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Abstract Electronic cigarettes (e-cigs) use, especially among youngsters, has been on the rise in recent years. However, little is known about the long-term effects of the use of e-cigs on brain functional activity. We acquired the resting-state functional magnetic resonance imaging (rs-fMRI) data from 93 e-cigs users with nicotine dependence and 103 health controls (HC). The local synchronization was analyzed via the regional homogeneity (ReHo) method at voxel-wise level. The functional connectivity (FC) between the nucleus accumbens (NAcc), the ventral tegmental area (VTA), and the insula was calculated at ROI-wise level. The support vector machining classification model based on rs-fMRI measures was used to identify e-cigs users from HC. Compared with HC, nicotine-dependent e-cigs users showed increased ReHo in the right rolandic operculum and the right insula (p

Abstract Background The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. Results We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. Conclusion Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract

Abstract This study aimed to assess the safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy (HE) associated with large spontaneous portosystemic shunts (SPSS). Inverse probability of treatment weighting (IPTW) was employed to minimize potential bias. A total of 123 patients were included in this study (34 in the embolization group and 89 in the control group). In the unadjusted cohort, the embolization group demonstrated significantly better liver function, a larger total area of SPSS, and a higher percentage of patients with serum ammonia levels > 60 µmol/L and the presence of hepatocellular carcinoma (HCC) (all P 0.05). Patients in the embolization group exhibited significantly longer HE-free survival compared to the control group in both the unadjusted and IPTW cohorts (both P 60 μmol/L, hepatopetal flow within the portal trunk, the presence of solitary SPSS, a baseline HE grade of II, and the absence of HCC at baseline showed statistically significant benefit from embolization treatment (all P 0.05). Hence, interventional embolization appears to be a safe and effective treatment modality for cirrhotic patients with refractory HE associated with large SPSS. However, the benefits of embolization were discernible only in a specific subset of patients.

Abstract Background Crohn’s disease (CD) is a chronic condition characterized by a high recurrence rate after surgery, which seriously affects the quality of life of patients. Many studies have explored the risk factors for the recurrence of CD after surgery, there is a lack of meta-analysis focusing on endoscopic postoperative recurrence (ePOR) as a clinical outcome. Therefore, this paper aims to identify the risk factors for ePOR in CD patients through systematic review and meta-analysis. Methods PubMed, Embase, Cochrane Library, and Web of Science databases were searched for related literature from inception to 17th October 2023. Two researchers independently screened the literature and extracted information. Data analysis was performed using Stata18.0. Results Twenty-three papers were included, with 5 case-control studies and 18 cohort studies. The National Institutes of Health quality assessment tool rated 17 studies as good and 6 studies as fair. The sample size of the 23 studies ranged from 40 to 346, and the number of patients with ePOR ranged from 23 to 169. The results of multivariate meta-analysis showed that smoking [OR = 2.06, 95% CI (1.65, 2.57), P = 0.0001], previous ileocolonic resection [OR = 1.71, 95% CI (1.23, 2.38), P = 0.002], disease localization at ileocolic resection [OR = 2.68, 95% CI (1.38, 5.22), P = 0.004], perianal disease [OR = 1.47, 95% CI (1.07, 2.03), P = 0.017], and anastomotic scattered ulcer [OR = 3.39, 95% CI (1.83, 6.28), P = 0.001] were risk factors for ePOR in CD patients. Postoperative prophylactic medication [OR = 0.53, 95% CI (0.38,0.75), P = 0.0001] was a protective factor for ePOR in CD patients. Conclusions This systematic review identified multiple factors for ePOR in CD patients, as well as a protective factor. However, the number of articles included was limited. More high-quality clinical studies are required to further validate the conclusions. Trial registration This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023483671).

Abstract Background Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction. Methods Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study’s primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle. Discussion The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery. Trial registration ChiCTR2200064041, registered on 24th September, 2022.

Abstract Background Unprofessional behaviours between healthcare workers are highly prevalent. Evaluations of large-scale culture change programs are rare resulting in limited evidence of intervention effectiveness. We conducted a multi-method evaluation of a professional accountability and culture change program “Ethos” implemented across eight Australian hospitals. The Ethos program incorporates training for staff in speaking-up; an online system for reporting co-worker behaviours; and a tiered accountability pathway, including peer-messengers who deliver feedback to staff for ‘reflection’ or ‘recognition’. Here we report the final evaluation component which aimed to measure changes in the prevalence of unprofessional behaviours before and after Ethos. Methods A survey of staff (clinical and non-clinical) experiences of 26 unprofessional behaviours across five hospitals at baseline before (2018) and 2.5–3 years after (2021/2022) Ethos implementation. Five of the 26 behaviours were classified as ‘extreme’ (e.g., assault) and 21 as incivility/bullying (e.g., being spoken to rudely). Our analysis assessed changes in four dimensions: work-related bullying; person-related bullying; physical bullying and sexual harassment. Change in experience of incivility/bullying was compared using multivariable ordinal logistic regression. Change in extreme behaviours was assessed using multivariable binary logistic regression. All models were adjusted for respondent characteristics. Results In total, 3975 surveys were completed. Staff reporting frequent incivility/bullying significantly declined from 41.7% (n = 1064; 95% CI 39.7,43.9) at baseline to 35.5% (n = 505; 95% CI 32.8,38.3; χ2(1) = 14.3; P

Abstract Tuberculosis (TB) remains a significant global health threat, necessitating effective strategies for diagnosis, prognosis, and treatment. This study employs a multi-cohort analysis approach to unravel the immune microenvironment of TB and delineate distinct subtypes within pulmonary TB (PTB) patients. Leveraging functional gene expression signatures (Fges), we identified three PTB subtypes (C1, C2, and C3) characterized by differential immune-inflammatory activity. These subtypes exhibited unique molecular features, functional disparities, and cell infiltration patterns, suggesting varying disease trajectories and treatment responses. A neural network model was developed to predict PTB progression based on a set of biomarker genes, achieving promising accuracy. Notably, despite both genders being affected by PTB, females exhibited a relatively higher risk of deterioration. Additionally, single-cell analysis provided insights into enhanced major histocompatibility complex (MHC) signaling in the rapid clearance of early pathogens in the C3 subgroup. This comprehensive approach offers valuable insights into PTB pathogenesis, facilitating personalized treatment strategies and precision medicine interventions.

Background Anaplastic lymphoma kinase (ALK) fusion events account for 3 to 7% of genetic alterations in patients with nonsmall cell lung cancer (NSCLC). This study aimed to explore the landscape of ALK fusion-positive and ALK fusion-negative in a large cohort of NSCLC patients.

