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Based on the existing situation that natural aggregates are over-exploited and man-made aggregates have become a growing trend, this paper uses economical and abundant agricultural by-product, moso bamboo, as coarse aggregates to partially replace natural coarse aggregate (NCA) for casting a novel bamboo aggregate concrete (BAC), to minimize the use of NCA and to explore feasible sustainable construction materials. Monotonic axial compression tests were conducted on BAC to investigate the effects of bamboo coarse aggregate (BCA) replacement rate (r=0%∼45%) and modification methods (unmodified and epoxy mortar-modified) on failure modes, key mechanical property indexes, and compressive stress-strain relationship. Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy were utilized to analyze the chemical composition and microstructure of BAC. Results showed that when r ≥ 15%, the strength of epoxy mortar-modified BAC can meet the strength requirements of most non-special structural components in general construction while exhibiting good ductility, so it is recommended to use r ≥ 15% epoxy mortar-modified BCA. Finally, the conversion equations between the main mechanical property indexes and the stress-strain constitutive equations of BAC were proposed. The proposal of BAC is in line with the industry demand of vigorously promoting green building and sustainable building materials, and the study of its compression properties lays a theoretical foundation for its future engineering applications and structural design.

Abstract Objective At different times, public health faces various challenges and the degree of intervention measures varies. The research on the impact and prediction of meteorology factors on influenza is increasing gradually, however, there is currently no evidence on whether its research results are affected by different periods. This study aims to provide limited evidence to reveal this issue. Methods Daily data on influencing factors and influenza in Xiamen were divided into three parts: overall period (phase AB), non-COVID-19 epidemic period (phase A), and COVID-19 epidemic period (phase B). The association between influencing factors and influenza was analysed using generalized additive models (GAMs). The excess risk (ER) was used to represent the percentage change in influenza as the interquartile interval (IQR) of meteorology factors increases. The 7-day average daily influenza cases were predicted using the combination of bi-directional long short memory (Bi-LSTM) and random forest (RF) through multi-step rolling input of the daily multifactor values of the previous 7-day. Results In periods A and AB, air temperature below 22 °C was a risk factor for influenza. However, in phase B, temperature showed a U-shaped effect on it. Relative humidity had a more significant cumulative effect on influenza in phase AB than in phase A (peak: accumulate 14d, AB: ER = 281.54, 95% CI = 245.47 ~ 321.37; A: ER = 120.48, 95% CI = 100.37 ~ 142.60). Compared to other age groups, children aged 4–12 were more affected by pressure, precipitation, sunshine, and day light, while those aged ≥ 13 were more affected by the accumulation of humidity over multiple days. The accuracy of predicting influenza was highest in phase A and lowest in phase B. Conclusions The varying degrees of intervention measures adopted during different phases led to significant differences in the impact of meteorology factors on influenza and in the influenza prediction. In association studies of respiratory infectious diseases, especially influenza, and environmental factors, it is advisable to exclude periods with more external interventions to reduce interference with environmental factors and influenza related research, or to refine the model to accommodate the alterations brought about by intervention measures. In addition, the RF-Bi-LSTM model has good predictive performance for influenza.

Abstract Observational data suggest a link between gut microbiota and immune-related vasculitis, but causality remains unclear. A bidirectional mendelian randomization study was conducted using public genome-wide data. The inverse-variance-weighted (IVW) method identified associations and addressed heterogeneity.Families Clostridiaceae 1 and Actinomycetaceae correlated positively with granulomatosis with polyangiitis risk, while classes Lentisphaeria and Melainabacteria, and families Lachnospiraceae and Streptococcaceae showed negative associations. Behçet's disease was positively associated with the risk of family Streptococcaceae abundance. And other several gut microbiota constituents were identified as potential risk factors for immune-related vasculitis. Furthermore, combining positive association results from the IVW analysis revealed numerous shared gut microbiota constituents associated with immune-related vasculitis. MR analysis demonstrated a causal association between the gut microbiota and immune-related vasculitis, offering valuable insights for subsequent mechanistic and clinical investigations into microbiota-mediated immune-related vasculitis.

Abstract Objective Recent studies have indicated a potential association between giant cell arteritis (GCA) and diabetes mellitus, encompassing both type 1 diabetes (T1D) and type 2 diabetes (T2D). However, the exact nature of this relationship requires further investigation to be fully elucidated. Methods Genetic links between T1D/T2D and GCA were explored using data from genome-wide association studies available to the public, focusing on populations of European ancestry. We applied a bidirectional mendelian randomization (MR) approach to assess the potential association between these diseases. Confirmatory analyses, including additional datasets and a comprehensive meta-analysis, were utilized. The inverse-variance-weighted (IVW) method was applied to pinpoint heterogeneity and pleiotropy, while subsequent sensitivity analyses aimed to trace the origins of any heterogeneity. Results Initial analysis demonstrated a correlation between T1D and an elevated likelihood of developing GCA (IVW odds ratio = 1.33, with a 95% confidence interval of 1.22–1.46, and a P-value of 9.42E−10). The causal association was verified through four validation datasets and meta-analysis (all P-value

Abstract Background This study quantitatively analyzed the anatomic structure of the alveolar bone in the maxillary molar region at three potential locations for Temporary Anchorage Device (TAD) placement. Additionally, the study compared the variability in this region across different age groups, sagittal skeletal patterns, vertical facial types, and sexes. Methods In this retrospective cone-beam computed tomography study, the buccal alveolar bone was analyzed in the posterior molar area of 200 patients, the measurement items include buccal alveolar bone height, alveolar bone thickness, interradicular distance, and maxillary retromolar space. Results Buccal alveolar height was greatest in the U56 region. The interradicular space was largest in the U56 region and increased from the alveolar crest to the sinus floor. Buccal alveolar bone thickness was highest in the U67 region and generally increased from the alveolar crest to the sinus floor. The maxillary retromolar space gradually increased from the alveolar crest to the root apex. Conclusions TADs are safest when placed in the buccal area between the maxillary second premolar and the first molar, particularly at the 9 mm plane. The U67 region is the optimal safe zone for TAD placement for maxillary dentition distalization. TADs placement in adolescents can be challenging. Maxillary third molar extraction can be considered for maxillary dentition distalization.

