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AIM: To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy (DR) utilizing a two-sample Mendelian randomization (MR) analysis. METHODS: The research data were obtained from summary statistics of genome-wide association studies (GWAS). Genetic loci closely related to cheese intake were extracted as instrumental variables (IVs), and DR was the outcome variable. The data were extracted from individuals of European ethnicity. The data of cheese intake consisted of 451 486 samples with 9 851 867 single nucleotide polymorphisms (SNPs), while the DR data consisted of 206 234 samples with 16 380 446 SNPs. Sixty-one genetic loci closely related to cheese intake were selected as IVs. MR analysis was performed by inverse-variance weighted (IVW) method and MR-Egger regression respectively. The causal relationship between cheese intake and DR was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test. RESULTS: The P value of the IVW method was less than 0.05, indicating a significant negative correlation between cheese intake and DR. MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022, and a P-value of 0.634, indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors. Besides, heterogeneity tests confirmed the absence of heterogeneity, and the “leave-one-out” sensitivity analysis demonstrated that the results were stable. CONCLUSION: Cheese intake is causally negatively correlated with the occurrence of DR, and cheese intake could reduce the risk of DR.

Abstract Background Phosphofructokinase P (PFKP) is a key rate-limiting enzyme in glycolysis, playing a crucial role in various pathophysiological processes. However, its specific function in tumors remains unclear. This study aims to evaluate the expression and specific role of PFKP across multiple tumor types (Pan-cancer) and to explore its potential clinical significance as a therapeutic target in cancer treatment. Methods We analyzed the expression of PFKP, immune cell infiltration, and patient prognosis across various cancers using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we conducted a series of experiments in lung cancer cells, including Western blot, CCK-8 assay, colony formation assay, transwell migration assay, scratch wound healing assay, LDH release assay, and flow cytometry, to evaluate the impact of PFKP on tumor cells. Results PFKP was found to be highly expressed in most cancers and identified as a prognostic risk factor. Elevated PFKP expression is associated with poorer clinical outcomes, particularly in lung adenocarcinoma (LUAD). Receiver operating characteristic (ROC) curve analysis indicated that PFKP can effectively differentiate between cancerous and normal tissues. The expression of PFKP in most tumors showed significant correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune score, and immune cell infiltration. In vitro experiments demonstrated that PFKP overexpression promotes lung cancer cell proliferation and migration while inhibiting apoptosis, whereas PFKP deficiency results in the opposite effects. Conclusion PFKP acts as an oncogene involved in tumorigenesis and may influence the immune microenvironment within the tumor. Our findings suggest that PFKP could serve as a potential biomarker for predicting prognosis and the efficacy of immunotherapy in tumors.

Abstract Background HIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the ‘CDC-Public Security Bureau-NGO’. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions. Methods The research design of this study incorporates both a serial cross-sectional study and time-series analysis from 2014 to 2021, including a 4-year traditional intervention (2014–2017) and the 4-year ‘CDC-Public Security Bureau-NGO’ innovative intervention (2018–2021), was conducted to evaluate the effects of the new intervention. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018–2021; P and C values were used to evaluate the performance of the model. Mann-Kendall test and descriptive methods were used to analyzed the trend of traditional and innovative interventions models on HIV positive detection rate in FSWs and elderly clients. Results The condom usage rates during the last commercial sexual encounter for FSWs and elderly clients improved from 74.9% and 9.1%, respectively, to 96.9% and 28.1%. (P

As a “cold tumor”, triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an “in situ nanovaccine” Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an “in situ nanovaccine” to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid‐derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, “cold tumor” was transformed into a “hot tumor”, not only implementing a “turning foes to friends” therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

Abstract Background There is an increasing number of human immunodeficiency virus (HIV) reported cases among students in Southwest China. However, the data on HIV/sex-related knowledge, attitude toward sex, sexual behaviors, and correlates of pre-exposure prophylaxis (PrEP)-eligible behaviors among college students in this area is still limited. This study aimed to assess the prevalence of HIV/sex-related knowledge, sexual attitudes, sexual behaviors, and factors associated with PrEP-eligible behaviors among college students. Method An online survey from 2020 to 2021 based on a multistage stratified and cluster sampling method was conducted among college students in Southwest China, and a well-designed questionnaire collected data. Propensity score matching (PSM), logistic, and log-binomial regression were used to identify the determinants of PrEP-eligible behaviors. Result A total of 108,987 students participated in the survey, and 92,946 provided valid responses. 91.6% (85,145/92,946) had good HIV-related knowledge, while only 26.0% (24,137/92,946) reported awareness of sex-related knowledge. Furthermore, more than half of the participants (64.5%) held negative stances towards engaging in “one-night stand”, and 58.9% (617/1,047) reported PrEP-eligible behaviors. Log-binomial regression analysis indicated that unaware of HIV-related knowledge (aPR = 1.66, 95% CI:1.22–2.26, P = 0.001), not discussing about sex with their parent(s) (aPR = 1.16, 95% CI:1.01–1.33, P = 0.021), not receiving sex-related education in school(aPR = 1.24, 95% CI: 1.07–1.45, P = 0.005), not participating in HIV/AIDS prevention activities in the past year (aPR = 1.32, 95%CI:1.09–1.60, P = 0.004), experiencing forced sex (aPR = 2.08, 95% CI: 1.19–3.63, P = 0.010), and having the drug abuse (aPR = 22.21, 95% CI:5.59–88.31, P

Abstract Adversarial training suffers from poor effectiveness due to the challenging optimisation of loss with hard labels. To address this issue, adversarial distillation has emerged as a potential solution, encouraging target models to mimic the output of the teachers. However, reliance on pre‐training teachers leads to additional training costs and raises concerns about the reliability of their knowledge. Furthermore, existing methods fail to consider the significant differences in unconfident samples between early and late stages, potentially resulting in robust overfitting. An adversarial defence method named Clean, Performance‐robust, and Performance‐sensitive Historical Information based Adversarial Self‐Distillation (CPr & PsHI‐ASD) is presented. Firstly, an adversarial self‐distillation replacement method based on clean, performance‐robust, and performance‐sensitive historical information is developed to eliminate pre‐training costs and enhance guidance reliability for the target model. Secondly, adversarial self‐distillation algorithms that leverage knowledge distilled from the previous iteration are introduced to facilitate the self‐distillation of adversarial knowledge and mitigate the problem of robust overfitting. Experiments are conducted to evaluate the performance of the proposed method on CIFAR‐10, CIFAR‐100, and Tiny‐ImageNet datasets. The results demonstrate that the CPr&PsHI‐ASD method is more effective than existing adversarial distillation methods in enhancing adversarial robustness and mitigating robust overfitting issues against various adversarial attacks.