Abstract Background Faced with the high cost and limited efficiency of classical randomized controlled trials, researchers are increasingly applying adaptive designs to speed up the development of new drugs. However, the application of adaptive design to drug randomized controlled trials (RCTs) and whether the reporting is adequate are unclear. Thus, this study aimed to summarize the epidemiological characteristics of the relevant trials and assess their reporting quality by the Adaptive designs CONSORT Extension (ACE) checklist. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to January 2020. We included drug RCTs that explicitly claimed to be adaptive trials or used any type of adaptative design. We extracted the epidemiological characteristics of included studies to summarize their adaptive design application. We assessed the reporting quality of the trials by Adaptive designs CONSORT Extension (ACE) checklist. Univariable and multivariable linear regression models were used to the association of four prespecified factors with the quality of reporting. Results Our survey included 108 adaptive trials. We found that adaptive design has been increasingly applied over the years, and was commonly used in phase II trials (n = 45, 41.7%). The primary reasons for using adaptive design were to speed the trial and facilitate decision-making (n = 24, 22.2%), maximize the benefit of participants (n = 21, 19.4%), and reduce the total sample size (n = 15, 13.9%). Group sequential design (n = 63, 58.3%) was the most frequently applied method, followed by adaptive randomization design (n = 26, 24.1%), and adaptive dose-finding design (n = 24, 22.2%). The proportion of adherence to the ACE checklist of 26 topics ranged from 7.4 to 99.1%, with eight topics being adequately reported (i.e., level of adherence ≥ 80%), and eight others being poorly reported (i.e., level of adherence ≤ 30%). In addition, among the seven items specific for adaptive trials, three were poorly reported: accessibility to statistical analysis plan (n = 8, 7.4%), measures for confidentiality (n = 14, 13.0%), and assessments of similarity between interim stages (n = 25, 23.1%). The mean score of the ACE checklist was 13.9 (standard deviation [SD], 3.5) out of 26. According to our multivariable regression analysis, later published trials (estimated β = 0.14, p

Icebergs are big chunks of ice floating on the ocean surface, and melting of icebergs contributes for the major part of freshwater flux into ocean. Dynamic monitoring of the icebergs in Antarctica and accurate estimation of their volume are important for predicting the trend of freshwater budget of the Southern Ocean. The iceberg freeboard is a key parameter for measuring the thickness and volume of an iceberg and is defined as the difference between the elevation of iceberg surface and sea level. So far, freeboards of icebergs have been successfully extracted using InSAR DEM, and the laser and radar altimeter. However, uncertainties exist in these results mainly caused by missed detection of small icebergs due to the spatially sparse and temporally incomplete data coverage. In addition to the above techniques, optical images can also be used to extract the iceberg freeboard based on its geometric relationship with shadow length, which can effectively compensate for the above shortcomings. Although the feasibility has been preliminarily presented, the precision and extensive application of shadow-height method deserves further research, such as estimating the basal melting of icebergs. In this work, we tested an optical image-based freeboard extraction method over icebergs in Prydz Bay, Antarctica. A normalized shadow pixel index (NSPI) is designed to identify iceberg shadows with different shapes in HY-1C/D CZI and Sentinel-2 MSI optical images. The iceberg freeboard can be determined with an acceptable precision (2 m) in optical images compared with laser altimeter (i.e. ICESat-2) measurements. Moreover, basal melting of icebergs has been assessed according to the variation of freeboard using repeated optical observations. The results indicate that icebergs in the study area were with a mean freeboard of about 56 m in early December 2022, and experienced a decrease in freeboard of 1.9 m within two months, in correspondence with the Antarctic seasonal trend. The methodological framework, therefore, turns out to be a reliable complementary approach to studying the iceberg freeboard in polar regions.

Abstract Objective Most studies investigated the relationship between COVID-19 and Guillain-Barré syndrome (GBS) by comparing the incidence of GBS before and during the pandemic of COVID-19. However, the findings were inconsistent, probably owing to varying degrees of the lockdown policy. The quarantine requirements and travel restrictions in China were lifted around December 7, 2022. This study aimed to explore whether the relative frequency of GBS increased during the major outbreak in the absence of COVID-19-mandated social restrictions in China. Methods GBS patients admitted to the First Hospital, Shanxi Medical University, from December 7, 2022 to February 20, 2023, and from June, 2017 to August, 2019 were included. The relative frequencies of GBS in hospitalized patients during different periods were compared. The patients with and without SARS-CoV-2 infection within six weeks prior to GBS onset formed the COVID-GBS group and non-COVID-GBS group, respectively. Results The relative frequency of GBS among hospitalized patients during the major outbreak of COVID-19 (13/14,408) was significantly higher than that before the COVID-19 epidemic (29/160,669, P

Abstract Background Self-directed learning (SDL) ability is the basis for cultivating nursing students’ ability to find and solve problems, lifelong learning, and providing high-quality nursing talents for healthcare. The O-AMAS (Objective, Activation, Multi-learning, Assessment, Summary) model adheres to the teaching philosophy of student-centered, result-oriented, combines the advantages of online and offline teaching, enriching teaching resources and learning channels, diversifying teaching and evaluation methods, and emphasizing integrating and applying knowledge conducive to improving students’ SDL ability and achieving teaching objectives. This study explored the course design, practical, and application effects under the O-AMAS effective teaching model in internal medicine nursing to provide a basis and reference for combining effective teaching models with blended teaching in future nursing courses. Methods This study is a self-controlled before-after trial. The participants were 76 nursing undergraduates from Hunan Normal University. This study utilizes the O-AMAS effective teaching model to design internal medicine nursing courses and implement blended online and offline teaching. Main links: The overall course design and application are student-centered, after clarifying macro and micro multi-dimensional learning objectives, with online and offline blended teaching environments activated students’ learning behavior and diversified teachers’ teaching activities, then based on instant and dynamic provide effective feedback; finally, students take the initiate to make a brief and potent summary under the teacher guidance. After the course, a unified assessment of the learning effect of nursing students was conducted, including the evaluation of the SDL ability of nursing students, a final comprehensive evaluation grade, and a teaching satisfaction survey. Results The nursing students’ SDL ability scores are higher than before teaching, and the results were statistically significant (P

Abstract We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5d and 3d atoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.

Abstract Background Implicit absenteeism is very common among nurses. Poor perceived social support of intensive care unit nurses has a negative impact on their mental and physical health. There is evidence that lack of occupational coping self-efficacy can promote implicit absenteeism; however, the relationship between lack of occupational coping self-efficacy in perceived social support and implicit absenteeism of intensive care unit nurses is unclear. Therefore, this study aimed to evaluate the role of perceived social support between lack of occupational coping self-efficacy and implicit absenteeism of intensive care unit nurses, and to provide reliable evidence to the management of clinical nurses. Methods A cross-sectional study of 517 intensive care unit nurses in 10 tertiary hospitals in Sichuan province, China was conducted, of which 474 were valid questionnaires with a valid recovery rate of 91.6%. The survey tools included the Chinese version of Implicit Absenteeism Scale, the Chinese version of Perceived Social Support Scale, the Chinese version of Occupational Coping Self-Efficacy Scale and the Sociodemographic characteristics. Descriptive analysis and Pearson correlation analysis were performed using SPSS version 22.0, while the mediating effects were performed using AMOS version 24.0. Results The average of intensive care unit nurses had a total implicit absenteeism score of (16.87 ± 3.98), in this study, the median of intensive care unit nurses’ implicit absenteeism score was 17, there were 210 intensive care unit nurses with low implicit absenteeism (44.3%) and 264 ICU nurses with high implicit absenteeism (55.7%). A total perceived social support score of (62.87 ± 11.61), and a total lack of occupational coping self-efficacy score of (22.78 ± 5.98). The results of Pearson correlation analysis showed that implicit absenteeism was negatively correlated with perceived social support (r = -0.260, P

