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Abstract Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut–lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50–100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial–mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs (Ptbp1 flfl) and PTBP1-knockout (PTBP1-KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP.

Quantification of runoff change is vital for water resources management, especially in arid or semiarid areas. This study used the Soil and Water Assessment Tool (SWAT) distributed hydrological model to simulate runoff in the upper reaches of the Hailar Basin (NE China) and to analyze quantitatively the impacts of climate change and land-use change on runoff by setting different scenarios. Two periods, i.e., the reference period (before 1988) and the interference period (after 1988), were identified based on long-term runoff datasets. In comparison with the reference period, the contribution rates of both climate change and land-use change to runoff change in the Hailar Basin during the interference period were 83.58% and 16.42%, respectively. The simulation analysis of climate change scenarios with differential precipitation and temperature changes suggested that runoff changes are correlated positively with precipitation change and that the impact of precipitation change on runoff is stronger than that of temperature. Under different economic development scenarios adopted, land use was predicted to have a considerable impact on runoff. The expansion of forests within the basin might induce decreased runoff owing to enhanced evapotranspiration.

Abstract Background The advancement of nanotechnology underscores the imperative need for establishing in silico predictive models to assess safety, particularly in the context of chronic respiratory afflictions such as lung fibrosis, a pathogenic transformation that is irreversible. While the compilation of predictive descriptors is pivotal for in silico model development, key features specifically tailored for predicting lung fibrosis remain elusive. This study aimed to uncover the essential predictive descriptors governing nanoparticle-induced pulmonary fibrosis. Methods We conducted a comprehensive analysis of the trajectory of metal oxide nanoparticles (MeONPs) within pulmonary systems. Two biological media (simulated lung fluid and phagolysosomal simulated fluid) and two cell lines (macrophages and epithelial cells) were meticulously chosen to scrutinize MeONP behaviors. Their interactions with MeONPs, also referred to as nano-bio interactions, can lead to alterations in the properties of the MeONPs as well as specific cellular responses. Physicochemical properties of MeONPs were assessed in biological media. The impact of MeONPs on cell membranes, lysosomes, mitochondria, and cytoplasmic components was evaluated using fluorescent probes, colorimetric enzyme substrates, and ELISA. The fibrogenic potential of MeONPs in mouse lungs was assessed by examining collagen deposition and growth factor release. Random forest classification was employed for analyzing in chemico, in vitro and in vivo data to identify predictive descriptors. Results The nano-bio interactions induced diverse changes in the 4 characteristics of MeONPs and had variable effects on the 14 cellular functions, which were quantitatively evaluated in chemico and in vitro. Among these 18 quantitative features, seven features were found to play key roles in predicting the pro-fibrogenic potential of MeONPs. Notably, IL-1β was identified as the most important feature, contributing 27.8% to the model’s prediction. Mitochondrial activity (specifically NADH levels) in macrophages followed closely with a contribution of 17.6%. The remaining five key features include TGF-β1 release and NADH levels in epithelial cells, dissolution in lysosomal simulated fluids, zeta potential, and the hydrodynamic size of MeONPs. Conclusions The pro-fibrogenic potential of MeONPs can be predicted by combination of key features at nano-bio interfaces, simulating their behavior and interactions within the lung environment. Among the 18 quantitative features, a combination of seven in chemico and in vitro descriptors could be leveraged to predict lung fibrosis in animals. Our findings offer crucial insights for developing in silico predictive models for nano-induced pulmonary fibrosis.

Abstract To explore the effects of methionine (Met) supplementation on cognitive dysfunction and the associated mechanisms in aging mice. The mice were administrated 0.15 g/kg/day D-galactose subcutaneously and fed a normal (0.86% Met) or a Met-supplemented diet (1.72% Met) for 11 weeks. Behavioral experiments were conducted, and we measured the plasma metabolite levels, hippocampal and plasma redox and inflammatory states, and hippocampal transsulfuration pathway-related parameters. Met supplementation prevented aging-induced anxiety and cognitive deficiencies, and normalized the plasma levels of multiple systemic metabolites (e.g., betaine, taurine, and choline). Furthermore, dietary Met supplementation abolished oxidative stress and inflammation, selectively modulated the expression of multiple cognition-related genes and proteins, and increased flux via the transsulfuration pathway in the hippocampi of aging mice, with significant increase in H2S and glutathione production. Our findings suggest that dietary Met supplementation prevented cognitive deficiencies in aging mice, probably because of increased flux via the transsulfuration pathway.

