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Cellulose macrofibers (MFs) are gaining increasing interest as natural and biodegradable alternatives to fossil-derived polymers for both structural and functional applications. However, simultaneously achieving their exceptional mechanical performance and desired functionality is challenging and requires complex processing. Here, we reported a one-step approach using a tension-assisted twisting (TAT) technique for MF fabrication from bacterial cellulose (BC). The TAT stretches and aligns BC nanofibers pre-arranged in hydrogel tubes to form MFs with compactly assembled structures and enhanced hydrogen bonding among neighboring nanofibers. The as-prepared BC MFs exhibited a very high tensile strength of 1 057 MPa and exceptional lifting capacity (over 340 000 when normalized by their own weight). Moreover, due to the volume expansion of BC nanofibers upon water exposure, BC MFs quickly harvested energy from environmental moisture to untwist the bundled networks, thus generating a torsional spinning with a peak rotation speed of 884 r/(min·m). The demonstrated rapid and intense actuation response makes the MFs ideal candidates for diverse humidity-response-based applications beyond advanced actuators, remote rain indicators, intelligent switches, and smart curtains.

Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model. Cecal ligation and puncture (CLP) surgery was used to establish polymicrobial sepsis in mice. Mice depleted of gut microbiota by an antibiotic cocktail (ABX) exhibited a significantly higher level of mortality than controls. As determined by metabolomics analysis, ABX treatment has depleted many metabolites, and subsequent supplementation with l-rhamnose (rhamnose, Rha), a bacterial carbohydrate metabolite, exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis, which in turn improved organ damage and mortality. Mechanistically, rhamnose binds directly to and activates the solute carrier family 12 (potassium-chloride symporter), member 4 (SLC12A4) in macrophages and promotes phagocytosis by activating the small G-proteins, Ras-related C3 botulinum toxin substrate1 (Rac1) and cell division control protein 42 homolog (Cdc42). Interestingly, rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients. In conclusion, by identifying SLC12A4 as the host interacting protein, we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

Abstract Regulated cell death (RCD) is crucial for the elimination of abnormal cells. In recent years, strategies aimed at inducing RCD, particularly apoptosis, have become increasingly important in cancer therapy. However, the ability of tumor cells to evade apoptosis has led to treatment resistance and relapse, prompting extensive research into alternative death processes in cancer cells. A recent study identified a novel form of RCD known as disulfidptosis, which is linked to disulfide stress. Cancer cells import cystine from the extracellular environment via solute carrier family 7 member 11 (SLC7A11) and convert it to cysteine using nicotinamide adenine dinucleotide phosphate (NADPH). When NADPH is deficient or its utilization is impaired, cystine accumulates, leading to the formation of disulfide bonds in the actin cytoskeleton, triggering disulfidptosis. Disulfidptosis reveals a metabolic vulnerability in tumors, offering new insights into cancer therapy strategies. This review provides a detailed overview of the mechanisms underlying disulfidptosis, the current research progress, and limitations. It also highlights innovative strategies for inducing disulfidptosis and explores the potential of combining these approaches with traditional cancer therapies, particularly immunotherapy, to expedite clinical translation.

ObjectivesFormyl peptide receptor 1 (FPR1) is a member of G protein-coupled receptor (GPCR) family that detects potentially danger signals characterized by the appearance of N-formylated peptides which originate from either bacteria or host mitochondria during organ injury, including sepsis. Mitochondrial-encoded NADH dehydrogenase 6 (MT-ND6) and Annexin A1 (ANXA1), as mitochondrial damage-associated molecular patterns (mtDAMPs) agonist and endogenous agonist of FPR1 respectively, interact with FPR1 regulating polymorphonuclear leukocytes (PMNs) function and inflammatory response during sepsis. However, there is no direct evidence of MT-ND6 or ANXA1 in the circulation of patients with sepsis and their potential role in clinical significance, including diagnosis and mortality prediction during sepsis.MethodsA prospective cohort study was conducted in ICU within a large academic hospital. We measured serum MT-ND6 or ANXA1 in a cohort of patients with sepsis in ICU (n=180) and patients with non-sepsis in ICU (n=60) by Enzyme-linked immunosorbent assays (ELISA). The ROC curve and Kaplan Meier analysis was used to evaluate the diagnostic and prognostic ability of two biomarkers for patients with sepsis.ResultsThe concentration of MT-ND6 and ANXA1 were significantly elevated in the patients with sepsis, and the diagnostic values of MT-ND6 (0.789) for sepsis patients was second only to SOFA scores (AUC = 0.870). Higher serum concentrations of MT-ND6 (>1.41 ng/ml) and lower concentrations of ANXA1 (< 8.09 ng/mL) were closely related to the higher mortality in patients with sepsis, with the predictive values were 0.705 and 0.694, respectively. When patients with sepsis classified based on four pro-inflammation and two anti-inflammation cytokines, it was shown that combination of MT-ND6 and ANXA1 obviously improved the predictive values in the septic patients with mixed hyperinflammation or immunosuppression phenotypes.ConclusionOur findings provide valuable models testing patient risk prediction and strengthen the evidence for agonists of FPR1, MT-ND6 and ANXA1, as novel biomarker for patient selection for novel therapeutic agents to target mtDAMPs and regulator of GPCRs in sepsis.

The proteins were extracted from the Flammulina velutipes stembase by using alkali, ultrasonic-assisted alkali, colloid mill-assisted alkali and freeze-thaw-assisted alkali methods to investigate the effects of different extraction methods on the functional (water/oil-holding capacity, foaming and foaming stability, emulsification and emulsification stability, solubility), physicochemical (potential, particle size, surface hydrophobicity, sulfhydryl groups) and structural (infrared spectra, fluorescence spectra, secondary structure) properties of the Flammulina velutipes stembase proteins, in order to provide a theoretical basis for the co-utilisation of edible mushroom by-products. Differences between the properties of the Flammulina velutipes stembase proteins extracted by different physically assisted methods. The results showed that ultrasonic-assisted alkali extraction and colloid mill-assisted alkali extraction could significantly (P

Abstract Introduction Post-stroke depression (PSD) is a common neuropsychiatric complication that affects approximately one-third of stroke patients. The treatment and prognosis of this disease are poor. Socioeconomic status (SES) is closely related to health outcomes; however, only a few previous studies have focused on the association between SES and PSD. Given the substantial population of stroke patients in China, it is crucial to examine the potential risk factors associated with PSD. Conducting studies on this population and investigating the influence of economic conditions can provide valuable guiding theoretical insights into PSD prevention and management. Methods We used data from the 2018 China Health and Retirement Longitudinal Study and selected appropriate samples for analysis. Depression was estimated using the Center of Epidemiologic Studies Depression Scale-10, a validated tool for assessing depression in the general population. Multiple logistic regression analysis was employed to assess the association between SES and PSD and to evaluate any urban–rural differences. Results Of the 749 respondents, 370 (49.4%) had depression. Stroke patients with a middle school education demonstrated a greater risk of developing depression than those with a primary school education or below after adjusting for all control variables (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.03–2.51, P = 0.036). However, stroke patients with a high school education or above had a lower risk of developing depression than those with a primary school education or below (OR = 0.50, 95% CI: 0.28–0.88, P = 0.016). In rural areas, stroke patients with a high school or above education level had lower rates of depression than those with a primary school education or below (OR = 0.44, 95% CI: 0.21–0.91, P = 0.027). This difference was not significant in urban areas. Conclusions SES significantly influences the occurrence of PSD, which is reflected by education attainment and annual household expenditures. Education attainment was an independent influence on PSD, with a more pronounced effect in rural versus urban areas. We hope to reduce the prevalence of PSD and enhance the comprehensive management of this disease by modifying the influencing factors. Sex, self-reported health status, activities of daily living, night-time sleep duration, and life satisfaction also influenced the occurrence of PSD.