Abstract The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6–3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

Abstract Background Although broadband music with inaudible high-frequency components may benefit human well-being, this research area is largely unexplored and lacks sufficient studies on the topic. This study aimed to investigate and compare the effects of broadband and audible band music on relaxation states and cognitive function in young adults. Methods A single-blind randomized controlled trial was conducted in a professional soundproof laboratory from December 22, 2022, to January 18, 2023 with 32 participants randomly assigned to two groups, “Day 1 broadband + Day 2 audible band” (n = 16) and “Day 1 audible band + Day 2 broadband” (n = 16), listening to either broadband or audible band music (the same music piece played on the piano and harp) for two sessions of 15 min each on two consecutive days. Cognitive function was measured using CNS Vital Signs at pre-listening, after the 1st session, and after the 2nd session, while heart rate was monitored throughout the experiment. Visual Analog Scale was also administered for self-reported arousal, stress, thinking ability, and attention following each listening session. Results No significant differences were found in heart rate, cognitive flexibility, and executive function between the broadband listening group and the audible band-listening group (p > 0.05). However, the broadband group exhibited significant differences in mean heart rate at several time points, as well as a significant improvement in VAS stress level during the 2nd listening session compared to the 1st (p

The global energy issue and lack of fossil fuels are obviously difficult concerns, prompting experts to look for other solutions. In this paper, the day-ahead operation of the multi-carrier energy system (MCE) to minimize operational costs, emission polluting and maximizing consumers’ comfort is presented. The optimal energy scheduling of consumption by energy demand curtailment strategy (EDCS) in the peak demand of electrical energy is proposed. Also, the operation of the energy storage via an onsite generation strategy (OGS) for consumers is considered by energy storage systems. The EDCS and OGS are modelled based on Demandside Management (DSM). The fuzzy method is taken into account as an optimization approach and objective functions. Finally, two scenarios using numerical simulation are studied to demonstrate the effectiveness of the approach for energy optimization in MCE. The results of the scenarios are studied based on non-participation and participation of the consumers in the scenarios A and B, respectively. The objective functions such as operation costs and emission polluting in scenario B are minimized by 1.63% and 5.35% than scenario A.

Abstract Background Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. Methods Data of 1964 participants (40–75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008–2014 was analyzed. Serum TMAO concentration was quantified by HPLC–MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. Results After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P -trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P -trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 – 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 – 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. Conclusion Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. Trial registration NCT 03179657.

Abstract Background This study aimed to investigate the relationships between accelerometer-measured physical activity (PA) and sedentary behaviour (SB) with physical function (PF) among older Chinese women in the community. Methods The present study comprised 1,113 community-dwelling older females, with an average age of 65 ± 2 years. We employed a linear regression analysis to investigate the relationship between patterns of PA and SB with PF. PA variables consisted of total PA time, bouted PA time (a continuous PA that lasts equal to or more than 10 min), and sporadic PA time (a continuous PA that lasts less than 10 min). SB variables included total SB time, 30-min bout of SB (a continuous SB that lasts equal to or more than 30 min), and 60-min bout of SB (a continuous SB that lasts equal to or more than 60 min). PF variables comprised handgrip strength (HGS), one-legged stance test with eyes closed (OLSTEC), usual walking speed (UWS), maximum walking speed (MWS) and chair-stand time (CT). To explore the joint effects of moderate-to-vigorous-intensity PA (MVPA) and SB on PF, we divided the duration of SB and MVPA participation in older women into different combinations: low MVPA & high SB, low MVPA & low SB, high MVPA & high SB, high MVPA & low SB. Results The study revealed a significant association between 30-min bout of SB and CT, which remained after adjusting for total MVPA time (P = 0.021). Both total MVPA and bouted MVPA were found to be positively associated with better UWS, MWS, CT, and PF Z-score. When the combination of low MVPA & high SB was used as a reference, the regression coefficients for PF ascended by 1.32 (P

ABSTRACTIntroduction Following the coronavirus disease pandemic, respiratory mucosal vaccines that elicit both mucosal and systemic immune responses have garnered increasing attention. However, human physiological characteristics pose significant challenges in the evaluation of mucosal immunity, which directly impedes the development and application of respiratory mucosal vaccines.Areas Covered This study summarizes the characteristics of immune responses in the respiratory mucosa and reviews the current status and challenges in evaluating immune response to respiratory mucosal vaccines.Expert Opinion Secretory Immunoglobulin A (S-IgA) is a major effector molecule at mucosal sites and a commonly used indicator for evaluating respiratory mucosal vaccines. However, the unique physiological structure of the respiratory tract pose significant challenges for the clinical collection and detection of S-IgA. Therefore, it is imperative to develop a sampling method with high collection efficiency and acceptance, a sensitive detection method, reference materials for mucosal antibodies, and to establish a threshold for S-IgA that correlates with clinical protection. Sample collection is even more challenging when evaluating mucosal cell immunity. Therefore, a mucosal cell sampling method with high operability and high tolerance should be established. Targets of the circulatory system capable of reflecting mucosal cellular immunity should also be explored.

