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Abstract Aims To explore the university students' attitude and the potential influencing factors to receive the coronavirus disease 2019 (COVID‐19) vaccine in Sichuan Province, China. Design A cross‐sectional study. Methods The self‐designed questionnaire was distributed among university students online in June 2021. SPSS software was used for statistical analysis of the data. Descriptive statistics, Chi‐square, two independent samples t‐tests, one‐way analysis of variance (ANOVA), multivariate linear regression, and content analysis were performed. Results A total of 397 questionnaires were analysed, involving 316 (79.6%) respondents have received at least one dose of a COVID‐19 vaccine and 81 (20.4%) have not taken the vaccine. The total mean score of university students' vaccination attitude was 25.97 (standard deviation [SD] = 3.720), and the total scoring rate was 74.2%. Main factors influencing students' attitude included education level, major, living style, with chronic disease or not, self‐reported vaccination status, and number of medical units that can provide vaccination within 3 km of residence. Students were more willing to choose Chinese‐manufactured vaccines (66.8%) and participate in collective vaccination programs organized by the school (71.3%). The desired vaccine protection period was 5–10 years (42.1%). The top three reasons for refusing the vaccine or vaccine hesitancy were as follows: concern about the side effects of vaccine (44.8%), lack of information about vaccine (31.0%), and concern about the efficacy of vaccine (29.3%). Conclusion In general, most of the participants had relatively high level of positive attitude to receive the COVID‐19 vaccine. Nevertheless, more attention should be paid to postgraduate students, non‐medical students, those living alone, those with chronic disease, those have not received the COVID‐19 vaccine, and those living far away from the vaccination medical units. Findings of this study can help educational institutions in developing effective interventions to improve the vaccination rate in the university student population.

Abstract Watersheds are important suppliers of freshwater for human societies. Within mountainous watersheds, microbial communities impact water chemistry and element fluxes as water from precipitation events discharge through soils and underlying weathered rock, yet there is limited information regarding the structure and function of these communities. Within the East River, CO watershed, we conducted a depth‐resolved, hillslope to riparian zone transect study to identify factors that control how microorganisms are distributed and their functions. Metagenomic and geochemical analyses indicate that distance from the East River and proximity to groundwater and underlying weathered shale strongly impact microbial community structure and metabolic potential. Riparian zone microbial communities are compositionally distinct, from the phylum down to the species level, from all hillslope communities. Bacteria from phyla lacking isolated representatives consistently increase in abundance with increasing depth, but only in the riparian zone saturated sediments we found Candidate Phyla Radiation bacteria. Riparian zone microbial communities are functionally differentiated from hillslope communities based on their capacities for carbon and nitrogen fixation and sulfate reduction. Selenium reduction is prominent at depth in weathered shale and saturated riparian zone sediments and could impact water quality. We anticipate that the drivers of community composition and metabolic potential identified throughout the studied transect will predict patterns across the larger watershed hillslope system.

Transport from the soil surface to groundwater is commonly mediated through deeper portions of the vadose zone and capillary fringe, where variations in temperature and water saturation strongly influence biogeochemical processes. This technical note describes a sediment column design that allows laboratory simulation of thermal and hydrologic conditions found in many field settings. Temperature control is particularly important because room temperature is not representative of most subsurface environments. A 2.0-m-tall column was capable of simulating profiles with temperatures ranging from 3 to 22°C, encompassing the full range of seasonal temperature variation observed in the deep vadose zone and capillary fringe of a semiarid floodplain in western Colorado. The water table was varied within the lower 0.8-m section of the column, and profiles of water content and matric potential were measured. Vadose zone CO collected from depth-distributed gas samplers under representative seasonal conditions reflected the influences of temperature and water table depth on microbial respiration. Thus, realistic subsurface biogeochemical dynamics can be simulated in the laboratory through establishing column profiles that represent seasonal thermal and hydrologic conditions.

