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Keratoconjunctivitis sicca (KCS) is an ocular condition characterized by insufficient tear production and inflammatory irritation, with Sjögren's syndrome (SS) being a major causative factor. This study aimed to extract patient transcriptomic data from the GEO database to identify signature genes associated with the diagnosis and treatment of KCS and the expression of three key genes were experimentally verified. We performed a difference analysis on the SS patient dataset and performed a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the resulting genes. Additionally, a Weighted Gene Co-expression Network Analysis (WGCNA) was constructed. Machine learning techniques were employed to analyze the most strongly correlated gene modules with SS traits. These findings were further validated using KCS immune-correlation microarrays as a validation set. The correlation of the three identified genes with 22 immune cells was assessed through immune infiltration analysis. Subsequently, a rat model of desiccated keratoconjunctivitis was established, and the modeling situation and expression of characteristic genes were analyzed at the morphological, tissue, and molecular levels. Bioinformatic prediction revealed that the expression of JAK1, SKI, ZBTB16 not only differed in the machine learning validation set, but also correlated with some immune cells in the immune infiltration analysis. The results of animal experiments showed that the transcription and expression levels of these three genes were significantly different in rat KCS tissues and normal tissues, and there were also differences in the expression of JAK1 and SKI in rat peripheral blood, as well as significant up-regulation of the expression of related inflammatory factors in KCS tissues. Through bioinformatics prediction and animal experimental validation, this study identified three differentially expressed genes in SS mediated KCS patients, which provide new potential biological targets for the diagnosis and treatment of KCS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We investigated the safety, tolerability, and pharmacokinetics of ZX-7101A tablets, a novel cap-dependent endonuclease inhibitor, in healthy participants in a first-in-human study. The single ascending dose (SAD) part included 40, 80, 160, 240, and 320 mg dose cohorts with10 participants in each dose cohort (8 participants received ZX-7101A tablets and 2 participants received placebo). The food effect (FE) part was a randomised, two-cycle, two-way crossover design, which enrolled 16 participants to receive single oral dose of 80 mg ZX-7101A tablets. ZX-7101A tablets were safe and well-tolerated in both SAD and FE studies. No participant died or experienced SAE, or withdrew prematurely. The prodrug ZX-7101A was rapidly transformed into the active ingredient ZX-7101 after single oral dose of 40 - 320 mg. The blood concentration of ZX-7101A was below the lower limit of quantification at most time points. ZX-7101 reached peak concentration about 3-4 h postdose in all dose cohorts. The elimination half-life of ZX-7101 was 83.01-125.55 h and AUC 0-24 was 1655.4 to 11483.7 h*ng/mL. The FE part showed the high-fat meal significantly affected the exposure parameters compared to the fasted condition. The C max and AUC 0-t of ZX-7101 under fasted condition were 1.73 and 1.78 times those under fed condition, respectively. Single oral dose of 40 mg and 80 mg ZX-7101A tablets achieved sufficient ZX-7101 exposure for effectively inhibiting influenza A and B viruses and avian influenza viruses. These findings support 40 mg and 80 mg of ZX-7101A tablets as single dose regimens for use in phase II/III clinical trials. This study was registered at chinadrugtrials.org.cn (identifier: CTR20212778)., Competing Interests: Competing Interests Yilin Li, Mei Liu, Xiaoli Qin, and Yin Wang are employees of Nanjing Zenshine Pharmaceuticals Co., Ltd. Other authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier Ltd.)

In this study, chicken bone gelatin (CBG) was extracted as a new substitute for traditional pig bone gelatin, and bacterial cellulose (BC) was used as the compound to prepare Oregano essential oil (OEO) Pickering emulsion. To explore a protein/polysaccharide emulsion system that can effectively prolong the functional activity of OEO during storage. The results indicated that the variation in CBG and BC content significantly influenced the physicochemical properties of the emulsions. The optimal formulation of OEO Pickering emulsion, prepared with a CBG-BC ratio of 6:2 (v/v), exhibited superior characteristics including appearance, encapsulation efficiency, and stability during preservation. After 7 d of storage at 4 °C, the rheological properties remained stable, with no significant differences observed in antioxidant and antibacterial activities. It was verified in the beef fresh-keeping experiment that the shelf life of beef samples in the 6-2-2 treatment group was 6 d longer than that in the control group and 3 d longer than that in the pure OEO group. This experiment enhanced the utilization of poultry by-products and provided a valuable reference for exploring suitable protein-polysaccharide systems embedding active substances for food preservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Necrotizing enterocolitis (NEC) is a form of potentially lethal gastrointestinal inflammation that primarily affects preterm neonates. It is crucial to recognize that, while the disease carries significant risks, timely and effective medical intervention can greatly enhance the chances of survival. Additionally, NEC is closely linked to the activation of macrophages, highlighting the complex interplay between the immune response and disease progression. CD38, acting as an ectoenzyme, catalyzes the hydrolysis of NAD + to produce cyclic ADP-ribose (cADPR), a reaction critical for modulating cellular redox balance and energy homeostasis. This enzymatic activity is particularly pertinent in the context of necrotizing enterocolitis (NEC). In this research, we investigated whether CD38 deletion can elevate NAD + levels to reduce macrophage-mediated inflammation and improve NEC severity. We show that NEC patients was associated with the increased CD38 expression in intestine and blood. These results were also observed in NEC mice, and CD38 deletion ameliorated NEC intestinal injury. Mechanistically, CD38 deletion elevated NAD + levels that reduced oxidative stress and intestinal inflammation. Furthermore, CD38 deletion promoted M2 macrophage polarization, inhibited macrophage activation and phagocytosis ability. Thus, our results reveal a critical role for CD38 as an intracellular immune regulator for regulating macrophage activation and intestinal inflammation in NEC. Targeting CD38 and NAD + signal maybe a promising strategy for treatment of NEC., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Nanomaterials as an emerging tool are being used to improve plant's net photosynthetic rate (A N ) when suffering salt stress, but the underlying mechanisms remain unclear. To clarify this, a hydroponic experiment was conducted to study the effects of polyacrylic acid coated nanoceria (PNC) on the A N of salt-stressed cotton and related intrinsic mechanisms. Results showed that the PNC-induced A N enhancement of salt-stressed leaves was strongly facilitated by the mesophyll conductance to CO 2 (g m ). Further analysis showed that the PNC-induced improvement of g m was related to the increased chloroplast surface area exposed to intercellular airspaces, which was attribute to the increased mesophyll surface area exposed to intercellular airspaces and chloroplast number due to the increased K + content and decreased reactive oxygen species level in salt-stressed leaves. Interestingly, our results also showed that PNC-induced variations in cell wall composition of salt-stressed cotton leaves strongly influenced g m , especially, hemicellulose and pectin. Moreover, the proportion of pectin in cell wall composition played a more important role in determining g m . Our study demonstrated for the first time that nanoceria, through alterations to anatomical traits and cell wall composition, drove g m enhancement, which ultimately increased A N of salt-stressed leaves., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A 1 receptor (A 1 R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A 1 R using a specific antagonist DPCPX or knocking down the A 1 R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics., (© 2024. The Author(s).)