Groundwater vulnerability to nitrate assessment serves as a measure of potential groundwater nitrate pollution in a target area. This study applies the DRASTIC-LU framework, nitrate distribution data, and three machine learning models (RF, XGB, SVM) to classify nitrate levels (exceeding 10 mg/L as nitrogen) in Chongqing, China. Model evaluation uses accuracy and F1 score metrics, with RF achieving the highest accuracy (92.9%), kappa (0.857), and AUC (0.948) on test dataset. Furthermore, the SHAP interpreter revealed that aquifer conductivity, lithology, agricultural activities, areas with high-intensity development, and groundwater recharge are the most influential indicators of groundwater vulnerability. The final groundwater vulnerability level distribution map, with a resolution of 1 km × 1 km, reveals that high and extremely high vulnerability levels are concentrated in areas with high-intensity urban development and karst trough valleys in the southeastern, northeastern, and central urban areas. This work represents the first attempt of using machine learning models for groundwater vulnerability assessment in the Chongqing region. It provides theoretical support for the construction layout of groundwater monitoring stations and the prevention and control of groundwater pollution in the future. HIGHLIGHTS Predicting groundwater nitrate vulnerability in Chongqing region using DRASTIC-LU framework and machine learning models.; Random Forest outperforms other machine learning approaches.; Aquifer conductivity, lithology, agricultural activities and areas with high-intensity development predictors were most influential explanatory factors.; Distribution of groundwater nitrate vulnerability map at 1 km resolution.; Groundwater nitrate vulnerability map reveal the high vulnerability levels distributed karst trough valleys in the southeastern, northeastern, and central urban areas.;

Abstract Background Education in nursing has noticed a positive effect of simulation-based education. There are many studies available on the effects of simulation-based education, but most of those involve a single institution, nonrandomized controlled trials, small sample sizes and subjective evaluations of the effects. The purpose of this multicenter randomized controlled trial was to evaluate the effects of high-fidelity simulation, computer-based simulation, high-fidelity simulation combined with computer-based simulation, and case study on undergraduate nursing students. Methods A total of 270 nursing students were recruited from five universities in China. Participants were randomly divided into four groups at each institution: the high-fidelity simulation group, the computer-based simulation group, the high-fidelity simulation combined with computer-based simulation group, and the case study group. Finally, 239 participants completed the intervention and evaluation, with 58, 67, 57, and 57 participants in each group. The data were collected at three stages: before the intervention, immediately after the intervention, and three months after the intervention. Results The demographic data and baseline evaluation indices did not significantly differ among the four groups. A statistically significant difference was not observed between the four methods for improving knowledge, interprofessional collaboration, critical thinking, caring, or interest in learning. While skill improvement differed significantly among the different groups after the intervention (p = 0.020), after three months, no difference was observed (p = 0.139). The improvement in skill in the computer-based simulation group was significantly lower at the end of the intervention than that in the high-fidelity simulation group (p = 0.048) or the high-fidelity simulation combined with computer-based simulation group (p = 0.020). Conclusions Nursing students benefit equally from four methods in cultivating their knowledge, interprofessional collaboration, critical thinking, caring, and interest in learning both immediately and over time. High-fidelity simulation and high-fidelity simulation combined with computer-based simulation improve skill more effectively than computer-based simulation in the short term. Nursing educators can select the most suitable teaching method to achieve the intended learning outcomes depending on the specific circumstances. Trial registration This clinical trial was registered at the Chinese Clinical Trial Registry (clinical trial number: ChiCTR2400084880, date of the registration: 27/05/2024).

Abstract Objective Previous studies have shown a clear link between insulin resistance (IR) and an elevated risk of atrial fibrillation (AF). However, the relationship between the estimated glucose disposal rate (eGDR), which serves as a marker for IR, and the risk of AF recurrence after radiofrequency catheter ablation (RFCA) remains uncertain. Therefore, this study aimed to examine the potential association between the eGDR and the risk of AF recurrence following RFCA. Methods This retrospective study was conducted at Nanchang University Affiliated Second Hospital. The study enrolled 899 patients with AF who underwent RFCA between January 2015 and January 2022. The formula used to calculate the eGDR was as follows: 19.02 − (0.22 * body mass index) − (3.26 * hypertension) − (0.61 * HbA1c). Cox proportional hazard regression models and exposure–effect curves were used to explore the correlation between the baseline eGDR and AF recurrence. The ability of the eGDR to predict AF recurrence was evaluated using the area under the receiver operating characteristic curve (AUROC). Results The study observed a median follow-up period of 11.63 months, during which 296 patients experienced AF recurrence. K‒M analyses revealed that the cumulative incidence AF recurrence rate was significantly greater in the group with the lowest eGDR (log-rank p