Abstract Over‐estimation of summer precipitation over the Tibetan Plateau (TP) is a well‐known and persistent problem in most climate models. This study demonstrates the impact of a Gaussian Probability Density Function cloud fraction scheme on rainfall simulations using the Weather Research and Forecasting model. It is found that this scheme in both 0.1° and 0.05° resolutions significantly reduces the wet bias through both local feedbacks and large‐scale dynamic process. Specifically, increased cloud water/ice content with this scheme reduces surface shortwave radiation, and consequently surface heat fluxes and evapotranspiration. This, in turn, dampens the large‐scale thermal effect of the TP and weakens the exaggerated monsoon circulation and low‐level moisture convergence. It is this large‐scale dynamic process that contributes the most (∼70%) to the wet bias reduction. Although this paper presents a modeling study, it highlights the cloud radiative feedback to the large‐scale dynamics and precipitation over the TP.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated nuclease (Cas) system has been proven to play an irreplaceable role in bacteria immunity activity against exogenous genetic elements. In recent years, this system has emerged as a valid gene engineering method and could be used to detect and treat various microorganisms such as bacteria and viruses, etc. Staphylococcus aureus, as a Gram-positive, opportunistic human and animal pathogen, can cause a variety of diseases greatly threatening human health. Here, we mainly reviewed the applications of the CRISPR-Cas system in Staphylococcus aureus infections in detail. Furthermore, the prospects and drawbacks of the CRISPR-Cas system were also discussed.

ObjectivesEndoscopic full-thickness resection (EFTR) has proven effective and economical for patients with gastric submucosal tumors (SMTs). However, the poor operative field of view, the risk of massive hemorrhage, and the difficulties in defect closure have limited its widespread application. Herein, we described a modified EFTR technique developed to simplify the dissection and defect closure procedures using common and economical endoscopic accessories.MethodsForty-two patients who underwent the modified EFTR for gastric SMTs in the Shenzhen Guangming District People’s Hospital were enrolled in the case series. Following a cross incision to expose the intraluminal surface the tumors were captured by suction through a transparent cap and the roots were ligated using a loop. The tumors and part of the suction tissue were removed along the ligated root. A tension-relieving closure was performed by clipping the raised plica in four quadrants outside the ligated root. Patient demographics, tumor characteristics, and therapeutic outcomes were evaluated retrospectively.ResultsAll tumors had an R0 resection. The median procedure time was 51.8 min (IQR 34.25 min). No severe perioperative adverse events occurred. No residual lesion or recurrence was reported during the follow-up period of 9.84 months (IQR 5.0 months).ConclusionThe safety and practicability of Modified-EFTR could allow for wide clinical application in patients with micro-gastric SMTs.

In order to study the influence of the primary bedding structure on wave velocity and mechanical properties of coal-rock mass, multilayer and multi-directional ultrasonic and CT scanning tests were carried out in laboratory. It also aims to improve the accuracy, rapidity and convenience of obtaining the wave velocity and mechanical parameters of coal-rock mass in laboratory. Based on the ultrasonic test, the characteristics of wave velocity and wave velocity ratio at different layers of coal-rock mass under the primary bedding dip angle were obtained. Combined with CT scanning and 3D reconstruction technology, the calculation method of CT gray mean value in different layers was proposed by using the data of the gray frequency of coal and rock. And the variation law of gray value and coal and rock content of coal-rock mass in different layers under different primary bedding dip angle was obtained. Meanwhile, the relationships between CT gray mean value and wave velocity, mechanical parameters of coal-rock mass were established. Considering the effect of bedding dip angle and the content of coal and rock, the calculation model of longitudinal wave velocity of coal-rock mass was constructed. Then the correctness of the model is verified by comparing the test data. The results show that: ① the wave velocity and wave velocity ratio of coal-rock mass with primary bedding are linearly related to bedding dip angle; with the increase of bedding dip angle, the longitudinal wave velocity of coal-rock mass decreases linearly, while the distribution range of wave velocity ratio expands; ② the mean wave velocity of CT is linearly correlated under different bedding dip angles, and the wave velocity of coal-rock mass increases linearly with the increases of CT gray mean value; ③ the density of coal-rock mass increases linearly with the increase of CT gray mean value, the dynamic elastic modulus and shear modulus of coal-rock mass have third order polynomial relationships with the mean value of CT gray level, and they tend to increase with the increase of the mean value of CT gray level; ④ compared with the bedding dip angle, the wave velocity of coal-rock mass is more sensitive to the coal and rock content, and the wave velocity changes largest during the content of coal and rock similar.

Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.