Abstract Background The primary aim of this study was to quantitatively analysis the acetabular morphological feature and 2D/3D coverage of the Crowe IV DDH hip, dividing into subgroups by the false acetabulum. The secondary aim was to propose a 3D bone mapping to determine acetabular bone defect analysis from the perspective of the implanted simulation. Methods A total of 53 Crowe IV hips (27 hips without the false acetabulum in IVa group and 26 hips in IVb group) and 40 normal hips met the inclusion criteria and were retrospectively evaluated. Firstly, the anatomical size and volume of the acetabulum were measured quantitatively. Secondly, through the simulated implantation, morphological assessments of the true acetabulum included Cup-CE, Cup-Sharp, acetabular anteversion angle, and thickness of the medial wall. Last, Acetabular sector angles (ASAs) and the component coverage ratio were measured to provide coverage indices. Further, 3D bone mapping visualization was applied to determine the uncovered component portion distribution. Results The anatomic shape and volume of the acetabular triangle were significantly smaller in Crowe IV hips. At the level of the acetabular component center, IVb acetabula were found to be more anteverted and abductive, with smaller Cup-CE and larger Cup-Sharp angles. The coverage sector angles in Crowe IVa hips were larger in the anterosuperior and superior direction, while smaller in the posterosuperior and posterior direction, with no subgroup difference in total component coverage. Both 3D bone mapping and correlation analysis reveal that posterosuperior and posterior bone stock is highly associated with the component coverage. Conclusion With the presence of the false acetabulum, there existed acetabular anteversion and segmental coverage distinctions between subgroups. During the acetabular reconstruction, management of posterosuperior and posterior bone stock was important for ideal component coverage.

Background/purpose: External root resorption is a main side effect of orthodontic treatment and is more likely to occur on the pression side than the tension side. To explore the potential protective mechanisms on the tension side, this study investigated the influence of mechanical tension on cementoblast mineralization and elucidated the role of autophagy in mediating this process. Materials and methods: Mechanical tension was applied to cementoblasts using iStrain. The expression of mineralization-related and autophagy-related markers was detected by qRT-PCR, Western blot analysis, and immunofluorescence staining. RNA sequencing identified key regulators. Immunohistochemical staining assessed related markers expression in in vivo experiments. Results: Applying tension to cementoblasts increased mineralization-related gene expression in a force-dependent and time-dependent manner. The immunohistochemical staining result of in vivo experiments supported these findings, demonstrating elevated expression of mineralization markers under tension. Mechanical tension also enhanced autophagic activity in cementoblasts, which was demonstrated by the results of qRT-PCR, Western blot analysis, immunofluorescence staining, and in vivo experiments. Suppression of autophagy with chloroquine attenuated the mineralization of cementoblasts induced by tension stimulus. RNA-seq identified Postn as a key regulator, and the knockdown of Postn impaired the mechanical tension-promoted mineralization of cementoblasts. Conclusion: This study proposed the tension-induced promotion in mineralization of cementoblasts and emphasized the mediating role of autophagy in this process. Postn, a mediator connecting autophagy and mineralization, was identified as a key regulator. These discoveries helped elucidate orthodontic-related microprocesses on tooth roots and offer potential targets for therapeutic interventions to prevent and restore external root resorption clinically.

This study aims to explore the effects of fish collagen peptides (FCP) supplementation on skeletal muscle injury in high-fat (HF) diet mice and their possible mechanisms. Experimental mice were fed a normal diet (4 % fat), HF diet (20 % fat), or FCP diet (20 % fat and 1 % FCPs) for 22 consecutive weeks. Results show that FCP supplementation improves skeletal muscle motor function and histomorphology, and lipid levels; promotes protein synthesis, and inhibits protein degradation in skeletal muscle. Moreover, FCP supplementation also improves mitochondrial biogenesis, promotes energy metabolism and ATP production. Furthermore, FCP supplementation increases antioxidant defenses in the thyroid and skeletal muscle, improves thyroid morphological structure, promotes the synthesis and secretion of thyroid hormones, and enhances the actions of thyroid hormones on its receptor organ skeletal muscle. Cumulatively, these findings indicate that FCP supplementation can alleviate skeletal muscle injury induced by an HF diet associated with thyroid function recovery.