Arabinogalactan exhibits many biological activities, which is the candidate for functional food ingredients. However, there is limited research on the arabinogalactan from Moringa Oleifera leaf, and its structure needs to be more accurately characterized. This study investigated structural characteristics and immunomodulatory activity of a high-purity polysaccharide from Moringa oleifera leaf (i.e. MOLP-PE) to further explore arabinogalactan from Moringa Oleifera leaf and its potential application area. The results showed that MOLP-PE was a unique type II arabinogalactan: the main chain consisted of → 3, 4)-α-D-Galp-(1→, →3)-β-D-Galp-(1→ and →2, 4)-β-D-Rhap-(1→, with branches at the C-4 position of →3, 4)-α-D-Galp-(1→ and →2, 4)-β-D-Rhap-(1→, consisting of →5)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →6)-β-D-Galp-(1→ and →4)-β-D-GalpA-(1→. Compared with arabinogalactan from larch, galactan and arabinan, MOLP-PE exhibited stronger ability in stimulating proliferation, phagocytosis and cytokines release of macrophages and bound with Toll-like receptor 4 closer via more binding sites, which might be due to its higher contents of 1,3-linked-Galp and 1,5-linked-Araf. These findings elucidated that MOLP-PE, as type II arabinogalactan with a unique structure, could be exploited as an immunomodulatory food ingredient., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neuroendocrine tumors (NETs) are rare neoplasms that originate from peptidergic neurons and neuroendocrine cells. Due to their increasing incidence, effective treatment strategies are required. Surufatinib, a novel small-molecule inhibitor with antiangiogenic and immunomodulatory effects, has shown promise in clinical trials for advanced NETs. However, the efficacy and safety of surufatinib are influenced by multiple factors, and there is currently a lack of sufficient real-world studies to explore these potential influencing factors., Methods: We conducted a retrospective study on 133 patients with NETs who were treated with surufatinib at Sun Yat-sen University Cancer Center. Patients were histologically confirmed to have primary NETs. Statistical analyses, including Cox regression models and Kaplan-Meier curves, were conducted to assess the impact of the primary tumor site on progression-free survival (PFS) and overall survival (OS)., Results: Patients with gastroenteropancreatic NETs (GEP-NETs) exhibited significantly longer PFS and OS compared to extraGEP-NETs patients. Subgroup analyses also revealed variations in survival outcomes among patients with liver metastases depending on the primary tumor site. Adverse events (AEs), including proteinuria and increased bilirubin, were more common in GEP-NETs patients. These findings emphasize the importance of considering primary tumor site in treatment decisions for NETs., Conclusions: Primary tumor site is a critical factor influencing the efficacy of surufatinib in NETs. Clinicians should consider this factor when determining treatment strategies., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Sepsis presents complex pathophysiological challenges. Taohe Chengqi Decoction (THCQ), a traditional Chinese medicine, offers potential in managing sepsis-related complications, though its exact mechanisms are not fully understood., Aim of the Study: This research aimed to assess the therapeutic efficacy and underlying mechanisms of THCQ on sepsis-induced lung injury., Materials and Methods: The study began with validating THCQ's anti-inflammatory effects through in vitro and in vivo experiments. Network pharmacology was employed for mechanistic exploration, incorporating GO, KEGG, and PPI analyses of targets. Hub gene-immune cell correlations were assessed using CIBERSORT, with further scrutiny at clinical and single-cell levels. Molecular docking explored THCQ's drug-gene interactions, culminating in qPCR and WB validations of hub gene expressions in sepsis and post-THCQ treatment scenarios., Results: THCQ demonstrated efficacy in modulating inflammatory responses in sepsis, identified through network pharmacology. Key genes like MAPK14, MAPK3, MMP9, STAT3, LYN, AKT1, PTPN11, and HSP90AA1 emerged as central targets. Molecular docking revealed interactions between these genes and THCQ components. qPCR results showed significant modulation of these genes, indicating THCQ's potential in reducing inflammation and regulating immune responses in sepsis., Conclusion: This study sheds light on THCQ's anti-inflammatory and immune regulatory mechanisms in sepsis, providing a foundation for further research and potential clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Postoperative gastroparesis occurs after surgeries which affect the upper digestive tract. Gastric peroral endoscopic myotomy (G-POEM) is a treatment for postoperative gastroparesis. The present study boasts the long-term efficacy and safety of G-POEM in a large cohort of patients., Patients and Methods: Gastroparesis Cardinal Symptom Index (GCSI) and Gastroesophageal Reflux Disease Questionnaire (GERDQ) were utilized for the assessment of postsurgical gastroparesis symptoms. Gastroscope was used to observe the anastomotic site. Three-dimensional ultrasound was used to measure the morphological structure of the gastric antrum and pylorus tube. Gastric emptying time was calculated by analyzing the volume change of gastric antrum., Results: Significant clinical effectiveness of G-POEM was observed. The GCSI score, including each subscale score, showed significant decrease after G-POEM. Before G-POEM, there was a negative correlation between GCSI score and the inner diameter of pylorus, as well as a positive correlation with the length of pyloric tube. The similar results were found in the scores of nausea/vomiting and postprandial fullness/early satiety subscales. No correlation was observed between GCSI score and the emptying time, nor between the emptying time and the parameters of antrum morphology. After G-POEM, no correlation was found between GCSI (including subscales) score, the emptying time, and the parameters of antrum morphology. Patients who exhibited as clinical non-responders often accompanied with GERD symptoms. After G-POEM, the score of GERDQ decreased significantly. Either before or after G-POEM, no correlation was noticed between GERDQ scores, the emptying time and the parameters of antrum morphology., Conclusion: The technique of G-POEM was demonstrated as a minimally invasive approach with the long-term efficacy and safety in therapying postoperative gastroparesis., (© 2024. The Author(s).)

Deep sowing, as a method to mitigate drought and preserve soil moisture and seedlings, can effectively mitigate the adverse effects of drought stress on seedling growth. The elongation of the hypocotyl plays an important role in the emergence of maize seeds from deep-sowing stress. This study was designed to explore the function of exogenous methyl jasmonate (MeJA) in the growth of the maize mesocotyl and to examine its regulatory network. The results showed that the addition of a 1.5 μ mol L -1 MeJA treatment significantly increased the mesocotyl length (MES), mesocotyl and coleoptile length (MESCOL), and seedling length (SDL) of maize seedlings. Transcriptome analysis showed that exogenous MeJA can alleviate maize deep-sowing stress, and the differentially expressed genes (DEGs) mainly include ornithine decarboxylase, terpene synthase 7, ethylene responsive transcription factor 11, and so on. In addition, candidate genes that may regulate the length of maize hypocotyls were screened by Weighted Gene Co-expression Network Analysis (WGCNA). These genes may be involved in the growth of maize hypocotyls through transcriptional regulation, histones, ubiquitin protease, protein binding, and chlorophyll biosynthesis and play an important role in maize deep-sowing tolerance. Our research findings may provide a theoretical basis for determining the tolerance of maize to deep-sowing stress and the mechanism of exogenous hormone regulation of deep-sowing stress.

Microorganisms often actively respond to multiple external stimuli to navigate toward their preferred niches. For example, unicellular magnetotactic bacteria integrate both oxygen sensory information and the Earth's geomagnetic field to help them locate anoxic conditions in a process known as magneto-aerotaxis. However, for multicellular magnetotactic prokaryotes (MMPs), the colonial structure of 4-16 cells places fundamental constraints on collective sensing, colony motility and directed swimming. To investigate how colonies navigate environments with multiple stimuli, we performed microfluidic experiments of MMPs with opposing magnetic fields and oxygen gradients. These experiments reveal unusual back-and-forth excursions called 'escape motility', in which colonies shuttle along magnetic field lines, punctuated by abrupt-yet highly coordinated-changes in collective ciliary beating. Through cell tracking and numerical simulations, we demonstrate that escape motility can arise through a simple magneto-aerotaxis mechanism, which includes the effect of magnetic torques and chemical sensing. At sufficiently high densities of MMPs, we observe the formation of dynamic crystal structures, whose stability is governed by the magnetic field strength and near-field hydrodynamic interactions. The results shed light on how some of the earliest multicellular organisms navigate complex physico-chemical landscapes.