Parasite infection not only triggers the immune response of the host but also potentially affects the reproductive status, thereby influencing the population size. Therefore, understanding the impact of parasite infection on host immune and reproductive systems has long been an important issue in ecological research. To address this, we conducted field surveys (2021–2023) to investigate Capillaria hepatica infection status in Brandt's vole (Lasiopodomys brandtii) and performed controlled experiments in semi-natural enclosures and indoor laboratories. The results showed a negative correlation between the population size of Brandt's vole and the infection rate. To further explore the regulatory mechanisms, transcriptomic and proteomic analyses were performed on the infected BALB/c mice. The study found that post-infection with Capillaria hepatica, up-regulated genes and proteins in the mice liver were primarily associated with immune functions, while down-regulated genes and proteins were related to metabolic functions such as retinol metabolism. Through validation experiments supplementing retinol to the host infected with Capillaria hepatica, it was found that infection with Capillaria hepatica leads to a decrease in systemic available retinol levels, disrupting the expression of the hypothalamic-pituitary-gonadal (HPG) axis hormones, affecting the expression of CYP17A1, thereby regulating testosterone secretion related to spermatogenesis. This process results in abnormal spermatogenesis in the testes, thereby impacting the reproductive capacity of mice. This suggests that Capillaria hepatica regulates resource allocation in hosts, striking a “trade-off” between reproduction and survival, thereby exerting control over population size. These discoveries are crucial for comprehending the interaction between Capillaria hepatica and hosts, as well as their impacts on host reproduction and immune systems, and provide a scientific basis for controlling the transmission of Capillaria hepatica.

Abstract Objective To evaluate the clinical effectiveness and pregnancy rate after hysteroscopic resection (HR) and/or vaginal repair (VR) in patients with cesarean scar defect (CSD). Methods This prospective observational study enrolled 191 patients who received CSD surgery in the First affiliated hospital of Sun Yat-sen University between September 2019 to February 2022 (96 in HR and 95 in VR, respectively). Patient follow-up were performed three months after surgery in both groups by transvaginal ultrasound to confirm the presence of fluid in the niche, along with the resolution of prolonged menses at the same time. The primary outcome was the clinical effectiveness between HR and VR, identified by the resolution of prolonged menses. Results The rates of niche-fluid disappearance (70.1% vs 60.2%, P = 0.176) and prolonged menses resolution (74.8% vs 80.0%, P = 0.341) were comparable for HR and VR. A subgroup analysis for niche size revealed that HR provides patients with small niche a more favorable rate of menstrual resolution compared to VR (size of niche ≤ 15 mm2, aOR = 3.423, 95% confidence interval [CI] 1.073–10.918), but patients with large niche experience a lower rate of resolution compared to VR (size of niche > 25 mm2, aOR = 0.286, 95% CI 0.087- 0.938). During follow-up, 41 patients who wanted to conceive became pregnant. Kaplan–Meier estimates of the cumulative probability of pregnancy at 12 months and 24 months were 47.1% (95% CI: 34.5%, 58.8%) and 63.8% (95% CI: 52.5%, 72.9%), respectively. The median pregnancy time was 22 months (95% CI: 14.2, 29.8) after VR and 12 months (95% CI: 8.3, 15.7, Gehan-Breslow-Wilcoxon P = 0.021) after HR. Among patients with subsequent infertility, 31.6% achieved pregnancy by unassisted mode and 29.8% by IVF/ICSI. Moreover, among patients with previously failed IVF/ICSI treatment, 60% (12/20) obtained pregnancy, including 71.4% (10/14) after HR and 33.3% (2/6) after VR. Conclusions Hysteroscopic resection is as effective as vaginal repair at relieving symptoms of CSD-associated prolonged menses. Hysteroscopic resection is the modality of choice with an improvement in prolonged menses for small niche, while vaginal might be considered for a large niche. Furthermore, surgical intervention could improve the clinical pregnancy rate of CSD patients. All of these provide evidence for the individualized management of CSD.

Abstract Background Aquatic exercise (AE) is becoming ever more popular as a physical therapy, while it is unclear what precise improvements it will produce and how effective it will be in comparison with other non-surgical therapies. The study aimed to assess whether AE positively impacts chronic musculoskeletal disorder patients in terms of pain, physical function, and quality of life. Methods PRISMA guidelines were followed, and our study protocol was published online at PROSPERO under registration number CRD42023417411. We searched PubMed, Embase, Web of Science, and Cochrane library databases for English-language articles published before April 11, 2023, including studies from all relevant randomized controlled trials (RCTs). After screening, we ultimately included 32 RCTs with a total of 2,200 participants. We also performed subgroup analyses for all included studies. This meta-analysis calculated standardized mean difference (SMD) with 95% confidence interval (CI), and the variance was estimated using a random-effects model. The quality of the included studies was assessed by using the Cochrane collaborative "risk of bias" assessment tool (version 2.0). Thus ensuring that the literature included is of high quality. Results This meta-analysis included 32 trials with 2,200 participants; these patients were all between the ages of 38–80. The study showed that compared to the no exercise (NE) group, patients in the AE group experienced a remarkable reduction in pain (SMD: -0.64, P