The high cost of using the niobium (Nb) barrier for manufacturing magnesium diboride (MgB2) mono-and multi-filamentary wires for large-scale applications has become one of the barriers to replacing current commercial niobium-titanium superconductors. The potential of replacing the Nb barrier with a low-cost iron (Fe) barrier for multifilament MgB2 superconducting wires is investigated in this manuscript. Therefore, MgB2 wires with Fe barrier sintered with different temperatures are studied (from 650 °C to 900 °C for 1 h) to investigate the non-superconducting reaction phase of Fe-B. Their superconducting performance including engineering critical current density (Je) and n-value are tested at 4.2 K in various external magnetic fields. The best sample sintered at 650 °C for 1 h has achieved a Je value of 3.64 × 104 A cm−2 and an n-value of 61 in 2 T magnetic field due to the reduced formation of Fe2B, better grain connectivity and homogenous microstructure. For microstructural analysis, the focused ion beam (FIB) is utilised for the first time to acquire three-dimensional microstructures and elemental mappings of the interface between the Fe barrier and MgB2 core of different wires. The results have shown that if the sintering temperature can be controlled properly, the Je and n-value of the wire are still acceptable for magnet applications. The formation of Fe2B is identified along the edge of MgB2, as the temperature increases, the content of Fe2B also increases which causes the degradation in the performance of wires.

Abstract In deep‐ocean natural gas hydrate exploitation operation, the fatigue failure mechanism has attracted more and more attention from scholars, but it has not been effectively disclosed. Therefore, in this work, a multifield coupling and multiple‐nonlinear vibration model of lifting pipe is established, which can accurately determine the alternating stress of deep‐ocean lifting pipe. Second, according to Forman theory, the calculation method of crack propagation length and depth on the surface of a deep‐water riser is established, which is verified by the comparison between the experimental and theoretical model calculation results. The results demonstrate that, first, the effect of residual stress in the welded joint of deep‐ocean lifting pipe should be considered in the later parameter influence analysis. Second, the fatigue growth life of deep‐water pipe with small outflow velocity is mainly determined by tensile stress, and that is determined by both tensile stress and bending stress with large outflow velocity. Third, more attention should be paid to the vibration of the lower pipe on‐site to reduce its vibration frequency and vibration stress amplitude, which can effectively reduce the surface crack propagation state of the deep‐ocean pipe and improve the service life of the pipe. Fourth, properly adjusting the tension coefficient of the tensioner during field operation can effectively improve the safety of the pipe, and the optimal tension coefficient is related to the configuration of the deep‐ocean pipe system, which can be analyzed and determined by the model.

Abstract Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract. Various programmed cell death pathways in the intestinal mucosa are crucial to the pathogenesis of UC. Disulfidptosis, a recently identified form of programmed cell death, has not been extensively reported in the context of UC. This study evaluated the expression of disulfidptosis-related genes (DRGs) in UC through public databases and assessed disulfide accumulation in the intestinal mucosal tissues of UC patients and dextran sulfate sodium (DSS)-induced colitis mice via targeted metabolomics. We utilized various bioinformatics techniques to identify UC-specific disulfidptosis signature genes, analyze their potential functions, and investigate their association with immune cell infiltration in UC. The mRNA and protein expression levels of these signature genes were confirmed in the intestinal mucosa of DSS-induced colitis mice and UC patients. A total of 24 DRGs showed differential expression in UC. Our findings underscore the role of disulfide stress in UC. Four UC-related disulfidptosis signature genes—SLC7A11, LRPPRC, NDUFS1, and CD2AP—were identified. Their relationships with immune infiltration in UC were analyzed using CIBERSORT, and their expression levels were validated by quantitative real-time PCR and western blotting. This study provides further insights into their potential functions and explores their links to immune infiltration in UC. In summary, disulfidptosis, as a type of programmed cell death, may significantly influence the pathogenesis of UC by modulating the homeostasis of the intestinal mucosal barrier.

Abstract Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Abstract Accurate jet charge identification is essential for precise electroweak and flavor measurements at the high-energy frontier. We propose a novel method called the Leading Particle Jet Charge method (LPJC) to determine the jet charge based on information of the leading charged particle. Tested on Z → b b ¯ $$ b\overline{b} $$ and Z → c c ¯ $$ c\overline{c} $$ samples at center-of-mass energy of 91.2 GeV, the LPJC achieves an effective tagging power ϵ eff of 20%/9% for c/b jet, respectively. In combination with the Weighted Jet Charge method (WJC), we develop a Heavy Flavor Jet Charge method (HFJC), which achieves an effective tagging power ϵ eff of 39%/20% for c/b jet, respectively. This paper also discusses the dependencies between jet charge identification performance and the fragmentation process of heavy flavor jets, as well as critical detector performances.

Abstract Rapid and accurate detection of respiratory virus aerosols is highlighted for virus surveillance and infection control. Here, we report a wireless immunoassay technology for fast (within 10 min), on-site (wireless and battery-free), and sensitive (limit of detection down to fg/L) detection of virus antigens in aerosols. The wireless immunoassay leverages the immuno-responsive hydrogel-modulated radio frequency resonant sensor to capture and amplify the recognition of virus antigen, and flexible readout network to transduce the immuno bindings into electrical signals. The wireless immunoassay achieves simultaneous detection of respiratory viruses such as severe acute respiratory syndrome coronavirus 2, influenza A H1N1 virus, and respiratory syncytial virus for community infection surveillance. Direct detection of unpretreated clinical samples further demonstrates high accuracy for diagnosis of respiratory virus infection. This work provides a sensitive and accurate immunoassay technology for on-site virus detection and disease diagnosis compatible with wearable integration.