Abstract Background The real-world tuberculosis (TB) surveillance data was generally incomplete due to underreporting and underdiagnosis. The inventory study aimed to assess and quantify the incompletion of surveillance systems in southwestern China. Methods The inventory study was conducted at randomly selected health facilities (HF) by multi-stage stratified cluster sampling. The participants were included in the period between August of 2020 in province-level and prefecture-level HF, and in the period between June to December of 2020 in other categories of HF respectively. The clinical committee confirmed medical records were matched to the National Notifiable Disease Reporting System (NNDRS) and the Tuberculosis Information Management System (TBIMS) to define the report and register status. The underreporting and under-register rates were evaluated based on the matched data, and factors associated with underreport and under-register were assessed by the 2-level logistic multilevel model (MLM). Results We enrolled 7,749 confirmed TB cases in the analysis. The province representative overall underreport rate to NNDRS was 1.6% (95% confidence interval, 95% CI, 1.3 − 1.9), and the overall under-register rate to TBIMS was 9.6% (95% CI, 8.9–10.3). The various underreport and under-register rates were displayed in different stratifications of background TB disease burden, HF level, HF category, and data source of the medical record in HF among prefectures of the province. The intraclass correlation coefficient (ICC) was 0.57 for the underreporting null MLM, indicating the facility-level cluster effect contributes a great share of variation in total variance. The two-level logistic MLM showed the data source of medical records in HF, diagnostic category of TB, and type of TB were associated with underreporting by adjusting other factors (p

Abstract Improving access to HIV/AIDS healthcare services is of great concern to government and policymakers striving to strengthen overall public health. How to reasonably allocate HIV/AIDS healthcare resources and maximize the equality of access to healthcare services across subdistrict areas has become an urgent problem to be solved. However, there is limited research on this topic in China. It is necessary to evaluate spatial accessibility to improve the accessibility and equity of HIV/AIDS healthcare services. In this study, the improved multi-modal two-step floating catchment area (2SFCA) and inverted 2SFCA (i2SFCA) methods are used to measure the spatial accessibility of HIV/AIDS healthcare services and the crowdedness of the healthcare sites in Shandong Province, China. Then, the theoretical supply and the optimal spatial distribution of resources are calculated and visualized by minimizing the accessibility gaps between demand locations. This study showed that the spatial accessibility of HIV/AIDS service resources in Shandong Province was concentrated and unevenly distributed, and the accessibility scores in the marginal areas of prefecture-level cities were significantly lower than those in other areas. Regions with a large number of doctors had significantly higher levels of spatial accessibility. The ART accessibility scores in the southwest of Shandong Province were higher than those in other regions. As the travel friction coefficient increased, the accessibility scores formed an approximately circular cluster distribution centered on the healthcare sites in geographical distribution. More ART drugs needed to be supplied in marginal areas and more doctors were needed to work on HIV/AIDS in urban areas to address the spatial distribution imbalance of HIV/AIDS healthcare services. This study profoundly analyzed the spatial accessibility of HIV/AIDS healthcare services and provided essential references for decision-makers. In addition, it gives a significant exploration for achieving the goal of equal access to HIV/AIDS healthcare services in the future.

ABSTRACTCandida albicans is a common fungal pathogen that can cause life-threatening infections. MIR1 is considered to be a mitochondrial phosphate carrier of C. albicans, while its role in virulence has not been fully elucidated. In this study, we found that mir1Δ/Δ mutant exhibited severe virulence defect in both nematode and murine models. Further mechanism studies revealed that the mir1Δ/Δ mutant grew more slowly than the wild-type strain and showed severe filamentation defects on the hypha-inducing agar media, including YPD + serum, Lee, Spider + glucose, SLAD, SLD, and YPS. Furthermore, the loss of MIR1 resulted in unfermentable carbon utilisation defect, ATP decrease, and reactive oxygen species (ROS) accumulation in C. albicans. Antioxidant proanthocyanidins, vitamin E, and N-acetyl cysteine (NAC) could reduce intracellular ROS levels and partially rescue the filamentation defects of the mir1Δ/Δ mutant. Accordingly, hypha-specific genes, as well as CEK1 and RIM101 were down-regulated in the mir1Δ/Δ mutant, and this down-regulation could be partially rescued by the addition of the antioxidant NAC. Collectively, MIR1 plays an important role in C. albicans mitochondrial function, filamentation and virulence, and would be a promising antifungal target.

Objective: To compare the quantitative parameters of lung HRCT and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive idiopathic inflammatory myopathy (IIM) patients with different prognoses. Methods: The clinical and imaging data of 19 MDA5 antibody-positive IIM patients admitted to Beijing Shijitan Hospital Affiliated with Capital Medical University between February 2017 and November 2022 were retrospectively analyzed. According to the prognoses, the patients were divided into the good prognoses group (14 cases) and the poor prognoses (intubation or death) group (5 cases). The clinical and laboratory indexes, types of interstitial lung disease (ILD), and CT quantitative indexes were compared between the two groups. Results: There were significant differences in gender; carcinoembryonic antigen; blood oxygen saturation; and the percentages of lymphocytes, monocytes, neutrophils, lymphocytes, and neutrophils between the good versus the poor prognoses groups. The proportion of abnormal respiratory system changes was higher in the poor prognoses group. In terms of the type of ILD, acute interstitial pneumonia (AIP)-like lesions were the main type in the poor prognoses group, and nonspecific interstitial pneumonia (AIP) lesions were the main type in the good prognoses group. For NSIP-like lesions, there was a statistically significant difference between the two groups. The semi-quantitative score of the poor prognoses group was higher, and the volume of whole lung lesions as well as the proportion of whole lung lesions were also higher. Spearman correlation analysis showed that the blood oxygen saturation, monocyte percentage, semi-quantitative score, whole lung lesion volume, and proportion of whole lung lesion were negatively correlated, while carcinoembryonic antigen, neutrophil percentage, and neutrophils were positively correlated with the semi-quantitative score, whole lung lesion volume, and proportion of whole lung lesion. Conclusions: The lung HRCT quantitative indicators, clinical manifestations, and laboratory indicators are different in MDA5 antibody-positive IIM patients with different prognoses. Early evaluation of HRCT imaging manifestations, clinical manifestations, and laboratory indicators is of great significance in determining the prognosis of MDA5 antibody-positive IIM patients, which provides corresponding support for clinical diagnosis and treatment.

Abstract The use of genetic engineering to generate point mutations in induced pluripotent stem cells (iPSCs) is essential for studying a specific genetic effect in an isogenic background. We demonstrate that a combination of p53 inhibition and pro-survival small molecules achieves a homologous recombination rate higher than 90% using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in human iPSCs. Our protocol reduces the effort and time required to create isogenic lines.