Introduction Inactivated virus vaccines are the most widely used tool to prevent disease. To meet vaccine production demands, increasing attention has been placed on identifying methods to improve vaccine production efficiency. The use of suspended cells can greatly increase vaccine production. Suspension acclimation is a traditional method to convert adherent cells to suspension strains. Furthermore, as genetic engineering technology has developed, increasing attention has focused on the development of suspension cell lines using targeted genetic engineering techniques. Areas covered This review systematically summarizes and analyzes the development and research progress of various inactivated viral vaccine production suspension cell lines and provides protocols and candidate target genes for the engineered establishment of additional suspension cell lines for vaccine production. Expert opinion The use of suspended cells can significantly improve the production efficiency of inactivated virus vaccines and other biological products. Presently, cell suspension culture is the key component to improve many vaccine production processes.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR are effective in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. With the application and expansion of individualized and combined therapy, more and more studies have shown that combined administration of Metformin effectively solves the problem of acquired drug resistance to EGFR-TKIs in clinical treatment and prolongs the survival of patients with NSCLC. EGFR-TKIs combined with Metformin is expected to be the treatment method of choice for NSCLC patients with EGFR-TKIs resistance. This paper intends to summarize the research progress of EGFR-TKIs combined with Metformin in the treatment of EGFR-TKIs acquired resistance in NSCLC, in order to provide a new idea for the treatment of NSCLC patients with acquired resistance to EGFR-TKIs.

Abstract Background Oncomelania hupensis is the sole intermediate host of Schistosoma japonicum. Its emergence and recurrence pose a constant challenge to the elimination of schistosomiasis in China. It is important to accurately predict the snail distribution for schistosomiasis prevention and control. Methods Data describing the distribution of O. hupensis in 2016 was obtained from the Yunnan Institute of Endemic Disease Control and Prevention. Eight machine learning algorithms, including eXtreme Gradient Boosting (XGB), support vector machine (SVM), random forest (RF), generalized boosting model (GBM), neural network (NN), classification and regression trees (CART), k-nearest neighbors (KNN), and generalized additive model (GAM), were employed to explore the impacts of climatic, geographical, and socioeconomic variables on the distribution of suitable areas for O. hupensis. Predictions of the distribution of suitable areas for O. hupensis were made for various periods (2030s, 2050s, and 2070s) under different climate scenarios (SSP126, SSP245, SSP370, and SSP585). Results The RF model exhibited the best performance (AUC: 0.991, sensitivity: 0.982, specificity: 0.995, kappa: 0.942) and the CART model performed the worst (AUC: 0.884, sensitivity: 0.922, specificity: 0.943, kappa: 0.829). Based on the RF model, the top six important variables were as follows: Bio15 (precipitation seasonality) (33.6%), average annual precipitation (25.2%), Bio2 (mean diurnal temperature range) (21.7%), Bio19 (precipitation of the coldest quarter) (14.5%), population density (13.5%), and night light index (11.1%). The results demonstrated that the overall suitable habitats for O. hupensis were predominantly distributed in the schistosomiasis-endemic areas located in northwestern Yunnan Province under the current climate situation and were predicted to expand north- and westward due to climate change. Conclusions This study showed that the prediction of the current distribution of O. hupensis corresponded well with the actual records. Furthermore, our study provided compelling evidence that the geographical distribution of snails was projected to expand toward the north and west of Yunnan Province in the coming decades, indicating that the distribution of snails is driven by climate factors. Our findings will be of great significance for formulating effective strategies for snail control. Graphical Abstract

Abstract The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs.

The component analysis and structure characterization of complex mixtures of biomass conversion remain a challenging work. Hence, developing effective and easy to use techniques is necessary. Diffusion-ordered NMR spectroscopy (DOSY) is a non-selective and non-invasive method capable of achieving pseudo-separation and structure assignments of individual compounds from biomass mixtures by providing diffusion coefficients (D) of the components. However, the conventional 1H DOSY NMR is limited by crowded resonances when analyzing complex mixtures containing similar chemical structure resulting in similar coefficient. Herein we describe the application of an advanced diffusion NMR method, Pure Shift Yielded by CHirp Excitation DOSY (PSYCHE-iDOSY), which can record high-resolution signal diffusion spectra efficiently separating compounds in model and genuine mixture samples from cellulose, hemicellulose and lignin. Complicated sets of isomers (d-glucose/d-fructose/d-mannose and 1,2-/1,5-pentadiol), homologous compounds (ethylene glycol and 1,2-propylene glycol), model compounds of lignin, and a genuine reaction system (furfuryl alcohol hydrogenolysis with ring opening) were successfully separated in the diffusion dimension. The results show that the ultrahigh-resolution DOSY technique is capable of detecting and pseudo-separating the mixture components of C5/C6 sugar conversion products and its derivative hydrogenation/hydrogenolysis from lignocellulose biomass.

