy (breast cancer, n = 40; gastric cancer, n = 40) and 40 healthy volunteers (Control group) were retrospectively collected. Serum high-sensitivity cardiac troponin T (hs-cTnT) levels were detected by an automatic immunoassay analyzer. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were measured by cardiac MRI and 2-dimensional ECHO using the biplane Simpson’s method. Results Compared with baseline values, serum high-sensitivity cardiac troponin T (hs-cTnT) levels were significantly increased in patients with breast cancer and gastric cancer after 6 cycles of chemotherapy (P

Abstract Background In situ tumor vaccine has been gradually becoming a hot research field for its advantage of achieving personalized tumor therapy without prior antigen identification. Various in situ tumor vaccine regimens have been reported to exert considerable antitumor efficacy in preclinical and clinical studies. However, the design of in situ tumor vaccines still needs further optimization and the underlying immune mechanism also waits for deeper investigation. Methods A novel triple in situ vaccine strategy that combining local radiation with intratumoral injection of TLR9 agonist CpG and OX40 agonist was established in this sturdy. Local and abscopal antitumor efficacy as well as survival benefit were evaluated in the bilateral tumors and pulmonary metastasis model of B16F10 melanoma. In situ vaccine-induced immune responses and immune-associated variation in tumor environment were further investigated using multiparameter flow cytometry and RNA sequencing. Base on the analysis, the RT + CpG + αOX40 triple in situ vaccine was combined with checkpoint blockade therapy to explore the potential synergistic antitumor efficacy. Results Enhanced tumor suppression was observed with minimal toxicity in both treated and untreated abscopal tumors after receiving RT + CpG + αOX40 triple vaccine. The introduction of local radiation and OX40 agonist benefit more to the inhibition of local and abscopal lesions respectively, which might be partially attributed to the increase of effector memory T cells in the tumor microenvironment. Further analysis implied that the triple in situ vaccine did not only activate the microenvironment of treated tumors, with the upregulation of multiple immune-associated pathways, but also enhanced systemic antitumor responses, thus achieved superior systemic tumor control and survival benefit. Moreover, the triple in situ vaccine synergized with checkpoint blockade therapy, and significantly improved the therapeutic effect of anti-programmed cell death protein (PD)-1 antibody. Conclusion This triple combining in situ vaccine induced intensive antitumor responses, mediated effective systemic tumor control and survival benefit, and displayed impressive synergistic antitumor effect with checkpoint blockade therapy. These data preliminary confirmed the efficacy, feasibility and safety of the triple combining in situ vaccine, suggesting its great application potential as both monotherapy and a part of combined immunotherapeutic regimens in clinical scenario.

In order to reveal the mechanical behavior of short concrete columns reinforced with hybrid steel and glass FRP bars, 10 specimens were designed for eccentric compression tests. The effect of eccentricity and load–displacement/strain of the specimens was studied. Test results indicate that the damage process and failure mode of these hybrid RC columns was similar to those in the conventional steel-reinforced concrete columns. The mode of failure for all specimens is characterized as large eccentricity compression failure, and the ultimate bearing capacity of the columns decreases with the increase in eccentricity. However, the impact of the varying axial stiffness ratio between GFRP and steel bars on the bearing capacity can be considered negligible. In addition, based on theoretical analysis, two boundary states for distinguishing failure mode and the formulae for calculating ultimate bearing capacity in different failure modes of eccentrically loaded hybrid RC columns are proposed. The computed results agree well with test results.

The utilization of bismuth as a sensing material for the detection of heavy metal ions has gained significant attention due to its exceptional interfacial activity and selective absorption properties. However, it also poses challenges in terms of agglomeration and its inferior electrical conductivity during the synthesis process. This paper employed a facile in situ synthesis and electrodeposition approach to uniformly grow a bismuth film on a conductive carbon cloth, designated as Bi/Ag@CC. The Bi/Ag@CC electrode material exhibited benign electrochemical properties, enabling its application for detecting Pb2+ in tap water and lake water samples. Furthermore, this work investigated the impact of electrochemical parameters, including electrolyte pH, deposition potential and pre-enrichment time, on the detection performance. The results demonstrated the sensor’s wide linear range (from 20 to 400 ppb) and detection limits (0.15 ppb) for heavy metal ion detection, along with excellent anti-interference capabilities and satisfactory repeatability, with an RSD of less than 2.31% (n = 6). This paper offers a novel strategy for positioning the bismuth-based composite as a promising candidate for practical electrochemical sensing applications.