BackgroundPatients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis often experience severe symptoms. Resting-state functional MRI (rs-fMRI) has revealed widespread impairment of functional networks in patients. However, the changes in information flow remain unclear. This study aims to investigate the intrinsic functional connectivity (FC) both within and between resting-state networks (RSNs), as well as the alterations in effective connectivity (EC) between these networks.MethodsResting-state functional MRI (rs-fMRI) data were collected from 25 patients with anti-NMDAR encephalitis and 30 healthy controls (HCs) matched for age, sex, and educational level. Changes in the intrinsic functional connectivity (FC) within and between RSNs were analyzed using independent component analysis (ICA). The functional interaction between RSNs was identified by granger causality analysis (GCA).ResultsCompared to HCs, patients with anti-NMDAR encephalitis exhibited lower performance on the Wisconsin Card Sorting Test (WCST), both in terms of correct numbers and correct categories. Additionally, these patients demonstrated decreased scores on the Montreal Cognitive Assessment (MoCA). Neuroimaging studies revealed abnormal intra-FC within the default mode network (DMN), increased intra-FC within the visual network (VN) and dorsal attention network (DAN), as well as increased inter-FC between VN and the frontoparietal network (FPN). Furthermore, aberrant effective connectivity (EC) was observed among the DMN, DAN, FPN, VN, and somatomotor network (SMN).ConclusionPatients with anti-NMDAR encephalitis displayed noticeable deficits in both memory and executive function. Notably, these patients exhibited widespread impairments in intra-FC, inter-FC, and EC. These results may help to explain the pathophysiological mechanism of anti-NMDAR encephalitis.

Abstract Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of RNA modification regulators operating through various pathways, play pivotal roles in driving the progression of haematological malignancies. Among RNA modifications, N6‐methyladenosine (m6A) RNA modification, the most abundant internal mRNA modification, stands out as the most extensively studied modification. This prominence underscores the crucial role of the layer of epitranscriptomic regulation in controlling haematopoietic cell fate and therefore the development of haematological malignancies. Additionally, other RNA modifications (non‐m6A RNA modifications) have gained increasing attention for their essential roles in haematological malignancies. Although the roles of the m6A modification machinery in haematopoietic malignancies have been well reviewed thus far, such reviews are lacking for non‐m6A RNA modifications. In this review, we mainly focus on the roles and implications of non‐m6A RNA modifications, including N4‐acetylcytidine, pseudouridylation, 5‐methylcytosine, adenosine to inosine editing, 2′‐O‐methylation, N1‐methyladenosine and N7‐methylguanosine in haematopoietic malignancies. We summarise the regulatory enzymes and cellular functions of non‐m6A RNA modifications, followed by the discussions of the recent studies on the biological roles and underlying mechanisms of non‐m6A RNA modifications in haematological malignancies. We also highlight the potential of therapeutically targeting dysregulated non‐m6A modifiers in blood cancer.

Background In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation.Objective This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM).Trial design Single-centre, open-label, prospective RCT.Methods This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests.Ethics and dissemination Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations.Trial registration number NCT05850936.

Acid rain and nitrogen deposition are emerging as global scale environmental issues due to increasing industrial emissions and agricultural pollutants, which seriously impac t the sustainable development of global ecosystems. However, the specific effects both acid rain and nitrogen deposition interactions on forest soil ecosystems, particularly as relates to the soil nutrient content and enzyme activities, remain unclear. Therefore, we established a simulated sample plot of acid rain (SR, NR) and nitrogen deposition (N) and their interactions (SRN, NRN) in a subtropical Cunninghamia lanceolata (C. lanceolata) plantation in the Yangtze River Delta region of China to investigate the impacts of these factors via correlation analysis and structural equation model (SEM). The results showed that acid rain had a stronger effect on soil pH than nitrogen deposition in C. lanceolata plantation, while the simultaneous addition of acid rain and nitrogen deposition exacerbated soil acidification. Soil available potassium, ammonium nitrogen and nitrate nitrogen in C. lanceolata plantation responded more obviously to acid rain and nitrogen deposition, in which acid rain, nitrogen deposition and their interactions significantly reduced soil available potassium content, while acid rain and nitrogen deposition interactions significantly increased soil ammonium nitrogen and nitrate nitrogen content. Nitric acid rain, nitrogen deposition and their interactions significantly increased soil NAGase activity, but significantly decreased soil urease activity; the single-factor treatment of acid rain and nitrogen deposition significantly increased soil arylsulfatase activity, while the interaction of acid rain and nitrogen deposition significantly decreased soil arylsulfatase activity; in general, the interaction of acid rain and nitrogen deposition had a stronger effect on the soil ecosystem of the C. lanceolata plantation than that of single acid rain or nitrogen deposition, of which nitrogen deposition exacerbated the effects of acid rain on the soil ecosystem of C. lanceolata plantation mainly by changing the soil pH and the content of effective nutrients.

Abstract Background Whether cesarean section (CS) is a risk factor for asthma in offspring is controversial. The purpose of this study was to investigate the association between CS and asthma in children/adolescents. Methods Pubmed, Embase, Web of Science, and Cochrane Library electronic databases were searched for cohort studies on the relationship between mode of delivery and asthma in children/adolescents up to February 2023. Birth via CS was considered an exposure factor. Asthma incidence was taken as a result. Results Thirty-five cohort studies (thirteen prospective and twenty-two retrospective cohort studies) were included. The results showed that the incidence of asthma was higher in CS offspring (odds ratio (OR) = 1.18, P

Abstract Background The health‐related quality of life (HRQoL) of patients with localized prostate cancer (LPCa) after treatment mainly surgery and radiotherapy (RT) has received increasing attention. The aim of this study is to compare the HRQoL of LPCa after surgery and RT. Methods Web of Science, Embase, PubMed and Cochrane databases were searched after January 2000 to observe the HRQoL scores after surgery and RT at different treatment time points. Results A total of 28 studies were included in this study, and the results showed that LPCa received surgery had better bowel scores than RT at ≤3 (weighted mean differences [WMD] = 4.18; p = 0.03), 3–6 (WMD = 4.16; p

Abstract Background Soybean is one of the most important oil crops in the world. The domestication of wild soybean has resulted in significant changes in the seed oil content and seed size of cultivated soybeans. To better understand the molecular mechanisms of seed formation and oil content accumulation, WDD01514 (E1), ZYD00463 (E2), and two extreme progenies (E23 and E171) derived from RILs were used for weighted gene coexpression network analysis (WGCNA) combined with transcriptome analysis. Results In this study, both seed weight and oil content in E1 and E171 were significantly higher than those in E2 and E23, and 20 DAF and 30 DAF may be key stages of soybean seed oil content accumulation and weight increase. Pathways such as “Photosynthesis”, “Carbon metabolism”, and “Fatty acid metabolism”, were involved in oil content accumulation and grain formation between wild and cultivated soybeans at 20 and 30 DAF according to RNA-seq analysis. A total of 121 oil content accumulation and 189 seed formation candidate genes were screened from differentially expressed genes. WGCNA identified six modules related to seed oil content and seed weight, and 76 candidate genes were screened from modules and network. Among them, 16 genes were used for qRT-PCR and tissue specific expression pattern analysis, and their expression-levels in 33-wild and 23-cultivated soybean varieties were subjected to correlation analysis; some key genes were verified as likely to be involved in oil content accumulation and grain formation. Conclusions Overall, these results contribute to an understanding of seed lipid metabolism and seed size during seed development, and identify potential functional genes for improving soybean yield and seed oil quantity.