Pseudomonas aeruginosa, a notable pathogen frequently associated with hospital-acquired infections, displays diverse intrinsic and acquired antibiotic resistance mechanisms, posing a significant challenge in infection management. Antimicrobial blue light (aBL) has been demonstrated as a potential alternative for treating P. aeruginosa infections. In this study, we investigated the impact of blue light wavelength, bacterial growth stage, and growth medium composition on the efficacy of aBL. First, we compared the efficacy of light wavelengths 405 nm, 415 nm, and 470 nm in killing three multidrug resistant clinical strains of P. aeruginosa. The findings indicated considerably higher antibacterial efficacy for 405 nm and 415 nm wavelength compared to 470 nm. We then evaluated the impact of the bacterial growth stage on the efficacy of 405 nm light in killing P. aeruginosa using a reference strain PAO1 in exponential, transitional, or stationary phase. We found that bacteria in the exponential phase were the most susceptible to aBL, followed by the transitional phase, while those in the stationary phase exhibited the highest tolerance. Additionally, we quantified the production of reactive oxygen species (ROS) in bacteria using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe and flow cytometry, and observed a positive correlation between aBL efficacy and ROS production. Finally, we determined the influence of growth medium on aBL efficacy. PAO1 was cultivated in brain heart infusion (BHI), Luria-Bertani (LB) broth or Casamino acids (CAA) medium, before being irradiated with aBL at 405 nm. The CAA-grown bacteria exhibited the highest sensitivity to aBL, followed by those grown in LB broth, and the BHI-grown bacteria demonstrated the lowest sensitivity. By incorporating FeCl 3 , MnCl 2 , ZnCl 2 , or the iron chelator 2,2'-bipyridine (BIP) into specific media, we discovered that aBL efficacy was affected by the iron levels in culture media., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study employed a randomized controlled trial to assess the efficacy of virtual-reality (VR) simulators and physical model simulators on colonoscopy training to explore the optimal and evidence-based simulation training., Design: Forty participants were divided into 2 groups and randomized as dyads: the VR simulator group and the physical model simulator group. All the participants performed a baseline test through porcine colonoscopy. After a 6 h simulation training, each participant underwent a post-test on a pig after bowel preparation, and the procedures were video-recorded. Both the baseline test and the post-test were blindly assessed by 2 experienced assistant director physicians based on the GAGES-C scoring system., Setting: Simulation center, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai., Participants: Forty surgical residents without colonoscopy experience., Results: Both the VR simulator group and the physical model simulator group improved significantly over the baseline test. The VR simulator group performed significantly better than the physical model simulator group, p=0.042. The participants in both groups expressed a high level of simulator satisfaction., Conclusions: Novice residents can benefit from both VR simulators and physical model simulators. The VR simulator was shown to be more effective for colonoscopy training. VR simulators were more recommended for novices conducting basic colonoscopy training., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Natural resources are limited, and people often share these limited resources in groups, which creates an intergroup resource dilemma. To understand individuals' sustainable behaviours in intergroup resource dilemmas in the context of group interactions, the present research systematically investigates the effect of outgroup conspiracy theories on sustainable behaviours and preliminarily explores the internal mechanism underlying this effect. First, a survey study (Study 1) relying on real-world intergroup relations first confirmed the negative correlation between outgroup conspiracy beliefs and sustainable intentions in intergroup resource dilemmas. Then, an online experimental study that utilized the real situation of a region in China (Study 2) tested the causal relationship between exposure to an outgroup conspiracy theory and sustainable intentions, as well as showing the mediating role of intergroup threat perception underlying this relationship. Finally, a preregistered experimental laboratory study (Study 3) further verified the causal effect of exposure to an outgroup conspiracy theory on sustainable behaviours, again confirming the mediating role of intergroup threat perception. In general, our research demonstrates that exposure to an outgroup conspiracy theory stimulates individuals' environmental neglect and reduces their sustainable behaviours by increasing their perceptions of intergroup threat when faced with intergroup resource dilemmas., (© 2024 British Psychological Society.)

Protein hydrogels with tailored stimuli-responsive features and tunable stiffness have garnered considerable attention due to the growing demand for biomedical soft robotics. However, integrating multiple responsive features toward intelligent yet biocompatible actuators remains challenging. Here, a facile approach that synergistically combines genetic and chemical engineering for the design of protein hydrogel actuators with programmable complex spatial deformation is reported. Genetically engineered silk-elastin-like proteins (SELPs) are encoded with stimuli-responsive motifs and enzymatic crosslinking sites via simulation-guided genetic engineering strategies. Chemical modifications of the recombinant proteins are also used as secondary control points to tailor material properties, responsive features, and anisotropy in SELP hydrogels. As a proof-of-concept example, diazonium coupling chemistry is exploited to incorporate sulfanilic acid groups onto the tyrosine residues in the elastin domains of SELPs to achieve patterned SELP hydrogels. These hydrogels can be programmed to perform various actuations, including controllable bending, buckling, and complex deformation under external stimuli, such as temperature, ionic strength, or pH. With the inspiration of genetic and chemical engineering in natural organisms, this work offers a predictable, tunable, and environmentally sustainable approach for the fabrication of programmed intelligent soft actuators, with implications for a variety of biomedical materials and biorobotics needs., (© 2024 Wiley‐VCH GmbH.)

This study aimed to investigate the protective effects of glucose selenol on cadmium (Cd)-induced testicular toxicity. Twenty-four male Sprague-Dawley (SD) rats were randomly divided into four groups. Cd was administered orally at a dose of 40 mg/L or in combination with orally administered glucose selenol at doses of 0.15 mg/L and 0.4 mg/L for 30 days. The results showed that sperm quality decreased and testicular tissue was damaged in the Cd group; Glucose selenol significantly attenuated the negative effects by improving sperm quality and reducing testicular damage. Transcriptome sequencing analysis showed that Cd stress affected spermatogenesis, sperm motility, oxidative stress, blood-testis barrier and protein metabolism. Four clusters were obtained using the R Mfuzz package, which clustered highly expressed genes under different administrations, and 36 items were enriched. Notably, protein phosphorylation was enriched in the Cd group and is considered to play a key role in the response to Cd stress. We identified fifty-six target selenium (Se) and Cd co-conversion differentially expressed genes (DEGs), including three genes relating to spermatogenesis (Dnah8, Spata31d1b, Spata31d1c). In addition, the obtained DEGs were used to construct a protein-protein interaction network, co-processed with Se and Cd, and 5 modules were constructed. Overall, the analyses of rat testicular physiology and gene expression levels offer new insights into the reproductive toxicity of Cd in rats, and provide potential application prospects for glucose selenol in alleviating the impact of Cd-induced testicular damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Previous evidence on heatwaves' impact on mental health outpatient visits is limited, especially uncertainty on how different heatwave definitions affect this relationship. In this time-series study, we assessed the association between heatwaves and outpatient visits for mental disorders in Guangzhou, China. Daily outpatient visits for mental disorders and its specific categories (schizophrenia, mood, and neurotic disorders) were sourced from the Urban Resident-based Basic Medical Insurance (URBMI) and the Urban Employee-based Basic Medical Insurance (UEBMI) claims databases in Guangzhou from 2010 to 2014. The study employed nine heatwave definitions, based on combinations of three daily mean temperature thresholds (90th, 92.5th, and 95th percentiles) and durations (2, 3, and 4 days). Using quasi-Poisson generalized linear models (GLMs), we estimated the risks (at lag 0 day) and cumulative effects (lag 0-10 days) of heatwaves on mental disorder outpatient visits. Age, gender, types of medical insurance were considered as potential effect modifiers. We observed a positive association between heatwaves and increased total outpatient visits for mental disorders, both at lag 0 day and during lag 0-10 days. The impact of heatwave was significant at lag 0 day for schizophrenia, mood and neurotic disorders visits, it remained significant for neurotic and mood disorders visits during lag 0-10 days. Heatwave durations lasting more than 4 days were associated with higher relative risks of mental disorders at lag 0 day. Older adults had relatively higher effect estimations than younger individuals. This research highlights the effects of extreme heat on mental health., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2024 The Author(s). GeoHealth published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

Objective: Cisplatin-based chemotherapy is widely used for the treatment of oral squamous cell carcinoma (OSCC), but drug resistance and decreased sensitivity often occur during the treatment, greatly weakening its therapeutic effect. Caveolin-1 (CAV1), a protein related to ferroptosis, is involved in regulating the resistance and sensitivity of various tumor chemotherapies. This study aims to investigate whether CAV1 can regulate the sensitivity of OSCC to cisplatin through ferroptosis., Methods: Through bioinformatics analysis, we analyzed the expression of CAV1 in OSCC and its impact on prognosis analyzed the relationship between CAV1 and tumor immune infiltration, and verified the expression of CAV1 in OSCC through immunohistochemistry experiments. We silenced the expression of CAV1 in OSCC cells through lentiviral transfection and evaluated the cell migration and invasion abilities through wound healing and Transwell assays, respectively. CCK8 assay was used to assess the sensitivity of cells to cisplatin, and ferroptosis-related biochemical marker changes were measured. Western blot was performed to detect the expression of ferroptosis-related proteins., Results: The results revealed a high expression of CAV1 in OSCC, and its high expression predicted poor prognosis in OSCC. CAV1 is associated with drug metabolism pathways in OSCC, and its expression affects the infiltration levels of various immune cells in tumors. Further experiments indicated that CAV1 can inhibit ferroptosis and cisplatin sensitivity in cancer cells, promoting their migration and invasion., Conclusion: CAV1 promotes the progression of OSCC and can affect the sensitivity of cisplatin by regulating cellular ferroptosis., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Electroacupuncture (EA) has been shown to ameliorate brain injury and protect against intestinal injury after ischemic stroke. These protective effects are closely associated with the enhancement of regulatory T (Treg) cell numbers and function in the intestine, as well as the inhibition of intestinal γδ T cell production and their migration to the brain. This study aimed to elucidate the potential mechanism by which EA regulates intestinal Treg cell differentiation after stroke. Sprague-Dawley rats were divided into three groups: the sham group, the middle cerebral artery occlusion (MCAO) group, and the MCAO plus EA (MEA) group. The MCAO model was generated by occluding the middle cerebral artery. EA was applied to Baihui (GV20) acupoint once daily. Samples were collected 3 days after reperfusion. Our results showed that EA reduced the inflammatory response in the brain and intestine after ischemic stroke. EA treatment increased the percentage of Treg cells in the small intestine of rats. EA increased the levels of SCFAs, while also inhibiting histone deacetylase activity (HDAC). Additionally, acetylated Foxp3 protein in the small intestine was increased after EA treatment. These results suggest that EA at GV20 alleviates brain and intestinal inflammatory injury in stroke rats, potentially through the enhancement of SCFA-mediated Foxp3 acetylation in Treg cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sulfur dots (SDs) have emerged as promising photoluminescence (PL) materials owing to their intrinsic merits such as abundant electronic effects, outstanding biocompatibility and available photocatalytic activity. Typically based on quantum confinement effects, SDs are reported usually confined emission in blue-to-green region. However, it is challenging to achieve their broad emission tunability in the visible region, restricted by inherent band gap of bulk sulfur (ca. 2.79 eV). Herein, we present white-light-emitting SDs achieved by surface charge engineering that hybridizes the surface of SDs with oleylamine. The resulting SDs exhibit broadband emissions (full width at half maximum of 187 nm) with PL quantum yields of up to 12.1 % and Commission International de I'Eclairage color coordinates of (0.27, 0.32). Detailed experimental and theoretical analysis reveal that the strong orbital coupling between oleylamine and sulfur on the hybrid surfaces of the SDs causes electron delocalization, leading to the generation of low-energy charge transfer (CT) states. These CT states are highly sensitive to sulfur-oleylamine hybrid structures, which complicate the transition dynamics and promote multi-energy emissions, accounting for efficient white-light emission. The demonstration of white-light SDs based on surface charge engineering is an important step towards the development of sulfur-based PL materials., (© 2024 Wiley-VCH GmbH.)