Abstract Background Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. Method Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. Results A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507–0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116–1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425–0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135–0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322–0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells

BackgroundThere is increasing focus on HIV-1 CRF55_01B in China. However, there is limited information regarding the dissemination of CRF55_01B across different regions and populations in Guangxi. This study was performed to elucidate the evolutionary history of the introduction and dissemination of CRF55_01B in Guangxi.MethodsMolecular network and phylogenetic analyses were used to investigate the transmission characteristics of CRF55_01B in China. The analyses particularly focused on the cross-provincial spatial and temporal transmission patterns between Guangdong Province and Guangxi, as well as the transmission dynamics among different regions and populations within Guangxi.ResultsIn total, 2226 partial pol sequences of CRF55_01B strains sampled from 2007 to 2022 were collected, including 1895 (85.09%) sequences from Guangdong, 199 (8.94%) sequences from Guangxi, and 172 (7.59%) sequences from other provinces of China. Most people living with HIV in Guangxi were infected with HIV-1 through heterosexuals (52.76%). Among these, 19.10% had a history of commercial heterosexual contact (CHC) and 15.58% had a history of non-marital non-commercial heterosexual contact (NMNCHC). Overall, 1418 sequences were identified in the molecular network. Notably, the sequences from Guangdong Province were most closely linked to those from Guangxi. Phylogenetic analysis showed that CRF55_01B was first introduced from Shenzhen City to Nanning City around 2007. Subsequently, CRF55_01B established local transmission within Guangxi, with Nanning City serving as the transmission center from 2008 to 2017. After 2017, the CRF55_01B strain spread to other regions of Guangxi. Men who have sex with men (MSM) and men with a history of CHC have played a significant role in the transmission of CRF55_01B among different populations in Guangxi.ConclusionsThis study provides evidence on the transmission trajectory of CRF55_01B among different regions and populations in Guangxi. Given the bridging role of men with a history of CHC in the dissemination of CRF55_01B from MSM to the general population, it is imperative to enhance surveillance among key populations to mitigate the secondary transmission of HIV-1.

An adaptive maneuvering target tracking algorithm based on fuzzy inference is proposed to deal with the low adaptive capacity of variable structure interacting multi-model algorithms for target maneuver uncertainty and measurement uncertainty in maneuvering target tracking. A two-stage maneuvering discrimination model based on fuzzy inference is designed, which uses the probability of models and residual weighted norm of the main model to infer the reliability of the main model and the possibility of maneuvering discrimination. The two-stage maneuvering discriminant is introduced into the framework of expected-model augmentation based on likely model-set (EMA-LMS). A kind of fuzzy inference-based EMA-LMS algorithm is proposed to adjust the parameter and strategy of model-set adaption online. This algorithm generates an expected model that is closer to the real motion model and makes better choices for model selection. The simulation results show that the proposed algorithm can strengthen the adaptive capacity for the uncertainty of target maneuver and measurement, and improve accuracy.

Abstract The close link between HIV-1 infection and the occurrence of pulmonary arterial hypertension (PAH). However, the underlying molecular mechanisms of their interrelation remain unclear. The microarray data of HIV-1 and PAH were downloaded from GEO database. We utilized WGCNA to identify shared genes between HIV-1 and PAH, followed by conducting GO and pathway enrichment analyses. Subsequently, differentially genes analysis was performed using external validation datasets to further filter hub genes. Immunoinfiltration analysis was performed using CIBERSORT. Finally, hub gene expression was validated using scRNA-seq data. We identified 109 shared genes through WGCNA, primarily enriched in type I interferon (IFN) pathways. By taking the intersection of WGCNA important module genes and DEGs, ISG15 and IFI27 were identified as pivotal hub genes. Immunoinfiltration analysis and scRNA-seq results indicated the significant role of monocytes in the shared molecular mechanisms of HIV-1 and PAH. In summary, our study illustrated the possible mechanism of PAH secondary to HIV-1 and showed that the heightened IFN response in HIV-1 might be a crucial susceptibility factor for PAH, with monocytes being pivotal cells involved in the type I IFN response pathway. This provides potential new insights for further investigating the molecular mechanisms connecting HIV-1 and PAH.

Abstract Background No uniform consensus has been achieved regarding the ambulation protocol after transfemoral cerebral angiography (TFA). Until now, in most hospitals patients are prescribed 8-12 h strict immobilization along with bed rest in the supine position after TFA in China, which causes great discomfort to patients. Objective To evaluate the effect of an evidence-based early ambulation protocol on the prevention of vascular complications and general discomfort in patients following transfemoral cerebral angiography (TFA). Methods A prospective quasi-experimental study was conducted on 214 patients undergoing TFA with manual compression. Patients in the experimental group were placed supine position for 2 h with a sandbag placed on the wound dressing, followed by a semi-seated position for another 2 h. After this period, patients took 2 h bed rest (move freely) with the sandbag removed, and were allowed to get out of bed 6 h after TFA. Patients in the control group were restricted to an 8 h bed rest in a supine position with the affected leg straight and immobilized. The vascular complications (bleeding, hematoma, ecchymosis) and levels of comfort (low back pain, leg pain, and blood pressure) were evaluated after the procedure. Numeric Rating Scale (NRS) pain scores, systolic blood pressure (SBP); diastolic blood pressure (DBP) were measured hourly for 8 h after TFA. Results There was no significant difference in the two groups with regard to vascular complications including bleeding events (P = 0.621), bleeding volume (P = 0.321), and area of hematoma (P = 0.156). The area of ecchymosis in the experimental group was significantly smaller than the control group (P = 0.031). Compared with the control group, the NRS score for low back pain in the 4th, 5th, 6th, 7th, and 8th hour after TFA were significantly lower (P

Abstract Background The Guangxi government initiated two rounds of the Guangxi AIDS Conquering Project (GACP) in 2010 (Phase I) and 2015 (Phase II) to control human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemics. However, the effectiveness of GACP in HIV prevention and treatment has rarely been reported. This study aimed to assess the effectiveness of the GACP implemented in Guangxi, China and provide data for strategy and praxis improvements to achieve Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95 targets. Methods We used spatial approaches to trace the spatiotemporal distribution properties, epidemic trends, and correlation between macroscopic factors and HIV incidence using data from the Chinese HIV/AIDS case reporting system to explore the effects of the GACP. Results During the GACP era, the HIV epidemic stabilized in urban centers, showing a downward trend in the Hengzhou and Binyang Counties in the eastern region, whereas it continued to increase in rural areas of the northwest region, such as the Long’an, Mashan, Shanglin, and Wuming Districts. The linear directional mean (LDM) of HIV infection reported cases displayed a southeast–northwest direction, with an LDM value of 12.52°. Compared with that in Phase I, Hengzhou withdrew from the high-high clustering area, and the west–north suburban counties pulled out the low-low clustering area during Phase II. Significant HIV clusters were identified in the eastern region during Phase I, whereas these clusters emerged in the northwestern areas during Phase II. Regarding HIV, socioeconomic status, population mobility, and medical care levels were the key social drivers of heterogeneous spatial distribution. Conclusions The GACP assisted in effectively managing the HIV epidemic in urban and eastern areas of Nanning City. However, prevention and control efforts in rural regions, particularly those located in the northwest, may not have yielded comparable outcomes. To address this disparity, allocating additional resources and implementing tailored intervention measures for these rural areas are imperative.

