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Abstract Background Immune factors are crucial in the pathogenesis of rheumatoid arthritis (RA), and immune cells play a key role in the development of RA. However, there is still disagreement regarding the specific roles of each type of immune cell in the pathological process of RA. Methods This study used bidirectional two-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and RA. Utilizing publicly available genetic data, we initially treated immune cell characteristics as exposures to investigate their causal effects on the risk of RA. Subsequently, we performed reverse two-sample MR using the positively selected cells from the initial analysis as outcomes, aiming to identify the core immune cells involved. Finally, a comprehensive sensitivity analysis was conducted to validate the robustness, heterogeneity, and horizontal pleiotropy of the results. Results Using data from 731 immune cells as exposures and cell SNPs as instruments, we independently conducted two-sample MR analysis for each patient with RA. The main analytical method used was the IVW method, with a significance level set at P

Abstract Objective To investigate the effects of different drug treatments on uterine artery blood flow parameters, serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and sFlt-1/PLGF in patients with recurrent spontaneous abortion and to explore the predictive value of uterine artery blood flow parameters, serum PLGF, sFlt-1, and sFlt-1/PLGF for pregnancy outcomes. Methods This retrospective cohort study included 173 patients who experienced recurrent spontaneous abortion and 100 control patients. Patients with recurrent spontaneous abortion were divided into an aspirin group (75 patients), aspirin combined with low molecular weight heparin (LMWH) group (68 patients), and non-drug group (30 patients) based on different drug treatments. Uterine artery blood flow parameters at gestational weeks 30-31+6 were monitored for the four groups, and serum samples were collected at gestational weeks 30-31+6 to measure the levels of serum PLGF and sFlt-1 and calculate the sFlt-1/PLGF ratio. Results 1. Uterine artery blood flow parameters at gestational weeks 30-31+6 were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p

Abstract Background Non-Alcoholic Steatohepatitis (NASH) is a crucial stage in the progression of Non-Alcoholic Fatty Liver Disease(NAFLD). The purpose of this study is to explore the clinical value of ultrasound features and radiological analysis in predicting the diagnosis of Non-Alcoholic Steatohepatitis. Method An SD rat model of hepatic steatosis was established through a high-fat diet and subcutaneous injection of CCl4. Liver ultrasound images and elastography were acquired, along with serum data and histopathological results of rat livers.The Pyradiomics software was used to extract radiomic features from 2D ultrasound images of rat livers. The rats were then randomly divided into a training set and a validation set, and feature selection was performed through dimensionality reduction. Various machine learning (ML) algorithms were employed to build clinical diagnostic models, radiomic models, and combined diagnostic models. The efficiency of each diagnostic model for diagnosing NASH was evaluated using Receiver Operating Characteristic (ROC) curves, Clinical Decision Curve Analysis (DCA), and calibration curves. Results In the machine learning radiomic model for predicting the diagnosis of NASH, the Area Under the Curve (AUC) of ROC curve for the clinical radiomic model in the training set and validation set were 0.989 and 0.885, respectively. The Decision Curve Analysis revealed that the clinical radiomic model had the highest net benefit within the probability threshold range of > 65%. The calibration curve in the validation set demonstrated that the clinical combined radiomic model is the optimal method for diagnosing Non-Alcoholic Steatohepatitis. Conclusion The combined diagnostic model constructed using machine learning algorithms based on ultrasound image radiomics has a high clinical predictive performance in diagnosing Non-Alcoholic Steatohepatitis.

Abstract Environmental DNA (eDNA) monitoring of species distribution has become a critical tool in ecology, conservation biology and fisheries for identifying the presence and distribution of diverse organisms, including important, threatened and invasive species. However, eDNA detection still has room for improvement in sensitivity, requiring time‐consuming real‐time polymerase chain reaction (qPCR) steps and costly machines. In this study, we report a CRISPR‐Cas13‐based method for rapid, easy, sensitive, low‐cost and on‐site detection of eDNA. The assay for the detection of common carp (Cyprinus carpio) and medaka (Oryzias latipes) nucleic acid employs a two‐step process, starting with recombinase polymerase amplification (RPA) and followed by cleavage using Cas13 nuclease, to effectively identify mitochondrial DNA or RNA. Our results showed that the Cas13‐based method has a higher sensitivity than the qPCR‐based method in detecting tiny amounts of eDNA. When combined with reverse transcription of environmental RNA (eRNA), our method increased detection sensitivity by approximately one order of magnitude. Cas13‐based detection could achieve on‐site detection of eDNA using a quick nucleic acid extraction solution and lateral flow strips. Cas13‐based detection of eDNA and eRNA requires minimal training efforts and can be performed in 1 h, without the need for centrifugation and qPCR machines. The portability of the Cas13‐based method, along with its accuracy and relative ease in designing primers and CRISPR RNA (crRNA), underscores its potential to broaden the application of eDNA and eRNA in various fields, including biodiversity conservation.

This study sought to determine the effects of rosemary leaf powder (RP) on laying performance, egg quality, serum indices, gut barrier function, and cecal microbiota and metabolites of late-phase laying hens. A total of 84 “Jing Tint 6” laying hens at 65-week old were randomly divided into 2 groups and fed either a basal diet (CON) or a basal diet supplemented with 0.3% RP. Our study revealed that RP improved the Haugh unit and decreased yolk n-6/n-3 polyunsaturated fatty acid (PUFA) ratio of laying hens, increased serum superoxide dismutase (SOD), jejunal activities of SOD and catalase (CAT), and jejunal zonula occludens-1 (ZO-1) expression, as well as decreased serum tumor necrosis factor-α (TNF-α) level and jejunal TNF-α mRNA expression. Rosemary leaf powder markedly enhanced (P