The assessment of freeze desalination (FD) efficiency is lagging behind due to the lack of an effective means of determining ice total dissolved solid (TDS). In this paper, an ice TDS prediction model was constructed by utilizing the law of conservation of matter (LCMat) and conservation of mass (LCMas) in the icing process. It was concluded that the average TDS ice crystals in any icing process was correlated with the TDS of the raw (concentrated) water at the starting of freezing, the salt mass change rate of the concentrate water, and the volume of ice crystals. A one-way FD test was carried out using the saltwater from South Xinjiang, and the exponential equation model and linear equation model of LCMat-LCMas were derived, and the simulation accuracy of LCMat-LCMas was verified by using the test data. The results show that the model has high prediction accuracy. The exponential equation model is suitable for predicting the ice TDS for ice with thickness within 15 cm, and the linear equation is suitable for predicting the ice crystal TDS for ice thicker than 15 cm. Further validation of the model accuracy is needed for larger cooled areas and icing thicknesses, and multidirectional icing processes.

Abstract Background Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign bone tumor, it is also called “Nora’s lesion”. The lesion is characterized by heterotopic ossification of the normal bone cortex or parosteal bone. The etiology of BPOP is unclear and may be related to trauma. In most BPOPs, the lesion is not connected to the medullary cavity. Here we report an atypical case, characterized by reversed features compared to the typical BPOP, which demonstrated continuity of the lesion with the cavity. Case presentation An 11-year-old female child had a slow-growing mass on her right wrist for 8 months with forearm rotation dysfunction. Plain X-rays showed an irregular calcified mass on the right distal ulna, and computed tomography (CT) showed a pedunculated mass resembling a mushroom protruding into the soft tissue at the distal ulna. The medulla of this lesion is continuous with the medulla of the ulna. A surgical resection of the lesion, together with a portion of the ulnar bone cortex below the tumor was performed, and the final pathology confirmed BPOP. After the surgery, the child’s forearm rotation function improved significantly, and there was no sign of a recurrence at 1-year follow-up. Conclusion It is scarce for BPOP lesions to communicate with the medullary cavity. However, under-recognition of these rare cases may result in misdiagnosis or inappropriate treatment thereby increasing the risk of recurrence. Therefore, special cases where BPOP lesions are continuous with the medulla are even more important to be studied to understand better and master these lesions. Although BPOP is a benign tumor with no evidence of malignant transformation, the recurrence rate of surgical resection is high. We considered the possibility of this particular disease prior to surgery and performed a surgical resection with adequate safety margins. Regular postoperative follow-up is of utmost importance, without a doubt.

Abstract Background Mediation analysis is a powerful tool to identify factors mediating the causal pathway of exposure to health outcomes. Mediation analysis has been extended to study a large number of potential mediators in high-dimensional data settings. The presence of confounding in observational studies is inevitable. Hence, it’s an essential part of high-dimensional mediation analysis (HDMA) to adjust for the potential confounders. Although the propensity score (PS) related method such as propensity score regression adjustment (PSR) and inverse probability weighting (IPW) has been proposed to tackle this problem, the characteristics with extreme propensity score distribution of the PS-based method would result in the biased estimation. Methods In this article, we integrated the overlapping weighting (OW) technique into HDMA workflow and proposed a concise and powerful high-dimensional mediation analysis procedure consisting of OW confounding adjustment, sure independence screening (SIS), de-biased Lasso penalization, and joint-significance testing underlying the mixture null distribution. We compared the proposed method with the existing method consisting of PS-based confounding adjustment, SIS, minimax concave penalty (MCP) variable selection, and classical joint-significance testing. Results Simulation studies demonstrate the proposed procedure has the best performance in mediator selection and estimation. The proposed procedure yielded the highest true positive rate, acceptable false discovery proportion level, and lower mean square error. In the empirical study based on the GSE117859 dataset in the Gene Expression Omnibus database using the proposed method, we found that smoking history may lead to the estimated natural killer (NK) cell level reduction through the mediation effect of some methylation markers, mainly including methylation sites cg13917614 in CNP gene and cg16893868 in LILRA2 gene. Conclusions The proposed method has higher power, sufficient false discovery rate control, and precise mediation effect estimation. Meanwhile, it is feasible to be implemented with the presence of confounders. Hence, our method is worth considering in HDMA studies.