New co-processed excipients comprising lactose (filler and sweetener), microcrystalline cellulose (MCC, filler), and low-substituted hydroxypropyl cellulose (L-HPC, disintegrant and binder) were developed via solvent evaporation for the preparation of metoclopramide orally disintegrating tablets (MCP ODTs). Single-factor and Box–Behnken experimental designs were employed to optimize the formulation. The optimized formulation ratios were water: MCC: lactose (g/g) = 17.26:2.79:4.54:1. The results demonstrated that particles formed by solvent evaporation had superior flowability and compressibility compared to the physical mixture. Tablets compressed with these co-processed excipients exhibited a significantly reduced disintegration time of less than 25 s and achieved complete dissolution within 5 min. Pharmacokinetic studies revealed that MCP ODTs significantly improved Cmax, which was 1.60-fold higher compared to conventional tablets. In summary, the lactose/L-HPC/MCC triple-based co-processed excipients developed in this study are promising and could be successfully utilized in orally disintegrating and fast-release tablets.

Abstract BackgroundThe 3-Minute Diagnostic Interview for Confusion Assessment Method–Defined Delirium (3D-CAM) is an instrument specially developed for the assessment of delirium in general wards, with high reported sensitivity and specificity. However, the use of the 3D-CAM by bedside nurses in routine practice showed relatively poor usability, with multiple human errors during assessment. ObjectiveThis study aimed to develop a mobile app–based delirium assessment tool based on the 3D-CAM and evaluate its usability among older patients by bedside nurses. MethodsThe Delirium Assessment Tool With Decision Support Based on the 3D-CAM (3D-DST) was developed to address existing issues of the 3D-CAM and optimize the assessment process. Following a randomized crossover design, questionnaires were used to evaluate the usability of the 3D-DST among older adults by bedside nurses. Meanwhile, the performances of both the 3D-DST and the 3D-CAM paper version, including the assessment completion rate, time required for completing the assessment, and the number of human errors made by nurses during assessment, were recorded, and their differences were compared. ResultsThe 3D-DST included 3 assessment modules, 9 evaluation interfaces, and 16 results interfaces, with built-in reminders to guide nurses in completing the delirium assessment. In the usability testing, a total of 432 delirium assessments (216 pairs) on 148 older adults were performed by 72 bedside nurses with the 3D-CAM paper version and the 3D-DST. Compared to the 3D-CAM paper version, the mean usability score was significantly higher when using the 3D-DST (4.35 vs 3.40; PPP ConclusionsThis study demonstrated that the 3D-DST significantly improved the efficiency of delirium assessment and was considered highly acceptable by bedside nurses.

Abstract Background Prompt recognition of delirium is the first key step in its proper management. A previous study has demonstrated that nurses’ delirium screening using the usual paper version assessment tool has no effect on clinical outcomes. Clinical decision assessment systems have been demonstrated to improve patients’ adherence and clinical outcomes. Therefore, We developed a clinical decision assessment system (3D-DST) based on the usual paper version (3-min diagnostic interview for CAM-defined delirium), which was developed for assessing delirium in older adults with high usability and accuracy. However, no high quality evidence exists on the effectiveness of a 3D-DST in improving outcomes of older adults compared to the usual paper version. Methods A pair-matched, open-label, parallel, cluster randomized controlled superiority trial following the SPIRIT checklist. Older patients aged 65 years or older admitted to four medical wards of a geriatric hospital will be invited to participate in the study. Prior to the study, delirium prevention and treatment interventions will be delivered to nurses in both the intervention and control groups. The nurses in the intervention group will perform routine delirium assessments on the included older patients with 3D-DST, while the nurses in the control group will perform daily delirium assessments with the usual paper version. Enrolled patients will be assessed twice daily for delirium by a nurse researcher using 3D-DST. The primary outcome is delirium duration. The secondary outcomes are delirium severity, incidence of delirium, length of stay, in-hospital mortality, adherence to delirium assessment, prevention, and treatment of medical staff. Discussion This study will incorporate the 3D-DST into clinical practice for delirium assessment. If our study will demonstrate that 3D-DST will improve adherence with delirium assessment and clinical outcomes in older patients, it will provide important evidence for the management of delirium in the future. Trial registration Chinese Clinical Trial Registry, Identifier: ChiCTR1900028402. https://www.chictr.org.cn/showproj.aspx?proj=47127 . Protocol version: 1, 29/7/22.