Chinese cabbage (Brassica rapa ssp. pekinensis) has a long cultivation history and is one of the vegetable crops with the largest cultivation area in China. However, salt stress severely damages photosynthesis and hormone metabolism, nutritional balances, and results in ion toxicity in plants. To better understand the mechanisms of salt-induced growth inhibition in Chinese cabbage, RNA-seq and physiological index determination were conducted to explore the impacts of salt stress on carbon cycle metabolism and photosynthesis in Chinese cabbage. Here, we found that the number of thylakoids and grana lamellae and the content of starch granules and chlorophyll in the leaves of Chinese cabbage under salt stress showed a time-dependent response, first increasing and then decreasing. Chinese cabbage increased the transcript levels of genes related to the photosynthetic apparatus and carbon metabolism under salt stress, probably in an attempt to alleviate damage to the photosynthetic system and enhance CO2 fixation and energy metabolism. The transcription of genes related to starch and sucrose synthesis and degradation were also enhanced; this might have been an attempt to maintain intracellular osmotic pressure by increasing soluble sugar concentrations. Soluble sugars could also be used as potential reactive oxygen species (ROS) scavengers, in concert with peroxidase (POD) enzymes, to eliminate ROS that accumulate during metabolic processes. Our study characterizes the synergistic response network of carbon metabolism and photosynthesis under salt stress.

Abstract Background HIV-1 CRF65_cpx strain carries drug-resistant mutations, which raises concerns about its potential for causing virologic failure. The CRF65_cpx ranks as the fourth most prevalent on Hainan Island, China. However, the origin and molecular epidemiology of CRF65_cpx strains in this area remain unclear. This study aims to estimate the spatial origins and dissemination patterns of HIV-1 CRF65_cpx in this specific region. Methods Between 2018 and 2021, a total of 58 pol sequences of the CRF65_cpx were collected from HIV-positive patients on Hainan Island. The available CRF65_cpx pol sequences from public databases were compiled. The HIV-TRACE tool was used to construct transmission networks. The evolutionary history of the introduction and dissemination of HIV-1 CRF65_cpx on Hainan Island were analyzed using phylogenetic analysis and the Bayesian coalescent-based approach. Results Among the 58 participants, 89.66% were men who have sex with men (MSM). The median age was 25 years, and 43.10% of the individuals had a college degree or above. The results indicated that 39 (67.24%) sequences were interconnected within a single transmission network. A consistent expansion was evident from 2019 to 2021, with an incremental annual addition of four sequences into the networks. Phylodynamic analyses showed that the CRF65_cpx on Hainan Island originated from Beijing (Bayes factor, BF = 17.4), with transmission among MSM on Hainan Island in 2013.2 (95%HPD: 2012.4, 2019.5), subsequently leading to an outbreak. Haikou was the local center of the CRF65_cpx epidemic. This strain propagated from Haikou to other locations, including Sanya (BF > 1000), Danzhou (BF = 299.3), Chengmai (BF = 27.0) and Tunchang (BF = 16.3). The analyses of the viral migration patterns between age subgroups and risk subgroups revealed that the viral migration directions were from "25–40 years old" to "17–24 years old" (BF = 14.6) and to "over 40 years old" (BF = 17.6), and from MSM to heterosexuals (BF > 1000) on Hainan Island. Conclusion Our analyses elucidate the transmission dynamics of CRF65_cpx strain on Hainan Island. Haikou is identified as the potential hotspot for CRF65_cpx transmission, with middle-aged MSM identified as the key population. These findings suggest that targeted interventions in hotspots and key populations may be more effective in controlling the HIV epidemic.

Abstract The limited differentiation ability of adipose-derived stem cells (ADSCs) limits their application in stem cell therapy and regenerative medicine. Here, we explore the molecular mechanism by which miR-204-5p regulates ADSCs differentiation into cells derived from the three germ layers (i.e., adipocytes, neurocytes, and hepatocytes). Although miR-204-5p overexpression inhibited ADSCs differentiation into adipocytes, neurocyte and hepatocyte differentiation were promoted. Mechanistically, miR-204-5p inhibited the expression of PPARG by regulating the AMPK signaling pathway, thereby inhibiting ADSCs differentiation into adipocytes. Further, miR-204-5p regulated JAG1/NOTCH3 axis for the inhibition of differentiation into adipocytes and promotion of differentiation into neurocytes. miR-204-5p might also promote ADSCs differentiation into hepatocytes by upregulating E2F8. The findings of this study provide novel insights into the regulatory mechanisms underlying early embryonic development and will help to facilitate the application of ADSCs in stem cell therapy and regenerative medicine.

Abstract Quarks (except top quarks) and gluons produced in collider experiments hadronize and fragment into sprays of stable particles, called jets. Identification of quark flavor is desired for collider experiments in high-energy physics, relying on flavor tagging algorithms. In this study, using a full simulation of the Circular Electron Positron Collider (CEPC), we investigate the flavor tagging performance of two different algorithms: ParticleNet, based on a Graph Neural Network, and LCFIPlus, based on the Gradient Booted Decision Tree. Compared to LCFIPlus, ParticleNet significantly enhances flavor tagging performance, resulting in a significant improvement in benchmark measurement accuracy, i.e., a 36% improvement for $$\sigma (ZH)\cdot Br(Z\rightarrow \nu \bar{\nu }, H\rightarrow c\bar{c})$$ σ ( Z H ) · B r ( Z → ν ν ¯ , H → c c ¯ ) measurement and a 75% improvement for $$|V_{cb}|$$ | V cb | measurement via W boson decay, respectively, when the CEPC operates as a Higgs factory at the center-of-mass energy of 240 GeV and collects an integrated luminosity of 5.6 ab $$^{-1}$$ - 1 . We compare the performance of ParticleNet and LCFIPlus at different vertex detector configurations, observing that the inner radius is the most sensitive parameter, followed by material budget and spatial resolution.