Objective: To examine the effects of an internet-based Developmental Home Care Support program (DHCSP) to reduce maternal psychological symptoms and improve preterm infants' physical growth outcomes., Methods: A randomized controlled trial was conducted. The mother-infant dyads (nm = 34, np = 40) were randomly assigned to either the DHCSP intervention group or the control group. Data were collected at discharge (T0), 1-month corrected age (T1), and 2-month follow-up (T2), including mothers' postpartum depressive and posttraumatic stress disorder (PTSD) symptoms and mother-proxy infants' body length, weight, and head circumference., Results: There were no significant differences in sociodemographic characteristics between the 2 groups at T0, except for mothers' age and monthly household income (both P = .01). Mothers in the DHCSP group reported significantly higher decreases in depression symptoms (β = -2.24; 95% confidence interval [CI], -4.31 to -0.16, P = .03), and their preterm infants showed significantly more increases in body length (β = 2.09; 95% CI, 0.30-3.87, P = .02) than the control participants at T2. The 2 groups did not show significant differences in mothers' PTSD symptoms or infants' body weight and head circumference., Conclusion: The internet-based DHCSP intervention was effective in improving mothers' depressive symptoms and infants' body length., Competing Interests: All authors declare that there are no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While the significant association between leisure activities and frailty risk among older adults is well-established, the impact of integrated leisure activity scores and different categories of them on frailty trajectories over time remains unclear., Methods: This study utilized longitudinal data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which enrolled participants aged 65 years and older between 2002 and 2018. Frailty trajectories were derived using group-based trajectory modelling, and based on these trajectories, subjects were classified into various categories. Leisure activity was measured by integrated scores as well as three distinct categories: physically, cognitively, and socially stimulating activity. The effect of leisure activity on frailty trajectories was examined using multinomial logistic regression., Results: By analysing data from 2,299 older adults, three frailty trajectories were identified: non-frail, moderate progressive, and high progressive. The results indicated that an increase in the score of integrated leisure activity was associated with 11% (odds ratio [OR] 0.89; 95% Confidence Interval [CI] 0.85-0.93) and 14% (OR 0.86; 95% CI 0.80-0.91) decrease in the likelihood of being in the moderate and high progressive frailty trajectories, respectively. Engaging in physically stimulating activity lowered the odds of belonging to the moderate and high progressive trajectory by 43% (OR 0.57; 95% CI 0.40-0.81; OR 0.57; 95% CI 0.36-0.92, respectively). Participation in socially stimulating activity showed a lower odd of being in the moderate progressive trajectory (OR 0.68; 95% CI 0.49-0.93) and the high progressive trajectory (OR, 0.61; 95% CI, 0.39-0.95). The effects of leisure activities on frailty trajectories were observed not to vary by age, education level and retirement status., Conclusions: This study suggests that older adults should be encouraged to increase both the amount and variety of their leisure activities. Physically stimulating activities should be considered the primary choice, followed by socially and cognitively stimulating activities., (© 2024. The Author(s).)

Atomically dispersed single atom (SA) and atomic cluster (AC) metallic materials attract tremendous attentions in various fields. Expanding monometallic SA and AC to multimetallic SA/AC composites opens vast scientific and technological potentials yet exponentially increasing the synthesis difficulty. Here, we present a general energy-selective-clustering methodology to build the largest reported library of carbon supported bi-/multi-metallic SA/AC materials. The discrepancy in cohesive energy results into selective metal clustering thereby driving the symbiosis of multimetallic SA or/and AC. The library includes 23 bimetallic SA/AC composites, and expanded compositional space of 17 trimetallic, quinary-metallic, septenary-metallic SA/AC composites. We chose bimetallic M 1 SA M 2 AC to demonstrate the electrocatalysis utility. Unique decoupled active sites and inter-site synergy lead to 8/47 mV overpotential at 10 mA cm -2 for alkaline/acidic hydrogen evolution and over 1000 h durability in water electrolyzer. Moreover, delicate modulations towards composition and configuration yield high-performance catalysts for multiple electrocatalysis systems. Our work broadens the family of atomically dispersed materials from monometallic to multimetallic and provides a platform to explore the complex composition induced unconventional effects., (© 2024. The Author(s).)

Atomically dispersed Fe-N-C catalysts emerged as promising alternatives to commercial Pt/C for the oxygen reduction reaction. However, the majority of Fe-N-C catalysts showed unsatisfactory activity and durability due to their inferior O-O bond-breaking capability and rapid Fe demetallization. Herein, we create a pseudo-phthalocyanine environment coordinated diatomic iron (Fe 2 -pPc) catalyst by grafting the core domain of iron phthalocyanine (Fe-N α -C α -N β ) onto defective carbon. In situ characterizations and theoretical calculation confirm that Fe 2 -pPc follows the fast-kinetic dissociative pathway, whereby Fe 2 -pPc triggers bridge-mode oxygen adsorption and catalyzes direct O-O radical cleavage. Compared to traditional Fe-N-C and FePc-based catalysts exhibiting superoxo-like oxygen adsorption and an *OOH-involved pathway, Fe 2 -pPc delivers a superior half-wave potential of 0.92 V. Furthermore, the ultrastrong N α -C α bonds in the pPc environment endow the diatomic iron active center with high tolerance for reaction-induced geometric stress, leading to significantly promoted resistance to demetallization. Upon an unprecedented harsh accelerated degradation test of 150,000 cycles, Fe 2 -pPc experiences negligible Fe loss and an extremely small activity decay of 17 mV, being the most robust candidate among previously reported Fe-N-C catalysts. Zinc-air batteries employing Fe 2 -pPc exhibit a power density of 255 mW cm -2 and excellent operation stability beyond 440 h. This work brings new insights into the design of atomically precise metallic catalysts.

Improving the water stability of metal-organic frameworks (MOFs) is essential for their use in water pollution treatment and environmental remediation, though it remains technically challenging. Herein, we report a novel cationic MOF constructed with [Th 6 O 4 (OH) 4 (COO) 12 ] units and [CoN 4 ·Cl 2 ] units possessing a ftw-type topology (denoted as 1-Th-Co ). 1-Th-Co itself exhibited poor water stability but excellent stability following a palladium(II) modulation strategy. Experimental studies reveal that Co(II) ions in 1-Th-Co were replaced by Pd(II) ions through cation exchange in N,N-diethylformamide (yielding 1-Th-Pd ). The planar PdN 4 units in 1-Th-Pd were responsible for improving the water stability of the framework. As a result, 1-Th-Pd offered excellent stability, fast adsorption kinetics, and high removal ratios for 99 TcO 4 - and ReO 4 - (as a 99 TcO 4 - surrogate) in contaminated water. When used in packed columns, 1-Th-Pd can dynamically capture ReO 4 - from groundwater. This work provides a new avenue for improving the water stability of MOFs, offering new vistas for the decontamination of aqueous solutions containing 99 TcO 4 - and ReO 4 - .