During the exploitation of deep geothermal resources, the thermal fractures of high-temperature rocks are usually induced by the impact of low-temperature fluids to improve the permeability of reservoir rocks. In order to reveal the damage and fracture mechanism of rock after thermal shock, the granites heated at high temperature (20 ℃, 150 ℃, 300 ℃, 450 ℃, 600 ℃ and 750 ℃) were treated by natural cooling and water cooling respectively, and the wave velocity test, uniaxial compression test and CT scanning were carried out on the treated granites. The mechanical effect of thermal shock on P-wave velocity, compressive strength and elastic modulus of granite were also discussed. The experimental results show that with the increase of heat treatment temperature, the P-wave velocity, compressive strength, and elastic modulus of rock gradually decrease, and the peak strain gradually increases. Compared with natural cooling, the wave velocity and mechanical properties of rock deteriorate more significantly after water cooling. Based on CT scanning, the spatial distribution characteristics of pore and fracture structure of granite under different heating temperatures and heat treatment methods were obtained, which can directly reflect the thermal damage degree of rock microstructure. When the heat treatment temperature is not higher than 450 ℃, the number and size of thermally induced cracks in granite scanning slices are less and the connectivity of cracks is relatively poor. When the temperature exceeds 450 ℃, the micro-cracks in granite develop and expand rapidly, and tend to form fracture network gradually, and the damage and cracking effect of water cooling on the microscomic-structure of granite is more obvious than that of natural cooling. In addition, based on triangular mesh discretization technique, ellipsoid model reconstruction algorithm and fracture tensor calculation theory, the three-dimensional fracture field of granite after thermal shock is quantitatively characterized, and the relationship between fracture fabric tensor and peak strength was established, which further reveals the influence mechanism of granite microscomic-structure on its mechanical properties under thermal shock.

Abstract Background There is an increasing demand for prenatal diagnostic testing in twin pregnancies, however, anecdotally there is a higher incidence of procedure-related complications after amniocentesis than that in singleton pregnancies. There is a paucity of data regarding risk factors of amniocentesis in twin pregnancies. Methods Women with twin pregnancies who underwent amniocentesis between January 2016 and December 2020 were enrolled in this retrospective study. Procedure-related complications including spontaneous miscarriage, intrauterine fetal death, spontaneous preterm delivery, preterm premature rupture of membranes, and placental abruption in one or both fetuses after amniocentesis were assessed. Meanwhile, potential risk factors related to amniocentesis including chorionicity, gestational age, conception, number of needle insertions, parity, history of miscarriage, indications, and pregnancy-related complications (pregnancy-induced hypertension and gestational diabetes) were also recorded. Results A total of 811 women with twin pregnancies underwent amniocentesis were included, with a procedure-related complications rate of 3.83%. Risk factors associated with increased risk of procedure-related complications after amniocentesis in twin pregnancies were chorionicity (adjusted odds ratio [aOR]: 4.06), gestational age at the procedure (aOR: 2.76), and numbers of needle insertions (aOR: 3.26). In the monochorionic twin pregnancy, hemorrhage during this pregnancy (aOR: 12.01), polyhydramnios (aOR: 5.03), and numbers of needle insertions (aOR: 3.15) were risk factors after amniocentesis. In the dichorionic twin pregnancy, gestational age at the procedure (OR:4.47) affected the risk of procedure-related complications after amniocentesis. In the subgroup of gestational age at the procedure ≤ 24+ 0 weeks, risk factors associated with increased risk of procedure-related complications after amniocentesis in twin pregnancies were chorionicity (aOR: 5.14), and numbers of needle insertions (aOR: 3.76). Conclusion The procedure-related complications rate is 3.83% in our institution during the study period. The present study has emphasized the significance of certain risk factors for adverse outcome and will be useful in counseling patients with twin pregnancies.