Abstract Background MicroRNA (miRNA)-based therapies have shown great potential in myocardial repair following myocardial infarction (MI). MicroRNA-302 (miR302) has been reported to exert a protective effect on MI. However, miRNAs are easily degraded and ineffective in penetrating cells, which limit their clinical applications. Exosomes, which are small bioactive molecules, have been considered as an ideal vehicle for miRNAs delivery due to their cell penetration, low immunogenicity and excellent stability potential. Herein, we explored cardiomyocyte-targeting exosomes as vehicles for delivery of miR302 into cardiomyocyte to potentially treat MI. Methods To generate an efficient exosomal delivery system that can target cardiomyocytes, we engineered exosomes with cardiomyocyte specific peptide (CMP, WLSEAGPVVTVRALRGTGSW). Afterwards, the engineered exosomes were characterized and identified using transmission electron microscope (TEM) and Nanoparticle Tracking Analysis (NTA). Later on, the miR302 mimics were loaded into the engineered exosomes via electroporation technique. Subsequently, the effect of the engineered exosomes on myocardial ischemia and reperfusion (I/R) injury was evaluated in vitro and in vivo, including MTT, ELISA, real-time quantitative polymerase chain reaction (PCR), western blot, TUNNEL staining, echocardiogram and hematoxylin and eosin (HE) staining. Results Results of in vitro experimentation showed that DSPE-PEG-CMP-EXO could be more efficiently internalized by H9C2 cells than unmodified exosomes (blank‐exosomes). Importantly, compared with the DSPE-PEG-CMP-EXO group, DSPE-PEG-CMP-miR302-EXO significantly upregulated the expression of miR302, while exosomes loaded with miR302 could enhance proliferation of H9C2 cells. Western blot results showed that the DSPE-PEG-CMP-miR302-EXO significantly increased the protein level of Ki67 and Yap, which suggests that DSPE-PEG-CMP-miR302-EXO enhanced the activity of Yap, the principal downstream effector of Hippo pathway. In vivo, DSPE-PEG-CMP-miR302-EXO improved cardiac function, attenuated myocardial apoptosis and inflammatory response, as well as reduced infarct size significantly. Conclusion In conclusion, our findings suggest that CMP-engineered exosomes loaded with miR302 was internalized by H9C2 cells, an in vitro model for cardiomyocytes coupled with potential enhancement of the therapeutic effects on myocardial I/R injury.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.

Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The “gut-heart” axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5 mg kg−1·d−1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating co-metabolism and regulating the TMAO-inflammation axis.

BackgroundYunnan, a southwest highland and newly industrialized region of China, has an unknown hospitalization burden of inflammatory bowel disease (IBD). The study was conducted to explore territorial hospitalization burden of IBD.MethodsThe formatted medical records of patients with IBD were collected from a territory-wide database in Yunnan Province, China, from 2015 to 2020. General characteristics of the study population were reported using descriptive statistics. To evaluate the length of stay, hospitalization costs, surgery, complications, and trends in patients with inflammatory bowel disease. The logistic regression analysis was established to explore the factors affecting the hospitalization costs.ResultsA total of 12,174 records from 8192 patients were included. The annual hospitalization cost of IBD in Yunnan Province increased significantly from 2015 to 2020. From 2015 to 2020, the regional hospitalization burden of IBD increased, but it represented a decline in cost per hospitalization (r = −0.024, P = 0.008) and the length of stay (r = −0.098, P < 0.001). Surgery rates for hospitalized patients with Crohn’s disease (CD) did not decrease (r = −0.002, P = 0.932), and even increased for patients with ulcerative colitis (UC) (r = 0.03, P = 0.002). The costs per hospitalization were $ 827.49 (540.11–1295.50) for UC and $ 1057.03 (644.26–1888.78) for CD. Among the identifiable cost items during the period, drug costs accounted for the highest proportion, accounting for 33% and 37.30% in patients with UC and CD, respectively. Surgical intervention [OR 4.87 (3.75–6.31), P < 0.001], comorbidities [OR 1.72 (1.52–1.94), P < 0.001], complications [OR 1.53 (1.32–1.78), P < 0.001], and endoscopy [OR 2.06 (1.86–2.28), P < 0.001] were predictor of high hospitalization costs.ConclusionThe increasing burden of IBD is noteworthy a newly industrialized region of China. Interventions targeting surgery, complications, and comorbidities may be effective means of controlling the increasing hospitalization costs of IBD in the regions.

With the recent expansion of structural variant identification in the human genome, understanding the role of these impactful variants in disease architecture is critically important. Currently, a large proportion of genome-wide-significant genome-wide association study (GWAS) single nucleotide polymorphisms (SNPs) are functionally unresolved, raising the possibility that some of these SNPs are associated with disease through linkage disequilibrium with causal structural variants. Hence, understanding the linkage disequilibrium between newly discovered structural variants and statistically significant SNPs may provide a resource for further investigation into disease-associated regions in the genome. Here we present a resource cataloging structural variant-significant SNP pairs in high linkage disequilibrium. The database is composed of (i) SNPs that have exhibited genome-wide significant association with traits, primarily disease phenotypes, (ii) newly released structural variants (SVs), and (iii) linkage disequilibrium values calculated from unphased data. All data files including those detailing SV and GWAS SNP associations and results of GWAS-SNP-SV pairs are available at the SV-SNP LD Database and can be accessed at ‵https://github.com/hliang-SchrodiLab/SV_SNPs. Our analysis results represent a useful fine mapping tool for interrogating SVs in linkage disequilibrium with disease-associated SNPs. We anticipate that this resource may play an important role in subsequent studies which investigate incorporating disease causing SVs into disease risk prediction models.

BackgroundProstate cancer (PCa) is the second most prevalent malignant tumor in male, and bone metastasis occurs in about 70% of patients with advanced disease. The STING pathway, an innate immune signaling mechanism, has been shown to play a key role in tumorigenesis, metastasis, and cancerous bone pain. Hence, exploring regulatory mechanism of STING in PCa bone metastasis will bring novel opportunities for treating PCa bone metastasis.MethodsFirst, key genes were screened from STING-related genes (SRGs) based on random forest algorithm and their predictive performance was evaluated. Subsequently, a comprehensive analysis of key genes was performed to explore their roles in prostate carcinogenesis, metastasis and tumor immunity. Next, cellular experiments were performed to verify the role of RELA in proliferation and migration in PCa cells, meanwhile, based on immunohistochemistry, we verified the difference of RELA expression between PCa primary foci and bone metastasis. Finally, based on the key genes to construct an accurate and reliable nomogram, and mined targeting drugs of key genes.ResultsIn this study, three key genes for bone metastasis were mined from SRGs based on the random forest algorithm. Evaluation analysis showed that the key genes had excellent prediction performance, and it also showed that the key genes played a key role in carcinogenesis, metastasis and tumor immunity in PCa by comprehensive analysis. In addition, cellular experiments and immunohistochemistry confirmed that overexpression of RELA significantly inhibited the proliferation and migration of PCa cells, and RELA was significantly low-expression in bone metastasis. Finally, the constructed nomogram showed excellent predictive performance in Receiver Operating Characteristic (ROC, AUC = 0.99) curve, calibration curve, and Decision Curve Analysis (DCA) curve; and the targeted drugs showed good molecular docking effects.ConclusionIn sum, this study not only provides a new theoretical basis for the mechanism of PCa bone metastasis, but also provides novel therapeutic targets and novel diagnostic tools for advanced PCa treatment.