Abstract Background Influenza is an acute respiratory infection caused by influenza virus. Maxing Shigan Decoction (MXSGD) is a commonly used traditional Chinese medicine prescription for the prevention and treatment of influenza. However, its mechanism remains unclear. Method The mice model of influenza A virus pneumonia was established by nasal inoculation. After 3 days of intervention, the lung index was calculated, and the pathological changes of lung tissue were detected by HE staining. Firstly, transcriptomics technology was used to analyze the differential genes and important pathways in mouse lung tissue regulated by MXSGD. Then, real-time fluorescent quantitative PCR (RT-PCR) was used to verify the changes in mRNA expression in lung tissues. Finally, intestinal microbiome and intestinal metabolomics were performed to explore the effect of MXSGD on gut microbiota. Results The lung inflammatory cell infiltration in the MXSGD group was significantly reduced (p

Abstract Zinc-alpha2-glycoprotein (AZGP1) has been implicated in peripheral metabolism; however, its role in regulating energy metabolism in the brain, particularly in POMC neurons, remains unknown. Here, we show that AZGP1 in POMC neurons plays a crucial role in controlling whole-body metabolism. POMC neuron-specific overexpression of Azgp1 under high-fat diet conditions reduces energy intake, raises energy expenditure, elevates peripheral tissue leptin and insulin sensitivity, alleviates liver steatosis, and promotes adipose tissue browning. Conversely, mice with inducible deletion of Azgp1 in POMC neurons exhibit the opposite metabolic phenotypes, showing increased susceptibility to diet-induced obesity. Notably, an increase in AZGP1 signaling in the hypothalamus elevates STAT3 phosphorylation and increases POMC neuron excitability. Mechanistically, AZGP1 enhances leptin-JAK2-STAT3 signaling by interacting with acylglycerol kinase (AGK) to block its ubiquitination degradation. Collectively, these results suggest that AZGP1 plays a crucial role in regulating energy homeostasis and glucose/lipid metabolism by acting on hypothalamic POMC neurons.

Abstract Accurate on‐board state‐of‐health (SOH) prediction is crucial for lithium‐ion battery applications. This study presents an in situ prediction technique for minorly deformed battery SOH, utilizing a Gaussian process regression (GPR) model tuned by a Bayesian optimization algorithm. Unlike previous methods that interpret voltage–time data as incremental capacitance curves, our approach directly operates on raw voltage–time data. We apply gray relational analysis to select feature variables as inputs and train the Bayesian Gaussian process regression (BGPR) model using experimental data from batteries under different working conditions. To demonstrate the performance of the BGPR model, we compare it with stepwise linear regression, neural network, and Bayesian support vector machine (BSVM) models. The performance of these four models is evaluated using different performance indicators: mean absolute percentage error (MAPE), root‐mean‐squared percentage error (RMSPE), and coefficient of determination (R²). The results demonstrate that the BGPR model exhibits superior prediction performance with the lowest MAPE (0.11%), RMSPE (0.12%), and the highest R² (0.9915) for minorly deformed batteries. Furthermore, the BGPR model exhibits excellent robustness for SOH prediction of normal batteries under different conditions. This study provides an effective and robust method for accurate on‐board SOH prediction in lithium‐ion battery applications.

Abstract Background The outbreak of Corona Virus Disease (COVID-19) in 2019 has continued until now, posing a huge threat to the public’s physical and mental health, resulting in different degrees of mental health problems. As a vulnerable segment of the public, anxiety is one of the most common mental health problems among COVID-19 patients. Excessive anxiety aggravates the physical and psychological symptoms of COVID-19 patients, which is detrimental to their treatment and recovery, increases financial expenditure, affects family relations, and adds to the medical burden. Objective This study aimed to explore the role of psychological capital and self-esteem in the relationship between insomnia and anxiety, thereby shedding light on the mechanism of the effect of insomnia on anxiety in COVID-19 patients. Methods A cross-sectional study was conducted from April to May 2022 in Fangcang hospital in Shanghai, China. The self-administered questionnaires were distributed to 718 COVID-19 patients via cell phone using the Internet platform “Questionnaire Star”, which included Athens Insomnia Scale, Psychological Capital Questionnaire, Self-esteem Scale, Self-Rating Anxiety Scale, gender, age, marital status, education. Data analysis was performed using descriptive analysis, independent-samples t-test, one-way analysis of variance, Pearson correlation analysis, ordinary least-squares regression, and bootstrap method. Results Education background had significant impact on anxiety in COVID-19 patients (F = 7.70, P

Abstract Cancer testis antigen (CTA) Melanoma Antigen Gene A3 (MAGEA3) were overexpressed in multiple tumor types, but the expression pattern of MAGEA3 in the serum of lung adenocarcinoma (LUAD) remains unclear. Clinically derived serum and serum exosome samples were used to assess the mRNA expression of MAGEA3 and MAGEA4 by qRT-PCR, and serum MAGEA3 and MAGEA4 protein expression were evaluated by ELISA in total 133 healthy volunteers’ and 289 LUAD patients’ serum samples. An analysis of the relationship of the mRNA and protein expression of MAGEA3 and MAGEA4 with clinicopathologic parameters was performed and the diagnostic value of MAGEA3 and MAGEA4 was plotted on an ROC curve. In addition, the correlation of MAGEA3 mRNA with infiltrating immune cells was investigated through TIMER, the CIBERSORT algorithm and the TISIDB database. Expression of serum and serum exosome MAGEA3 and MAGEA4 mRNA were significantly higher in LUAD patients than in healthy donors. MAGEA3 mRNA associated with tumor diameter, TMN stage, and NSE in LUAD serum samples, and MAGEA3 mRNA correlated with N stage in serum-derived exosomes, possessing areas under the curve (AUC) of 0.721 and 0.832, respectively. Besides, serum MAGEA3 protein levels were elevated in LUAD patients, and were closely related to stage and NSE levels, possessing AUC of 0.781. Further analysis signified that the expression of MAGEA3 mRNA was positive correlation with neutrophil, macrophages M2, dendritic cells resting, and eosinophilic, but negatively correlated with B cells, plasma cells, CD8 + T cells, CD4 + T cells, Th17 cells, macrophages and dendritic cells. Collectively, our results suggested that the MAGEA3 expression in mRNA and protein were upregulated in LUAD, and MAGEA3 could be used as a diagnostic biomarker and immunotherapy target for LUAD patients.