Objective: To understand the virulence genes and molecular epidemiological characteristics of human-infected strains of Streptococcus suis in Rui'an, Zhejiang Province, from 2021 to 2022, and to provide a scientific basis for diagnosis, treatment, prevention, and control. Methods: Three blood-borne strains of Streptococcus suis were analysed by morphological observation, identification, and drug sensitivity tests. We performed polymerase chain reaction (PCR) amplification of their main seven virulence factors and housekeeping genes. This was followed by virulence analysis and multilocus sequence typing. We analysed their relationships with local pathogens from previous years. Results: Three Streptococcus suis strains were isolated from the blood samples of three patients. From these, the virulence genotypes demonstrated that the two strains were orf2+ and ef+/orf2+/sly+, respectively. The Multilocus sequence typing (MLST) typing results demonstrated that the two strains were ST25 and ST7, respectively. Conclusion: The first isolation of ST25 Streptococcus suis in Rui'an was presumed to have a close affinity with the endemic strain in North America. The other strain was an ST7 clone, consistent with the endemic strain in Sichuan, and which may have originated from Sichuan. Virulence genotype analysis demonstrated that different virulence genes of the pathogens resulted in different clinical manifestations.

Summary: Background: Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects. Methods: We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV. Findings: The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R + sM1R + sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35 + M1 + B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice. Interpretation: Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines. Funding: National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.

AIM: To investigate the long-term changes of corneal densitometry (CD) and its contributing elements after small incision lenticule extraction (SMILE). METHODS: Totally 31 eyes of 31 patients with mean spherical equivalent of -6.46±1.50 D and mean age 28.23±7.38y were enrolled. Full-scale examinations were conducted on all patients preoperatively and during follow-up. Visual acuity, manifest refraction, axial length, corneal thickness, corneal higher-order aberrations, and CD were evaluated. RESULTS: All surgeries were completed successfully without complications or adverse events. Ten-year safety index was 1.17±0.20 and efficacy 1.04±0.28. CD value of 0–6 mm zones in central layer was statistically significantly lower 10y postoperatively, compared with preoperative values (0–2 mmΔ=-1.62, 2–6 mmΔ=-1.24, P

ABSTRACTGenerating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.

ObjectivesTo construct deep learning-assisted diagnosis models based on automatic segmentation of ultrasound images to facilitate radiologists in differentiating benign and malignant parotid tumors.MethodsA total of 582 patients histopathologically diagnosed with PGTs were retrospectively recruited from 4 centers, and their data were collected for analysis. The radiomics features of six deep learning models (ResNet18, Inception_v3 etc) were analyzed based on the ultrasound images that were obtained under the best automatic segmentation model (Deeplabv3, UNet++, and UNet). The performance of three physicians was compared when the optimal model was used and not. The Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) were utilized to evaluate the clinical benefit of the optimal model.ResultsThe Deeplabv3 model performed optimally in terms of automatic segmentation. The ResNet18 deep learning model had the best prediction performance, with an area under the receiver-operating characteristic curve of 0.808 (0.694−0.923), 0.809 (0.712−0.906), and 0.812 (0.680−0.944) in the internal test set and external test sets 1 and 2, respectively. Meanwhile, the optimal model-assisted clinical and overall benefits were markedly enhanced for two out of three radiologists (in internal validation set, NRI: 0.259 and 0.213 [p = 0.002 and 0.017], IDI: 0.284 and 0.201 [p = 0.005 and 0.043], respectively; in external test set 1, NRI: 0.183 and 0.161 [p = 0.019 and 0.008], IDI: 0.205 and 0.184 [p = 0.031 and 0.045], respectively; in external test set 2, NRI: 0.297 and 0.297 [p = 0.038 and 0.047], IDI: 0.332 and 0.294 [p = 0.031 and 0.041], respectively).ConclusionsThe deep learning model constructed for automatic segmentation of ultrasound images can improve the diagnostic performance of radiologists for PGTs.

X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor (IL2RG), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. The incidence of disseminated bacillus Calmette-Guérin (BCG) disease among children with SCID is much higher than in the general population. Here, we report the case of a 4-month-old male infant who presented with subcutaneous induration, fever, an unhealed BCG vaccination site, and hepatosplenomegaly. Metagenomic next-generation sequencing in blood, and the detection of gastric juice and skin nodule pus all confirmed the infection of Mycobacterium tuberculosis. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Whole-exome and Sanger sequencing revealed a novel microdeletion insertion mutation (c.316_318delinsGTGAT p.Leu106ValfsTer42) in the IL2RG gene, resulting in a rare shift in the amino acid sequence of the coding protein. Consequently, the child was diagnosed with X-SCID caused by a novel mutation in IL2RG, complicated by systemic disseminated BCG disease. Despite receiving systemic anti-infection treatment and four days of hospitalization, the patient died three days after discharge. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. In our systemic review, we outline the efficacy of systemic anti-tuberculosis therapy, hematopoietic stem cell transplantation, and gene therapy in children with SCID and BCG diseases caused by IL2RG gene mutation.

BackgroundHearing loss (HL) is the third most prevalent condition, significantly affecting individuals and society. Recent research has explored the potential impact of nutrition, particularly caffeine intake, on HL. While some studies focus on coffee, caffeine intake should be assessed across all dietary sources. This study examines the association between dietary caffeine intake and HL.MethodsOur cross-sectional study included 6,082 participants from the National Health and Nutrition Examination Survey (NHANES). Participants were divided into two groups based on their median caffeine intake: low and high. The study investigated two types of HL: speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL). Binary logistic regression analyzed the correlation between caffeine intake and HL, and a restricted cubic spline (RCS) model assessed potential non-linear associations. Subgroup analyses were also conducted.ResultsHigh caffeine intake was associated with significantly higher rates of SFHL and HFHL compared to low intake (SFHL: 15.4% vs. 10%, HFHL: 30.5% vs. 20.6%, both p

Abstract Metal halide perovskites (MHPs) are considered as promising candidates in the application of nonvolatile high‐density, low‐cost resistive switching (RS) memories and artificial synapses, resulting from their excellent electronic and optoelectronic properties including large light absorption coefficient, fast ion migration, long carrier diffusion length, low trap density, high defect tolerance. Among MHPs, 2D halide perovskites have exotic layered structure and great environment stability as compared with 3D counterparts. Herein, recent advances of 2D MHPs for the RS memories and artificial synapses realms are comprehensively summarized and discussed, as well as the layered structure properties and the related physical mechanisms are presented. Furthermore, the current issues and developing roadmap for the next‐generation 2D MHPs RS memories and artificial synapse are elucidated.