Abstract Background Snail abundance varies spatially and temporally. Few studies have elucidated the different effects of the determinants affecting snail density between upstream and downstream areas of the Three Gorges Dam (TGD). We therefore investigated the differential drivers of changes in snail density in these areas, as well as the spatial–temporal effects of these changes. Methods A snail survey was conducted at 200 sites over a 5-year period to monitor dynamic changes in snail abundance within the Yangtze River basin. Data on corresponding variables that might affect snail abundance, such as meteorology, vegetation, terrain and economy, were collected from multiple data sources. A Bayesian spatial–temporal modeling framework was constructed to explore the differential determinants driving the change in snail density and the spatial–temporal effects of the change. Results Volatility in snail density was unambiguously detected in the downstream area of the TGD, while a small increment in volatility was detected in the upstream area. Regarding the downstream area of the TGD, snail density was positively associated with the average minimum temperature in January of the same year, the annual Normalized Difference Vegetation Index (NDVI) of the previous year and the second, third and fourth quartile, respectively, of average annual relative humidity of the previous year. Snail density was negatively associated with the average maximum temperature in July of the previous year and annual nighttime light of the previous year. An approximately inverted “U” curve of relative risk was detected among sites with a greater average annual ground surface temperature in the previous year. Regarding the upstream area, snail density was positively associated with NDVI and with the second, third and fourth quartile, respectively, of total precipitation of the previous year. Snail density was negatively associated with slope. Conclusions This study demonstrated a rebound in snail density between 2015 and 2019. In particular, temperature, humidity, vegetation and human activity were the main drivers affecting snail abundance in the downstream area of the TGD, while precipitation, slope and vegetation were the main drivers affecting snail abundance in the upstream area. These findings can assist authorities to develop and perform more precise strategies for surveys and control of snail populations. Graphical Abstract

Abstract The transcriptional repressor Snail induces EMT during embryonic development and tumor metastasis. Growing evidence indicates that Snail functions as a trans-activator to induce gene expression; however, the underlying mechanism remains elusive. Here, we report that Snail cooperates with GATA zinc finger protein p66β to transactivate genes in breast cancer cells. Biologically, depletion of p66β reduces cell migration and lung metastasis in BALB/c mice. Mechanistically, Snail interacts with p66β and cooperatively induces gene transcription. Notably, a group of genes induced by Snail harbor conserved G-rich cis-elements (5′-GGGAGG-3′, designated as G-box) in their proximal promoter regions. Snail directly binds to G-box via its zinc fingers and transactivates the G-box-containing promoters. p66β enhances Snail binding affinity to G-box, whereas depletion of p66β results in a decreased binding affinity of Snail to the endogenous promoters and concomitantly reduces the transcription of Snail-induced genes. Taken together, these data demonstrated that p66β is critical for Snail-mediated cell migration by acting as a co-activator of Snail to induce genes containing G-box elements in the promoters.

Abstract Background This protocol is for a multi-centre randomised controlled trial to determine whether the computer-aided system ENDOANGEL-GC improves the detection rates of gastric neoplasms and early gastric cancer (EGC) in routine oesophagogastroduodenoscopy (EGD). Methods Study design: Prospective, single-blind, parallel-group, multi-centre randomised controlled trial. Settings: The computer-aided system ENDOANGEL-GC was used to monitor blind spots, detect gastric abnormalities, and identify gastric neoplasms during EGD. Participants: Adults who underwent screening, diagnosis, or surveillance EGD. Randomisation groups: 1. Experiment group, EGD examinations with the assistance of the ENDOANGEL-GC; 2. Control group, EGD examinations without the assistance of the ENDOANGEL-GC. Randomisation: Block randomisation, stratified by centre. Primary outcomes: Detection rates of gastric neoplasms and EGC. Secondary outcomes: Detection rate of premalignant gastric lesions, biopsy rate, observation time, and number of blind spots on EGD. Blinding: Outcomes are undertaken by blinded assessors. Sample size: Based on the previously published findings and our pilot study, the detection rate of gastric neoplasms in the control group is estimated to be 2.5%, and that of the experimental group is expected to be 4.0%. With a two-sided α level of 0.05 and power of 80%, allowing for a 10% drop-out rate, the sample size is calculated as 4858. The detection rate of EGC in the control group is estimated to be 20%, and that of the experiment group is expected to be 35%. With a two-sided α level of 0.05 and power of 80%, a total of 270 cases of gastric cancer are needed. Assuming the proportion of gastric cancer to be 1% in patients undergoing EGD and allowing for a 10% dropout rate, the sample size is calculated as 30,000. Considering the larger sample size calculated from the two primary endpoints, the required sample size is determined to be 30,000. Discussion The results of this trial will help determine the effectiveness of the ENDOANGEL-GC in clinical settings. Trial registration ChiCTR (Chinese Clinical Trial Registry), ChiCTR2100054449, registered 17 December 2021.