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory reactions and tissue damage in the joints. Long-term drug use in clinical practice is often accompanied by adverse reactions. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy with few side effects, offering a potential and safe therapeutic alternative for RA through the induction of immune tolerance. This study aimed to investigate the therapeutic effects of ECP on RA using a collagen-induced arthritis (CIA) murine model, as well as to explore its immunomodulatory effects in vivo. Additionally, particular attention was given to the significant role of monocytes during the ECP process. Methods A murine model of rheumatoid arthritis was established by administering two injections of bovine type II collagen to DBA/1J mice. ECP, ECP-MD (mononuclear cells were depleted during the ECP), MTX, and PBS treatment were applied to the CIA mice. During the treatment process, clinical scores and body weight changes of CIA mice were closely monitored. After six treatment sessions, micro-CT images of the hind paws from live mice were captured. Ankle joints and paws of the mice were collected and processed for histological evaluation. Spleen samples were collected to measure the Th17/Treg cells ratio, and serum samples were collected to assess cytokine and anti-type II collagen IgG levels. Monocytes and dendritic cells populations before and after ECP in vitro were detected by flow cytometry. Result ECP therapy significantly attenuated the progression of CIA, alleviated the severity of clinical symptoms in CIA mice and effectively suppressed synovial hyperplasia, inflammation, and cartilage damage. There was an expansion in the percentage of CD3 + CD4 + CD25 + FoxP3 + Tregs and a decrease in CD3 + CD4 + IL17A + Th17 cells in vivo. Furthermore, ECP reduced the serum levels of pro-inflammatory cytokines IL-6 (53.47 ± 7.074 pg/mL vs 5.142 ± 1.779 pg/mL, P

Abstract Background Plant diseases caused by pathogenic fungi are devastating. However, commonly used fungicides are harmful to the environment, and some are becoming ineffective due to fungal resistance. Therefore, eco-friendly biological methods to control pathogenic fungi are urgently needed. Results In this study, a strain, Paenibacillus sp. lzh-N1, that could inhibit the growth of the pathogenic fungus Mycosphaerella sentina (Fr) Schrorter was isolated from the rhizosphere soil of pear trees, and the complete genome sequence of the strain was obtained, annotated, and analyzed to reveal the genetic foundation of its antagonistic ability. The entire genome of this strain contained a circular chromosome of 5,641,488 bp with a GC content of 45.50%. The results of species identification show that the strain belongs to the same species as P. polymyxa Sb3-1 and P. polymyxa CJX518. Sixteen secondary metabolic biosynthetic gene clusters were predicted by antiSMASH, including those of the antifungal peptides fusaricidin B and paenilarvins. In addition, biofilm formation-related genes containing two potential gene clusters for cyclic lactone autoinducer, a gene encoding S-ribosylhomocysteine lyase (LuxS), and three genes encoding exopolysaccharide biosynthesis protein were identified. Conclusions Antifungal peptides and glucanase biosynthesized by Paenibacillus sp. lzh-N1 may be responsible for its antagonistic effect. Moreover, quorum sensing systems may influence the biocontrol activity of this strain directly or indirectly.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture. Methods/design This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. Discussion This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Abstract Background To compare the bleb morphologies of phacoemulsification combined with Ex-PRESS implantation (Phaco-ExPRESS), phaco trabeculectomy (Phaco-Trab), and trabeculectomy (Trab) in postoperative two years. Methods Patients with primary open-angle glaucoma (POAG) with or without cataracts were included in this study. All patients underwent surgeries of either Phaco-ExPRESS, Phaco-Trab, or Trab. The morphologic structures of the filtering bleb, including microcysts area, hyperreflective dot density, and stromal connective tissue under in vivo confocal microscope (IVCM), were compared between the three groups. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months. Results Eighty-nine eyes from 89 patients were enrolled, including 32 in the Phaco-ExPRESS group, 25 in the Phaco-Trab group, and 32 in the Trab group. In a 24-month follow-up, bleb morphologies in Phaco-ExPRESS were similar to the Trab group. The area of epithelial microcysts was significantly increased in Phaco-ExPRESS and Trab groups while significantly decreased in Phaco-Trab. At postoperative 24 months, the complete success rate was 65.1% in Phaco-ExPRESS, 32.0% in Phaco-Trab, and 59.4% in the Trab group (P = 0.03). The phaco-Trab group had more postoperative anti-glaucoma medications than the other two groups (P

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder (MDD). Vitamin D-binding protein (VDBP) is altered in plasma and postmortem dorsolateral prefrontal cortex (DLPFC) tissues of MDD patients. Thereby, the role of VDBP as a potential biomarker of MDD diagnosis was further assessed. Total extracellular vesicles (EVs) and brain cell-derived EVs (BCDEVs) were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls (HCs) in discovery (20 MDD patients and 20 HCs) and validation cohorts (88 MDD patients and 38 HCs). VDBP level in the cerebrospinal fluid (CSF) from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide (LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles (MDEVs). VDBP was significantly decreased in MDD plasma MDEVs compared to HCs, and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs. VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice. A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques. VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice. The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

Recently， approximately 20% of the products unqualified in the national sampling inspection of imported food have been found through food label inspection， which has become one of the most important inspection methods for imported prepackaged food. In this study， the labels of imported prepackaged food were analyzed to determine the important inspection points， noting that particular attention should be paid to the conformity of products with the entry and registration requirements of the general administration of customs， the use of compliant raw materials， and the standardization of the special labeling content. The results suggest that the quality and efficiency of label inspection should be improved from four aspects： enhancing the awareness and ability to prevent and control unqualified risks， strengthening the training of inspectors’ professional skills， developing an artificial intelligence label verification system， and optimizing the relevant laws and standards to improve the safety of imported prepackaged food.

Objective To evaluate the safety and efficacy of skin care product containing artemisia naphtha in individuals with sensitive skin. Methods A single-center and self-controlled (before and after application) clinical trial was conducted in 31 subjects with sensitive skin. Test product was applied to the face of the subjects twice daily for 4 weeks. Measurement of physiological function, VISIA-CR photography and lactic acid test were carried out on the skin before and on the days 7,14,28 of the trial. 16S rRNA gene sequencing technology was used to analyze the microecological diversity of the skin surface meanwhile physician and subject' self-assessments were performed. Results Physician assessment scores for erythema were decreased at all three follow-up visits (P

Abstract Peste des petits ruminants (PPR) is an acute, contact infectious disease caused by the small ruminant morbillivirus (SRMV), and its morbidity in goats and sheep can be up to 100% with significant mortality. Nanobody generated from camelid animals such as alpaca has attracted wide attention because of its unique advantages compared with conventional antibodies. The main objective of this study was to produce specific nanobodies against SRMV and identify its characteristics. To obtain the coding gene of SRMV-specific nanobodies, we first constructed an immune phage-displayed library from the VHH repertoire of alpaca that was immunized with SRMV-F and -H proteins. By using phage display technology, the target antigen-specific VHHs can be obtained after four consecutive rounds of biopanning. Results showed that the size of this VHH library was 2.26 × 1010 CFU/mL and the SRMV-F and -H specific phage particles were greatly enriched after four rounds of biopanning. The positive phage clones were selected and sequenced, and total of five independent different sequences of SRMV-specific nanobodies were identified. Subsequently, the DNA fragments of the five nanobodies were cloned into E. coli BL21(DE3), respectively, and three of them were successfully expressed and purified. Specificity and affinity towards inactivated SRMV of these purified nanobodies were then evaluated using the ELISA method. Results demonstrated that NbSRMV-1-1, NbSRMV-2-10, and NbSRMV-1-21 showed no cross-reactivity with other antigens, such as inactivated BTV, inactivated FMDV, His-tag labeled protein, and BSA. The ELISA titer of these three nanobodies against inactivated SRMV was up to 1:1000. However, only NbSRMV-1-21 displayed SRMV neutralizing activity at a maximum dilution of 1:4. The results indicate that the nanobodies against SRMV generated in this study could be useful in future applications. This study provided a novel antibody tool and laid a foundation for the treatment and detection of SRMV.