Abstract Background This study aimed to determine the incidence and influencing factors of venous thromboembolism (VTE) in patients with traumatic rib fractures. Methods The retrospective study analyzed medical records of patients with traumatic rib fractures from 33 hospitals. Results The overall incidence of VTE in hospitalized patients with traumatic rib fractures was 8.1%. Patients with isolated traumatic rib fractures had a significantly lower incidence of VTE (4.4%) compared to patients with rib fractures combined with other injuries (12.0%). Multivariate analysis identified the number of rib fractures as an independent risk factor for thrombosis. Surgical stabilization of isolated rib fractures involving three or more ribs was associated with a lower VTE incidence compared to conservative treatment. Conclusions Patients with rib fractures have a higher incidence of VTE, positively correlated with the number of rib fractures. However, the occurrence of thrombosis is relatively low in isolated rib fractures. Targeted thromboprophylaxis strategies should be implemented for these patients, and surgical stabilization of rib fractures may be beneficial in reducing the risk of VTE.

Abstract Background Malaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive. Methods We first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays. Results The results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects. Conclusions In conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel. Video Abstract

Estimating ecological environmental flow in tidal rivers is one of the major challenges for sustainable water resource management in estuaries and river basins. This paper presents an ecological environmental flow framework that was developed to accommodate highly dynamic medium tidal estuaries found along the Yellow Sea coast of China. The framework not only proposes a method of water quality-based ecological flow for tidal gate-controlled rivers but also proposes a method of water demand for scouring and silting to protect ports in coastal viscous sediment environments. The framework integrates the instream water requirements of water quality, sediment and basic ecological flow, and considers the temporal and spatial variation differences for the environmental flow requirements of tidal rivers. This study emphasizes the significance and necessity of continuous monitoring of ecological data in determining the environmental flow of tidal rivers. The output of this study could provide vital references for decision-making and management of the water resource allocation and ecological protection in tidal rivers. HIGHLIGHTS This study develops an ecological environmental flow framework for highly dynamic medium tidal estuaries.; This study suggests a method of water quality-based ecological flow for tidal gate-controlled rivers.; This study proposes a method of water demand for scouring and silting.;

Abstract The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials. Graphical Abstract

Abstract Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field. Graphical abstract

Abstract Background Rosemary extract (RE) has been reported to exert antioxidant property. However, the application of RE in late-phase laying hens on egg quality, intestinal barrier and microbiota, and oviductal function has not been systematically studied. This study was investigated to detect the potential effects of RE on performance, egg quality, serum parameters, intestinal heath, cecal microbiota and metabolism, and oviductal gene expressions in late-phase laying hens. A total of 210 65-week-old “Jing Tint 6” laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet (CON) or basal diet supplemented with chlortetracycline at 50 mg/kg (CTC) or RE at 50 mg/kg (RE50), 100 mg/kg (RE100), and 200 mg/kg (RE200). Results Our results showed that RE200 improved (P

Tripterygium glycosides tablet (TGT), the classical commercial drug of Tripterygium wilfordii Hook. F. has been effectively used in the treatment of rheumatoid arthritis, nephrotic syndrome, leprosy, Behcet's syndrome, leprosy reaction and autoimmune hepatitis. However, due to its narrow and limited treatment window, TGT-induced organ toxicity (among which liver injury accounts for about 40% of clinical reports) has gained increasing attention. The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing (scRNA-seq) technology. The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Using the mouse model, we identified 15 specific subtypes of cells in the liver tissue, including endothelial cells, hepatocytes, cholangiocytes, and hepatic stellate cells. Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations; led to marked inflammatory response, apoptosis and fatty acid metabolism dysfunction in hepatocytes; activated hepatic stellate cells; brought about the activation, inflammation, and phagocytosis of liver capsular macrophages cells; resulted in immune dysfunction of liver lymphocytes; disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways. Thus, these findings elaborate the mechanism underlying TGT-induced acute liver injury, provide new insights into the safe and rational applications in the clinic, and complement the identification of new biomarkers and therapeutic targets for liver protection.

Small incision lenticule extraction (SMILE) has become one of the mainstream refractive surgeries in recent years, with satisfactory efficacy, safety, and predictability. SMILE-derived refractive lenticule, the byproduct of the surgery, holds great potential in clinical practice given its easy access and good biocompatibility. Numerous studies have been published to describe its applications in refractive correction, corneal ectasia diseases, and corneal defects. The feasibility and safety were validated in both animal models and clinical studies. Moreover, the preservation method is also crucial for its further promotion and application. Novel techniques are also evaluated and applied in lenticule preservation. We covered the recent advances in the preservation of corneal stromal lenticules and their clinical reuse in this review.

Rheumatoid arthritis (RA) is an autoimmune disease with features of synovial inflammation, cartilage erosion, bone destruction, and pain and is currently lacking a satisfactory treatment strategy. Dihydroartemisinin (DHA), the active metabolite of artemisinin, has exhibited outstanding suppressive effects on RA without obvious side effects. However, the underlying mechanisms remain unclear, which limits its further clinical application. The purpose of this study is to reveal the pharmacodynamic mechanism of DHA against RA by means of a combination of single-cell RNA sequencing (RNA-seq), proteomics, as well as transcriptomics both in vivo and in vitro. In our results, DHA effectively reduced the degree of redness, swelling, and pain in RA rats and dramatically changed the synovial tissue microenvironment under the pathological state. Within this microenvironment, fibroblasts, macrophages, B cells, and endothelial cells were the major affected cell types, primarily through DHA targeting the extracellular matrix (ECM) structural constituent signaling pathway. In addition, we confirmed that DHA regulated the ECM by modulating matrix metalloproteinase 2 (MMP2) and MMP3 in the synovial tissue of RA rats. Moreover, DHA induced apoptosis in MH7A cells, further validating the bioinformatics data. In conclusion, DHA effectively reduced the inflammatory response and improved the immune microenvironment in synovial tissue by inhibiting MMP2 and MMP3. Our findings provide a basis for the application of DHA in the treatment of RA.