Summary: ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA) to promote cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here, we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppressor of the inflammatory signaling mediated by full-length ZBP1. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Ripk1D325A/D325A) with cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-dependent cell death. Intriguingly, Ripk1D325A/D325A cells die spontaneously when ZBP1-S is deleted, indicating that cell death driven by ZBP1 is under the control of ZBP1-S. Thus, our findings reveal that alternative splicing of Zbp1 represents autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against autoinflammations.

Estimating Visual Quality of Street Space (VQoSS) is pivotal for urban design, environmental sustainability, civic engagement, etc. Recent advancements, notably in deep learning, have enabled large-scale analysis. However, traditional deep learning approaches are hampered by extensive data annotation requirements and limited adaptability across diverse VQoSS tasks. Multimodal Large Language Models (MLLMs) have recently demonstrated proficiency in various computer vision tasks, positioning them as promising tools for automated VQoSS assessment. In this paper, we pioneer the application of MLLMs to VQoSS change estimation, with our empirical findings affirming their effectiveness. In addition, we introduce Street Quality Generative Pre-trained Transformer (SQ-GPT), a model that distills knowledge from the current most powerful but inaccessible (not free) GPT-4V, requiring no human efforts. SQ-GPT approaches GPT-4V’s performance and is viable for large-scale VQoSS change estimation. In a case study of Nanjing, we showcase the practicality of SQ-GPT and knowledge distillation pipeline. Our work promises to be a valuable asset for future urban studies research.

Abstract Objective To compare the effects of laparoscopic hepatectomy (LH) on the short-term and long-term outcomes in hepatocellular carcinoma (HCC) patients with and without clinically significant portal hypertension (CSPH). Methods A systematic literature search of the PubMed, EMBASE, and Cochrane databases was performed for articles published from inception to March 1, 2023. Meta-analysis of surgical and oncological outcomes was performed using a random effects model. Data were summarized as mean difference and risk ratio with 95% confidence intervals. Results Five cohort studies with a total of 310 HCC patients were included (CSPH 143; Non-CSPH 167). In terms of surgical outcomes, estimated blood loss and the length of hospital stay were significantly lower in the Non-CSPH group than in the CSPH group. There were no significant differences between the two groups regarding other surgical outcomes, including the operative time, ratio of conversion to open surgery, and overall complication rate. In addition, there were also no significant differences between the two groups regarding the oncological outcomes, such as 1-, 3-, and 5-year overall survival. Conclusions HCC patients with and without CSPH who underwent LH had comparable surgical and oncological outcomes. LH is a safe and effective treatment for HCC patients with CSPH under the premise of rational screening of patients.

Abstract Background Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional. Methods A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method. Results In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found. Conclusion Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.

Natural disasters and health pandemics have occurred more frequently in the 21st century. Research show that the large blackouts caused by natural disasters are more intractable, especially striking during health pandemics. In this sense, power grid resilience becomes a topical area both in industry and academia. The resilience can be enhanced by making the grid “Smarter”, utilizing advanced techniques such as distributed generation, microgrids, sensing, communication, and computing. In this paper, a structured review framework for decision support for smart distribution system (SDS) resilience against natural disasters during health pandemics is proposed. The challenges and negative impacts of natural disasters during health pandemics on SDS resilience are well illustrated. The stochastic impact assessment methods of natural disasters and human activities on SDSs are extensively discussed. The SDS planning and operation models against natural disasters during health pandemics are comprehensively reviewed. The strategic decision-making for resilient SDS against natural disasters during health pandemics are extensively surveyed. Future research directions are also presented.

The development of superconducting joining technology for reacted magnesium diboride (MgB2) conductors remains a critical challenge for the advancement of cryogen-free MgB2-based magnets for magnetic resonance imaging (MRI). Herein, the fabrication of superconducting joints using reacted carbon-doped multifilament MgB2 wires for MRI magnets is reported. To achieve successful superconducting joints, the powder-in-mold method was employed, which involved tuning the filament protection mechanism, the powder compaction pressure, and the heat treatment condition. The fabricated joints demonstrated clear superconducting-to-normal transitions in self-field, with effective magnetic field screening up to 0.5 T at 20 K. To evaluate the interface between one of the MgB2 filaments and the MgB2 bulk within the joint, serial sectioning was conducted for the first time in this type of superconducting joint. The serial sectioning revealed space formation at the interface, potentially caused by the volume shrinkage associated with the MgB2 formation or the combined effect of the volume shrinkage and the different thermal expansion coefficients of the MgB2 bulk, the filament, the mold, and the sealing material. These findings are expected to be pivotal in developing MgB2 superconducting joining technology for MRI magnet applications through interface engineering.

Esophageal cancer is a prevalent disease in thoracic surgery, and surgery is currently the main treatment method. It can completely remove the tumor and improve the patient's quality of life. The da Vinci robot-assisted McKeown surgery for esophageal cancer has the advantages of less trauma, less pain, good results, faster postoperative recovery, and beautiful incisions. The da Vinci robotic system has a three-dimensional enlarged actual surgical field of view and can perform all-round operations. It has been gradually accepted to clearly observe the lesion and its relationship with surrounding tissues, nerves, and lymph nodes, safely remove the lesion, reduce nerve damage, and remove enough lymph nodes. This article will introduce the surgical experience of our center in detail.

Abstract Background N6-methyladenosine (m6A) methylation has become an active research area in viral infection, while little bibliometric analysis has been performed. In this study, we aim to visualize hotspots and trends using bibliometric analysis to provide a comprehensive and objective overview of the current research dynamics in this field. Methods The data related to m6A methylation in viral infection were obtained through the Web of Science Core Collection form 2000 to 2022. To reduce bias, the literature search was conducted on December 1, 2022. Bibliometric and visual analyzes were performed using CiteSpace and Bibliometrix package. After screening, 319 qualified records were retrieved. Results These publications mainly came from 28 countries led by China and the United States (the US), with the US ranking highest in terms of total link strength.The most common keywords were m6A, COVID-19, epitranscriptomics, METTL3, hepatitis B virus, innate immunity and human immunodeficiency virus 1. The thematic map showed that METTL3, plant viruses, cancer progression and type I interferon (IFN-I) reflected a good development trend and might become a research hotspot in the future, while post-transcriptional modification, as an emerging or declining theme, might not develop well. Conclusions In conclusion, m6A methylation in viral infection is an increasingly important topic in articles. METTL3, plant viruses, cancer progression and IFN-I may still be research hotspots and trends in the future.