Abstract Traditional residential location choice (RLC) models are based on the characteristics of location and demographics, revealing important patterns of RLC, but no RLC models have yet incorporated individual preferences. This study fills this gap by integrating the pattern of home-based travel into the RLC model. Firstly, by analysing residential trajectory data collected from Beijing and Shenzhen, we find that both residents’ commuting time, that is, time spent commuting to work, and home-based non-commuting (HBNC) time, that is, time spent on the consumption of amenities when departing from homes, follow an extreme value distribution (EVT). This indicates that, based on time budget and financial constraints, residents strive to minimise commuting time and maximise HBNC time. Subsequently, by integrating these findings into individual-level RLC analysis, we obtain an RLC model that aligns with the gravity model. Throughout the model training process, we demonstrate that the RLC model exhibits strong robustness by incorporating control variables, changing the spatial scale of the observation unit, testing for endogeneity, and considering historical RLC. Moreover, the model performs well in applications including assessing dynamic changes in RLC behaviours and making predictions based on previous travel behaviours. The RLC model in this study advances our understanding of human habitat selection behaviour and can be utilised by policymakers to develop and implement effective urban planning and epidemic management policies.

Abstract Background Ovarian cancer (OC) is a prevalent malignancy in the female reproductive system, and developing effective targeted therapies for this disease remains challenging. The aim of this study was to use clinically-relevant OC models to evaluate the therapeutic effectiveness of RC48, an antibody-drug conjugate (ADC) targeting HER2, either alone or in combination with the VEGFR inhibitor Cediranib Maleate (CM), for the treatment of advanced OC. Methods OC tumor specimens and cell lines were analyzed to determine HER2 and VEGFR expression by Western blot, immunocytochemistry and immunofluorescence. Moreover, the OC cell lines, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models were treated with RC48 and/or CM and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for OC both in vitro and in vivo. Additionally, RNA-Seq was performed to investigate the critical mechanism underlying the combination therapy of RC48 and CM. Results Our results demonstrated that RC48 alone effectively targeted and inhibited the growth of HER2-positive OC tumors in both cell lines and PDX models. Furthermore, the combination of RC48 and CM synergistically induced tumor regression in human OC cell lines, as well as CDX and PDX models. Mechanistically, we observed that the combination treatment inhibited the growth of OC cells involved inducing apoptosis and suppressing cell motility. RNA-seq analysis provided further mechanistic insights and revealed that co-administration of RC48 and CM downregulated multiple cancer-related pathways, including the AKT/mTOR pathway, cell cycle, and cell proliferation. Notably, our data further confirmed that the PI3K-AKT pathway played a key role in the inhibition of proliferation triggered by combinational treatment of RC48 and CM in OC cells. Conclusions These findings provide a preclinical framework supporting the potential of dual targeting HER2 and VEGFR as a promising therapeutic strategy to improve outcomes in patients with OC.

Centipedegrass (Eremochloa ophiuroides) is an important warm-season grass plant used as a turfgrass as well as pasture grass in tropical and subtropical regions, with wide application in land surface greening and soil conservation in South China and southern United States. In this study, the complete cp genome of E. ophiuroides was assembled using high-throughput Illumina sequencing technology. The circle pseudomolecule for E. ophiuroides cp genome is 139,107 bp in length, with a quadripartite structure consisting of a large single copyregion of 82,081 bp and a small single copy region of 12,566 bp separated by a pair of inverted repeat regions of 22,230 bp each. The overall A + T content of the whole genome is 61.60%, showing an asymmetric nucleotide composition. The genome encodes a total of 131 gene species, composed of 20 duplicated genes within the IR regions and 111 unique genes comprising 77 protein-coding genes, 30 transfer RNA genes, and 4 ribosome RNA genes. The complete cp genome sequence contains 51 long repeats and 197 simple sequence repeats, and a high degree of collinearity among E. ophiuroide and other Gramineae plants was disclosed. Phylogenetic analysis showed E. ophiuroides, together with the other two Eremochloa species, is closely related to Mnesithea helferi within the subtribe Rottboelliinae. These findings will be beneficial for the classification and identification of the Eremochloa taxa, phylogenetic resolution, novel gene discovery, and functional genomic studies for the genus Eremochloa.

Abstract Progressive cerebral infarction (PCI) is a common complication in patients with ischemic stroke that leads to poor prognosis. Blood pressure (BP) can indicate post‐stroke hemodynamic changes which play a key role in the development of PCI. The authors aim to investigate the association between BP‐derived hemodynamic parameters and PCI. Clinical data and BP recordings were collected from 80 patients with cerebral infarction, including 40 patients with PCI and 40 patients with non‐progressive cerebral infarction (NPCI). Hemodynamic parameters were calculated from the BP recordings of the first 7 days after admission, including systolic and diastolic BP, mean arterial pressure, and pulse pressure (PP), with the mean values of each group calculated and compared between daytime and nighttime, and between different days. Hemodynamic parameters and circadian BP rhythm patterns were compared between PCI and NPCI groups using t‐test or non‐parametric equivalent for continuous variables, Chi‐squared test or Fisher's exact test for categorical variables, Cox proportional hazards regression analysis and binary logistic regression analysis for potential risk factors. In PCI and NPCI groups, significant decrease of daytime systolic BP appeared on the second and sixth days, respectively. Systolic BP and fibrinogen at admission, daytime systolic BP of the first day, nighttime systolic BP of the third day, PP, and the ratio of abnormal BP circadian rhythms were all higher in the PCI group. PCI and NPCI groups were significantly different in BP circadian rhythm pattern. PCI is associated with higher systolic BP, PP and more abnormal circadian rhythms of BP.

Abstract Salt marshes can export considerable nutrients and carbon to the ocean through submarine groundwater discharge (SGD). However, the complicated SGD processes in salt marshes remain poorly understood. Here, we first report the phenomenon of numerous highly saline artesian springs found in a salt marsh system of East China. Multiple methods including time‐series thermal monitoring, isotope signatures, and high‐resolution electrical resistivity tomography were combined to determine their origin and trajectory. Strong evidence suggests that these springs keep discharging even during high tide and represent a long‐term re‐distribution process of the ancient marine water trapped in the unconfined aquifer. This new pattern of spring‐derived groundwater flow indicates a hidden SGD pathway and has significant implications for studies concerning SGD‐derived fluxes in similar multi‐aquifer‐aquitard coastal systems.

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.