The sandstone uranium deposits in the Kelulun Depression are the first commercially viable uranium deposits discovered in the Hailar Basin and the ore-bearing strata corresponding to the Lower Cretaceous Yimin Formation. However, the source of sedimentary matter, uranium source conditions, and uranium mineralization processes in the region have not been characterized. Accordingly, we analyzed the lithology, whole-rock geochemistry, zircon U-Pb ages, and trace elements of the Yimin Formation sandstones. The Yimin Formation sandstones were primarily composed of detrital grains with low compositional maturity. A geochemical analysis indicated that the parent rocks are felsic igneous rocks formed at an active continental margin with a moderately high degree of weathering. The detrital zircon U-Pb ages of the Yimin Formation 215-287 Ma with a peak at 230-260 Ma. Based on chronological, geochemical, and lithological data, we conclude that the Yimin Formation matter is derived from the Adunchulu Uplift on the western side of the Kelulun Depression and its parent rocks are Triassic granites. The Adunchulu uplift since the late Early Cretaceous and weathering and denudation of its uranium-rich granites provided ample matter and uranium. Therefore, the Kelulun Depression is a promising area for the exploration of sandstone uranium deposits.

ABSTRACTSince May 2022, human mpox cases have increased unexpectedly in non-endemic countries. The first imported case of human mpox in Hong Kong was reported in September 2022. Here we report the isolation and identification of MPXV from the vesicle swabs of this patient. In this research, the vesicle swabs were inoculated in Vero and Vero E6 cells. In addition to observing cytopathic effects (CPEs) in Vero or Vero E6 cells, the isolated virus was identified as mpox virus (MPXV) using quantitative Real-Time PCR (RT–PCR), transmission electron microscopy, and high-throughput sequencing. The experiment also assessed the cross-protective efficacy of sera from the smallpox vaccinated population and preliminarily assessed the inhibitory effect of anti-smallpox virus drugs against MPXV. CPEs can be observed on Vero E6 cells at 24 h and Vero cells at 48 h. The virus particles could be observed by transmission electron microscope, showing typical orthopoxvirus morphology. In addition, F3L and ATI genes which from MPXV A39R, B2R, HA genes which from orthopoxvirus were confirmed by conventional PCR and Sanger sequencing. The next generation sequencing (NGS) suggests that the MPXV strain belongs to B.1 branch of the West African linage, and has a high identity with the sequence of the 2022 ongoing outbreak. PRNT50 results showed that 26.7% of sera from individuals born before 1981 who had been immunized with smallpox were positive, but no MPXV-neutralizing antibodies were found in sera from individuals born later. All four anti-smallpox virus drugs evaluated demonstrated inhibition of mpox virus.

To reveal the characteristics and environmental indications for the combination of the grain size and magnetic susceptibility of coastal sediments, we provided a necessary basis for further study on their genetic mechanisms. Based on the data of grain size and magnetic susceptibility of the 36.10 m long core 07SR01 sediments in the Xiyang tidal channel of western South Yellow Sea, we analyzed their variations and correlations and further revealed their environmental indications and corresponding regional sedimentary evolution via the combination of the aforementioned analysis results, the reinterpretation results of the sedimentary sequence and the age of core 07SR01 and shallow seismic profiles, and the findings of climate and glacial–eustatic cycles during Late Quaternary. The three stages of the sedimentary evolution of the Xiyang tidal channel between marine isotope stage (MIS) 7 and MIS 5 were summarized as follows: First is the stage of marginal bank and riverbed developments in the tidal estuary under a relatively high sea level and strong hydrodynamic conditions during MIS 7 (core section: 36.10–26.65 m). The sediments deposited in this stage were mainly affected by the paleo-Changjiang River and characterized by a coarse grain size (mean: 4.02 Φ) and relatively high magnetic susceptibilities (mean: 27.06 × 10−8 m3·kg−1), with small fluctuations which were strongly and positively correlated with the sand component. Second is the stage dominated by fluviolacustrine and littoral environments with the weak hydrodynamics during MIS 6–5, in which the climate changed from cold and dry to warm and humid as the sea level rose after a drop (core section: 26.65–15.77 m). The sediments deposited in this stage were characterized by a fine grain size (mean: 5.27 Φ) and low magnetic susceptibilities with minor variations (mean: 10.83 × 10−8 m3·kg−1) which were weakly and positively correlated with the coarse silt component. Third is the stage of delta front in the tidal estuary with a relatively high sea level and strong hydrodynamics during MIS 5 (core section: 15.77–0 m). The sediments deposited in this stage were strongly influenced by the paleo-Yellow River and characterized by a relatively coarse grain size (mean: 4.86 Φ), and high magnetic susceptibilities (mean: 37.15 × 10−8 m3·kg−1) with large fluctuations which were weakly and positively correlated with the sand and coarse silt components.

The sandstone-type uranium deposit of the Kelulun Depression is the first industrially valuable uranium deposit discovered in the Hailar Basin. This study performed a systematic examination of 17 sandstone samples from the Yimin Formation in the Kelulun Depression based on various analytical techniques. The findings of the current study were synthesized with previous research to investigate the impact of the redox conditions and the tectonic background of the source area, as well as the paleoclimatic evolution of the Yimin Formation on uranium mineralization. The elemental Mo, U/Th, V/Cr, Ni/Co, and V/(V + Ni) ratios indicate that the paleowater was in an oxygen-rich environment during the deposition of the Yimin Formation. Additionally, the C-value, Sr/Cu, Al2O3/MgO, and Rb/Sr ratios indicate that the Yimin Formation was formed in a paleoclimate characterized by arid-to-semi-arid conditions. The geochemical characteristics of the observed elements indicated that the sediment source of the Yimin Formation was mainly felsic rocks from the upper continental crust, the weathering of the rock was weak, and the tectonic background was a passive continental margin. Coffinite is distributed in the form of cementation and stellates within or around pyrite crystals, and uranium-titanium oxide is mostly distributed in an irregular granular distribution in the biotite cleavage fractures of the study area. In summary, the findings of this study reveal that the tectonic settings, provenance, uranium source, paleoclimate, and oxygen-rich paleowater of the Yimin Formation have important geological significance for the large-scale uranium mineralization of the Kelulun Depression.