Exploring the influencing factors of construction quality management is the key to ensuring the quality of rural drinking water safety projects. Based on grounded theory, the influencing factors were identified and 65 relevant staff were selected by the objective sampling method for in-depth interviews to obtain the original data. In this study, 34 initial concepts, 18 main categories, and five core categories were collected and extracted for the rural drinking water project's safety engineering and construction quality management evaluation system. Furthermore, the incremental model of influencing factors on construction quality management performance of rural drinking water safety projects was established by the Decision-Making Trial and Evaluation Laboratory–Interpretive Structural Modeling (DEMATEL-ISM) model. Through calculation and analysis, the key influencing factors of construction quality management performance of rural drinking water safety projects were identified as controls on common quality problems, quality specification implementation, leadership level, acceptance management, design disclosure and modification, and human environment. Countermeasures and suggestions are proposed to improve the construction quality management performance of rural drinking water safety construction projects. HIGHLIGHTS Construction quality management evaluation systems for rural drinking water safety projects were established based on grounded theory.; Based on the DEMATEL-ISM model, the quality management performance evaluation model of rural drinking water safety project construction was constructed, which is convenient for clarifying the relationship between influencing elements at different levels in the system.;

Abstract Background Kidney disease is an important comorbidity in people living with HIV(PLWH), and is associated with poor outcomes. However, data on renal function of PLWH are limited in China so far. In this study we assessed the prevalence of kidney disease in patients either on antiretroviral therapy (ART) or not respectively in a single center in China and explored the possible risk factors associated. Methods In the cross-sectional study, we recruited hospitalized adult PLWH. Demographic characteristics, clinical information and laboratory variables were collected. Kidney disease was defined as estimated glomerular filtration rate (eGFR)

Salt substitute has been widely used to prepare low-salt foods due to potential health benefits, though the role of CaCl2 in salt substitute and its unique impacts on food quality have been rarely investigated. In this study, comprehensive research has been conducted to elucidate the effects of replacing NaCl with varying concentrations of CaCl2 on the surimi gel characteristics. The introduction of CaCl2 interacted with surimi proteins differently from NaCl, thus leading to difference in protein aggregation behaviors and surimi gel properties. It has been found that a proper proportion of CaCl2 for NaCl substitution could create salt bridges between surimi proteins more effectively, resulting in an ordered, smooth and dense gel network with an increased water holding capacity (WHC) and improved gel strength. Furthermore, TGase activated by Ca2+ boosted the formation of ε-(γ-glutamyl) lysine bonds, which cross-linked surimi proteins to form a firm gel with a better three-dimensional structure. However, replacing NaCl with excessive amount of CaCl2 as divalent salts induced more serious protein aggregation, leading to water loss and gel properties deterioration. More specially, replacing NaCl with CaCl2 at 50% showed the best performance, as evidenced by the most abundant disulfide bonds and hydrophobic interactions, highest hardness and chewiness, and greatest storage modulus. This study provided new insights on developing high-quality surimi gels with significantly reduced salt concentration and improved gel characteristics.

Herein, we proposed a metal-ion-induced surface nano-engineering technology for transforming hydrophilic waste newspaper (WNP) into a hydrophobic material suitable for oil-water separation, without using hydrophobic chemicals/materials. WNPs were swelled in a dilute ferric ion solution (i.e., 50 mM FeCl3) followed by oven-drying to induce the coordination between ferric ions and hydroxyls of lignocellulose nanofibrils of the paper. This resulted in the crosslinking of lignocellulose nanofibrils and converted the hydrophilic WNP to the hydrophobic membrane (HM). The HM exhibited remarkable oil sorption capacity for various oils, up to 3.4 times its weight, and demonstrated good recyclability after undergoing 10 cycles of absorption-desorption-drying. Additionally, HM demonstrated the ability to effectively separate both immiscible oil-water mixtures and surfactant-stabilized water-in-oil emulsions in continuous gravity-driven oil-water separation processes. With the modification method and advantages in oil-water separation, the as-prepared HM exhibits great potential for application in oil spill treatment and environmental remediation.

Aspergillus niger is the main industrial workhorse for global citric acid production. This fungus has complex sensing and signaling pathways to respond to environmental nutrient fluctuations. As the preferred primary carbon source, glucose also acts as a critical signal to trigger intracellular bioprocesses. Currently, however, there is still a knowledge gap in systems-level understanding of metabolic and cellular responses to this vital carbon source. In this study, we determined genome-wide transcriptional changes of citric acid-producing Aspergillus niger in response to external glucose gradient. It demonstrated that external glucose fluctuation led to transcriptional reprogramming of many genes encoding proteins involved in fundamental cellular process, including ribosomal biogenesis, carbon transport and catabolism, glucose sensing and signaling. The major glucose catabolism repressor creA maintained a stable expression independent of external glucose, while creB and creD showed significant downregulation and upregulation by the glucose increase. Notably, several high-affinity glucose transporters encoding genes, including mstA, were greatly upregulated when glucose was depleted, while the expression of low-affinity glucose transporter mstC was glucose-independent, which showed clear concordance with their protein levels detected by in situ fluorescence labeling assay. In addition, we also observed that the citric acid exporter cexA was observed to be transcriptionally regulated by glucose availability, which was correlated with extracellular citric acid secretion. These discoveries not only deepen our understanding of the transcriptional regulation of glucose but also shed new light on the adaptive evolutionary mechanism of citric acid production of A. niger.

Abstract Background Kidney insults due to various pathogenic factors, such as trauma, infection, and inflammation, can cause tubular epithelial cell injury and death, leading to acute kidney injury and the transformation of acute kidney injury to chronic kidney disease. There is no definitive treatment available. In previous studies, human umbilical cord mesenchymal stem cells have been shown to promote kidney injury. In this preclinical study, we investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (HucMSC-Exos) on the repair of renal tubular epithelial cells after injury. Methods C57BL/6 mice underwent unilateral ureteral obstruction, and epithelial cell injury was induced in HK-2 cells by cisplatin. HucMSC-Exos were assessed in vivo and in vitro. The extent of renal cell injury, activation of necroptosis pathway, and mitochondrial quality-control-related factors were determined in different groups. We also analyzed the possible regulatory effector molecules in HucMSC-Exos by transcriptomics. Results HucMSC-Exo inhibited necroptosis after renal tubular epithelial cell injury and promoted the dephosphorylation of the S637 site of the Drp1 gene by reducing the expression of PGAM5. This subsequently inhibited mitochondrial fission and maintained mitochondrial functional homeostasis, mitigating renal injury and promoting repair. In addition, HucMSC-Exo displayed a regulatory role by targeting RIPK1 through miR-874-3p. Conclusion The collective findings of the present study demonstrate that HucMSC-Exos can regulate necroptosis through miR-874-3p to attenuate renal tubular epithelial cell injury and enhance repair, providing new therapeutic modalities and ideas for the treatment of AKI and the process of AKI to CKD transformation to mitigate renal damage.

The origins of late-life depression are multifaceted and remain challenging to fully understand. While the traditional monoamine neurotransmitter hypothesis provides some insights, it falls short in explaining the disease’s onset and progression, leaving treatments often less than optimal. There is an emergent need to uncover new underlying mechanisms. Among these, the “inflammation hypothesis” has been gaining traction in scientific discussions regarding late-life depression. There is compelling evidence linking inflammation processes to the emergence of this form of depression. This review delves into the nuanced relationship between inflammation and late-life depression, emphasizing the pivotal role and implications of inflammation in its pathogenesis. Changes in Ca2+ homeostasis, cytokine levels, brain-derived neurotrophic factor (BDNF), white cell ratios, and the involvement of the NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) inflammasome have all been suggested as potential biomarkers that tie inflammation to late-life depression. Furthermore, factors such as aging-induced DNA damage, oxidative stress, mitochondrial impairments, disruptions in the hypothalamic-pituitary-adrenal axis, activated microglia and associated neuroinflammation, as well as the gut-brain axis dynamics, could serve as bridges between inflammation and depression. Deepening our understanding of these connections could usher in innovative anti-inflammatory treatments and strategies for late- life depression.