Abstract Background Cardiac fibrosis after myocardial infarction (MI) has been considered an important part of cardiac pathological remodeling. Immune cells, especially macrophages, are thought to be involved in the process of fibrosis and constitute a niche with fibroblasts to promote fibrosis. However, the diversity and variability of fibroblasts and macrophages make it difficult to accurately depict interconnections. Methods We collected and reanalyzed scRNA-seq and snRNA-seq datasets from 12 different studies. Differentiation trajectories of these subpopulations after MI injury were analyzed by using scVelo, PAGA and Slingshot. We used CellphoneDB and NicheNet to infer fibroblast-macrophage interactions. Tissue immunofluorescence staining and in vitro experiments were used to validate our findings. Results We discovered two subsets of ECM-producing fibroblasts, reparative cardiac fibroblasts (RCFs) and matrifibrocytes, which appeared at different times after MI and exhibited different transcriptional profiles. We also observed that CTHRC1+ fibroblasts represent an activated fibroblast in chronic disease states. We identified a macrophage subset expressing the genes signature of SAMs conserved in both human and mouse hearts. Meanwhile, the SPP1hi macrophages were predominantly found in the early stages after MI, and cell communication analysis indicated that SPP1hi macrophage-RCFs interactions are mainly involved in collagen deposition and scar formation. Conclusions Overall, this study comprehensively analyzed the dynamics of fibroblast and macrophage subsets after MI and identified specific subsets of fibroblasts and macrophages involved in scar formation and collagen deposition.

Electroplating wastewater contains heavy metal ions and organic matter. These contaminants not only endanger the environment but also pose risks to human health. Despite the development of various treatment processes such as chemical precipitation MBR, electrocoagulation (EC) ceramic membrane (CM), coagulation ultrafiltration (UF) reverse osmosis (RO), and CM RO. These methods are only effective for low concentrations of heavy metals and struggle with high concentrations. To address the challenge of treating electroplating wastewater with high heavy metal content, this study focuses on the wastewater from Dongfang Aviation Machinery Processing Plant. It introduces an EC and integrated membrane (IM) treatment process for electroplating wastewater. The IM comprises microfiltration (MF) membrane, nanofiltration (NF) membrane, and RO membrane. Results indicated that under specific conditions, such as a pH of 8, current density of 5 A/dm2, electrode plate spacing of 2 cm, 35 min of electrolysis time, and influent pH of 10 for the IM, removal rates of Zn2+, Cu2+, Ni2+, and TCr in the wastewater exceeded 99%. The removal rates of chemical oxygen demand (COD), suspended solids (SS), total phosphorus (TP), total nitrogen (TN), and petroleum in wastewater exceed 97%. Following a continuous cleaning process, the membrane flux can consistently recover to over 94.3%. HIGHLIGHTS Comprehensive treatment of wastewater pollution.; Application of environmental protection and energy conservation technology.; Efficient removal of harmful substances.; Systematic wastewater treatment solution.; Effectively removing heavy metals.;

Abstract Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.

Abstract Purpose The purpose of this study was to compare the learning in the implant dentistry hands-on course to that of the flipped classroom (FC) and the traditional lecture cohorts (control). Materials and methods In this study,80 students were enrolled for the first time in an implant dentistry program. Subsequently, they were divided into two groups. The first, the FC group, which had free access to a video with a PowerPoint presentation on the Chaoxing-WHU-MOOC platform about the implant placement on first molar sites before class. The second, the control group, which attended a didactic lecture describing implant practice on the first molar site via a bidirectional multimedia interactive teaching demonstration and then operated on a simulation model. Cone beam computed tomography (CBCT) and the deviation gauge were utilized to analyze the accuracy of the implant placement in the students’ models. An online satisfaction questionnaire was distributed to both groups one week after the class. Results The linear deviation of the CBCT examination did not show any statistical difference between the two groups concerning cervical, apex, and angular. A significant buccal deviation was observed in the control group compared with the FC group (mean: 0.7436 mm vs. 0.2875 mm, p = 0.0035), according to the restoration-level deviation gauge. A total of 74.36% of students in the FC group placed implant within 0.5 mm buccal-to-lingual deviations, but only 41.03% of students in the control group reached within 0.5 mm buccal-to-lingual deviation ranges. Additionally, 91.67% of the students in the FC group and 97.5% of the students in the control group were satisfied with the practical implant class. Conclusion FC was more effective than a didactic lecture for implant dentistry practical skill acquisition.

Abstract Mesenchymal stem/stromal cells (MSCs) represent a heterogeneous cell population distributed throughout various tissues, demonstrating remarkable adaptability to microenvironmental cues and holding immense promise for disease treatment. However, the inherent diversity within MSCs often leads to variability in therapeutic outcomes, posing challenges for clinical applications. To address this heterogeneity, purification of MSC subpopulations through marker-based isolation has emerged as a promising approach to ensure consistent therapeutic efficacy. In this review, we discussed the reported markers of MSCs, encompassing those developed through candidate marker strategies and high-throughput approaches, with the aim of explore viable strategies for addressing the heterogeneity of MSCs and illuminate prospective research directions in this field.

Abstract The highly unique zigzag-shaped stem phenotype in tea plants boasts significant ornamental value and is exceptionally rare. To investigate the genetic mechanism behind this trait, we developed BC1 artificial hybrid populations. Our genetic analysis revealed the zigzag-shaped trait as a qualitative trait. Utilizing whole-genome resequencing, we constructed a high-density genetic map from the BC1 population, incorporating 5,250 SNP markers across 15 linkage groups, covering 3,328.51 cM with an average marker interval distance of 0.68 cM. A quantitative trait locus (QTL) for the zigzag-shaped trait was identified on chromosome 4, within a 61.2 to 97.2 Mb range, accounting for a phenotypic variation explained (PVE) value of 13.62%. Within this QTL, six candidate genes were pinpointed. To better understand their roles, we analyzed gene expression in various tissues and individuals with erect and zigzag-shaped stems. The results implicated CsXTH (CSS0035625) and CsCIPK14 (CSS0044366) as potential key contributors to the zigzag-shaped stem formation. These discoveries lay a robust foundation for future functional genetic mapping and tea plant genetic enhancement.