Abstract Introduction Over the past decade, numerous studies have described the types of pathogens and their antibiotic resistance patterns in patients with burn injuries in China; however, the findings have generally been inconsistent. We conducted a literature search and meta-analysis to summarize the infection spectra and antimicrobial resistance patterns in patients with burn injuries. Methods We searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Biomedical Literature, Wanfang, and Weipu databases for relevant articles published between January 2010 and December 2023. The DerSimonian–Laird random-effects model was used to estimate the proportions and 95% confidence intervals (CIs) of pathogens among Chinese patients with burn injuries. Meta-regression analyses were performed to explore differences in the proportions of pathogens among different subgroups and their resistance patterns. This study was registered with PROSPERO (CRD42024514386). Results The database searches yielded 2017 records; after removing duplicates and conducting initial screening, 219 articles underwent full-text screening. Ultimately, 60 studies comprising a total of 62,819 isolated strains reported the proportions of pathogens in patients with burn injuries and were included in this meta-analysis. Meta-analyses were conducted on 18 types of pathogens. The most common pathogens causing infections in Chinese patients with burn injuries were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus epidermidis. Similar results were observed in the subgroup analysis focusing on wound infections. Since 2015, there has been a significant decrease in the proportion of Pseudomonas aeruginosa (R 2 = 4.89%) and a significant increase in the proportion of Klebsiella pneumoniae (R 2 = 9.60%). In terms of antibiotic resistance, there has been a significant decrease in the resistance of Staphylococcus aureus to multiple antibiotics and an increasing trend in the resistance of Klebsiella pneumoniae. Conclusions We systematically summarized the epidemiological characteristics and antibiotic resistance patterns of pathogens among individuals suffering from burns in China, thus providing guidance for controlling wound infections and promoting optimal empirical antimicrobial therapy. The observed high levels of antibiotic resistance underscore the need for ongoing monitoring of antibiotic usage trends.

Study region: The source regions of the Yangtze and Yellow Rivers Study focus: The purpose of this study is to analyze the latest evolution trends of runoff and sediment load in the source areas of the Yangtze and Yellow Rivers, quantitatively attribute the evolution drivers of runoff and sediment load in the region by Structural Equation Model, and predict the future evolution trends. New hydrological insights for the region: The results showed that from 2000 to 2020, the runoff of the source region Yangtze and Yellow Rivers increased at rates of 2.56 × 108 m3/a and 5.98 × 108 m3/a, and the sediment load increased at rates of 33.24 × 104t/a and 36.82 × 104t/a, respectively. Attribution analysis found precipitation has the greatest impact on runoff and sediment changes. Although snowmelt is also an important factor, its contribution is still relatively small compared to precipitation. The vegetation in the region did not significantly reduce sediment under freeze-thaw conditions. The prediction results show that the runoff and sediment load in the region will continue to increase in the future. From 2025–2098, the runoff in the source area of the Yangtze River and the source area of the Yellow River will increase at a rate of 0.21–1.11 × 108 m3/a and 0.14–0.68 × 108 m3/a, and the sediment load will increase at a rate of 1.62–6.12 × 105t/a and 2.44–5.78 × 105t/a, respectively.