Sivelestat sodium (SIV), a neutrophil elastase inhibitor, is mainly used for the clinical treatment of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). However, studies investigating the effects of SIV treatment of ALI are limited. Therefore, this study investigated the potential molecular mechanism of the protective effects of SIV against ALI. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with tumor necrosis factor α (TNF-α), and male Sprague-Dawley rats were intratracheally injected with Klebsiella pneumoniae (KP) and treated with SIV, ML385, and anisomycin (ANI) to mimic the pathogenetic process of ALI in vitro and in vivo, respectively. The levels of inflammatory cytokines and indicators of oxidative stress were assessed in vitro and in vivo. The wet/dry (W/D) ratio of lung tissues, histopathological changes, inflammatory cells levels in bronchoalveolar lavage fluid (BALF), and survival rates of rats were analyzed. The JNK/NF-κB (p65) and Nrf2/HO-1 levels in the HPMECs and lung tissues were analyzed by western blot and immunofluorescence analyses. Administration of SIV reduced the inflammatory factors levels, intracellular reactive oxygen species (ROS) production, and malondialdehyde (MDA) levels and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues. Meanwhile, SIV alleviated pathological injuries, decreased the W/D ratio, and inflammatory cell infiltration in lung tissue. In addition, SIV also inhibited the activation of JNK/NF-κB signaling pathway, promoted nuclear translocation of Nrf2, and upregulated the expression of heme oxygenase 1 (HO-1). However, ANI or ML385 significantly reversed these changes. SIV effectively attenuated the inflammatory response and oxidative stress. Its potential molecular mechanism was related to the JNK/NF-κB activation and Nrf2/HO-1 signaling pathway inhibition. This further deepened the understanding of the protective effects of SIV against ALI.

Antimicrobial peptides (AMPs) may be the most promising substitute for antibiotics due to their effective antimicrobial activities and multiple function mechanisms against pathogenic microorganisms. In this study, a novel AMP containing 51 amino acids, named Lc1687, was screened from the large yellow croaker (Larimichthys crocea) via a B. subtilis system. Bioinformatics and circular dichroism (CD) analyses showed that Lc1687 is a novel anionic amphiphilic α-helical peptide, which was derived from the C-terminal of a Ferritin heavy subunit. The recombinant Lc1687 (named rLc1687) purified from Escherichia coli exhibited strong activities against Gram-positive (Gram+) bacterium Staphylococcus aureus, Gram-negative (Gram-) bacteria Vibrio vulnificus, V. parahaemolyticus, and Scuticociliatida. Scanning electron microscope (SEM) and transmission electron microscopy (TEM) revealed the possible function mechanisms of this peptide, which is to target and disrupt the bacterial cell membranes, including pore-forming, loss of fimbriae, and cytoplasm overflow, whereas gel retardation assay revealed that peptide Lc1687 cannot bind bacterial DNA. The peptide stability analysis showed that rLc1687 acts as a stable antimicrobial agent against Gram+ and Gram- bacteria at temperatures ranging from 25 to 100°C, pH 3-12, and UV radiation time ranging from 15 to 60 min. A hemolytic activity assay confirmed that this peptide may serve as a potential source for clinical medicine development. Taken together, Lc1687 is a novel AMP as it is a firstly confirmed Ferritin fragment with antimicrobial activity. It is also a promising agent for the development of peptide-based antibacterial and anti-parasitic therapy.

BackgroundLate-life depression (LLD) is linked to various medical conditions and influenced by aging-related processes. Sleep disturbances and insomnia symptoms may be early indicators or risk factors for depression. Neuroimaging studies have attempted to understand the neural mechanisms underlying LLD, focusing on different brain networks. This study aims to further delineate discriminative brain structural profiles for LLD with insomnia using MRI.MethodsWe analyzed 24 cases in the LLD with insomnia group, 26 cases in the LLD group, and 26 in the healthy control (HC) group. Patients were evaluated using the Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Mini-Mental State Examination (MMSE), and Pittsburgh Sleep Quality Index (PSQI). Structural MRI data were gathered and analyzed using voxel-based morphometry (VBM) to identify differences in gray matter volume (GMV) among the groups. Correlation analyses were conducted to explore the relationships between GMV and clinical characteristics.ResultsSignificant difference in sex distribution was observed across the groups (p = 0.029). However, no significant differences were detected in age and MMSE scores among the groups. LLD with insomnia group exhibited significantly higher HAMA (p = 0.041) and PSQI scores (p

Fusarium root rot (FRR) caused by Fusarium graminearum poses a threat to global food security. Biological control is a promising control strategy for FRR. In this study, antagonistic bacteria were obtained using an in-vitro dual culture bioassay with F. graminearum. Molecular identification of the bacteria based on the 16S rDNA gene and whole genome revealed that the species belonged to the genus Bacillus. We evaluated the strain BS45 for its mechanism against phytopathogenic fungi and its biocontrol potential against FRR caused by F. graminearum. A methanol extract of BS45 caused swelling of the hyphal cells and the inhibition of conidial germination. The cell membrane was damaged and the macromolecular material leaked out of cells. In addition, the mycelial reactive oxygen species level increased, mitochondrial membrane potential decreased, oxidative stress-related gene expression level increased and oxygen-scavenging enzyme activity changed. In conclusion, the methanol extract of BS45 induced hyphal cell death through oxidative damage. A transcriptome analysis showed that differentially expressed genes were significantly enriched in ribosome function and various amino acid transport pathways, and the protein contents in cells were affected by the methanol extract of BS45, indicating that it interfered with mycelial protein synthesis. In terms of biocontrol capacity, the biomass of wheat seedlings treated with the bacteria increased, and the BS45 strain significantly inhibited the incidence of FRR disease in greenhouse tests. Therefore, strain BS45 and its metabolites are promising candidates for the biological control of F. graminearum and its related root rot diseases.

Background. Metformin is one of the most common drugs for type 2 diabetes mellitus (T2DM) treatment. In addition, metformin intends to have a positive effect on the prognosis of several cancers. However, the therapeutic effect of metformin on gastric cancer (GC) remains controversial. This study explores and updates the therapeutic effect of metformin in GC patients with T2DM. Methods. We searched through PubMed, Embase, Web of Science, and the Cochrane Library for relevant articles by July 2022. The relationship between metformin therapy and the prognosis of GC patients with T2DM was evaluated based on the hazard ratio (HR) at a 95% confidence interval (95% CI). Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were the primary outcomes analyzed. Results. Seven retrospective cohort studies with a combined 2,858 patients met the inclusion criteria. OS and CSS were reported in six studies, and PFS was reported in four studies. Pooled results showed that, compared to the nonmetformin group, the prolonged OS (HR = 0.72, p = 0.001), CSS (HR = 0.81, p = 0.001), and PFS (HR = 0.70, p = 0.008) of the experimental group may be associated with the exposure to metformin. Conclusion. Metformin may have a beneficial effect on the prognosis of GC patients with T2DM.