Cucumbers produce by-products such as cucumber pomace during processing and most of them are discarded without being utilized. To effectively utilize the waste, cucumber pomace is used to extract both insoluble and soluble dietary fibers (DFs) using compound enzyme method (ME), High pressure processing assisted ME (HPP-ME), and dynamic high-pressure microfluidization-assisted ME (DHPM-ME). The results showed that DHPM-ME improved the extraction rate of soluble DFs most effectively, increasing it from 1.74 % to 4.08 %. The modified DFs exhibited enhanced hydration properties and functional properties after HPP-ME- and DHPM-ME-mediated auxiliary treatment. Additionally, the modified DFs exhibited improved thermal stability, increased absorption peaks in the infrared spectra, decreased crystallinity, improved glucose and cholesterol adsorption ability, and delayed glucose adsorption. The cucumber pomace-derived modified DFs can be used as a functional food additive in bakery, meat, dairy products, and beverages, and their effective use can further enhance the economic benefits., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Luminescent materials that simultaneously embody bright singlet and triplet excitons hold great potential in optoelectronics, signage, and information encryption. However, achieving high-performance white-light emission is severely hampered by their inherent unbalanced contribution of fluorescence and phosphorescence. Herein, we address this challenge by pressure treatment engineering via the hydrogen bonding cooperativity effect to realize the mixture of n-π*/π-π* transitions, where the triplet state emission was boosted from 7% to 40% in isophthalic acid (IPA). A superior white-light emission based on hybrid fluorescence and phosphorescence was harvested in pressure-treated IPA, and the photoluminescence quantum yield was increased to 75% from the initial 19% (blue-light emission). In-situ high-pressure IR spectra, X-ray diffraction, and neutron diffraction reveal continuous strengthening of the hydrogen bonds with the increase of pressure. Furthermore, this enhanced hydrogen bond is retained down to the ambient conditions after pressure treatment, awarding the targeted IPA efficient intersystem crossing for balanced singlet/triplet excitons population and resulting in efficient white-light emission. This work not only proposes a route for brightening triplet states in organic small molecules, but also regulates the ratio of singlet and triplet excitons to construct high-performance white-light emission., (© 2024. The Author(s).)

The assessment of compound blood-brain barrier (BBB) permeability poses a significant challenge in the discovery of drugs targeting the central nervous system. Conventional experimental approaches to measure BBB permeability are labor-intensive, cost-ineffective, and time-consuming. In this study, we constructed six machine learning classification models by combining various machine learning algorithms and molecular representations. The model based on ExtraTree algorithm and random partitioning strategy obtains the best prediction result, with AUC value of 0.932±0.004 and balanced accuracy (BA) of 0.837±0.010 for the test set. We employed the SHAP method to identify important features associated with BBB permeability. In addition, matched molecular pair (MMP) analysis and representative substructure derivation method were utilized to uncover the transformation rules and distinctive structural features of BBB permeable compounds. The machine learning models proposed in this work can serve as an effective tool for assessing BBB permeability in the drug discovery for central nervous system disease., (© 2024 Wiley-VCH GmbH.)

Background: Helicobacter pylori (H. pylori) infects over 50% of the global population and is a significant risk factor for gastric cancer. The pathogenicity of H. pylori is primarily attributed to virulence factors such as vacA. Timely and accurate identification, along with genotyping of H. pylori virulence genes, are essential for effective clinical management and controlling its prevalence., Methods: In this study, we developed a dual-target RAA-LFD assay for the rapid, visual detection of H. pylori genes (16s rRNA, ureA, vacA m1/m2), using recombinase aided amplification (RAA) combined with lateral flow dipstick (LFD) methods. Both 16s rRNA and ureA were selected as identification genes to ensure reliable detection accuracy., Results: A RAA-LFD assay was developed to achieve dual-target amplification at a stable 37 °C within 20 min, followed by visualization using the lateral flow dipstick (LFD). The whole process, from amplification to results, took less than 30 min. The 95 % limit of detection (LOD) for 16 s rRNA and ureA, vacA m1, vacA m2 were determined as 3.8 × 10 -2 ng/μL, 5.8 × 10 -2 ng/μL and 1.4 × 10 -2 ng/μL, respectively. No cross-reaction was observed in the detection of common pathogens including Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis, showing the assay's high specificity. In the evaluation of the clinical performance of the RAA-LFD assay. A total of 44 gastric juice samples were analyzed, immunofluorescence staining (IFS) and quantitative polymerase chain reaction (qPCR) were used as reference methods. The RAA-LFD results for the 16s rRNA and ureA genes showed complete agreement with qPCR findings, accurately identifying H. pylori infection as confirmed by IFS in 10 out of the 44 patients. Furthermore, the assay successfully genotyped vacA m1/m2 among the positive samples, showing complete agreement with qPCR results and achieving a kappa (κ) value of 1.00., Conclusion: The dual-target RAA-LFD assay developed in this study provides a rapid and reliable method for detecting and genotyping H. pylori within 30 min, minimizing dependency on sophisticated laboratory equipment and specialized personnel. Clinical validation confirms its efficacy as a promising tool for effectively control of its prevalence and aiding in the precise treatment of H. pylori-associated diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study was to assess the lot-to-lot consistency, immunogenicity and safety of three manufacturing lots of a quadrivalent inactivated influenza vaccine (IIV4)., Methods: A randomized, double-blind, phase IV clinical trial was conducted in healthy children, adolescents and adults aged 9-59 years in Guizhou Province, China. Eligible participants were enrolled and randomized into three groups in a ratio of 1:1:1 to receive a single dose of one of three manufacturing lots of IIV4. Serum samples were collected before and 28 days after vaccination for hemagglutination inhibition (HI) antibody testing. Safety data were collected for up to 28 days after vaccination. The primary objective was to evaluate the lot-to-lot consistency of immune response as assessed by the geometric mean titer (GMT) of HI antibody at 28 days after vaccination., Results: Between November 27, 2022 and December 18, 2022, 1260 eligible participants were enrolled, with similar participant demographics among groups. Immune responses after vaccination were comparable across groups, with the 95% confidence intervals (CIs) of GMT ratios for all 4 strains falling into the equivalence criterion of (0.67, 1.5). The seroconversion rates (SCRs) and seroprotection rates (SPRs) met the US Center or Biologics Evaluation and Research (CBER) criteria for all strains for each lot (lower limit of 95% CI of SCR ≥ 40% and SPR ≥ 70%). The incidences of solicited and unsolicited adverse reactions were similar among three groups, most of which (91.9%) were mild or moderate in severity. A total of 11 serious adverse events were reported during the study, and all were considered unrelated to vaccination., Conclusion: The three manufacturing lots of IIV4 demonstrated consistent immunogenicity. IIV4 can elicit satisfactory immune responses for all four strains and no safety concerns were identified., Clinical Trial Registration: Identifier No. NCT05512494., Competing Interests: Declaration of competing interest Yuwei Li, Danyu and Jieru Wang are employed by Sinovac Biotech Co., Ltd. Xinyi Yang, and Siliang Zhou are employed by Sinovac Life Sciences Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pyruvate dehydrogenase complex is a crucial enzyme involved in the oxidation of glucose. It is regulated by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase. Studies have demonstrated that pyruvate dehydrogenase kinase 1 (PDHK1), a key enzyme in glucose metabolism, behaves like oncogenes. It is highly expressed in tumors and is associated with poor patient prognosis. However, there is limited research on how PDHK1 affects immune cell function. We have established a model of natural killer (NK) cell exhaustion to investigate the impact of dichloroacetate (DCA) on NK cell function. The production of Granzyme B, IFN-γ, TNF-α, and CD107a by NK cells was explored by flow cytometry. The real-time live cell imaging system was used to monitor the ability of NK cells against tumor cells. The Seahorse analyzer was utilized to measure the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of NK cells. The mouse model was used to investigate the potential of combining DCA with adjuvant NK cell infusion. Our study demonstrated that the hepatocellular carcinoma (HCC) microenvironment mediated NK cellular exhaustion, high expression of PDHK1 and reduced cytokine secretion. We discovered that the PDHK1 inhibitor DCA enhances the activity and function of exhausted NK cells infiltrating the tumor microenvironment. Furthermore, in a subcutaneous HCC mouse model, DCA combined with NK cell treatment resulted in retarding cancer progression. This study indicates the potential of DCA in rescuing NK cell exhaustion and eliciting anti-tumor immunity.