Abstract Background China has thousands years of goat breeding and abundant goat genetic resources. Additionally, the Hainan black goat is one of the high-quality local goat breeds in China. In order to conserve the germplasm resources of the Hainan black goat, facilitate its genetic improvement and further protect the genetic diversity of goats, it is urgent to develop a single nucleotide polymorphism (SNP) chip for Hainan black goat. Results In this study, we aimed to design a 10K liquid chip for Hainan black goat based on genotyping by pinpoint sequencing of liquid captured targets (cGPS). A total of 45,588 candidate SNP sites were obtained, 10,677 of which representative SNP sites were selected to design probes, which finally covered 9,993 intervals and formed a 10K cGPS liquid chip for Hainan black goat. To verify the 10K cGPS liquid chip, some southern Chinese goat breeds and a sheep breed with similar phenotype to the Hainan black goat were selected. A total of 104 samples were used to verify the clustering ability of the 10K cGPS liquid chip for Hainan black goat. The results showed that the detection rate of sites was 97.34% -99.93%. 84.5% of SNP sites were polymorphic. The heterozygosity rate was 3.08%-36.80%. The depth of more than 99.4% sites was above 10X. The repetition rate was 99.66%-99.82%. The average consistency between cGPS liquid chip results and resequencing results was 85.58%. In addition, the phylogenetic tree clustering analysis verified that the SNP sites on the chip had better clustering ability. Conclusion These results indicate that we have successfully realized the development and verification of the 10K cGPS liquid chip for Hainan black goat, which provides a useful tool for the genome analysis of Hainan black goat. Moreover, the 10K cGPS liquid chip is conducive to the research and protection of Hainan black goat germplasm resources and lays a solid foundation for its subsequent breeding work.

Enhancing photosynthetic efficiency is a major goal for improving crop yields under agricultural field conditions and is associated with chloroplast biosynthesis and development. In this study, we demonstrate that Golden2-like 1a (BnGLK1a) plays an important role in regulating chloroplast development and photosynthetic efficiency. Overexpressing BnGLK1a resulted in significant increases in chlorophyll content, the number of thylakoid membrane layers and photosynthetic efficiency in Brassica napus, while knocking down BnGLK1a transcript levels through RNA interference (RNAi) had the opposite effects. A yeast two-hybrid screen revealed that BnGLK1a interacts with the abscisic acid receptor PYRABACTIN RESISTANCE 1-LIKE 1–2 (BnPYL1–2) and CONSTITUTIVE PHOTOMORPHOGENIC 9 SIGNALOSOME 5A subunit (BnCSN5A), which play essential roles in regulating chloroplast development and photosynthesis. Consistent with this, BnGLK1a-RNAi lines of B. napus display hypersensitivity to the abscisic acid (ABA) response. Importantly, overexpression of BnGLK1a resulted in a 10% increase in thousand-seed weight, whereas seeds from BnGLK1a-RNAi lines were 16% lighter than wild type. We propose that BnGLK1a could be a potential target in breeding for improving rapeseed productivity. Our results not only provide insights into the mechanisms of BnGLK1a function, but also offer a potential approach for improving the productivity of Brassica species.

Abstract Human bocavirus (HBoV) 1 is considered an important pathogen that mainly affects infants aged 6–24 months, but preventing viral transmission in resource‐limited regions through rapid and affordable on‐site diagnosis of individuals with early infection of HBoV1 remains somewhat challenging. Herein, we present a novel faster, lower cost, reliable method for the detection of HBoV1, which integrates a recombinase polymerase amplification (RPA) assay with the CRISPR/Cas12a system, designated the RPA‐Cas12a‐fluorescence assay. The RPA‐Cas12a‐fluorescence system can specifically detect target gene levels as low as 0.5 copies of HBoV1 plasmid DNA per microliter within 40 min at 37°C without the need for sophisticated instruments. The method also demonstrates excellent specificity without cross‐reactivity to non‐target pathogens. Furthermore, the method was appraised using 28 clinical samples, and displayed high accuracy with positive and negative predictive agreement of 90.9% and 100%, respectively. Therefore, our proposed rapid and sensitive HBoV1 detection method, the RPA‐Cas12a‐fluorescence assay, shows promising potential for early on‐site diagnosis of HBoV1 infection in the fields of public health and health care. The established RPA‐Cas12a‐fluorescence assay is rapid and reliable method for human bocavirus 1 detection. The RPA‐Cas12a‐fluorescence assay can be completed within 40 min with robust specificity and sensitivity of 0.5 copies/μl.