Background Ischemic stroke (IS) accounts large amount of stroke incidence. The aim of this study was to discover the risk and prognostic factors that affecting the occurrence of IS in hypertensive patients. Method Study data were obtained from the Medical Information Mart for Intensive Care (MIMIC)-IV database. To avoid biased factors selection process, several approaches were studied including logistic regression, elastic net regression, random forest, correlation analysis, and multifactor logistic regression methods. And seven different machine-learning methods are used to construct predictive models. The performance of the developed models was evaluated using AUC (Area Under the Curve), prediction accuracy, precision, recall, F1 score, PPV (Positive Predictive Value) and NPV (Negative Predictive Value). Interaction analysis was conducted to explore potential relationships between influential factors. Results The study included 92,514 hypertensive patients, of which 1746 hypertensive patients experienced IS. The Gradient Boosted Decision Tree (GBDT) model outperformed the other prediction model terms of prediction accuracy and AUC values in both ischemic and prognosis cases. By using the SHapley Additive exPlanations (SHAP), we found that a range of factors and corresponding interactions between factors are important risk factors for IS and its prognosis in hypertensive patients. Conclusion The study identified factors that increase the risk of IS and poor prognosis in hypertensive patients, which may provide guidance for clinical diagnosis and treatment.

Abstract Treatment strategies for hard tissue defects aim to establish a mineralized microenvironment that facilitates tissue remodeling. As a mineralized tissue, cementum shares a similar structure with bone and exhibits an excellent capacity to resist resorption under compression. Macrophages are crucial for mineralized remodeling; however, their functional alterations in the microenvironment of cementum remain poorly understood. Therefore, this study explores the mechanisms by which cementum resists resorption under compression and the regulatory roles of cementoblasts in macrophage functions. As a result, extracellular vesicles from compression‐loaded cementoblasts (Comp‐EVs) promote macrophage M2 polarization and enhance the clearance of apoptotic cells (efferocytosis) by 2‐ to 3‐fold. Local injection of Comp‐EVs relieves cementum destruction in mouse root resorption model by activating the tissue repair function of macrophages. Moreover, Comp‐EV‐loaded hydrogels achieve significant bone healing in calvarial bone defect. Unexpectedly, under compression, EV secretion in cementoblasts is reduced by half. RNA‐Seq analysis and verification reveal that Rab35 expression decreases by 60% under compression, thereby hampering the release of EVs. Rab35 overexpression is proposed as a modification of cementoblasts to boost the yield of Comp‐EVs. Collectively, Comp‐EVs activate the repair function of macrophages, which will be a potential therapeutic strategy for hard tissue repair and regeneration.

Abstract The distribution of density of states (DOS) holds fundamental importance in determining charge transport within organic field–effect transistors (OFETs). Herein, the modulation of DOS distribution in OFET devices is demonstrated by altering the chain conformation of the polymer dielectrics. A rapid film‐formation technique, specifically the spin‐casting method, is used to fabricate the dielectric layer using poly(methyl methacrylate) (PMMA). This method allows for the retention of some memory of the chain conformations from the solution to the resulting dry film. This memory effect is employed to prepare thin PMMA films with different local chain conformations by adjusting the quality of the solvent. Good solvent forms solidified films with a reduced amount of gauche conformer in the PMMA chain, resulting in a narrow DOS distribution width. Consequently, the device exhibited enhanced charge mobility and a reduced subthreshold swing. The observed change in the width of the DOS distribution can be attributed to the alteration of the local energy state of the semiconductor, induced by the local chain conformation of PMMA dielectrics through electrostatics and steric interactions.

Abstract Background Outliers, data points that significantly deviate from the norm, can have a substantial impact on statistical inference and provide valuable insights in data analysis. Multiple methods have been developed for outlier detection, however, almost all available approaches fail to consider the spatial dependence and heterogeneity in spatial data. Spatial data has diverse formats and semantics, requiring specialized outlier detection methodology to handle these unique properties. For now, there is limited research exists on robust spatial outlier detection methods designed specifically under the spatial error model (SEM) structure. Method We propose the Spatial-Θ-Iterative Procedure for Outlier Detection (Spatial-Θ-IPOD), which utilizes a mean-shift vector to identify outliers within the SEM. Our method enables an effective detection of spatial outliers while also providing robust coefficient estimates. To assess the performance of our approach, we conducted extensive simulations and applied it to a real-world empirical study using life expectancy data from multiple countries. Results Simulation results showed that the masking and JD (Joint Detection) indicators of our Spatial-Θ-IPOD method outperformed several commonly used methods, even in high-dimensional scenarios, demonstrating stable performance. Conversely, the Θ-IPOD method proved to be ineffective in detecting outliers when spatial correlation was present. Moreover, our model successfully provided reliable coefficient estimation alongside outlier detection. The proposed method consistently outperformed other models (both robust and non-robust) in most cases. In the empirical study, our proposed model successfully detected outliers and provided valuable insights in the modeling process. Conclusions Our proposed Spatial-Θ-IPOD offers an effective solution for detecting spatial outliers for SEM while providing robust coefficient estimates. Notably, our approach showcases its relative superiority even in the presence of high leverage points. By successfully identifying outliers, our method enhances the overall understanding of the data and provides valuable insights for further analysis.