Background The hospital environment, particularly the intensive care unit (ICU), contributes to the transmission of several nosocomial pathogens, which can survive in this setting for a longer period of time and, in turn, contaminate the surfaces or the medical tools. Thus, appropriate disinfection of these areas and devices are crucial for controlling and preventing further infection. In this study, we examined the effect of different concentrations of chlorine-containing disinfectants (500mg/L, 1000mg/L, and 2000mg/L) on the ICU environment. Methods This quasi-experimental study was based on a convenient sampling method. In this study, High-frequency objects were selected as subjects in ICU, with a total sample of 216.A hall including 6 beds was examined,selecting 4 high-frequency surfaces per bed unit:a bed gear, infusion system, bed end table, and monitor were disinfected with 500, 1000, and 2000 mg/L of chlorine (as Cl2), respectively.The surface dissection was performed at 21:00 o’clock daily, after which ATP fluorescence monitoring and bacterial count detection were performed. Results There was no significant difference in ATP bioluminescence (F = 2.03, P > 0.05) and bacterial counting (χ2 = 2.03, P > 0.05) when using different concentrations of chlorine-containing disinfectant in the ICU. Yet, compared with high concentration (2000mg/L), a low concentration disinfectant reduced the hospital cost. Conclusion By reducing the concentration of ICU high-frequency contact table disinfectants, it is possible to reduce the risk of long-term contamination with chlorine-containing disinfectants and reduce the cost of using ICU chlorine-containing disinfectants.

BackgroundThe kangaroo-mother care method (KMC) is a skin-to-skin contact-centered care approach with numerous benefits for neonates, but its impact on the treatment of jaundiced neonates is unknown. This study aimed to investigate the efficacy of KMC combined with neonatal phototherapy (NNPT) in treating neonates with non-pathological jaundice.MethodsRelevant articles were searched in PubMed, Embase, Web of Science, and Cochrane Library databases from database establishment to April 2022. The outcomes included, without limitation, serum bilirubin levels, and duration of phototherapy.ResultsThis meta-analysis included five studies (4 randomized controlled trials and 1 observational study) involving four hundred eighty-two neonates with non-pathological jaundice. The results showed that the group receiving KMC combined with NNPT had lower serum bilirubin at 72 h after intervention [weighted mean difference (WMD) = −1.51, p = 0.03], shorter duration of phototherapy [standard mean difference (SMD) = −1.45, p

In this study, we discovered that two human oral squamous carcinoma cell (OSCC) lines, SCC9 and SCC25, exhibited varied levels of permissivity to oncolytic HSV-1 T1012G replication and the differential virus yields may associate with the constitutive accumulation of two deubiquitinating enzymes USP18 and USP20 in tumor cells. USP18 and USP20 belong to the ubiquitin-specific protease family, mediating the deubiquitination of targets and promoting antiviral responses. Depletion of USP18 or USP20 in SCC9 cells increased T1012G virus yields; overexpression of USP18 or USP20 in SCC25 cells down-regulated T1012G virus replication. In addition, STING as a verified substrate of USP18 and USP20, was found to affect the virus multiplication of T1012G in SCC9 cells. STING knockdown led to an increase in T1012G virus yields in SCC9 cells. Besides, we introduced a deubiquitinating enzyme inhibitor GSK2643943A targeting USP20 and evaluated its effects on viral replication and tumor killing in vitro and in vivo. The results showed that the combination of GSK2643934A and T1012G treatment brought a profound anti-tumor efficacy in mice bearing SCC9 tumors. This report explored factors that play roles in mediating oHSV-1 replication in OSCC tumor cells, facilitating to offer potential targets to improve oHSV-1 oncolytic efficacy and develop candidates of biomarkers to predict the efficiency of oHSV-1 multiplication in tumors.

Abstract HIV-associated malignancies are responsible for morbidity and mortality increasingly in the era of potent antiretroviral therapy. This study aimed to investigate the distribution of HIV-associated malignancies among inpatients, the immunodeficiency and the effect of antiretroviral therapy (ART) on spectrum of HIV-associated malignancies. A total of 438 cases were enrolled from 2007 to 2020 in Beijing Ditan Hospital. Demographic, clinical and laboratory data, managements, and outcomes were collected and analyzed retrospectively. Of 438 cases, 433 were assigned to non-AIDS-defining cancers (NADCs) (n = 200, 45.7%) and AIDS-defining cancers (ADCs) (n = 233, 53.2%), 5 (1.1%) with lymphoma were not specified further. No significant change was observed in the proportion of NADCs and ADCs as time goes on. Of NADCs, lung cancer (n = 38, 19%) was the most common type, followed by thyroid cancer (n = 17, 8.5%). Patients with ADCs had lower CD4 counts(104.5/μL vs. 314/μL), less suppression of HIVRNA(OR 0.23, 95%CI 0.16–0.35) compared to those with NADCs. ART did not affect spectrum of NADCs, but affect that of ADCs (between patients with detectable and undetectable HIVRNA). ADCs remain frequent in China, and NADCs play an important role in morbidity and mortality of HIV positive population.

Abstract The first branchial arch (BA1), which is derived from cranial neural crest (CNC) cells, gives rise to various orofacial tissues. Cre mice are widely used for the determination of CNC and exploration of gene functions in orofacial development. However, there is a lack of Cre mice specifically marked BA1’s cells. Pax2-Cre allele was previously generated and has been widely used in the field of inner ear development. Here, by compounding Pax2-Cre and R26R-mTmG mice, we found a specific expression pattern of Pax2 + cells that marked BA1’s mesenchymal cells and the BA1-derivatives. Compared to Pax2-Cre; R26R-mTmG allele, GFP+ cells were abundantly found both in BA1 and second branchial arch in Wnt1-Cre;R26R-mTmG mice. As BMP4 signaling is required for orofacial development, we over-activated Bmp4 by using Pax2-Cre; pMes-BMP4 strain. Interestingly, our results showed bilateral hyperplasia between the upper and lower teeth. We also compare the phenotypes of Wnt1-Cre; pMes-BMP4 and Pax2-Cre; pMes-BMP4 strains and found severe deformation of molar buds, palate, and maxilla-mandibular bony structures in Wnt1-Cre; pMes-BMP4 mice; however, the morphology of these orofacial organs were comparable between controls and Pax2-Cre; pMes-BMP4 mice except for bilateral hyperplastic tissues. We further explore the properties of the hyperplastic tissue and found it is not derived from Runx2 + cells but expresses Msx1, and probably caused by abnormal cell proliferation and altered expression pattern of p-Smad1/5/8. In sum, our findings suggest altering BMP4 signaling in BA1-specific cell lineage may lead to unique phenotypes in orofacial regions, further hinting that Pax2-Cre mice could be a new model for genetic manipulation of BA1-derived organogenesis in the orofacial region.

Abstract Increasing studies demonstrated that oncolytic activities of oHSV-1 are limited to the capacity of virus replicating in tumors. In order to potentiate the oHSV-1 oncolytic activity and expand the application of oHSV-1 treatment in multiple types of tumors, it is critical to explore the potential factors or mechanisms mediating tumor resistance to oHSV-1 infection. Here we evaluated the levels of oHSV-1 multiplication in various tumor cell lines and showed that glioblastoma cell line A172 had the lowest virus yields but intrinsically accumulated the highest levels of Mx2 protein. Subsequently we demonstrated that genetic depletion of Mx2 specifically enhanced oHSV-1 productive replication in A172 cells through promoting the nuclear translocation of uncoated viral genomic DNA and down-regulating innate antiviral response. In the further investigation, we found that Mx2 knockdown could alter the intrinsic mRNA accumulation of diverse sets innate immune genes in A172 cells, in particular DHX36 and MyD88. Mx2 depletion led to a decrease in mRNA levels of MyD88 and DHX36 in A172 cells and MyD88/DHX36 knockdown increased virus yield in A172 cells and decreased the production of IFNα, activation of IRF3 activity and NF-κB signaling in A172 cells. This shed new lights on understanding the roles of some intrinsic antiviral genes in oHSV-1 resistance, facilitating to offer potential targets to improve oHSV-1 oncolytic efficacy and develop candidates of biomarkers to predict the efficiency of oHSV-1 multiplication in tumors.