Abstract Cryptococcus neoformans has been designated as critical fungal pathogens by the World Health Organization, mainly due to limited treatment options and the prevalence of antifungal resistance. Consequently, the utilization of novel antifungal agents is crucial for the effective treatment of C. neoformans infections. This study exposed that the minimum inhibitory concentration (MIC) of isobavachalcone (IBC) against C. neoformans H99 was 8 µg/mL, and IBC dispersed 48-h mature biofilms by affecting cell viability at 16 µg/mL. The antifungal efficacy of IBC was further validated through microscopic observations using specific dyes and in vitro assays, which confirmed the disruption of cell wall/membrane integrity. RNA-Seq analysis was employed to decipher the effect of IBC on the C. neoformans H99 transcriptomic profiles. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis was performed to validate the transcriptomic data and identify the differentially expressed genes. The results showed that IBC exhibited various mechanisms to impede the growth, biofilm formation, and virulence of C. neoformans H99 by modulating multiple dysregulated pathways related to cell wall/membrane, drug resistance, apoptosis, and mitochondrial homeostasis. The transcriptomic findings were corroborated by the antioxidant analyses, antifungal drug sensitivity, molecular docking, capsule, and melanin assays. In vivo antifungal activity analysis demonstrated that IBC extended the lifespan of C. neoformans-infected Caenorhabditis elegans. Overall, the current study unveiled that IBC targeted multiple pathways simultaneously to inhibit growth significantly, biofilm formation, and virulence, as well as to disperse mature biofilms of C. neoformans H99 and induce cell death.

The Yellow River Basin in China, which is characterized by significant soil erosion and arid to semi-arid conditions, has experienced severe ecological issues due to prolonged excessive development and land-use changes. Studies on ecosystem vulnerability have become a major basis for supporting the sustainable and healthy development of watershed ecosystems. Based on the land-use data of 2000, 2005, 2010, 2015, and 2020, this study used a complex network model to identify the key types of land-use transformation in the Yellow River Basin. The cascade failure model was used to evaluate the impact of land-use transformation on ecological vulnerability in the Yellow River Basin of China. The land-use changes in the Yellow River Basin from 2000 to 2020 exhibit significant heterogeneity in both quantity and direction. Among them, the total area of agricultural land showed a downward trend as a whole, and the area rebounded slightly from 2000 to 2015. The growth trend of construction land area is obvious, with a year-on-year increase of 46.81 % in 20 years. Through network identification, we found that ecological land types such as forest, grassland, and dryland are the primary factors contributing to land area outflow. Conversely, artificial land types including urban land, rural residential land, and other built-up land predominantly serve as factors for land area inflow. The Yellow River Basin experiences frequent land-use transitions, resulting in the poor stability of the land transfer network. However, the study reveals that the ecosystem service value increases as the areas of paddy fields, dryland, urban land, rural residential land, and bare land decrease; this trend contributes to mitigating ecological vulnerability. To ensure the overall stability of the ecosystem and implement healthy and sustainable development, the maximum reduction in the areas of dryland, forest, paddy, and grass should be limited to 40 %, 30 %, 50 %, and 50 %, respectively, in future planning and design processes. In conclusion, the land-use transformation in the Yellow River Basin of China has profound implications for ecological vulnerability. The research findings can provide valuable references for future ecological research on areas facing similar challenges in protecting ecological fragility.

BackgroundPolycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder that affects women of reproductive age, characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology. Emerging evidence indicates that neurological disorders play a significant role in the etiology of PCOS, highlighting the complex interplay between the central nervous system (CNS) and ovarian function. Yulinzhu, a traditional Chinese medicine (TCM) formulation, has been traditionally used to regulate menstrual cycles and improve fertility. This study aims to investigate the efficacy and mechanisms of Yulinzhu in treating PCOS induced by neurological disorders.MethodsAn extensive literature search was performed across electronic databases such as PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI), covering publications up to 1 June 2024. The review included randomized controlled trials (RCTs) that compared Yulin Zhu with placebo, standard care, or other active treatments in patients with PCOS. Two reviewers independently carried out data extraction and quality assessment. Meta-analyses were conducted using both fixed and random-effects models, with heterogeneity evaluated using the I2 statistic.ResultsWe screened 891 records and included 6 studi es in the meta-analysis. The meta-analysis revealed that Yulinzhu about effective rate [RR = 1.19, 95% CI (1.10, 1.29), p < 0.0001], pregnancy rate [RR = 2.80, 95% CI (1.65, 4.76), p < 0.0001] and ovulation rate [RR = 1.33, 95% CI (1.10, 1.62), p = 0.04]. Meta-analysis shows the results of follicle estrogen [WMD = 0.69, 95% CI (−0.39, 1.78), p = 0.21], luteinizing hormone [WMD = −2.27, 95% CI (−3.86, −0.67), p = 0.005], testosterone [WMD = −0.44, 95% CI (−0.64, −0.25), p < 0.0001], estradiol [WMD = 16.20, 95% CI (2.74, 29.67), p < 0.0001].ConclusionThis study demonstrates that plant medicine compund Yulinzhu may effectively treats PCOS including hormonal regulation, anti-inflammatory actions, and neuroprotection. We expect further research with larger, well-designed clinical trials to substantiate our conclusions.

The accumulation of rare earth elements (REEs) in the global environment poses a threat to plant health and ecosystem stability. Stomata located on leaves serve as the primary site for plant responses to REE-related threats. This study focused on lanthanum [La(III)], a prevalent REE in the atmospheric environment. Using interdisciplinary techniques, it was found that La(III) (≤80 µM) interfered with the fundamental rhythms of stomatal opening, related gene expression, and evapotranspiration in plants. Specifically, when exposed to low concentrations of La(III) (15 and 30 µM), the expression levels of six genes were increased, stomatal opening was enhanced, and the evapotranspiration rate was accelerated. The interference on stomatal rhythms was enhanced with higher concentrations of La(III) (60 and 80 µM), increasing the expression levels of six genes, stomatal opening, and evapotranspiration rate. To counter the interference of low concentrations of La(III) (15 and 30 μM), plants accelerated nutrient replenishment through La(III)-induced endocytosis, which the redundant nutrients enhanced photosynthesis. However, replenished nutrients failed to counter the disruption of plant biological rhythms at higher concentrations of La(III) (60 and 80 μM), thus inhibiting photosynthesis due to nutrient deficit. The interference of La(III) on these biological rhythms negatively affected plant health and ecosystem stability.