Abstract Background Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. Methods Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum–dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). Results At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum–dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1–

Abstract The bacterial divisome is a macromolecular machine composed of more than 30 proteins that controls cell wall constriction during division. Here, we present a model of the structure and dynamics of the core complex of the E. coli divisome, supported by a combination of structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis. We focus on the septal cell wall synthase complex formed by FtsW and FtsI, and its regulators FtsQ, FtsL, FtsB, and FtsN. The results indicate extensive interactions in four regions in the periplasmic domains of the complex. FtsQ, FtsL, and FtsB support FtsI in an extended conformation, with the FtsI transpeptidase domain lifted away from the membrane through interactions among the C-terminal domains. FtsN binds between FtsI and FtsL in a region rich in residues with superfission (activating) and dominant negative (inhibitory) mutations. Mutagenesis experiments and simulations suggest that the essential domain of FtsN links FtsI and FtsL together, potentially modulating interactions between the anchor-loop of FtsI and the putative catalytic cavity of FtsW, thus suggesting a mechanism of how FtsN activates the cell wall synthesis activities of FtsW and FtsI.

Abstract Innovative modes of response can greatly push forward chemical sensing processes and subsequently improve sensing performance. Classical chemical sensing modes seldom involve the transition of a delicate molecular assembly during the response. Here, we display a sensing mode for polyamine detection based on an order–order transition of iron–sulfur complexes upon their assembly. Strong validation proves that the unique order–order transition of the assemblies is the driving force of the response, in which the polyamine captures the metal ion of the iron–sulfur complex, leading it to decompose into a metal–polyamine product, accompanied by an order–order transition of the assemblies. This mechanism makes the detection process more intuitive and selective, and remarkably improves the detection efficiency, achieving excellent polyamines specificity, second-level response, convenient visual detection, and good recyclability of the sensing system. Furthermore, this paper also provides opportunities for the further application of the iron–sulfur platform in environment-related fields.

Abstract Aims The study aims to explore the real‐world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow‐up management system and the effect on the recovery of ventricular remodelling and cardiac function in China. Methods and results This is a single‐centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow‐up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow‐up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end‐diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12 months. Among the patients, 69.3% were male, with a median age of 49 years. The baseline systolic blood pressure (SBP) was 117.6 ± 18.3 mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1–5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21–34) % vs. 42 (IQR 37.0–54.3) %, P 40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12 month follow‐up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N‐terminal pro‐B‐type natriuretic peptide (P

ABSTRACT The infection cycle of phage λ terminates in lysis mediated by three types of lysis proteins, each disrupting a layer in the bacterial envelope: the S105 holin, the R endolysin, and the Rz/Rz1 spanin complex targeting the inner membrane, cell wall or peptidoglycan, and the outer membrane, respectively. Video microscopy has shown that in most infections, lysis occurs as a sudden, explosive event at a cell pole, such that the initial product is a less refractile ghost that retains rod-shaped morphology. Here, we investigate the molecular basis of polar lysis using time-lapse fluorescence microscopy. The results indicate that the holin determines the morphology of lysis by suddenly forming two-dimensional rafts at the poles about 100 s prior to lysis. Given the physiological and biochemical similarities between the lambda holin and other class I holins, dynamic redistribution and sudden concentration may be common features of holins, probably reflecting the fitness advantage of all-or-nothing lysis regulation.IMPORTANCEIn this study, we use fluorescent video microscopy to track -green fluorescent protein (GFP)-labeled holin in the minutes prior to phage lysis. Our work contextualizes prior genetic and biochemical data, showing when hole formation starts and where holin oligomers form in relation to the site of lytic rupture. Furthermore, prior work showed that the morphology of lambda-infected cells is characterized by an explosive event starting at the cell pole; however, the basis for this was not clear. This study shows that holin most often oligomerizes at cell poles and that the site of the oligomerization is spatially correlated with the site of lytic blowout. Therefore, the holin is the key contributor to polar lysis morphology for phage lambda.

Discogenic low back pain (DLBP) is a multifactorial disease and associated with intervertebral disc degeneration. Calcitonin gene-related protein (CGRP) plays a critical role in pain processing, while the role in DLBP remains unclear. This study aims to investigate the anti-nociceptive role and related mechanisms of CGRP in DLBP. Here we established the DLBP rat and validated the model using histology and radiography. Minocycline, a microglial inhibitor, and CGRP were intrathecally injected and the behavioral test was performed to determine hyperalgesia. Further, BV2 microglial cells and microglial activation agent lipopolysaccharide (LPS) were employed for the in vitro experiment. We observed obvious lumbar intervertebral disc degeneration and hyperalgesia at 12 weeks postoperation in DLBP group, with significantly activated microglia in the spinal cord. CGRP treatment significantly inhibited the upregulation of proinflammatory cytokines and NLRP3/caspase-1 expression induced by LPS in BV2 cells, whereas treatment with CGRP alone had little effect on BV2 cells. The intrathecal injection of CGRP into DLBP rats relieved mechanical and thermal hyperalgesia, reverted the microglial activation and decreased the expression of NLRP3/caspase-1, similar to the effects produced by minocycline. Our results provide evidence that microglial activation in the spinal cord play a key role in hyperalgesia in DLBP rats. CGRP alleviates DLBP induced hyperalgesia and inhibits microglial activation in the spinal cord. Regulation of CGRP and microglial activation may provide a new strategy for ameliorating DLBP.