Este artigo investiga a visão gramatical do padre lazarista português Joaquim Afonso Gonçalves (1781–1841), através da análise das suas reflexões metalinguísticas presentes na Arte China (1829), um compêndio gramatical elaborado para o ensino-aprendizagem do chinês a europeus em Macau no início do século XIX. Iniciando-se com as referências gramaticais incluídas nos capítulos III (Grammatica) e IV (Syntaxe) deste manual didático, a pesquisa centra-se na formação e classificação das palavras chinesas sob a perspetiva contrastiva do gramático português. O estudo revela que os processos de formação de palavras distinguidos no seu método gramatical se fundamentam nas características morfológicas dos vocábulos chineses. Além disso, as partes da oração utilizadas para classificar o léxico chinês não apenas herdam o modelo analítico e descritivo greco-latino como também incorporam aspetos da tradição local e adotam novas categorias para retratar os aspetos mais peculiares do chinês, em comparação com a língua materna de Gonçalves. Esta análise visa lançar luz sobre as interpretações gramaticais do sinólogo português, originalmente destinadas aos discípulos diretos, que podem parecer incompletas e obscuras para os leitores contemporâneos.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is known to infect people of all ages and both sexes. Senior populations have the greatest risk of severe COVID-19, and sexual dimorphism in clinical outcomes has been reported. Neurological symptoms are widely observed in COVID-19 patients, with many survivors exhibiting persistent neurological and cognitive impairment. The present study aims to investigate the impact of age and sex on the neuroinflammatory response to SARS-CoV-2 infection using a mouse model. Wild-type C57BL/6J mice were intranasally inoculated with SARS-CoV-2 lineage B.1.351, a variant known to infect mice. Older male mice exhibited a significantly greater weight loss and higher viral loads in the lung at 3 days post infection. Notably, no viral RNA was detected in the brains of infected mice. Nevertheless, expression of IL-6, TNF-α, and CCL-2 in the lung and brain increased with viral infection. RNA-seq transcriptomic analysis of brains showed that SARS-CoV-2 infection caused significant changes in gene expression profiles, implicating innate immunity, defense response to virus, and cerebrovascular and neuronal functions. These findings demonstrate that SARS-CoV-2 infection triggers a neuroinflammatory response, despite the lack of detectable virus in the brain. Aberrant activation of innate immune response, disruption of blood-brain barrier and endothelial cell integrity, and suppression of neuronal activity and axonogenesis underlie the impact of SARS-CoV-2 infection on the brain. Understanding the role of these affected pathways in SARS-CoV-2 pathogenesis helps identify appropriate points of therapeutic interventions to alleviate neurological dysfunction observed during COVID-19.

The water quality index (WQI) is a widely used tool for comprehensive assessment of river environments. However, its calculation involves numerous water quality parameters, making sample collection and laboratory analysis time-consuming and costly. This study aimed to identify key water parameters and the most reliable prediction models that could provide maximum accuracy using minimal indicators. Water quality from 2020 to 2023 were collected including nine biophysical and chemical indicators in seventeen rivers in Yancheng and Nantong, two coastal cities in Jiangsu Province, China, adjacent to the Yellow Sea. Linear regression and seven machine learning models (Artificial Neural Network (ANN), Self-Organizing Maps (SOM), K-Nearest Neighbor (KNN), Support Vector Machines (SVM), Random Forest (RF), Extreme Gradient Boosting (XGB) and Stochastic Gradient Boosting (SGB)) were developed to predict WQI using different groups of input variables based on correlation analysis. The results indicated that water quality improved from 2020 to 2022 but deteriorated in 2023, with inland stations exhibiting better conditions than coastal ones, particularly in terms of turbidity and nutrients. The water environment was comparatively better in Nantong than in Yancheng, with mean WQI values of approximately 55.3–72.0 and 56.4–67.3, respectively. The classifications ''Good'' and ''Medium'' accounted for 80 % of the records, with no instances of ''Excellent'' and 2 % classified as ''Bad''. The performance of all prediction models, except for SOM, improved with the addition of input variables, achieving R2 values higher than 0.99 in models such as SVM, RF, XGB, and SGB. The most reliable models were RF and XGB with key parameters of total phosphorus (TP), ammonia nitrogen (AN), and dissolved oxygen (DO) (R2 = 0.98 and 0.91 for training and testing phase) for predicting WQI values, and RF using TP and AN (accuracy higher than 85 %) for WQI grades. The prediction accuracy for ''Medium'' and ''Low'' water quality grades was highest at 90 %, followed by the ''Good'' level at 70 %. The model results could contribute to efficient water quality evaluation by identifying key water parameters and facilitating effective water quality management in river basins.

Background and aimsThe American Heart Association (AHA) recently introduced the Life’s Essential 8 (LE8) to improve cardiovascular health (CVH). However, the association between LE8 and the risk of prediabetes or diabetes is not yet fully understood. Consequently, this study aims to assess the association between CVH, as evaluated by LE8, and the risk of prediabetes and diabetes.Methods and ResultsThis cross-sectional study encompassed 7,739 participants aged ≥20 years from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES). The CVH of participants was evaluated using the LE8, combining four health behaviors and three health factors. Glucose metabolic status categories included normal glucose metabolism, prediabetes including isolated impaired fasting glucose, isolated impaired glucose tolerance, both IFG and IGT, and diabetes. The associations between CVH and prediabetes and diabetes were analyzed using logistic regression, linear regression, restricted cubic splines, and subgroup analyses. Among 7,739 participants, 1,949 had iIFG, 1,165 were diagnosed with iIGT, 799 were IFG+IGT, and 537 were diagnosed with diabetes. After multivariable adjustments, CVH scores were inversely associated with prediabetes and diabetes, with the most robust inverse association observed between IFG+IGT and CVH across all prediabetes subgroups. Of all CVH components not directly in the causal pathway, body mass index (BMI) had the most robust associations with prediabetes and diabetes. Subgroup analyses indicated that the negative correlation between CVH and prediabetes was stronger among those with university or higher education.ConclusionCVH, as defined by LE8, showed a significant negative association with prediabetes and diabetes.

Background: As a political, economic, and cultural exchange channel between ancient China and countries in Asia, Europe, and Africa, the Silk Road has promoted political, trade, and cultural exchanges between China and foreign countries in Chinese history and also promoted the development of traditional Chinese medicine. Methods: This article summarizes the introduction of medicinal materials from the Han to Qing Dynasties, spanning approximately 2000 years. Results: A total of 235 types of medicinal plant materials were imported. An analysis of 178 medicinal herbs of known origin, belonging to 72 families revealed their effectiveness in treating 20 diseases. The maximum number of medicinal herbs used to treat gastrointestinal and digestive disorders (GAS) was 122. The applications and origin of exotic medicinal materials, including draconis sanguis and olibanum have changed during the development of the Silk Road. Imported medicinal materials are affected by five factors, including local demand, adaptability, cultural exchange, scarcity, and medical theory. Five modes for introducing medicinal materials include the onshore Silk Road, the maritime Silk Road, diplomatic envoys and gifts, overseas Chinese, cultural exchange, and medical integration. The application of exotic medicinal materials expands the resources and application fields of traditional Chinese medicine, enriching the theory of traditional Chinese medicine. Conclusion: Traditional Chinese medicinal compounds introduced to China through the ancient Silk Road not only promoted their integration into foreign medicine but also had long-lasting impacts to date and over a wide range, thereby considerably affecting the pharmaceutical and general healthcare industries.