Androgenetic alopecia (AGA) is a common clinical condition, affecting over 200 million people globally each year. For decades, Minoxidil (Mi) tincture has been the primary treatment for this disease, but its low utilization rate and significant side effects necessitate new therapeutic strategies. Nitric oxide (NO) is a signaling molecule in various physiological processes, including vasodilation, immune responses, and cell proliferation. Herein, we constructed a hyaluronic acid liposome (HL) complex as a novel transdermal delivery system (HL@Mi/NONOate) for NO and Mi, which displayed promising transdermal and hair-regrowth effects. In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy. First, NO promoted capillary dilation and accelerated blood flow, thus achieving efficient penetration of Mi. Due to the structural advantage of liposomes, the residence time of the Mi in the skin was prolonged. Moreover, HL@Mi/NONOate promoted cell proliferation and angiogenesis, and upregulated the expression of regulatory factors involved in follicle stem cell differentiation. In the AGA model, HL@Mi/NONOate down-regulated the expression of inflammatory factors, inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth. Concurrently, HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues, inducing follicle regeneration and development, ultimately achieving the synergistic multimodal AGA therapy.

Background Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. Methods A total of 114 patients were randomly assigned to intravenous (IV) group ( n = 57) and periarticular injection (PI) group ( n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. Results The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. Conclusions Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

Myocardial ischemia/reperfusion injury (MIRI) is a major cause of cardiac death particularly in patients with diabetes. When the coronary artery is partially or completely blocked, restoration of blood perfusion can normally be achieved within a certain time due to the development of advanced techniques such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery. However, cardiac tissue injury may aggravate progressively even after the ischemic myocardium is restored to normal perfusion. MIRI is often associated with various forms of cell death, including apoptosis, autophagy, programmed necrosis, pyroptosis, and ferroptosis, among others. Ferroptosis is known as iron-dependent cell death that is distinct from other programmed modes of cell death. Ferroptosis is under constitutive control by glutathione peroxidase 4 (GPX4), and the reduction of GPX4 may result in ferroptosis even if iron homeostasis is physiologically maintained. The essences of ferroptosis are substantial iron accumulation and lipid peroxidation that trigger cell death. Under impaired antioxidant system, cellular reactive oxygen species (ROS) accumulation leads to lipid peroxidation which consequently results in ferroptosis. Ferroptosis shares a few common features with several types of cell death and interplays with various forms of cell death such as autophagy and apoptosis in the development of cardiovascular diseases. More and more recent studies have demonstrated that ferroptosis plays an important role in MIRI. However, few studies have addressed the relative importance of ferroptosis in MIRI relative to other forms of cell deaths. In this review, we summarized the basic aspects and advances regarding the molecular pathogenesis of ferroptosis, evaluated its role in MIRI, and propose that the levels of ferroptosis may function as a major determinant of myocardial susceptibility to ischemia/reperfusion injury (IRI) in general and of the enhanced vulnerability to MIRI specifically in diabetes.