Both the Shandong Plain in China and the Greater Houston Area in the United States have land subsidence problems that were caused by excessive groundwater pumping. Houston has accumulated more than 100 years of monitoring results and more than 50 years of prevention and control experience, which has certain similarities with the ground subsidence monitoring and control experience of Shandong Plain area in the past 30 years. To further promote and strengthen land subsidence monitoring and prevention, groundwater resource management, digital empowerment, and data sharing in Shandong Province, in this article a comparative study was conducted on the causes of land subsidence, monitoring techniques, groundwater management, and land subsidence prevention and control in the Shandong Plain and the Greater Houston Area. The results indicate that excessive extraction of groundwater is the main cause of land subsidence, and land subsidence management measures based on limiting groundwater extraction have been taken. Currently, the area and rate of subsidence are decreasing in both places. The monitoring methods and techniques used in two places are basically the same, mainly using precision leveling surveying, bench mark fixed on different stratum or borehole extensometers, Global Navigation Satellite Systems (GNSS), and Interferometric Synthetic Aperture Radar (InSAR) techniques, and the density and frequency of observations are gradually increasing. Meanwhile, the management and sharing of observation data is different. The land subsidence management administration agencies in the Houston area are mainly responsible for the collection and sharing of observation data, and do not undertake data processing and research tasks. All observation data are open to the public, and scientific researches based on observation data is mainly undertaken by the U.S. Geological Survey (USGS) and universities. Research results are published on USGS reports or journal articles. Differently, land subsidence and groundwater level monitoring in Shandong Plain are undertaken by the Ministry of Natural Resources and the Ministry of Water Resources, and its affiliated institutions are responsible for field observation, data storage, data analysis and research, as well as formulating regulations for groundwater management. There are certain difficulties in data sharing and integration between departments, which limits in-depth and systematic research on land subsidence.

Abstract Background The studies on SARS-CoV-2 and human microbiota have yielded inconsistent results regarding microbiota α-diversity and key microbiota. To address these issues and explore the predictive ability of human microbiota for the prognosis of SARS-CoV-2 infection, we conducted a reanalysis of existing studies. Methods We reviewed the existing studies on SARS-CoV-2 and human microbiota in the Pubmed and Bioproject databases (from inception through October 29, 2021) and extracted the available raw 16S rRNA sequencing data of human microbiota. Firstly, we used meta-analysis and bioinformatics methods to reanalyze the raw data and evaluate the impact of SARS-CoV-2 on human microbial α-diversity. Secondly, machine learning (ML) was employed to assess the ability of microbiota to predict the prognosis of SARS-CoV-2 infection. Finally, we aimed to identify the key microbiota associated with SARS-CoV-2 infection. Results A total of 20 studies related to SARS-CoV-2 and human microbiota were included, involving gut (n = 9), respiratory (n = 11), oral (n = 3), and skin (n = 1) microbiota. Meta-analysis showed that in gut studies, when limiting factors were studies ruled out the effect of antibiotics, cross-sectional and case–control studies, Chinese studies, American studies, and Illumina MiSeq sequencing studies, SARS-CoV-2 infection was associated with down-regulation of microbiota α-diversity (P

Hydraulic fracturing is an effective method for developing oil and gas in unconventional reservoirs. The openings of natural fractures directly affect the complexity of the fracture body. The failure characteristics of natural fractures are critical factors in determining their activation by hydraulic fractures. Based on the three-dimensional displacement discontinuity method, a three-dimensional mechanical model of the interaction between hydraulic and natural fractures was established. Based on the shear and tensile failure criteria of the natural fractures, the failure characteristics of different natural fractures were clarified. Research has shown that the failure characteristics of natural fractures are influenced by factors such as three-dimensional stress, spatial distribution, and roughness. After the hydraulic fractures pass through the natural fractures, tensile and shear failures occur simultaneously; the failure of natural fractures is primarily affected by their strike and dip angles. During the process of hydraulic fracture approximation, the shear stress increases as the distance between the hydraulic fracture tip and natural fracture decreases. When the strike angle of the natural fractures near the tips of the hydraulic fractures was greater than 35°, the stress became consistent. As the dip angle of the natural fractures increased, the lowest point of the shear stress gradually moved from the upper to the lower half. This research studies the tensile and shear failure of natural fractures under different conditions, in order to facilitate engineering judgment of the types and characteristics of natural fracture failure. It is of great significance for us to understand the formation mechanism of complex fracture network morphology in volume fracturing.

The inactivated COVID-19 vaccine has demonstrated high efficacy in the general population through extensive clinical and real-world studies. However, its effectiveness in immunocompromised individuals, particularly those living with HIV (PLWH), remains limited. In this study, 20 PLWH and 15 HIV-seronegative individuals were recruited to evaluate the immunogenicity of an inactivated COVID-19 vaccine in PLWH through a prospective cohort study. The median age of the 20 PLWH and 15 HIV-seronegative individuals was 42 years and 31 years, respectively. Of the PLWH, nine had been on ART for over five years. The median anti-SARS-CoV-2 S-RBD IgG antibody level on d224 was higher than that on d42 (8188.7 ng/mL vs. 3200.9 ng/mL, P < 0.05). Following COVID-19 infection, the antibody level increased to 29,872.5 ng/mL on dre+90, 12.19 times higher than that on d300. Compared with HIV-seronegative individuals, the antibody level in PLWH was lower on d210 (183.3 ng/mL vs. 509.3 ng/mL, P < 0.01), while there was no difference after d224. The symptoms of COVID-19 infection in PLWH were comparable to those in HIV-seronegative individuals. In this study, the inactivated COVID-19 vaccine demonstrated good immunogenicity in PLWH. The protective benefit of booster vaccinations for PLWH cannot be ignored. Implementing a booster vaccination policy for PLWH is an effective approach to providing better protection against the COVID-19 pandemic.