This paper presents a high-performance and synthesizable asynchronous pipeline (HPSAP). First, a 4-phase pipeline controlled by the relative-timing (RT) controller is designed. The controller is small (7 gates) and its handshake protocol is highly concurrent, resulting in fewer component delays in cycle time. However, the RT pipeline’s throughput is limited by the inherent reset phase in the 4-phase protocol. Thus, the variant HPSAP pipeline is proposed with the quasi-2phase conversion method. Unlike other existing solutions which aimed at reducing the reset time of the 4-phase protocol, this method imitates the behavior of the 2-phase pipeline and re-activates the reset edge by two steps: 1) replacing all delay-matched units with the maximum delay; 2) adding a small pulse generator on each RT controller. The post-layout HSPICE simulation of a 4-bit 10-stage HPSAP first-in-first-out (FIFO) pipeline indicated a throughput of 5.382 giga data item per second (GDI/s) under SMIC 55nm CMOS technology, which was 77.5% and 14.65% higher than the Click pipeline and Mousetrap pipeline. In the pipeline with processing, a $32\times 32$ bits multiplier was built, and the maximum working frequency of the HPSAP multiplier was faster than Mousetrap and the synchronous counterparts.

The goal of privacy-preserving social graph publishing is to protect individual privacy while preserving graph utility. Node nearest neighbor structure is a crucial social graph utility as it is the basis for many graph analysis tasks. Most existing methods with differential privacy focus on preserving degree distribution yet neglect the maintenance of connections between nodes’ neighbors. Moreover, they require massive noise added to mask the change of a single edge, thereby rendering poor utility on the neighbor structure. As a result, it is tough to preserve high utility on the neighbor structure under differential privacy. To tackle these problems, we propose Priv-NNS, a private graph publishing algorithm to preserve the neighbor structure while guaranteeing individual privacy. This algorithm first decomposes a graph into subgraphs via extracting a nearest neighbor structure around each node. Then to yield node vectors satisfying differential privacy while preserving the neighbor structure, we design a private graph encoding approach with structure-awareness, which learns topological features of the subgraph by maximizing the co-occurrence probability among nodes. During this process, a novel objective perturbation approach with a random term, only requiring a scalar noise rather than a vector noise, is devised to balance the neighbor structure retained against the noise injected. Through formal privacy analysis, we prove that the yielded synthetic graph obeys $\varepsilon $ -edge differential privacy. Experimental results demonstrate that Priv-NNS preserves high utility on the neighbor structure.

The composition of serum is extremely complex, which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and diagnosis. Recently, nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum. Here, we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona (PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis. We identified 1,070 proteins with a median coefficient of variation of 12.56% using PC-based proteomic analysis, which was twice the number of proteins identified by direct digestion. There were also more biological processes enriched with these proteins. We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis (CIA) rat model treated with methotrexate (MTX). The bioinformatic results indicated that 485 differentially expressed proteins (DEPs) were found in CIA rats, of which 323 DEPs recovered to near normal levels after treatment with MTX. This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies, but also provide more pharmacodynamic biomarkers for disease prediction, diagnosis, and treatment.

Abstract The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed. Nevertheless, the antibody response decreased over time, and the Omicron variant exhibited more pronounced resistance to neutralization than the prototype and Delta strains. Moreover, the intensity of the SARS-CoV-2-specific CD4+ T cell response was also increased in recovered patients who received COVID-19 vaccines. Overall, the repeated antigen exposure provided by inactivated COVID-19 vaccination greatly boosted both the potency and breadth of the humoral and cellular immune responses against SARS-CoV-2, effectively protecting recovered individuals from reinfection by circulating SARS-CoV-2 and its variants.

AIM: To investigate the one-year refractive outcomes and optical quality following PRESBYOND laser-blended vision (LBV). METHODS: This retrospective study included 20 patients who underwent PRESBYOND treatment between Jan 2019 and Aug 2020. The patients were asked to attend a follow-up outpatient visit one year after surgery. Distance and near visual acuity as well as subjective refraction were examined. Optical quality was assessed using wavefront-supported custom ablation. A questionnaire evaluating optical quality and satisfaction was completed at the last visit. RESULTS: The average patient age was 48.1±7.4y (range, 41 to 58y). The mean preoperative spherical equivalent was -7.59±2.39 D. At the one-year follow-up, two eyes (both dominant eyes) lost one line of corrected distance visual acuity (CDVA), while the remaining eyes (38/40) maintained or gained lines of CDVA. The average binocular uncorrected distance visual acuity improved from 0.15±0.03 to 0.90±0.26 (decimal vision; P