BackgroundDeveloping adverse lifestyle behaviors increases the risk of a variety of chronic age-related diseases, including cardiovascular disease, obesity, and Alzheimer disease. There is limited evidence regarding the effectiveness of eHealth-based multiple health behavior change (MHBC) interventions to manage lifestyle risk behaviors. ObjectiveThe purpose of this systematic evaluation was to assess the effectiveness of eHealth MHBC interventions in changing ≥2 major lifestyle risk behaviors in people aged ≥50 years. MethodsThe literature search was conducted in 6 electronic databases—PubMed, Embase, Web of Science, Scopus, Cochrane Library, and SPORTDiscus—from inception to May 1, 2024. Eligible studies were randomized controlled trials of eHealth interventions targeting ≥2 of 6 behaviors of interest: alcohol use, smoking, diet, physical activity (PA), sedentary behavior, and sleep. ResultsA total of 34 articles with 35 studies were included. eHealth-based MHBC interventions significantly increased smoking cessation rates (odds ratio 2.09, 95% CI 1.62-2.70; P

BackgroundIn the early postoperative stage after heart transplantation, there is a lack of predictive tools to guide postoperative management. Whether the vasoactive-inotropic score (VIS) can aid this prediction is not well illustrated.MethodsIn total, 325 adult patients who underwent heart transplantation at our center between January 2015 and December 2018 were included. The maximum VIS (VISmax) within 24 h postoperatively was calculated. The Kaplan-Meier method was used for survival analysis. A logistic regression model was established to determine independent risk factors and to develop a nomogram for a composite severe adverse outcome combining early mortality and morbidity.ResultsVISmax was significantly associated with extensive early outcomes such as early death, renal injury, cardiac reoperation and mechanical circulatory support in a grade-dependent manner, and also predicted 90-day and 1-year survival (p < 0.05). A VIS-based nomogram for the severe adverse outcome was developed that included VISmax, preoperative advanced heart failure treatment, hemoglobin and serum creatinine. The nomogram was well calibrated (Hosmer-Lemeshow p = 0.424) with moderate to strong discrimination (C-index = 0.745) and good clinical utility.ConclusionVISmax is a valuable prognostic index in heart transplantation. In the early post-transplant stage, this VIS-based nomogram can easily aid intensive care clinicians in inferring recipient status and guiding postoperative management.

Hydrostatic pressure is a crucial tool to regulate the structure and properties of materials. However, the influence of hydrostatic pressure on the microstructure of metastable β-Ti alloys remains unclear. In this work, the microstructure and microhardness evolution of a metastable β-type Ti-30Zr-10Nb alloy under hydrostatic pressure (≤10 GPa) were investigated and compared with those under uniaxial pressure (≤1106 MPa). The results revealed that under hydrostatic pressure, Ti-30Zr-10Nb alloy formed a peculiar hierarchical microstructure composed of submicron-scaled α” plates with self-accommodating morphologies, nanoscale ω particles, and microscale shear bands containing nanoscale α” domains. The formation of a hierarchical microstructure effectively coordinates not only the isotropic macroscopic strains but also the local shear stresses under hydrostatic pressure. Compared to uniaxial pressure, the hydrostatic pressure facilitates the β to ω transformation, but hinders the β to α” transformation. The microhardness of the Ti3010 alloy reaches approximately 319 HV at a hydrostatic pressure of 10 GPa, which is 28 % higher than the highest microhardness obtained under uniaxial pressure. The current results highlight the promising potential of hydrostatic pressure in optimizing the mechanical properties of metastable β-Ti alloys.

Objective The First Member of the Zhujiang Formation in the Zhu Ⅲ Depression underwent significant changes in its sedimentary system. It transitioned from a large-scale delta system to a shallow sea shelf system. Understanding the evolutionary process and controlling factors of this basin is important for studying the sedimentary system during transgression and predicting favorable sedimentary facies zones on shallow sea shelves. Methods In this study, we used core, well logging, and high-resolution 3D seismic data to establish a stratigraphic framework for the First Member of the Zhujiang Formation. By combining geology and geophysics, we determined the temporal and spatial evolution characteristics of the sedimentary system and discussed the main controlling factors. Results Our findings show that the First Member of the Zhujiang Formation can be divided into four sequences: PS1, PS2, PS3, and PS4. PS3 and PS4 were dominated by delta deposits, including underwater distributary channels, estuarine dams, and distal dams. PS1 and PS2 were characterized by the development of large-scale shallow-sea shelf systems, with tidal sand ridges in the west and offshore sand dams in the east. The evolution of the sedimentary system in the Zhu Ⅲ Depression is influenced by sea level changes, source supply intensity, structural subsidence, and paleogeomorphology. Conclusion Microfacies sandstones, such as underwater distributary channels, tidal sand ridges, and coastal sand dams, have high percentages and good physical properties, making them favorable sedimentary facies zones for oil and gas reservoirs.