Pancreatic cancer is a lethal malignancy with a 5-year survival rate of about 10% in the United States, and it is becoming an increasingly prominent cause of cancer death. Among pancreatic cancer patients, pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of all cases and has a very poor prognosis with an average survival of only 1 year in about 18% of all tumor stages. In the past years, there has been an increasing interest in cancer-associated fibroblasts (CAFs) and their roles in PDAC. Recent data reveals that CAFs in PDAC are heterogeneous and various CAF subtypes have been demonstrated to promote tumor development while others hinder cancer proliferation. Furthermore, CAFs and other stromal populations can be potentially used as novel prognostic markers in cancer. In the present study, in order to evaluate the prognostic value of CAFs in PDAC, CAF infiltration rate was evaluated in 4 PDAC datasets of TCGA, GEO, and ArrayExpress databases and differentially expressed genes (DEGs) between CAF-high and CAF-low patients were identified. Subsequently, a CAF-based gene expression signature was developed and studied for its association with overall survival (OS). Additionally, functional enrichment analysis, somatic alteration analysis, and prognostic risk model construction was conducted on the identified DEGs. Finally, oncoPredict algorithm was implemented to assess drug sensitivity prediction between high- and low-risk cohorts. Our results revealed that CAF risk-high patients have a worse survival rate and increased CAF infiltration is a poor prognostic indicator in pancreatic cancer. Functional enrichment analysis also revealed that “extracellular matrix organization” and “vasculature development” were the top enriched pathways among the identified DEGs. We also developed a panel of 12 genes, which in additional to its prognostic value, could predict higher chemotherapy resistance rate. This CAF-based panel can be potentially utilized alone or in conjunction with other clinical parameters to make early predictions and prognosticate responsiveness to treatment in PDAC patients. Indeed, it is necessary to conduct extensive prospective investigations to confirm the clinical utility of these findings.

The introduction of the Sepsis 3.0 guidelines in 2016 improved our understanding of sepsis diagnosis and therapy. Personalized treatment strategies and nursing methods for sepsis patients are recommended in the “Save Sepsis Campaign” in 2021. However, mortality in sepsis patients remains high. Patients with sepsis-related acute respiratory distress syndrome account for around 30% of them, with fatality rates ranging from 30 to 40%. Pathological specimens from individuals with sepsis-related ARDS frequently demonstrate widespread alveolar damage, and investigations have revealed that pulmonary epithelial and pulmonary endothelial injury is the underlying cause. As a result, the purpose of this work is to evaluate the mechanism and research progress of pulmonary epithelial and pulmonary endothelial damage in sepsis-related ARDS, which may provide new directions for future research, diagnosis, and therapy.

Soybean cyst nematode (SCN) is a serious damaging disease in soybean worldwide. Peking- and PI 88788-type sources of resistance are two most important germplasm used in breeding resistant soybean cultivars against this disease. However, until now, no comparisons of constitutive resistances to soybean cyst nematode between these two types of sources had been conducted, probably due to the influences of different backgrounds. In this study, we used pooled-sample analysis strategy to minimize the influence of different backgrounds and directly compared the molecular mechanisms underlying constitutive resistance to soybean cyst nematode between these two types of sources via transcriptomic and metabolomic profilings. Six resistant soybean accessions that have identical haplotypes as Peking at Rgh1 and Rhg4 loci were pooled to represent Peking-type sources. The PI88788-type and control pools were also constructed in a same way. Through transcriptomic and metabolomics anaylses, differentially expressed genes and metabolites were identified. The molecular pathways involved in the metabolism of toxic metabolites were predicted to play important roles in conferring soybean cyst nematode resistance to soybean. Functions of two resistant candidate genes were confirmed by hairy roots transformation methods in soybean. Our studies can be helpful for soybean scientists to further learn about the molecular mechanism of resistance to soybean cyst nematode in soybean.

Alzheimer’s disease (AD) is a common neurodegenerative disorder causing dementia in the elderly population. Functional disconnection of brain is considered to be the main cause of AD. In this study, we applied a newly developed association (Asso) mapping approach to directly quantify the functional disconnections and to explore the diagnostic effects for AD with resting-state functional magnetic resonance imaging data from 36 AD patients and 42 age-, gender-, and education-matched healthy controls (HC). We found that AD patients showed decreased Asso in left dorsoanterior insula (INS) while increased functional connections of INS with right medial prefrontal cortex (MPFC) and left posterior cingulate cortex (PCC). The changed Asso and functional connections were closely associated with cognitive performances. In addition, the reduced Asso and increased functional connections could serve as effective neuromarkers to distinguish AD patients from HC. Our research provided new evidence for functional disconnections in AD and demonstrated that functional disconnections between cognition-memory networks may be potential early biomarkers for AD.

Objective: The real-time polymerase chain reaction (RT-PCR) test is recommended for the diagnosis of COVID-19 and provides a powerful tool to identify new infections and facilitate contact tracing. In fact, as the prevalence of COVID-19 decreases, this RT-PCR testing remains as the main preventive measure to avoid rebound. However, inconsistent results can lead to misdiagnoses in the clinic. These inconsistencies are due to the variability in (1) the collection times of biological samples post infection, and (2) sampling procedures. Methods: We applied the Kaplan–Meier method and multivariate logistic regression on RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the proportion (%) of negative conversion among patients who had tested twice or more, and compared the proportions arising from oropharyngeal swabs, sputum, and combined double testing, respectively. Main results: The proportion of negative conversion was 6.7% on day 4, 16.4% on day 7, 41.0% at 2 weeks, and 61.0% at 3 weeks post-admission. We also found that 34.1% and 60.3% of subjects had at least one negative RT-PCR result on days 7 and 14 after the onset of symptoms, respectively. The proportion of negative conversions following sputum testing was higher than that from oropharyngeal swabs in the early stages but this declined after the onset of symptoms. Conclusion: In the absence of effective treatments or vaccines, efficient testing strategies are critical if we are to control the COVID-19 epidemic. According to this study, early, consecutive and combined double testing, will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases. These strategies will minimize misdiagnosis and the ineffective isolation of infected patients.

Abstract Bamboo is an anisotropic, hierarchical, and hygroscopic material. Moisture transport in bamboo is one of the most fundamental properties affecting almost all other physical and mechanical properties of the material. This study investigated the water vapor sorption behaviors of bamboo at various structural levels: cell walls, cells (with pits) and bamboo blocks. The specimens with two sorption directions, longitudinal (L) and transverse (T), were measured by saturated salt solution method and dynamic vapor sorption. The parallel exponential kinetics model was used to analyze the sorption kinetics. The results showed that at the cell wall level, the sorption rate and equilibrium moisture content (EMC) of cell wall in the L specimens were larger than those in the T specimens. The differences were probably caused by the looser cell wall layers in the L specimens. At the cellular scale, pits in the cell wall resulted in an enhanced sorption rate and EMC of the T specimens compared with the L specimens where the pits in the parenchyma cells were only distributed in the lateral walls but not in end walls. At the macro scale, the sorption rate and moisture content of bamboo blocks were largely controlled by the vessel cells. As a hierarchically-structured plant, bamboo performs the biological function of moisture transport at all these scales. This work helps improve the understanding of water transport behavior in bamboo, which may lead to better bamboo drying and impregnation processes.