Sintering lunar regolith simulants as building materials is an effective method to establish long-term lunar bases. However, the high energy consumption of conventional thermal sintering is a challenge for energy-scarce lunars. The cold sintering process (CSP), which densifies ceramics with the assistance of transient solvent, offers a solution to overcome the aforementioned problems. Utilizing the CSP at 150 °C, 200 MPa, and 15 wt% 10 mol NaOH for 90 min, the density and compressive strength of the samples reached 2.44 g/cm3 and 207 MPa, respectively. The energy consumption of CSP equipment is only 0.86 kW·h, which is 6.66 times lower than that of conventional thermal sintering (5.73 kW·h). Furthermore, the compressive strength of the samples after three cool-heat cycles temperature between −196 °C and 150 °C was 205 MPa, indicating that the samples maintained high reliability in a simulated lunar environment. This excellent performance is attributed to the NaOH solution dissolving the oxide clusters on the particle surface, and the precipitation-generated glass phase connecting adjacent particles, making the particles consolidated and densified. Therefore, the cold sintering process presents promising prospects for the energy-efficient fabrication of lunar construction materials with excellent mechanical strength and durability.

Summary: The beneficial effects of physical exercise on human cardiorespiratory fitness might be through reduced systemic inflammation, but the mechanism remains a controversy. Recent studies have highlighted the importance of spleen microbiomes in immune regulation. Hence, we conducted a study using a high-fat diet and exercise mouse model to investigate the relationships among different exercise intensities, spleen microbiome composition, and cardiac function. The mice spleen contained a diverse array of microbiota. Different intensities of exercise resulted in varying compositions of the spleen microbiome, Treg cell levels, and mouse heart function. Additionally, the abundance of Lactobacillus johnsonii in the mouse spleen exhibited a positive correlation with Treg cell levels, suggesting that Lactobacillus johnsonii may contribute to the production of Treg cells, potentially explaining the protective role of moderate-intensity exercise on cardiac function. In conclusion, our findings provide evidence that moderate-intensity exercise may promote cardiac function protection by influencing the spleen microbiome composition.

Obstructive uropathy is a common kidney disease caused by elevated hydrostatic pressure (HP), but relevant molecular and cellular mechanisms have not yet been well understood. In this study, we ex vivo investigated the effects of elevated HP on human renal epithelial cells (HREpCs). Primary HREpCs were subjected to 100 cmH2O HP for 8 or 48 h. Then, the cells were cultured without HP stimulation for another 24 h or 72 h. Cell morphology showed almost no change after 8h HP treatment, but exhibited reversible elongation after 48h HP treatment. HP treatment for 8 h increased the expression of TGFB1 and VEGFA but decreased the expression of CSF2 and TGFB2. On the other hand, HP treatment for 48 h downregulated the expression of CSF2, TGFB2, PDGFB, VEGFA, and VEGFB, while upregulated the expression of TGFB3. Interestingly, all changes induced by 48 h HP treatment were detected more severe compared to 8 h HP treatment. In conclusion, elongated ex vivo HP loading to renal epithelial cells induces reversible changes on cell morphology and disturbs the expression of several growth factors, which provides novel mechanistic insight on elevated HP-caused kidney injury such as obstructive uropathy.

PurposeInvestigating the association between red cell distribution width (RDW) and all-cause mortality in patients with breast cancer, to evaluate the potential clinical prognostic value of RDW.MethodsBased on the RDW index, patients with breast cancer in the Medical Information Mart for Intensive Care (MIMIC-IV) database were categorized into quartiles. The primary outcomes included in-hospital mortality from all causes during the first six months, the first year, and the first three years. Cox hazards regression and restricted cubic spline (RCS) models were developed to investigate the effects of RDW on primary outcomes.ResultsThe study included 939 patients (female). The 6-month, 1-year, and 3-year mortality rates were 14.0%, 21.4%, and 28.4%, respectively. Multivariate Cox proportional hazards analyses demonstrated that RDW exhibited an autonomous association with an increased risk of all-cause mortality. After adjusting for confounders, higher RDW quartiles were significantly associated with 6-month mortality (adjusted hazard ratio (HR), 3.197; 95% confidence interval (CI), 1.745-5.762; P < 0.001), 1-year mortality (adjusted HR, 2.978; 95% CI, 1.867-4.748; P < 0.001), and 3-year mortality (adjusted HR, 2.526; 95% CI, 1.701-3.750; P < 0.001). The RCS curves demonstrated that high RDW (> 14.6) was associated with a greater risk of all-cause mortality. Subgroup analyses revealed no statistically significant differences in the interactions between the subgroups.ConclusionThe study revealed a highly pronounced relationship between RDW and overall mortality, indicating its potential as an autonomous prognostic factor for increased mortality among patients with breast cancer.