Background: Neolamarckia cadamba (Rubiaceae) is a well-recognized medicinal plant with recorded therapeutical attributes. However, a thorough assessment of active compounds in its fruits is lacking, limiting their use and valorization in pharmacological industries. Methods: Thus, this study investigated variations in the fruits’ secondary metabolite (SM) profiles, as well as antioxidant activities in aqueous (WA) and ethanol (ET) extracts. Results: Liquid chromatography–electrospray ionization tandem mass spectrometry identified 541 SMs, of which 14 and 1 (di-O-glucosylquinic acid) were specifically detected in ET and WA, respectively. Phenolic acids (36.97%), flavonoids (28.10%), terpenoids (12.20%), and alkaloids (9.98%) were the dominant SMs. The SM profiles of the fruits in WA and ET were quite different. We revealed 198 differentially extracted (DE) metabolites between WA and ET, including 62 flavonoids, 57 phenolic acids, 45 terpenoids, 14 alkaloids, etc. Most DE flavones (36 out of 40), terpenoids (45 out of 45), and alkaloids (12 out of 14) had higher content in ET. Catechin and its derivatives, procyanidins, and tannins had higher content in WA. ABTS and DPPH assays showed that the antioxidant activity of ET was significantly higher than that of WA. Conclusions: Our findings will facilitate the efficient extraction and evaluation of specific active compounds in N. cadamba.

ABSTRACTHospital-acquired infections (HAIs) represent one of the significant causes of morbidity and mortality worldwide, and controlling pathogens in the hospital environment is of great importance. Currently, the standard disinfection method in the hospital environment is chemical disinfection. However, disinfectants are usually not used strictly according to the label, making them less effective in disinfection. Therefore, there is an emergent need to find a better approach that can be used in hospitals to control pathogenic bacteria in the clinical environment. Bacteriophages (phages) are effective in killing bacteria and have been applied in the treatment of bacterial infections but have not received enough attention regarding the control of contamination in the clinical environment. In this study, we found that various phages remain active in the presence of chemical disinfectants. Moreover, the combined use of specific phages and chemical disinfectants is more effective in removing bacterial biofilms and eliminating bacteria on hard surfaces. Thus, this proof-of-concept study indicates that adding phages directly to chemical disinfectants might be an effective and economical approach to enhance clinical environment disinfection.IMPORTANCEIn this study, we investigated whether the combination of bacteriophages and chemical disinfectants can enhance the efficacy of reducing bacterial contamination on hard surfaces in the clinical setting. We found that specific phages are active in chemical disinfectants and that the combined use of phages and chemical disinfectants was highly effective in reducing bacterial presence on hard surfaces. As a proof-of-concept, we demonstrated that adding specific phages directly to chemical disinfectants is an effective and cost-efficient strategy for clinical environment disinfection.

The resource recovery and reuse of precious metal-laden wastewater is widely recognized as crucial for sustainable development. Superalloy electrolytes, produced through the electrolysis of superalloy scrap, contain significant quantities of precious metal ions, thereby possessing substantial potential for recovery value. This study first explores the feasibility of utilizing fungi to treat Superalloy electrolytes. Five fungi resistant to high concentrations of heavy metals in electrolytes (mainly containing Co, Cr, Mo, Re, and Ni) were screened from the soil of a mining area to evaluate their adsorption characteristics. All five fungi were identified by ITS sequencing, and among them, Paecilomyces lilacinus showed the best adsorption performance for the five heavy metals; therefore, we conducted further research on its adsorption characteristics. The best adsorption effect of Co, Cr, Mo, Re, and Ni was 37.09, 64.41, 47.87, 41.59, and 25.38%, respectively, under the conditions of pH 5, time 1 h, dosage 26.67 g/L, temperature 25–30°C, and an initial metal concentration that was diluted fivefold in the electrolyte. The biosorption of Co, Mo, Re, and Ni was better matched by the Langmuir model than by the Freundlich model, while Cr displayed the opposite pattern, showing that the adsorption process of P. lilacinus for the five heavy metals is not a single adsorption mechanism, but may involve a multi-step adsorption process. The kinetics study showed that the quasi-second-order model fitted better than the quasi-first-order model, indicating that chemical adsorption was the main adsorption process of the five heavy metals in P. lilacinus. Fourier transform infrared spectroscopy revealed that the relevant active groups, i.e., hydroxyl (-OH), amino (-NH2), amide (- CONH2), carbonyl (-C = O), carboxyl (-COOH), and phosphate (PO43–), participated in the adsorption process. This study emphasized the potential application of P. lilacinus in the treatment of industrial wastewater with extremely complex background values.