Systemic lupus erythematosus (SLE) is recognized as a prevalent autoimmune disorder characterized by a multifaceted pathogenesis potentially influenced by a combination of environmental factors, genetic predisposition, and hormonal regulation. The continuous study of immune system activation is especially intriguing. Analysis of blood samples from individuals with SLE reveals an abnormal increase in interferon levels, along with the existence of anti-double-stranded DNA antibodies. This evidence suggests that the development of SLE may be initiated by innate immunity. The presence of abnormal dsDNA fragments can activate DNA sensors within cells, particularly immune cells, leading to the initiation of downstream signaling cascades that result in the upregulation of relevant cytokines and the subsequent initiation of adaptive immune responses, such as B cell differentiation and T cell activation. The intricate pathogenesis of SLE results in DNA sensors exhibiting a wide range of functions in innate immune responses that are subject to variation based on cell types, developmental processes, downstream effector signaling pathways and other factors. The review aims to reorganize how DNA sensors influence signaling pathways and contribute to the development of SLE according to current studies, with the aspiration of furnishing valuable insights for future investigations into the pathological mechanisms of SLE and potential treatment approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Vasculogenic mimicry (VM) induced by Epstein-Barr virus (EBV) infection plays an important role in resistance to anti-vascular endothelial growth factor (VEGF) therapy in EBV-associated epithelial cancers; however, the interaction between VM and the immune microenvironment has not been systematically investigated. Methods: IHC and multiplex IHC analysis the relationships among tumour-associated macrophage (TAM), VM and EBV infection in EBV-associated epithelial cancer biopsies. In vitro and in vivo evidence using CRISPR-Cas9 system engineered EBV-infected epithelial cancer cells and mouse models support functional role and mechanism for M2c-like macrophages in the VM formation. The prediction of VM in the effectiveness of anti-angiogenic agent was analysed using clinical datasets. Results: EBV-associated epithelial cancer biopsies revealed that infiltration of the TAM surrounding the VM is closely associated with EBV infection. AKT/mTOR/HIF-1α pathway in EBV-infected epithelial cancer cells control the secretion of CCL5 and CSF-1, enabling the recruitment of monocytes and their differentiation into M2c macrophages which promote VM formation by MMP9. Combination of anti-angiogenesis agents and HIF-1α inhibitor caused marked decreases in CD31-positive micro-vessels, VM, and M2c-like macrophages. VM scores can be used as biomarkers to predict the efficacy of anti-angiogenic agent therapy in EBV-associated epithelial cancers. Conclusions: Our findings define a secretory cross-talk between tumour cells and the immune microenvironment in EBV-associated epithelial cancer, revealing an unexpected role of EBV in epithelial cancer cells, controlling VM formation via M2c-like macrophages., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Stroke is a globally dangerous disease capable of causing irreversible neuronal damage with limited therapeutic options. Meldonium, an inhibitor of carnitine-dependent metabolism, is considered an anti-ischemic drug. However, the mechanisms through which meldonium improves ischemic injury and its potential to protect neurons remain largely unknown., Methods: A rat model with middle cerebral artery occlusion (MCAO) was used to investigate meldonium's neuroprotective efficacy in vivo. Infarct volume, neurological deficit score, histopathology, neuronal apoptosis, motor function, morphological alteration and antioxidant capacity were explored via 2,3,5-Triphenyltetrazolium chloride staining, Longa scoring method, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, rotarod test, transmission electron microscopy and Oxidative stress index related kit. A primary rat hippocampal neuron model subjected to oxygen-glucose deprivation reperfusion was used to study meldonium's protective ability in vitro. Neuronal viability, mitochondrial membrane potential, mitochondrial morphology, respiratory function, ATP production, and its potential mechanism were assayed by MTT cell proliferation and cytotoxicity assay kit, cell-permeant MitoTracker ® probes, mitochondrial stress, real-time ATP rate and western blotting., Results: Meldonium markedly reduced the infarct size, improved neurological function and motor ability, and inhibited neuronal apoptosis in vivo. Meldonium enhanced the morphology, antioxidant capacity, and ATP production of mitochondria and inhibited the opening of the mitochondrial permeability transition pore in the cerebral cortex and hippocampus during cerebral ischemia-reperfusion injury (CIRI) in rats. Additionally, meldonium improved the damaged fusion process and respiratory function of neuronal mitochondria in vitro. Further investigation revealed that meldonium activated the Akt/GSK-3β signaling pathway to inhibit mitochondria-dependent neuronal apoptosis., Conclusion: Our study demonstrated that meldonium shows a neuroprotective function during CIRI by preserving the mitochondrial function, thus prevented neurons from apoptosis., (© 2024. The Author(s).)

Both the phyllosphere and rhizosphere are inhabited by different kinds of microorganisms that are closely related to plant growth and health. However, it is not clear whether disease-resistant cultivars shape the microbiome to facilitate disease resistance. In this study, significant differences were found in the aboveground and belowground bacterial communities of disease-resistant and disease-susceptible cultivars grown in the same kiwifruit orchard. The phyllosphere of the resistant cultivar 'Wanjin' showed greater enrichment of Pseudomonas spp. and Sphingomonas spp. than the susceptible cultivar 'Donghong'. The rhizosphere microbes of 'Wanjin' were less affected by field location, with significantly greater bacterial abundance than those of 'Donghong' and more bacteria with potential biocontrol properties. Pseudomonas syringae pv. actinidiae ( Psa ) infection significantly affected the microbiome of the phyllosphere of kiwifruit plants, especially that of 'Donghong'. Resistant and susceptible kiwifruit cultivars exhibit distinct beneficial microbial recruitment strategies under Psa challenge. The phyllosphere of 'Donghong' in Jinzhai was enriched with Sphingomonas spp. and Pantoea spp. under Psa infection, while the rhizosphere of 'Wanjin' was enriched with Sphingomonas spp. and Novosphingobium spp. We further identified five key biomarkers within the microbial community associated with Psa infection. Inoculation experiments showed that Lysobacter sp. R34, Stenotrophomonas sp. R31, Pseudomonas sp. R10 and RS54, which were isolated from belowground compartments of 'Wanjin', could positively affect plant performance under Psa challenge. The combination use of Pseudomonas sp. R10 and Stenotrophomonas sp. R31 significantly improve the management of kiwifruit canker. Our findings provided novel insights into soil-microbe-plant interactions and the role of microbes in plant disease resistance and susceptibility., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

The technology of combining multiple emission centers to exploit white-light-emitting (WLE) materials by taking advantage of porous metal-organic frameworks (MOFs) is mature, but preparing undoped WLE MOFs remains a challenge. Herein, a pressure-treated strategy is reported to achieve efficient white photoluminescence (PL) in undoped [Zn(Tdc)(py)] n nanocrystals (NCs) at ambient conditions, where the Commission International del'Eclairage coordinates and color temperature reach (0.31, 0.37) and 6560 K, respectively. The initial [Zn(Tdc)(py)] n NCs exhibit weak-blue PL consisting of localized excited (LE) and planarized intramolecular charge transfer (PLICT) states. After pressure treatment, the emission contributions of LE and PLICT states are balanced by increasing the planarization of subunits, thereby producing white PL. Meanwhile, the reduction of nonradiative decay triggered by the planarized structure results in 5-fold PL enhancement. Phosphor-converted light-emitting diodes based on pressure-treated samples show favorable white-light characteristics. The finding provides a new platform for the development of undoped WLE MOFs.

Chemotherapy, particularly with oxaliplatin, is a key treatment for advanced gastric cancer (GC), and exosomes derived from human bone marrow mesenchymal stem cells (hBM-MSCs) play a vital role in the tumor microenvironment. The study aims to elucidate the previously unexplored role of exosomes derived from hBM-MSCs in GC tumorigenesis, especially under the influence of chemotherapy. We conducted an experimental study, utilizing miRNA sequencing and biological experiments, to analyze the tumorigenicity of exosomal miR-424-3p secreted by hBM-MSCs and its target gene RHOXF2 in GC cell lines. The results were confirmed through experimentation using a xenograft mouse model. This study demonstrated the role of hBM-MSCs in the GC microenvironment, focusing on their epithelial-mesenchymal transition (EMT) facilitation through exosomes, which led to enhanced tumorigenicity in GC cells. Intriguingly, this pro-tumor effect was abrogated when hBM-MSCs were treated with oxaliplatin. Exosomal miRNA sequencing revealed that oxaliplatin can upregulate the levels of miR-424-3p in exosomes secreted by hBM-MSCs, thereby inhibiting the EMT process in GC cells. Furthermore, miR-424-3p was identified to target and downregulate RHOXF2 expression, impeding the malignant behavior of GC cells both in vitro and in the mouse model. These findings uncover a potential hidden mechanism of oxaliplatin's anti-tumor action and propose the delivery of miR-424-3p via exosomes as a promising avenue for anti-tumor therapy., (© 2024. The Author(s).)