Abstract Snail is a denoted transcriptional repressor that plays key roles in epithelial-mesenchymal transition (EMT) and metastasis. Lately, a plethora of genes can be induced by stable expression of Snail in multiple cell lines. However, the biological roles of these upregulated genes are largely elusive. Here, we report identification of a gene encoding the key GlcNAc sulfation enzyme CHST2 is induced by Snail in multiple breast cancer cells. Biologically, CHST2 depletion results in inhibition of breast cancer cell migration and metastasis, while overexpression of CHST2 promotes cell migration and lung metastasis in nude mice. In addition, the expression level of MECA79 antigen is elevated and blocking the cell surface MECA79 antigen with specific antibodies can override cell migration mediated by CHST2 upregulation. Moreover, the sulfation inhibitor sodium chlorate effectively inhibits the cell migration induced by CHST2. Collectively, these data provide novel insights into the biology of Snail/CHST2/MECA79 axis in breast cancer progression and metastasis as well as potential therapeutic strategy for the diagnosis and treatment of breast cancer metastasis.

Abstract Background The area of Oncomelania hupensis snail remains around 3.6 billion m2, with newly emerging and reemergent habitats continuing to appear in recent years. This study aimed to explore the long-term dynamics of snail density before and after the operation of Three Gorges Dam (TGD). Methods Data of snail survey between 1990 and 2019 were collected from electronic databases and national schistosomiasis surveillance. Meta-analysis was conducted to estimate the snail density. Joinpoint model was used to identify the changing trend and inflection point. Inverse distance weighted interpolation (IDW) was used to determine the spatial distribution of recent snail density. Results A total of 3777 snail survey sites with a precise location of village or beach were identified. For the downstream area, snail density peaked in 1998 (1.635/0.11 m2, 95% CI: 1.220, 2.189) and fluctuated at a relatively high level before 2003, then declined steadily from 2003 to 2012. Snail density maintained lower than 0.150/0.11 m2 between 2012 and 2019. Joinpoint model identified the inflection of 2003, and a significant decreasing trend from 2003 to 2012 with an annual percentage change (APC) being − 20.56% (95% CI: − 24.15, − 16.80). For the upstream area, snail density peaked in 2005 (0.760/0.11 m2, 95% CI: 0.479, 1.207) and was generally greater than 0.300/0.11 m2 before 2005. Snail density was generally lower than 0.150/0.11 m2 after 2011. Snail density showed a significant decreasing trend from 1990 to 2019 with an APC being − 6.05% (95% CI: − 7.97, − 7.09), and no inflection was identified. IDW showed the areas with a high snail density existed in Poyang Lake, Dongting Lake, Jianghan Plain, and the Anhui branch of the Yangtze River between 2015 and 2019. Conclusions Snail density exhibited a fluctuating downward trend in the Yangtze River basin. In the downstream area, the operation of TGD accelerated the decline of snail density during the first decade period, then snail density fluctuated at a relatively low level. There still exists local areas with a high snail density. Long-term control and monitoring of snails need to be insisted on and strengthened. Graphical Abstract

Tuberculous meningitis (TBM) is not only one of the most fatal forms of tuberculosis, but also a major public health concern worldwide, presenting grave clinical challenges due to its nonspecific symptoms and the urgent need for timely intervention. The severity and the rapid progression of TBM underscore the necessity of early and accurate diagnosis to prevent irreversible neurological deficits and reduce mortality rates. Traditional diagnostic methods, reliant primarily on clinical findings and cerebrospinal fluid analysis, often falter in delivering timely and conclusive results. Moreover, such methods struggle to distinguish TBM from other forms of neuroinfections, making it critical to seek advanced diagnostic solutions. Against this backdrop, magnetic resonance imaging (MRI) has emerged as an indispensable modality in diagnostics, owing to its unique advantages. This review provides an overview of the advancements in MRI technology, specifically emphasizing its crucial applications in the early detection and identification of complex pathological changes in TBM. The integration of artificial intelligence (AI) has further enhanced the transformative impact of MRI on TBM diagnostic imaging. When these cutting-edge technologies synergize with deep learning algorithms, they substantially improve diagnostic precision and efficiency. Currently, the field of TBM imaging diagnosis is undergoing a phase of technological amalgamation. The melding of MRI and AI technologies unquestionably signals new opportunities in this specialized area.