Abstract Purpose The application of bio-control plants in the agricultural processes is one of the effective ways to solve the traditional agricultural synthetic pesticide residues. This study will investigate the effect of bio-control plant Litsea cubeba branch inter-row cover on soil bacterial community, soil-enriched metabolites, and soil mineral nutrition in tea plantation, which will provide a basis for the use of bio-control plant in agroecological farming systems. Methods The fruit-bearing (F-Pr) and vegetative (F-Ab) branches of Litsea cubeba were inter-row covered (the use of plants for partial coverage of soil between the rows) in the tea plantation. And we determined the soil microbial community, soil mineral nutriment, and soil-enriched metabolites composition with the methods of 16S rRNA gene sequencing, inductively coupled plasma-atomic emission spectroscopy (ICP-AEC), inductively coupled plasma-optical emission spectrometry (ICP-OES), and gas chromatography-mass spectrometry (GS-MS). We also predict the function of soil bacteria with the Tax4Fun software. Results Litsea cubeba inter-row cover modified the soil microbial structure and diversity; Litsea cubeba inter-row cover significantly decreased the relative abundance of Acidobacteria, Chloroflexi, and Planctomycetes while increased the relative abundance of Proteobacteria. Litsea cubeba inter-row cover significantly antagonized the plant pathogen community, and its OTUs number decreased from 907 ± 81 in the control to 337 ± 25 in F-Pr treatment; compared with F-Pr treatment, F-Ab treatment had weaker effect on the abundance of nutrition metabolism and transport, carbohydrate utilization, and nitrate reduction A. The aluminum element in the F-Pr treatment was significantly reduced, while phosphorus was increased. The soil-enriched metabolites of F-Pr treatment contained some antibacterial substance, including 14.2 ± 3.32% citronellol, 10.38 ± 4.79% alpha-terpineol, and 8.25 ± 2.62% (+)-2-bornanone, which was the main environment factor that affects the soil bacterial structure and diversity. Conclusion Litsea cubeba inter-row cover significantly affected bacterial structure and diversity, slightly increased the soil pH, and improved soil aluminum and phosphorus status; soil-enriched metabolites were the major environment factor affecting soil bacterial community and should be considered in the application of bio-control plants; Litsea cubeba vegetative branch inter-row cover will be a feasible measure for integrated pest management in tea plantation.

This study was to evaluate whether Intracytoplasmic sperm injection (ICSI) can improve the quality of embryo in patients with poor-quality embryos in the previous In-vitro fertilization (IVF) cycle, which was cancelled before transfer. This was a retrospective cohort study of 178 IVF and 158 ICSI cycles for patients with poor-quality embryos in the previous IVF cycle in the Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University from March 2016 to June 2022. The 2 PN rate, oocyte utilization rate , high-quality embryo rate and clinical pregnancy rate were compared between the two groups. Furthermore, the implantation rate, miscarriage rate and cycle cancelation rate were measured and compared. ICSI resulted in a comparable 2 PN rate, oocyte utilization rate and cycle cancelation rate with IVF. The high-quality embryo rate of ICSI group was significantly higher than that of IVF group (5.56% vs. 2.60%, P

Over the past decade, optical wavefront shaping has been developed to focus light through highly opaque scattering layers, opening new possibilities for biomedical applications. To probe light intensity deep inside soft scattering media such as biological tissues, internal guide-stars are required. Here, we give an overview of the main principles and describe in depth the use of a photoacoustic feedback signal for this purpose. We further present first principles calculations and simulations to estimate important experimental parameters, and detailed instructions on designing and conducting these experiments. Finally, we provide guidance towards selecting suitable equipment for building a typical experimental setup, paving the way for further innovative biomedical imaging and therapy applications.

Uranium mining activities have contributed to the distribution and uptake of radionuclides, which have increased the active concentrations of natural radionuclides in environmental media, causing elevated human health risks. The present study aims to assess the spatial distribution characteristics of natural radionuclides in the surface soils and river sediments of the typical granite uranium mining area in South China, as well as investigate the geochemical features of natural radionuclides in the soil and sediments to understand their migration processes. The activity concentrations for 238U, 226Ra, 232Th, and 40K ranged from 17–3925 Bq/kg, 50–1180 Bq/kg, 29–459 Bq/kg, and 240–1890 Bq/kg, respectively. The open-pit mining areas and tailings pond locations exhibited the highest concentrations of activity for all these radionuclides. This distribution points to an elevated potential health risk due to radiological exposure in these specific areas. Additionally, the values of radium equivalent activity (Raeq) and annual gonadal dose equivalent (AGDE) in those areas were higher than the limits recommended by ICRP (2021). 238U and 226Ra have a significant correlation (0.724), and the cluster analysis was showing a statistically meaningful cluster below 5 indicated that they have similar behavior during parent rock weathering and watershed erosion, and the distribution of 232Th and 40K were influenced by the addition of rock types. The activity ratios of 226Ra/238U, 226Ra/232Th, 238U/40K, and 226Ra/40K variation indicated that 40K more mobile than 226Ra and 238U, U(VI) was reduced to U(IV) by organic matter in the downstream area and re-entered into the sediment during the sediment surface runoff in the small watershed of the uranium ore open-pit mining area. Therefore, it is necessary to further seal up and repair the tailings landfill area.

Background: Mpox virus (MPXV) infections have increased in many countries since May 2022, increasing demand for diagnostic tests and research on the virus. To ensure personnel safety, appropriate and reliable measures are needed to disinfect and inactivate infectious samples; Methods: We evaluated the stability of infectious MPXV cultures stored at different temperatures and through freeze–thaw cycles. Heat physical treatment (56 °C, 70 °C, 95 °C), chemical treatment (beta-propiolactone (BPL)) and two commercialized disinfectants (Micro-Chem Plus (MCP) and ethanol) were tested against infectious MPXV cultures; Results: The results indicated that MPXV stability increases with lower temperatures. The MPXV titer was stable within three freeze–thaw cycles and only decreased by 1.04 log10 (lg) 50% cell culture infective dose (CCID50) per milliliter (12.44%) after twelve cycles. MPXV could be effectively inactivated at 56 °C for 40 min, 70 °C for 10 min, and 95 °C for 5 min. For BPL inactivation, a 1:1000 volume ratio (BPL:virus) could also effectively inactivate MPXV. A total of 2% or 5% MCP and 75% ethanol treated with MPXV for at least 1 min could reduce >4.25 lg; Conclusions: MPXV shows high stability to temperature and freeze–thaw. Heat and BPL treatments are effective for the inactivation of MPXV, while MCP and ethanol are effective for disinfection, which could help laboratory staff operate the MPXV under safer conditions and improve operational protocols.