Background: Congenital cataracts, which can arise due to a combination of factors like environmental influences and genetic predisposition, significantly impact children's visual health globally. The occurrence rate of congenital cataracts varies from 0. 63 to 9.74 per 10,000 births. There are 7.4 instances per 10,000 children, with the highest occurrence seen in Asia. Symptoms of the disease include clouding of the lens and visual impairment. Timely identification of the condition plays a crucial role in the management and outlook of pediatric patients., Objective: This investigation aimed to discover causative mutations in four separate Chinese family lineages., Methods: The detailed clinical data and family history of four Chinese families with autosomal dominant congenital cataracts were carefully documented. Examination of the Whole Exome Sequencing was utilized to identify the genetic anomalies present in the familial cases. Subsequent validation of the identified mutations was carried out using PCR and Sanger sequencing. Following this, various computational predictive programs were utilized to evaluate how the mutations impact the structure and function of the protein., Results: The sequencing results reveal four potential disease-causing mutations: c.436G > A (p.V146M) of CRYBB2 Family 1, c.26G > T (p.R9I) of GJA3 in family 2, c.227G > A (p.R76H) of GJA8 in family 3, c.-168G > T of FTL in family 4. Among them, the causative mutation in Family GJA3 is novel, and Family FTL is a rare cataract syndrome. These familial mutations showed complete co-segregation with the affected individuals, with no presence in unaffected family members or the 100 controls. Several bioinformatic prediction tools also support the likely pathogenicity of these mutations., Conclusion: Our findings expand the mutational and phenotypic spectrum of genes associated with congenital cataracts and provide clues to the pathogenesis of congenital cataracts. These data also demonstrate the importance of NGS technology for the molecular diagnosis of congenital cataract patients., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

The deep molecular generative model has recently become a research hotspot in pharmacy. This paper analyzes a large number of recent reports and reviews these models. In the central part of this paper, four compound databases and two molecular representation methods are compared. Five model architectures and applications for deep molecular generative models are emphatically introduced. Three evaluation metrics for model evaluation are listed. Finally, the limitations and challenges in this field are discussed to provide a reference and basis for developing and researching new models published in future., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Recent studies have introduced the weight-adjusted waist circumference index (WWI) as a viable obesity indicator that may better reflect centripetal obesity and its associated risks. In examining the connection between WWI and prostate-specific antigen (PSA), this study leveraged data from the National Health and Nutrition Examination Survey 2003-2010, including 5732 participants. Our initial analysis indicated a significant positive association between WWI and PSA levels. However, subsequent models that adjusted for covariates such as age, race, and a range of metabolic and cardiovascular health-related factors revealed that the strength and significance of this relationship were attenuated. Model 1 showed a highly significant correlation (p < 0.0001). Yet, in Model 2, which accounted for age and race, the association softened (p = 0.0520). Moreover, when a full spectrum of health covariates was included in Model 3, the association was no longer significant (p = 0.9775). These findings suggest that while an unadjusted correlation exists, its potential use as a diagnostic predictor is limited without considering the broader health context. Therefore, it is crucial to review such data with multiple considerations in mind, and extensive attention should be paid to the evaluation of covariates., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill" strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to "shock" the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The treatment of sepsis caused by multidrug-resistant (MDR) Gram-negative bacterial infections remains challenging. With these pathogens exhibiting resistance to carbapenems and new generation cephalosporins, the traditional antibiotic polymyxin B (PMB) has reemerged as a critical treatment option. However, its severe neurotoxicity and nephrotoxicity greatly limit the clinical application. Therefore, we designed negatively charged high-density lipoprotein (HDL) mimicking nanodiscs as a PMB delivery system, which can simultaneously reduce toxicity and enhance drug efficacy. The negative charge prevented the PMB release in physiological conditions and binding to cell membranes, significantly reducing toxicity in mammalian cells and mice. Notably, nanodisc-PMB exhibits superior efficacy than free PMB in sepsis induced by carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Nanodisc-PMB shows promise as a treatment for carbapenem-resistant Gram-negative bacterial sepsis, especially caused by Acinetobacter baumannii, and the nanodiscs could be repurposed for other toxic antibiotics as an innovative delivery system. STATEMENT OF SIGNIFICANCE: Multidrug-resistant Gram-negative bacteria, notably carbapenem-resistant Acinetobacter baumannii, currently pose a substantial challenge due to the scarcity of effective treatments, rendering Polymyxins a last-resort antibiotic option. However, their therapeutic application is significantly limited by severe neurotoxic and nephrotoxic side effects. Prevailing polymyxin delivery systems focus on either reducing toxicity or enhancing bioavailability yet fail to simultaneously achieve both. In this scenario, we have developed a distinctive HDL-mimicking nanodisc for polymyxin B, which not only significantly reduces toxicity but also improves efficacy against Gram-negative bacteria, especially in sepsis caused by CRAB. This research offers an innovative drug delivery system for polymyxin B. Such advancement could notably improve the therapeutic landscape and make a significant contribution to the arsenal against these notorious pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Native ants have long been considered for their potential to suppress the red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae), a highly invasive and destructive species. However, the knowledge in this field is limited to behavioral observations of a few related native ants. In this study, by setting up a series of ant combinations of three native ants, i.e., Monomorium chinense Santschi, the robust crazy ant Nylanderia bourbonica Forel, and Iridomyrmex anceps Roger, with S. invicta , we observed the aggression levels and mortality rates. Using baited vials, we also investigated the abundance of native ants in four types of habitats in Eastern China that are preferred by S. invicta (woodland, green belts on roadsides, grassland, and farmland), as well as their seasonal abundance when co-existing with S. invicta and their spatial distribution before and after control of S. invicta . We found that M. chinense and N. bourbonica show a degree of aggression towards S. invicta and can kill substantial proportions of S. invicta under laboratory conditions, but I. anceps does not. Both M. chinense and N. bourbonica can occur in each type of habitat investigated and are more abundant in green belts (particularly lawns with turf) and grasslands relative to other habitats. In grasslands with S. invicta , M. chinense maintained a low density before early July; however, its abundance increased thereafter and reached a peak in September. N. bourbonica also had a low density early in the season and increased steadily from April. Its abundance began to decrease substantially from November. In grasslands invaded by S. invicta , both M. chinense and N. bourbonica were restricted to sites close to the margins before S. invicta was controlled; however, they spread to a larger range within a few weeks after control of S. invicta . In conclusion, M. chinense and N. bourbonica have the potential to suppress S. invicta invasion in habitats that are abundant with these two native ants.

The cost-effective and green separation of dye pollutants from wastewater is of great importance in environmental remediation. Industrial seaweed residue (SR), as a low-cost cellulose source, was used to produce carboxylated nanorized-SR (NSR) via oxalic acid (OA)-water pretreatments followed by ultrasonic disintegration. Fourier transform infrared spectroscopy, X-ray polycrystalline diffraction, nitrogen isotherms, scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, X-ray photoelectron spectrometry, particle charge detection, zeta potential and retro titration experiments were utilized to explore the physiochemical properties of samples. The NSRs with carboxyl content of 4.58-6.73 mmol g -1 were prepared using 10-60% OA-water pretreatment. In the case of 20% OA-water pretreatment, the highest NSR yield (73.9%) and nanocellulose content (80.2%) were obtained. Through self-assembly induced by the electrostatic interaction, magnetic NSR composite adsorbents (MNSRs) were prepared with the combination of NSR and Fe 3 O 4 nanoparticles (NPs). The carboxylated NSR with negative charge demonstrated good affinity for Fe 3 O 4 NPs. The Fe 3 O 4 NPs were perfectly microencapsulated with the NSR when the NSR/Fe 3 O 4 mass ratio was higher than 1/1. The adsorption properties of the MNSR for methylene blue (MB) removal from aqueous solution were investigated. The adsorbent with NSR/Fe 3 O 4 mass ratio of 1/1 (MNSR1/1) exhibited optimum performance in terms of the magnetic properties and adsorption capacity. The MNSR1/1 showed high adsorption ability in a pH ≥7 environment. According to the Langmuir fitting, the maximum adsorption capacity of MNSR1/1 for MB reached 184.25 mg g -1 . The adsorption of MB complies with the pseudo-second-order kinetic model. MNSR1/1 still maintained good adsorption properties after the fifth cycle of adsorption-desorption. MNSR1/1 could selectively adsorb cationic dye ( i.e. , MB and methyl violet) from wastewater, with hydrogen bonding and electrostatic interaction as the main force., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: The emergency response to the COVID-19 pandemic may disrupt hospital management activities of antimicrobial resistance (AMR). This study aimed to determine the changing AMR trend over the period in China when stringent COVID-19 response measures were implemented., Methods: This retrospective study was conducted in a designated hospital for COVID-19 patients in Guangzhou, China from April 2018 to September 2021. The prevalence of 13 antimicrobial-resistant bacteria was compared before and after the COVID-19 responses through Chi-square tests. Interrupted time series (ITS) models on the weekly prevalence of AMR were established to determine the changing trend. Controlled ITS models were performed to compare the differences between subgroups., Results: A total of 10,134 isolates over 1,265 days were collected. And antimicrobial-resistant strains presented in 38.6% of the testing isolates. The weekly AMR prevalence decreased by 0.29 percentage point (95% CI [0.05-0.80]) after antimicrobial stewardship (AMS) policy, despite an increase in the prevalence of penicillin-resistant Streptococcus pneumoniae (from 0/43 to 15/43, p  < 0.001), carbapenem-resistant Escherichia coli (from 20/1254 to 41/1184, p  = 0.005), and carbapenem-resistant Klebsiella pneumoniae (from 93/889 to 114/828, p  = 0.042). And the changing trend did not vary by gender (male vs. female), age (<65 vs. ≥65 years), service setting (outpatient vs. inpatient), care unit (ICU vs. non-ICU), the primary site of infection (Lung vs. others), and Gram type of bacteria (positive vs. negative)., Conclusion: The response to COVID-19 did not lead to an increase in overall AMR; however, it appears that management strategy on the prudent use of antimicrobials likely contributed to a sizable long-term drop. The frequency of several multidrug-resistant bacteria continues to increase after the COVID-19 epidemic. It is crucial to continue to monitor AMR when COVID-19 cases have surged in China after the relaxation of restriction measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Yang, Liu, Liu, Shi, Zeng, Xia, Li, Zhao, Yang, Li, Hu and Yang.)