Abstract As emerging alternatives to natural enzymes, nanoscale materials featuring enzyme‐like catalytic behaviors (nanozymes) exhibit some attractive merits including robust activity, low cost, and easy‐to‐regulate performance. These merits have enabled them to be intensively used in the biomedical field in recent years. To remedy the lack of catalytic selectivity in most nanozymes, deoxyribonucleic acid (DNA) chains with specific recognition functions are utilized to integrate with nanozymes to produce various nanozyme–DNA combinations via adsorption/desorption. In the formed combinations, the DNA component provides the molecular/ionic recognition role, and the nanozyme part offers response with catalytically amplified signals, enabling them to detect analytes and biomarkers selectively and sensitively. To highlight this interesting topic, here we made a critical review of the interactions between nanozymes and DNA and their applications in biosensing and disease diagnosis. First, strategies for the conjugation of DNA chains onto nanozyme surface were introduced briefly. Then, the interactions between DNA and nanozymes were summarized in detail, where flexible modulations of nanozyme activity by DNA adsorption/desorption as well as various factors were analyzed, and potential impacts caused by nanozymes on the recognition characteristics of DNA chains were pointed out. After that, typical applications of DNA‐mediated nanozyme modulation in toxic ion sensing, health risk factor monitoring, and biomedical diagnosis were introduced. In the end, prospects of the combination of nanozymes and DNA chains were presented, and future challenges of the emerging field were also discussed, to attract more interest and effort to advance this promising area.

Abstract Introduction Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long‐acting GLP‐1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. Methods Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety‐ and depression‐like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography–tandem mass spectrometry‐based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. Results Three weeks of dulaglutide treatment significantly reversed depressive‐like but not anxiety‐like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy. Conclusion The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant‐like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.

Primary membranous nephropathy (PMN) is the most common cause for adult nephrotic syndrome. Rituximab has demonstrated promising clinical efficacy by random controlled trials and the off-label use is widely adopted in PMN. However, the standard dosage is borrowed from B cell lymphoma treatment with far more antigens and is oversaturated for PMN treatment, accompanied with additional safety risk and unnecessary medical cost. More than 15% serious adverse events were observed under standard dosage and low dose therapies were explored recently. Dose optimization by clinical trials is extremely time- and cost-consuming and can be significantly accelerated with the aid of model-informed drug development. Here, we aim to establish the first population pharmacokinetic and pharmacodynamic (PPK/PD) model for rituximab in PMN to guide its dosage optimization. Rituximab pharmacokinetic and pharmacodynamic data from 41 PMN patients in a retrospective study under a newly proposed monthly mini-dose were used to construct quantitative dose-exposure-response relationship via mechanistic target-mediated drug disposition (TMDD) model followed by regression between the reduction of anti-PLA2R titer and time after the treatment. The final model, validated by goodness-of-fit plots, visual predictive checks and bootstrap, was used to recommend the optimized dosing regimen by simulations. The model was well validated for PK/PD prediction. The systemic clearance and half-life are 0.54 L/h and 14.7 days, respectively. Simulation of a novel regimen (6 monthly doses of 100 mg) indicated the comparable ability and superior duration time of CD20+ B cell depletion compared with standard dosage, while the cumulative dosage and safety risk was significantly decreased. We established the first PPK/PD model and provide evidence to support the dosage optimization based on monthly mini-dose. Our study can also efficiently accelerate dosage optimization of novel anti-CD20 antibodies in PMN and other indications.

Background: Lung cancer metastasis to the brain presents significant clinical challenges. Therefore, elucidating its underlying mechanisms and characterizing its transcriptomic landscape is essential for developing therapeutic interventions. Methods: We analyzed two distinct single-cell RNA sequencing datasets of lung cancer metastasis to analyze the evolutionary trajectory of brain metastatic tumors. In addition, a systematic comparison of cell-cell interaction between tumor cells and lymphocytes was conducted within primary and brain metastatic tumors. Results: The brain metastatic tumors showed greater transcriptomic changes (reflected by a higher pseudotime) than tumors in the lymph nodes and primary tumors. Furthermore, our investigation has not only revealed specific shared ligand-receptor pairs in both mLN and mBrain, exemplified by the interaction between SPP1 and CD99 in T cells, but has also unveiled a diverse array of ligand-receptor pairs exclusive to the mBrain. Notably, this includes distinctive pairs such as APP and IL1 observed specifically in myeloid cells. Conclusion: The distinct microenvironment in the brain may influence the observed transcriptomic changes in tumors, emphasizing the significance of the specific environment in determining tumor behavior and therapeutic response.

BackgroundThe May 2022 global outbreak of monkeypox (MPX) poses a threat to the health of men who have sex with men. However, there is limited data on the willingness of MSM to receive monkeypox vaccination in Southern China. This study aimed to assess the knowledge of MPX, concerns regarding MPX, and willingness to receive monkeypox vaccination, as well as their correlates, among MSM in China.MethodsWe conducted a Web-based online survey of MSM in Southern China from August to September 2022. Data were collected on the socio-demographic characteristics, knowledge, worries, concerns regarding MPX and willingness to receive monkeypox vaccination. Multivariate logistic regression was employed to explore the factors associated with willingness to receive monkeypox vaccination.ResultsA total of 1903 participants completed the survey. Among them, approximately 69.9% reported being aware of MPX awareness, 94.1% of the participants supported the promotion of monkeypox vaccination. The majority of participants (91.4%) expressed their willingness to receive monkeypox vaccination. Participants who considered monkeypox vaccination safe [adjusted odds ratio (aOR) = 4.82, 95% CI: 1.35–17.18], agreed on the necessity of government promotion of monkeypox vaccination in China (aOR = 6.03, 95% CI: 1.07–33.93), believed in prioritizing monkeypox vaccination for MSM (aOR = 5.01, 95% CI: 1.10–22.71), and had friends or sexual partners who had already received the monkeypox or smallpox vaccination (aOR = 10.37, 95% CI: 2.11–50.99) are more likely to be vaccinated. Conversely, married individuals (aOR = 0.13, 95% CI: 0.03–0.47), those engaging in anal sex 4–6 times per week in the past 3 months (aOR = 0.26, 95% CI: 0.09–0.77) expressed hesitancy toward monkeypox vaccination.ConclusionThere was a high willingness to receive monkeypox vaccination among MSM in China. The hesitancy toward the monkeypox vaccine can be effectively mitigated by addressing concerns about its safety and potential adverse reactions. Moreover, increasing acceptance of the monkeypox vaccination among MSM and their peers is crucial, as social influence significantly impacts vaccine attitudes and behaviors.