The Yellow River Source Area (YRSA) functions as an ecological barrier within the Yellow River Basin, playing a significant role in providing indispensable ecosystem services. Analyzing the ecosystem service value (ESV) of YRSA holds great significance in establishing ecological protection awareness and promoting ecological actions. In this study, we reveal the spatial and temporal characteristics of ESV in YRSA from 2000 to 2020 based on the land use change and equivalent factor method, and explore the driving mechanisms behind ESV heterogeneity using geographical detector. The results showed that from 2000 to 2020, ESV in the YRSA increased significantly, with an average increase rate of 9.12 × 1021seJ/5a, showing a spatial distribution pattern of low in the northwest and high in the southeast, and this imbalance is gradually weakening. The average annual contribution of grassland ESV reached 45 %, followed by water bodies (23 %). Ecosystem services in the YRSA are mainly dominated by regulating services, among which hydrological regulating services are dominated, with an average annual contribution rate of more than 40 %. Supply and regulation, support and cultural services both form a strong correlation synergy. Climate factors are the main drivers of spatial heterogeneity in ESV, further illustrating the sensitivity of the YRSA to climate change. Moreover, our results accentuate the integral role of the YRSA in furnishing ESV to the broader Yellow River Basin, which provides a theoretical basis and reference for decision makers to assess the ecological security of the ecological barrier zones.

Abstract The enhancement of immunotherapy is an emerging direction to develop highly effective and practical cancer therapeutic methods. Here a triply enhanced immunotherapy drug (TEID) is designed for ingeniously integrating in situ dual glycan reforming with perforation on cell membrane. The TEID is composed of galactose and neuraminidase conjugated streptolysin O (SLO‐Gal and SLO‐NEU), which are encapsulated in a hyaluronic acid (HA) shell for targeted recognition to tumor tissue via cell surface CD44. After targeted delivery and HAase‐mediated degradation in the tumor region, the TEID releases SLO‐Gal and SLO‐NEU, which can easily anchor Gal and NEU on the tumor cell membrane via the perforation of SLO to perform dual glycan reforming for the introduction of Gal and the cleavage of sialic acid. The former can activate immune cells to secret cytokines for immune‐killing, and the latter can weaken the immune inhibition to improve the immunotherapeutic efficacy. Meanwhile, the perforation of SLO can promote the delivery of cytokines into the tumor cells to further enhance the efficacy. The designed triply enhanced immunotherapy strategy opens a significant and promising route to promote clinical immunotherapy of cancer.

IntroductionJujube is one of an important crop in Xinjiang, China, a area suffered by water scarcity and DI has been proven as a suitable mode for jujube cultivation. Soil bacterial community play a vital role in biogeochemical cycles to support the crop growth, and water content is considered as one of the important factors for them. However, limited research has explored the optimum irrigation strategies, such as water volume of DI, to maximize the benefits of jujube cultivation by regulating the soil bacterial communities.MethodsTherefore, in this study, we conducted DI experiments on jujube fields in Xinjiang with three different water volume levels, and measured the soil properties and bacterial communities of the flowering and fruit setting (FFS) and end of growth (EG) stages.Results and discussionSignificant lower jujube yield and soil available nutrients were observed in samples with low water amount. In addition, we discovered significant effects of the water amount of DI and jujube growth stages on soil bacterial communities. Based on the compare of samples among different growth stages and water amounts some growth stage related bacterial genera (Mycobacterium, Bradyrhizobium, and Bacillus) and water amount-related bacterial phyla (Chloroflexi, Nitrospirota, and Myxococcota) were recognized. Moreover, according to the results of null model, soil bacterial communities were governed by stochastic and deterministic processes under middle and low water volumes of DI, respectively. Finally, we deduced that middle water amount (600 mm) could be the optimal condition of DI for jujube cultivation because the higher jujube yield, deterministic assembly, and stronger correlations between soil properties and bacterial community under this condition. Our findings provide guidance for promoting the application of DI in jujube cultivation, and further research is needed to investigate the underlying mechanisms of soil bacterial community to promote the jujube yield.

Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of Cordyceps militaris, to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (TFH) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.