Bamboo scrimber (BS) is a novel renewable biocomposite material with excellent mechanical performance and stability that is suitable for load-bearing structural members. Beam-type components are among the most widely used members in structural engineering, and their flexural behaviour is crucial for the safety and applicability of structures. Based on a review of the existing literature, this article presents a comprehensive overview and discussion of the research and development of various forms of beam-type BS members with the aim of reaching a clearer understanding of the bending mechanisms and mechanical characteristics of BS beams. The members highlighted in this review include general BS beams, reinforced BS beams (with steel bars and fibre-reinforced polymer plates), composite BS beams (with profile steel and concrete), and strengthened damaged BS beams. Moreover, the factors affecting the flexural performance of BS beams, such as span-depth ratios, their mechanical properties, and reinforcing materials, are analysed quantitatively. Finally, the calculation models for the flexural bearing capacity and stiffness of BS beams are summarised and compared. This review aims to illustrate the potential of BS in the field of structural engineering and provide references for future research and design methods for BS flexural members.

Abstract The islet of Langerhans, functioning as a “mini organ”, plays a vital role in regulating endocrine activities due to its intricate structure. Dysfunction in these islets is closely associated with the development of diabetes mellitus (DM). To offer valuable insights for DM research and treatment, various approaches have been proposed to create artificial islets or islet organoids with high similarity to natural islets, under the collaborative effort of biologists, clinical physicians, and biomedical engineers. This review investigates the design and fabrication of artificial islets considering both biological and tissue engineering aspects. It begins by examining the natural structures and functions of native islets and proceeds to analyze the protocols for generating islets from stem cells. The review also outlines various techniques used in crafting artificial islets, with a specific focus on hydrogel‐based ones. Additionally, it provides a concise overview of the materials and devices employed in the clinical applications of artificial islets. Throughout, the primary goal is to develop artificial islets, thereby bridging the realms of developmental biology, clinical medicine, and tissue engineering.

Atomization is a treatment method to make inhaled liquids into aerosols and transport them to target organs in the form of fog or smoke. It has the advantages of improving the bioavailability of drugs, being painless, and non-invasive, and is now widely used in the treatment of lung and oral lesions. Aerosol inhalation as the route of administration of therapeutic proteins holds significant promise due to its ability to achieve high bioavailability in non-invasive pathways. Currently, a great number of therapeutic proteins such as alpha-1 antitrypsin and Dornase alfa are effective. Recombinant humanized collagen type III (rhCol III) as a therapeutic protein is widely used in the biomedical field, but atomization is not a common route of administration for rhCol III, presenting great potential for development. However, the structural stability of recombinant humanized collagen after atomization needs further investigation. This study demonstrated that the rhCol III subjected to atomization through compressed air had retained its original molecular weights, triple helical structures, and the ability to promote cell adhesion. In other words, the rhCol III can maintain its stability after undergoing atomization. Although more research is required to determine the efficacy and safety of the rhCol III after atomization, this study can lay the groundwork for future research.

Recently, the influence of subsurface dams on solute transport in coastal aquifers has become a hot research topic. Although many studies have been conducted, the combined effects of subsurface dam and tides on variable-density solute transport remain unclear, and this study aimed to fill this research gap. In the current study, a numerical model representing a 2-D cross-shore coastal aquifer was established. The model simulated cases with and without a subsurface dam, and sensitivity analysis cases with different height and location of the subsurface dam and solute concentration. The results show that a subsurface dam blocks a portion of the solute plume, which can only be discharged by dilution at the edges, thereby altering its discharge pattern and reducing their discharge rate. The addition of a subsurface dam may either prolong or shorten the residence time of solute,depending on the location rather than the height of the subsurface dam. In particular, a more landward subsurface dam would significantly increase the residence time; sensitivity analysis demonstrates that both the landward shift and the height increase of the subsurface dam contribute to a heightened ratio of dynamic mass distribution for the solute plume within the freshwater and saltwater zones of the aquifer, with maximum changes in mass distribution ratios of 87.22% and 300%, respectively. Also, these factors cause the solute to migrate both seaward and landward, respectively, across the primary outflow regions of the aquifer-ocean interface. Results from this study may provide theoretical guidance for the optimal design and environmental impact assessment of subsurface dams.

Quantifying and interpreting the water–energy–food (WEF) nexus is critical to achieve the sustainable development of urban resources. The mismatch between urban water, energy and food allocations is a prominent problem that is particularly acute in the Yellow River Basin (YRB) of China. In this study, models for the WEF coupling degree and coupling efficiency were constructed. The WEF coupling efficiencies of the 94 cities in the YRB from 2011 to 2020 were quantified using a data envelopment analysis (DEA) model. On this basis, the spatial distribution characteristics and evolutionary trends of different urban WEF coupling efficiencies were analysed and explored using an exploratory spatial data analysis (ESDA) model and a parametric kernel density estimation model. The results show that the energy subsystem constrain the development of the WEF nexus, and the food subsystem, in turn, regulates the development of the WEF nexus. In some years, the phenomenon of ‘resource curse’ occurred, in which the WEF coupling degree increased while the coupling efficiency decreased. Overall, the values of the urban WEF coupling efficiency were low, ranging from 0.5300 to 0.6300, which is not effective. Spatial clustering was detected in the urban WEF coupling efficiency. The clustering types were ‘high–high’ clustering areas in less developed regions and ‘low–low’ clustering areas in developed regions. The two clusters and the median contiguous group had different evolutionary trends. Both efficiency and polarisation increased in the high-clustering group, efficiency improved in the low-clustering group, and a new efficiency pole was formed in the median contiguous group. Among the three grouped cities, we discuss the potential of policies such as cross-city cooperation, intra-city multi-sectoral cooperation and cultivating new central growth cities to improve the WEF coupling efficiency in the YRB.

This research aims to explore the influencing mechanism of fashion brand cultural content marketing on consumers’ willingness to buy. The concept of content marketing for fashion brand culture was analyzed from the four dimensions of functional content, entertainment content, emotional content, and interactive content according to content marketing theory, and the influencing mechanism was studied based on the information adoption theory. Furthermore, it is verified for the mediating role of information content quality perception, information utility quality perception, information expression quality perception, information carrier quality perception, information adoption, and the moderating role of information involvement and brand trust. The structural equation model was developed and empirically tested the hypothesis. The results show that fashion brand culture content marketing can promote consumers’ willingness to buy. Consumers generate purchase intention by perceiving information content quality, information utility quality, information expression quality, information carrier quality, and information adoption. It was found that consumers with high involvement degrees are more likely to perceive information. Moreover, consumers with high brand trust will promote the effect of information adoption on consumers’ purchase intention. This research provides new ideas and references for the content marketing of fashion brand culture. It provides quantitative scientific data for fashion enterprises to grasp the direction of fashion brand culture content marketing and implement brand culture shaping and communication strategies.