SARS-CoV-2 variants of concern (VOCs) show increasing transmissibility and infectivity and induce substantial injuries to human health and the ecology. Therefore, it is vital to understand the related features for controlling infection. In this study, SARS-CoV-2 WIV04 (prototype) and five VOCs (Beta, Delta, Omicron BA.1, BA.2 and BA.5 variants) were inoculated in Vero cells to observe their growth activities. Apart from evaluating the environmental stability at different temperatures, residual virus titers and infectivity at different temperatures (4 °C, room temperature (RT) and 37 °C) were measured over 7 days. The experiment also assessed the infectivity for different incubation durations. The growth capacity assay suggested that the WIV04, Beta and Delta variants replicated efficiently in Vero cells compared with Omicron Variants, and BA.2 replicated more efficiently in Vero cells than BA.1 and BA.5. In addition, all variants exhibited longer survivals at 4 °C and could remain infectious after 7 days, compared to RT’ survival after 5 days and at 37 °C after 1 day. The virus infection assay indicated that the Omicron variant had a weaker ability to infect cells compared to the WIV04, Beta and Delta strains, and a longer infection time was required for these strains, except for BA.2.

AIM: To compare the distribution characteristics of axial sagittal front power(ASF), true net power(TNP), total corneal refractive power(TCRP)and the difference in back-front corneal radius ratio(B/F ratio)after cataract surgery.METHODS: A prospective study. A total of 156 patients(156 eyes)with age-related cataract who attend Weifang Eye Hospital for cataract surgery from December 2020 to May 2021 were collected. Pentacam was performed before operation and 3mo after operation to collect ASF, TNP and TCRP on 2, 4 and 6mm diameters rings and areas on the corneal apex and pupil-centered, as well as B/F ratio.RESULTS: 3mo after operation, there was no statistical difference in ASF on the 2mm diameters ring and area centered on the corneal apex compared with preoperative values(all P>0.05), however, the ASF values on the 4 and 6mm diameters rings and areas were significantly different from those before surgery(all P0.05). The postoperative values of TNP and TCRP on the 2, 4 and 6mm diameters rings and areas centered on the corneal apex and centered on the pupil were statistically different before surgery(all P

Abstract Background Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine (CQ) has played an indispensable role, however, its mechanism of action (MoA) is not fully understood. Methods We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling (ABPP) and mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays. Results We developed a novel clickable, photo-affinity chloroquine analog probe (CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photo-crosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods. Conclusions We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled (ABPP) and label-free (MS-CETSA) methods.

ABSTRACT: Objectives: The prevalence of tet(X) genes threatens the clinical use of last-line tigecycline. The tet(X6) gene has been reported in Proteus strains, but its genetic context is rarely reported. This study aimed to investigate the prevalence and genetic contexts of tet(X6) gene in Proteus spp. Methods: A tet(X6) variant–bearing P. terrae subsp. cibarius strain was subjected to susceptibility testing, determination of growth curves, scanning electron microscopy, transmission electron microscopy and whole-genome sequencing (WGS). The genomic contexts of the tet(X6)-positive strain were analysed by sequence comparison and annotation. Results: ZJ19PC, a P. terrae subsp. cibarius strain harbouring the tet(X6) variant, was isolated from 20 cecum samples collected in Zhejiang, China. The chromosome size of ZJ19PC was 3 952 084 bp; the GC content was 38.2%; and hugA, sul2, tet(H), floR, dfra1, aadA1, aac(3)-IV and aph(4)-la were found in addition to the tet(X6) variant. Proteus spp. could be classified into three groups based on the tet(X6) gene contexts. Strain ZJ19PC belongs to group 1 (sra-sul2-ISCR2-floR-ISCR2-floR-ISCR2- tet(X6) variant-tnpA-ISEc59-aph(4)-la-aac(3)-Iva-IS26), and this region of group 1 was inserted between modA and guaA. The common antimicrobial resistance (AMR) genes of the three types of AMR gene islands were sul2, floR, tet(X6) and aac(3). The tet(X6) gene contexts and SNP tree showed that ZJ19PC was homologous to HNCF44W and HNCF43W, which indicated that these strains may be clonally transmitted. Conclusion: This study analysed the genetic contexts of the tet(X6) gene in Proteus spp. and highlighted the significance of monitoring tigecycline-resistant P. terrae subsp. cibarius.

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

The distribution patterns of the paleo-Changjiang River deltas formed during the MIS 3 period before the last glacial maximum (LGM) contain important information about the deltaic deposits in response to climate and sea-level changes. However, so far, they are still poorly understood. Here, we reconstruct the stratigraphic and chronological framework of the deltaic system based on the analysis of 1835 km of high-resolution seismic profiles obtained from the northern East China Sea, together with a comparison with the research results from four existing boreholes and three groups of published seismic profiles from the study area. Within the strata from MIS 5 to MIS 1 that are preserved on the northern shelf of the East China Sea, we discovered a large-scale paleodeltaic complex formed during the MIS 3 period. During MIS 3, sea level dropped slowly; the paleodelta formed was large in scale and was distributed between water depths of 40 and 150 m. It is now directly exposed at the seabed at a depth of more than 100 m. The paleodelta had extended from the northwest to the southeast, with maximum thickness of the deposits around 55 m. The extensions in the east–west and south–north directions both exceeded 300 km, with a total area around 1.35 × 105 km2. Since the late Pleistocene, the tectonic structure beneath the East China Sea has been relatively stable. As such, sea-level fluctuations, sediment supply, and original topography were the main controlling factors for the development of the delta.

In order to quickly and accurately non-destructive real-time monitoring of fish freshness, a visual colorimetric array sensor was constructed in this study based on anodized aluminum flakes as the substrate and 13 indicators selected as gas-sensitive materials. The freshness of turbot during storage was measured by using the constructed colorimetric array sensor. The results showed that the total volatile basic nitrogen (TVB-N) value of turbot reached 32.85 mg/100 g when the storage time was more than 22 h at 25 ℃, and the fish was rotten. At this time, the color of the array points in the colorimetric sensor array changed. The RGB values of sensor array points before and after response were extracted and subtracted, and the clustering analysis and principal component analysis were carried out. The results showed that the colorimetric array sensor was able to accurately distinguish the freshness of fish in different storage time periods. In addition, the array sensor was applied to detect the freshness of carp and American redfish at different storage times, and the results showed that there was no significant difference between the TVB-N values predicted by the colorimetric array sensor and the actual measured values. Therefore, it is feasible to apply the sensor to fish freshness monitoring.