IntroductionPrevious studies suggested that physical and cognitive function can be indicators to assess the risk of falls in the elderly. Various tests are widely used in geriatric clinical studies as assessment tools of physical and cognitive function. However, large sample studies comparing the fall predictive value of these tests are still sparse. This study was conducted to investigate the value of cognitive and physical function tests in predicting the risk of subsequent falls in the elderly, with the overarching goal of providing more evidence on fall-risk assessment.MethodsThe current study was based on the data of respondents aged 60 and above from the China Health and Retirement Longitudinal Study (CHARLS). Data from the 2015 CHARLS national survey were used as the baseline data, and the fall data in 2018 were used as the follow-up data. Physical function tests included balance, walking speed, the five times sit-to-stand test (FTSST), and grip strength. The value of cognitive and physical function tests in predicting falls was evaluated by logistic regression analysis and receiver operating characteristic (ROC) curves.ResultsThe incidence of falls among the 4,857 subjects included in this study was 20.86%. Results showed that cognition (OR = 0.83, 95% CI: 0.70–0.98), the FTSST (OR = 3.51, 95% CI: 1.66–7.46), and grip strength (OR = 1.02, 95% CI: 1.01–1.03) were independent predictors of falls in the full sample after adjusting for various confounders. Notably, the above tests showed better predictive value for falls for the oldest-old (≥ 80 years) subjects.ConclusionOverall, results showed that grip strength, the FTSST, and cognition tests are simple and practicable tools for identifying individuals at higher risk of falls in the community. Moreover, the fall predictive performance of physical and cognitive function tests was age-dependent, with a higher predictive value in older adults aged 80 and above.

IntroductionPrevious studies have suggested that cognitive impairment is associated with falls in older adults. However, the consistency of results among different subgroups defined by multiple characteristics of the elderly has not yet been tested. Additionally, results are inconsistent regarding the effects of different cognitive domains on falls. Therefore, this study sought to use representative data from a nationwide study to better understand the longitudinal association between cognitive impairment and subsequent falls in older adults.MethodsThe current study was conducted based on the China Health and Retirement Longitudinal Study (CHARLS) data of respondents aged ≥60 years in 2015 and the fall data in 2018. The respondents were divided into subgroups according to different demographic characteristics. Multiple logistic regression analysis was conducted to adjust for various confounding factors and evaluate the association between cognitive impairment and falls.ResultsOf the 5,110 respondents included in this study, 1,093 (21.39%) had falls within the last 2 years. A significant association was found between cognitive impairment and subsequent falls (OR = 0.97, 95% CI 0.95–0.99, P = 0.001) after adjusting for all of the covariates related to falls. Analysis of different cognitive domains showed that orientation (OR = 0.94, 95% CI 0.90–0.99, P = 0.013) and memory (OR = 0.93, 95% CI 0.90–0.97, P = 0.001) were significantly associated with falls. In subgroup analysis, the ORs of people aged 60–74 years, male, with lower education level were 0.97 (95% CI 0.95–0.99, P = 0.008), 0.96 (95% CI 0.93–0.98, P = 0.001), and 0.97 (95% CI 0.95–0.99, P = 0.001), respectively, suggesting that the associations were also statistically significant in these subgroups. There was also a significant association both in urban (OR = 0.97, 95% CI 0.95–0.99, P = 0.001) and in rural residents (OR = 0.97, 95% CI 0.95–0.99, P = 0.003).ConclusionsOur results suggest that the associations between cognition and falls vary depending on the different demographic characteristics of older adults. These findings may be useful for designing more accurate identification and intervention for the fall risk for specific high-risk groups.

Gene transcription in single cells is inherently a probabilistic process. The relationship between variance ($ \sigma^{2} $) and mean expression ($ \mu $) is of paramount importance for investigations into the evolutionary origins and consequences of noise in gene expression. It is often formulated as $ \log \left({{{\sigma}^{2}}}/{{{\mu}^{2}}}\; \right) = \beta\log\mu+\log\alpha $, where $ \beta $ is a key parameter since its sign determines the qualitative dependence of noise on mean. We reveal that the sign of $ \beta $ is controlled completely by external regulation, but independent of promoter structure. Specifically, it is negative if regulators as stochastic variables are independent but positive if they are correlated. The essential mechanism revealed here can well interpret diverse experimental phenomena underlying expression noise. Our results imply that external regulation rather than promoter sequence governs the mean-noise relationship.

Abstract Background Both COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. Methods By retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1–4). Results We reviewed the patients’ data of 94 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 37 severe influenza A. We found total lymphocytes (0.81 × 109/L vs 1.74 × 109/L, P = 0.001; 0.87 × 109/L vs 1.74 × 109/L, P

PurposeTo compare intraocular pressure (IOP) values obtained using Goldmann applanation tonometry (IOPGAT) and non-contact tonometry (IOPNCT) in a non-pathologic high myopia population.MethodsA total of 720 eyes from 720 Chinese adults with non-pathologic high myopia were enrolled in this cross-sectional study. Demographic and ocular characteristics, including axial length, refractive error, central corneal thickness (CCT), and corneal curvature (CC) were recorded. Each patient was successively treated with IOPNCT and IOPGAT. Univariate and multivariable linear regression analyses were conducted to detect factors associated with IOPNCT and IOPGAT, as well as the measurement difference between the two devices (IOPNCT−GAT).ResultsIn this non-pathologic high myopia population, the mean IOPNCT and IOPGAT values were 17.60 ± 2.76 mmHg and 13.85 ± 2.43 mmHg, respectively. The IOP measurements of the two devices were significantly correlated (r = 0.681, P < 0.001), however, IOPNCT overestimated IOPGAT with a mean difference of 3.75 mmHg (95% confidence interval: 3.60–3.91 mmHg). In multivariate regression, IOPNCT was significantly associated with body mass index (standardized β = 0.075, p = 0.033), systolic blood pressure (SBP) (standardized β = 0.170, p < 0.001), and CCT (standardized β = 0.526, p < 0.001). As for IOPGAT, only SBP (standardized β = 0.162, p < 0.001), CCT (standardized β = 0.259, p < 0.001), and CC (standardized β = 0.156, p < 0.001) were significantly correlated. The mean IOPNCT−GAT difference increased with younger age (standardized β = −0.134, p < 0.001), higher body mass index (standardized β = 0.091, p = 0.009), higher SBP (standardized β = 0.074, p = 0.027), thicker CCT (standardized β = 0.506, p < 0.001), and lower IOPGAT (standardized β = −0.409, p < 0.001).ConclusionIn the non-pathologic high myopia population, IOPNCT overestimated IOPGAT at 3.75 ± 2.10 mmHg. This study suggests that the difference between the values obtained by the two devices, and their respective influencing factors, should be considered in the clinical evaluation and management of highly myopic populations.

In this study, untargeted lipidomics based on UPLC-Q/TOF-MS, network pharmacology and atomic force microscopy were used to explore the common biomarkers of hyperlipidemia and coronary heart disease, the therapeutic mechanism of the main components of Salvia miltiorrhiza as well as the action mechanism of key lipids. Firstly, the serum samples of 30 healthy people, 30 patients with coronary heart disease and 30 patients with hyperlipidemia were analyzed by using lipidomics technology to obtain biomarkers which can be used to link hyperlipidemia and coronary heart disease and to find potential targets; then, the key components and core targets of Salvia miltiorrhiza intervention in hyperlipidemia and coronary heart disease were analyzed by network pharmacology, the results were verified by atomic force microscopy. It showed that SMS2 might be the key target. And through network pharmacology and atomic force microscope analysis, it can be inferred that salvianolic acid A can combine with SMS2 to play a therapeutic role.