The effects of dynamic high-pressure microfluidization (DHPM at 400 MPa) and heat treatment (HT) on the microbial inactivation, quality parameters, and flavor components of not-from-concentrate (NFC) cucumber juice were investigated. Total aerobic bacteria, yeasts and molds were not detected in the 400 MPa-treated cucumber juice. Total phenolic content increased by 16.2% in the 400 MPa-treated cucumber juice compared to the control check (CK). The significant reduction in pulp particle size (volume peak decreasing from 100-1000 μm to 10-100 μm) and viscosity increased the stability of the cucumber juice while decreasing the fluid resistance during processing. HT decreased the ascorbic acid content by 25.9% ( p < 0.05), while the decrease in ascorbic acid content was not significant after 400 MPa treatment. A total of 59 volatile aroma substances were identified by gas chromatography-ion mobility spectrometry (GC-IMS), and a variety of characteristic aroma substances (i.e., valeraldehyde, ( E )-2-hexenal, ( E )-2-nonenal, and ( E , Z )-2,6-nonadienal, among others) were retained after treatment with 400 MPa. In this study, DHPM technology was innovatively applied to cucumber juice processing with the aim of providing a continuous non-thermal processing technology for the industrial production of cucumber juice. Our results provide a theoretical basis for the application of DHPM technology in cucumber juice production.

Ferroptosis induces significant changes in mitochondrial morphology, including membrane condensation, volume reduction, cristae alteration, and outer membrane rupture, affecting mitochondrial function and cellular fate. Recent reports have described the intrinsic cellular iron metabolism and its intricate connection to ferroptosis, a significant kind of cell death characterized by iron dependence and oxidative stress regulation. Furthermore, updated molecular insights have elucidated the significance of mitochondria in ferroptosis and its implications in various cancers. In the context of cancer therapy, understanding the dual role of anastasis and ferroptosis in chemoresistance is crucial. Targeting the molecular pathways involved in anastasis may enhance the efficacy of ferroptosis inducers, providing a synergistic approach to overcome chemoresistance. Research into how DNA damage response (DDR) proteins, metabolic changes, and redox states interact during anastasis and ferroptosis can offer new insights into designing combinatorial therapeutic regimens against several cancers associated with stemness. These treatments could potentially inhibit anastasis while simultaneously inducing ferroptosis, thereby reducing the likelihood of cancer cells evading death and developing resistance to chemotherapy. The objective of this study is to explore the intricate interplay between anastasis, ferroptosis, EMT and chemoresistance, and immunotherapeutics to better understand their collective impact on cancer therapy outcomes. We searched public research databases including google scholar, PubMed, relemed, and the national library of medicine related to this topic. In this review, we discussed the interplay between the tricarboxylic acid cycle and glycolysis implicated in modulating ferroptosis, adding complexity to its regulatory mechanisms. Additionally, the regulatory role of reactive oxygen species (ROS) and the electron transport chain (ETC) in ferroptosis has garnered significant attention. Lipid metabolism, particularly involving GPX4 and System Xc- plays a significant role in both the progression of ferroptosis and cancer. There is a need to investigate the intricate interplay between anastasis, ferroptosis, and chemoresistance to better understand cancer therapy clinical outcomes. Integrating anastasis, and ferroptosis into strategies targeting chemoresistance and exploring its potential synergy with immunotherapy represent promising avenues for advancing chemoresistant cancer treatment. Understanding the intricate interplay among mitochondria, anastasis, ROS, and ferroptosis is vital in oncology, potentially revolutionizing personalized cancer treatment and drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Lu, Beeraka, Efetov, Enikeev, Fu, Yang, Basappa, He and Li.)

Objectives: The COVID-19 pandemic has posed a significant threat to the global healthcare system, presenting a major challenge to antimicrobial stewardship worldwide. This study aimed to provide a comprehensive and up-to-date picture of global antimicrobial resistance (AMR) and antibiotic use in COVID-19 patients., Methods: We conducted a systematic review to determine the prevalence of AMR and antibiotic usage among COVID-19 patients receiving treatment in healthcare facilities. Our search encompassed the PubMed, Web of Science, Embase, and Scopus databases, spanning studies published from December 2019 to May 2023. We utilized random-effects meta-analysis to assess the prevalence of multidrug-resistant organisms (MDROs) and antibiotic use in COVID-19 patients, aligning with both the WHO's priority list of MDROs and the AWaRe list of antibiotic products. Estimates were stratified by region, country, and country income. Meta-regression models were established to identify predictors of MDRO prevalence and antibiotic use in COVID-19 patients. The study protocol was registered with PROSPERO (CRD 42023449396)., Results: Among the 11,050 studies screened, 173 were included in the review, encompassing a total of 892,312 COVID-19 patients. MDROs were observed in 42.9% (95% CI 31.1-54.5%, I 2 = 99.90%) of COVID-19 patients: 41.0% (95% CI 35.5-46.6%) for carbapenem-resistant organisms (CRO), 19.9% (95% CI 13.4-27.2%) for methicillin-resistant Staphylococcus aureus (MRSA), 24.9% (95% CI 16.7-34.1%) for extended-spectrum beta-lactamase-producing organisms (ESBL), and 22.9% (95% CI 13.0-34.5%) for vancomycin-resistant Enterococcus species (VRE), respectively. Overall, 76.2% (95% CI 69.5-82.9%, I 2 = 99.99%) of COVID-19 patients were treated with antibiotics: 29.6% (95% CI 26.0-33.4%) with "Watch" antibiotics, 22.4% (95% CI 18.0-26.7%) with "Reserve" antibiotics, and 16.5% (95% CI 13.3-19.7%) with "Access" antibiotics. The MDRO prevalence and antibiotic use were significantly higher in low- and middle-income countries than in high-income countries, with the lowest proportion of antibiotic use (60.1% (95% CI 52.1-68.0%)) and MDRO prevalence (29.1% (95% CI 21.8-36.4%)) in North America, the highest MDRO prevalence in the Middle East and North Africa (63.9% (95% CI 46.6-81.2%)), and the highest proportion of antibiotic use in South Asia (92.7% (95% CI 90.4-95.0%)). The meta-regression identified antibiotic use and ICU admission as a significant predictor of higher prevalence of MDROs in COVID-19 patients., Conclusions: This systematic review offers a comprehensive and current assessment of MDRO prevalence and antibiotic use among COVID-19 patients in healthcare facilities. It underscores the formidable challenge facing global efforts to prevent and control AMR amidst the backdrop of the COVID-19 pandemic. These findings serve as a crucial warning to policymakers, highlighting the urgent need to enhance antimicrobial stewardship strategies to mitigate the risks associated with future pandemics., Competing Interests: Declaration of Competing Interest All authors declare no competing interests. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)