Abstract Background Myopia is a global public health issue. Controlling myopia progression is a primary focus of myopia studies today. Peripheral retinal myopic defocus is considered the mechanism for reduced myopia progression in orthokeratology studies. The topographic change in the front corneal surface after laser refractive surgery and orthokeratology procedures may appear similar. The purpose of this study was to explore the role of myopic laser ablation on axial length (AL) growth. Methods Myopic patients who underwent monocular excimer laser refractive surgery first in one eye and then in another eye several years later because of myopia occurrence or myopia progression were recruited. The axial length elongation and refraction (spherical equivalent) between the two eyes were observed and compared. Results A total of 8 myopic patients were enrolled in the study. The AL increased from 24.52 ± 0.96 mm to 24.68 ± 1.03 mm but without significance (T = 1.49, P > 0.05) in the ablated eyes. The AL increased significantly from 23.73 ± 0.91 mm to 24.26 ± 0.95 mm in the nonablated eyes (T = 6.76, P

Nanocarriers have therapeutic potential to facilitate drug delivery, including biological agents, small-molecule drugs, and nucleic acids. However, their efficiency is limited by several factors; among which, endosomal/lysosomal degradation after endocytosis is the most important. This review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport mechanisms. These strategies include promoting endosomal/lysosomal escape, using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/lysosomes. On the basis of the findings of this review, we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.

Deep learning has been widely used for plant disease recognition in smart agriculture and has proven to be a powerful tool for image classification and pattern recognition. However, it has limited interpretability for deep features. With the transfer of expert knowledge, handcrafted features provide a new way for personalized diagnosis of plant diseases. However, irrelevant and redundant features lead to high dimensionality. In this study, we proposed a swarm intelligence algorithm for feature selection [salp swarm algorithm for feature selection (SSAFS)] in image-based plant disease detection. SSAFS is employed to determine the ideal combination of handcrafted features to maximize classification success while minimizing the number of features. To verify the effectiveness of the developed SSAFS algorithm, we conducted experimental studies using SSAFS and 5 metaheuristic algorithms. Several evaluation metrics were used to evaluate and analyze the performance of these methods on 4 datasets from the UCI machine learning repository and 6 plant phenomics datasets from PlantVillage. Experimental results and statistical analyses validated the outstanding performance of SSAFS compared to existing state-of-the-art algorithms, confirming the superiority of SSAFS in exploring the feature space and identifying the most valuable features for diseased plant image classification. This computational tool will allow us to explore an optimal combination of handcrafted features to improve plant disease recognition accuracy and processing time.

The Qianjiadian uranium deposit is a typical interstratified oxidized zone sandstone-hosted uranium deposit hosted in the Upper Cretaceous Yaojia Formation of the southern Songliao Basin. Despite its significance, little research has been conducted on the relationship between trace elements, REEs, and uranium mineralization in this deposit. This study presents new geochemical data from sandstones in the oxidation, transition, and reduction zones. The sandstones in the transition zone are highly enriched in U and moderately enriched in Mo, Cd, and V compared to those in the oxidation and reduction zones. They are also weakly enriched in Co, Ni, and Zn. The oxidation and transition zone sandstones have higher ∑LREE and ∑HREE contents than those in the reduction zone. However, the oxidation zone sandstones are characterized by LREE enrichment and flat HRRE distribution, while the transition zone sandstones show HRRE enrichment and flat LREE distribution. These trace element and REE differentiation characteristics within each subzone are closely related to the geological process of interstratified oxygenation. Oxygenated uranium-bearing fluids from southwestern provenance areas carried multiple trace elements and REEs and infiltrated along the oxidation sandstones to reach the Yaojia Formation’s transition zone. During this process, a certain amount of Mo, V, Cd, and LREE from the oxygenated ore-forming fluids was precipitated by Fe-Mn hydroxide adsorption or calcite and siderite cementation. Meanwhile, about 20.33% of preexisting U in the oxidation zone sandstones was continuously extracted and entered into the oxygenated ore-forming fluids. In the transition zone, where dissolved oxygen was exhausted and hydrocarbons were continuously injected, U, Mo, Cd, V, Co, Ni, Zn, and REEs were unloaded and precipitated as uranium minerals, sulfide minerals, or carbonate minerals. The enrichment of Mo, Cd, V, and HREEs in the sandstones can serve as new prospecting indicators for the Qianjiadian uranium deposit.

BackgroundStreptococcus pneumoniae (S. pneumoniae) is the most common pathogen in community-acquired pneumonia (CAP) and takes the form of lobar pneumonia as typical computed tomography (CT) findings. Various patterns of radiological manifestation have also been reported in patients with S. pneumoniae pneumonia; however, the appearance of diffuse centrilobular nodules in both lungs is rarely reported.Case presentationWe report the case of a patient with a history of chronic lymphocytic leukemia (CLL) for 9 years who presented with new-onset fever, cough, excess sputum, and shortness of breath for 1 week. He was given intravenous antibacterial (cephalosporin) treatment for 4 days, but his condition did not improve and dyspnea became more serious. The chest CT indicated diffuse centrilobular nodules in both lungs at admission. Patient’s bronchoalveolar (BAL) fluid was sent for metagenomic next-generation sequencing, which only supported a diagnosis of S. pneumoniae infection. His condition improved gradually after antimicrobial treatment (moxifloxacin) and a follow-up CT showed that the diffuse centrilobular nodules in both lungs were absorbed completely.ConclusionThis case highlights a rare CT presentation of S. pneumoniae pneumonia that should alert clinicians, so as to avoid taking unnecessary treatment measures.