Renal fibrosis is a common pathological feature of various kidney diseases, leading to irreversible renal failure and end-stage renal disease. However, there are still no effective treatments to reverse renal fibrosis. This study aimed to explore the potential mechanism of a targeted drug for fibrosis. Here, unilateral ureteral obstruction (UUO)-treated mice and a TGF-β1-treated human renal tubular epithelial cell line (HK-2 cells) were used as models of renal fibrosis. Based on the changes of mRNA in UUO kidneys detected by transcriptome sequencing, MK-2206, an Akt inhibitor, was predicted as a potential drug to alleviate renal fibrosis through bioinformatics. We dissolved UUO mice with MK-2206 by gastric gavage and cultured TGF-β-induced HK-2 cells with MK-2206. Histopathological examinations were performed after MK-2206 intervention, and the degree of renal fibrosis, as well as the expression of Akt/mTOR pathway-related proteins, were evaluated by immunohistochemical staining, immunofluorescence staining, and Western blot. The results showed that MK-2206 significantly improved the pathological structure of the kidney. Furthermore, MK-2206 intervention effectively inhibited UUO- and TGF-β1-induced epithelial-mesenchymal transition, fibroblast activation, and extracellular matrix deposition. Mechanistically, MK-2206 treatment attenuated the activation of the Akt/mTOR signaling pathway. Taken together, our study revealed for the first time that MK-2206 is a promising drug for the improvement of renal fibrosis.

Aeschynanthus pulcher (Blume) G. Don, the “lipstick plant” is a prized ornamental plant with distinctive flowers. Here, we introduce a novel in vitro regeneration method for A. pulcher using leaf explants and an optimized combination of phytohormone plant growth regulators (PGRs). The optimal conditions for shoot regeneration included 1 mg L−1 polyvinyl pyrrolidone (PVP) plus 3 mg L−1 thidiazuron (TDZ), inducing a response rate of 82.4% and a shoot/explant ratio of 38.6. When the Murashige and Skoog (MS) medium contained indole-3-butyric acid (IBA) alone, leaves first differentiated into adventitious roots and then adventitious shoots. Leaves cultured on MS medium containing 1 g L−1 PVP, 3 mg L−1 TDZ, 5 mg L−1 casein, and 0.1 mg L−1 α-naphthaleneacetic acid (NAA) for 30 d exhibited the highest embryogenic callus (EC) induction rate (95.6%). The optimal shoot proliferation coefficient (21.5) was obtained when shoots derived from EC were cultured on the same medium as that used for EC induction for 5 weeks. The most effective medium for rooting of elongated shoots was MS medium containing 1 g L−1 PVP, 5 mg L−1 casein, 3 mg L−1 6-benzyladenine (BA), and 0.1 mg L−1 NAA, and the number of roots reached 18.8. The regenerated plants grown in a greenhouse had 100% survival following one week of hardening. Overall, our effective and efficient propagation method should result in shortened culture periods and reduced production costs, allowing for the future selective breeding and genetic improvement of A. pulcher.

Abstract We report on the first detection and isolation of B. pseudohinzii (Bordetella pseudohinzii) in laboratory mice in China. Forty‐one B. pseudohinzii strains were isolated from 3094 mice in 33 different laboratory animal facilities in southern China. The isolates were identified through culture and genome sequenceing. Phylogenetic analysis based on the sequences of 16S rRNA and OmpA genes demonstrated that these strains were on the same clade as other B. pseudohinzii strains isolated from mice. Experimental infected mice presented an asymptomatic infection. B. pseudohinzii replicated in both the respiratory tract and the digestive tract. Most importantly B. pseudohinzii shed via feces and infected a group of sentinel mice in a separate cage via cage padding contaminated with B. pseudohinzii‐positive feces, indicating that B. pseudohinzii could transmit efficiently among mice and contaminate environmental facilities. Our study highlights the importance of routine monitoring of the pathogen in laboratory mice and provides vital insights into the transmission of Brodetellae in rodents and human.

Cellulose-grafte-poly(L-lactide) (C-g-PLLA) copolymers synthesized in a CO2-switchable solvent are proposed for use as effective compatibilizers for the preparation of cellulose–PLLA composites with enhanced interfacial compatibility. The effect of the molar substitution (MSPLLA) of the grafted PLLA side chain in the C-g-PLLA copolymer and the feeding amount of this copolymer on the mechanical and thermal properties and hydrophilicity of the composites was investigated. The composites had a largely increased impact strength with the incorporation of the compatibilizer. With the increasing of MSPLLA and the feeding amount of the copolymer, the resulting composites had an increased impact strength. When 5 wt% C-g-PLLA with MSPLLA of 4.46 was used as a compatibilizer, the obtained composite containing 20 wt% cellulose presented an impact strength equal to that obtained for the neat PLLA. The composites had a slightly decreased melting temperature and thermal decomposition temperature, but increased hydrophilicity due to the incorporation of the compatibilizer. This work suggests an effective method to improve the interfacial compatibility between cellulose and PLLA for the fabrication of fully bio-based composites with high performance.

The rapid development in data science and the increasing availability of building operational data have provided great opportunities for developing data-driven solutions for intelligent building energy management. Data preprocessing serves as the foundation for valid data analyses. It is an indispensable step in building operational data analysis considering the intrinsic complexity of building operations and deficiencies in data quality. Data preprocessing refers to a set of techniques for enhancing the quality of the raw data, such as outlier removal and missing value imputation. This article serves as a comprehensive review of data preprocessing techniques for analysing massive building operational data. A wide variety of data preprocessing techniques are summarised in terms of their applications in missing value imputation, outlier detection, data reduction, data scaling, data transformation, and data partitioning. In addition, three state-of-the-art data science techniques are proposed to tackle practical data challenges in the building field, i.e., data augmentation, transfer learning, and semi-supervised learning. In-depth discussions have been presented to describe the pros and cons of existing preprocessing methods, possible directions for future research and potential applications in smart building energy management. The research outcomes are helpful for the development of data-driven research in the building field.

The ability of carbon dots (CDs) to emit afterglow emission in addition to fluorescence in response to UV-to-visible excitation allows them to be a new class of luminescent materials. When compared with traditional organic or inorganic afterglow materials, CDs have a set of advantages, including small size, ease of synthesis, and absence of highly toxic metal ions. In addition, high dependence of their afterglow color output on temperature, excitation wavelength, and aggregation degrees adds remarkable flexibility in the creation of multimode luminescence of CDs without the need for changing their intrinsic attributes. These characteristics make CDs particularly attractive in the fields of sensing, anticounterfeiting, and data encryption. In this review, we first describe the general attributes of afterglow CDs and their fundamental afterglow mechanism. We then highlight recent strategic advances in the generation or activation of the afterglow luminescence of CDs. Considerable emphasis is placed on the summarization of their emergent afterglow properties in response to external stimulation. We further highlight the emerging applications of afterglow CDs on the basis of their unique optical features and present the key challenges needed to be addressed before the realization of their full practical utility.

Introduction Myopic maculopathy and glaucoma belong to the most common causes of irreversible blindness worldwide and, having an ocular axial elongation as one of their main risk factors, can occur together. The detection of glaucomatous optic neuropathy (GON) in highly myopic eyes is clinically and technically difficult, and there is no information available, neither about the natural course of GON or about the course of GON under intraocular pressure-lowering therapy. We therefore designed this study to explore the natural course of GON in highly myopic eyes.Methods and analysis In this single-centred longitudinal registry cohort study, 813 highly myopic individuals will be recruited and undergo detailed ophthalmic examinations. High myopia is defined by a myopic refractive error of ≥−6 D or an axial length of ≥26.5 mm. GON is defined by a glaucomatous appearance of the optic nerve head or glaucomatous visual field (VF) defects. GON progression is defined by either change of the optic disc or VF.Ethics and dissemination Ethical approval has been obtained from the ethical committee of the Zhongshan Ophthalmic Center (ZOC), Sun Yat-sen University, China (ID: 2019KYPJ079). All the participants are required to provide informed consents. Results will be disseminated through scientific meetings and published in peer-reviewed journals. The data will be deposited at the clinical research centre in ZOC using electronic data capture system, and a copy of paper files will also be kept. Only members of the project team will have access to these data.Trial registration number NCT04302220.