Abstract Background Previously, we have demonstrated that the batch variations of human platelet lysate (conventional MSC expansion medium) induce MSC heterogeneity and therapeutic inconsistency. On the other hand, the MSCs expanded with chemical defined medium have improved therapeutic consistency. Methods In the current study, we studied the MSC subpopulation composition and variation in different types and batches of MSC expansion medium with scRNA-seq analysis. Results MSCs expanded with different batches of media have higher levels of heterogeneity from the perspective of cell subpopulation composition at transcriptome levels and therapeutic inconsistency. The CD317+ subpopulation has enhanced immune suppression activities. And the percentage of CD317+ MSCs within MSCs is tightly correlated with its immune suppression activities, and also contributes to the heterogeneity and therapeutic inconsistency of MSCs. the CD317+ MSCs have increased expression levels of PTX3, which might stabilize the TSG6 protein and improve the therapeutic effects Conclusions Thus, purifying CD317+ MSCs is one efficient strategy to reduce MSC heterogeneity and increase the therapeutic consistency of MSCs.

Abstract Background Parkinson’s disease (PD) is characterized by death of dopaminergic neurons leading to dopamine deficiency, excessive α-synuclein facilitating Lewy body formation, etc. Latroeggtoxin-VI (LETX-VI), a proteinaceous neurotoxin discovered from the eggs of spider L. tredecimguttatus, was previously found to promote the synthesis and release of PC12 cells, showing a great potential as a drug candidate for PD. However, the relevant mechanisms have not been understood completely. The present study explored the mechanism underlying the effects of LETX-VI on dopamine and α-synuclein of PC12 cells and the implications for PD. Results After PC12 cells were treated with LETX-VI, the level of dopamine was significantly increased in a dose-dependent way within a certain range of concentrations. Further mechanism analysis showed that LETX-VI upregulated the expression of tyrosine hydroxylase (TH) and L-dopa decarboxylase to enhance the biosynthesis of dopamine, and downregulated that of monoamine oxidase B to reduce the degradation of dopamine. At the same time, LETX-VI promoted the transport and release of dopamine through modulating the abundance and/or posttranslational modification of vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT). While the level of dopamine was increased by LETX-VI treatment, α-synuclein content was reduced by the spider toxin. α-Synuclein overexpression significantly decreased the dopamine level and LETX-VI efficiently alleviated the inhibitory action of excessive α-synuclein on dopamine. In the MPTP-induced mouse model of PD, application of LETX-VI ameliorated parkinsonian behaviors of the mice, and reduced the magnitude of MPTP-induced α-synuclein upregulation and TH downregulation. In addition, LETX-VI displayed neuroprotective effects by inhibiting MPTP-induced decrease in the numbers of TH-positive and Nissl-stained neurons in mouse brain tissues. Conclusions All the results demonstrate that LETX-VI promotes the synthesis and release of dopamine in PC12 cells via multiple mechanisms including preventing abnormal α-synuclein accumulation, showing implications in the prevention and treatment of PD.

The study of extreme weather and space events has gained paramount importance in modern society owing to rapid advances in high technology. Understanding and describing exceptional occurrences plays a crucial role in making decisive assessments of their potential impact on technical, economic, and social aspects in various fields. This research focuses on analyzing the hourly values of the auroral electrojet (AE) geomagnetic index from 1957 to 2019 by using the peak over threshold method in extreme value theory. By fitting the generalized Pareto distribution to extreme AE values, shape parameter indices were derived, revealing negative values that establish an upper bound for this time series. Consequently, it became evident that the AE values had reached a plateau, suggesting that extreme events exceeding the established upper limit are rare. As a result, although the need for diligent precautions to mitigate the consequences of such extreme events persists, surpassing the upper limit of AE values becomes increasingly challenging. It is also possible to observe an aurora in the middle- and low-latitude regions during the maximum period of the AE index.

Abstract Aim of this comparative cross-sectional study was to evaluate the effect of anterior teeth retraction and related hard and soft tissue change under physiologic anchorage control in patients with chief complain of protrusive teeth. 68 Class I or II orthodontic patients undergoing four-premolar extraction and requiring maximum or medium anchorage were included. Patients were treated with physiologic anchorage control technique (PASS group, n = 34, 18.6 ± 7.7 years, 10 male and 24 female) and self-ligation technique (Damon group, n = 34, 17.5 ± 5.4 years, 13 male and 21 female), respectively. TADs were used for anchorage reinforcement in Damon group. Pre- and post-treatment cephalograms were collected. Twenty-six skeletal, dental and soft tissue items were measured and analyzed using a blinded method. T test and paired rank-sum test were used for statistical analysis. The baseline characteristics were similar between groups (P > 0.05). After treatment, inter-group comparison showed statistically significant differences in the decrease of skeletal measurements ∠ANB (− 0.73 ± 1.05° in PASS group and − 0.25 ± 0.84° in the Damon group), Wits value (− 2.56 ± 2.29 mm in PASS group and − 0.47 ± 2.15 mm in Damon group) and soft tissue measurement UL-E (− 2.75 ± 1.36 mm in PASS group and − 2.03 ± 1.30 mm in Damon group) and the increase of FCA and Z angle, which was 2.03 ± 2.12°and 9.52 ± 4.78°in PASS group and 0.97 ± 2.12°and 6.96 ± 4.43°in Damon group, respectively (P

Abstract B-cell subsets in peripheral blood (PB) and tumor microenvironment (TME) were evaluated to determine myasthenia gravis (MG) severity in patients with thymoma-associated MG (TMG) and the distribution of B cells in type B TMG. The distribution of mature B cells, including Bm1–Bm5, CD19+ and CD20+ B cells and non-switched (NSMBCs) and switched (SMBCs) memory B cells, were determined in 79 patients with thymoma or TMG. Quantitative relationships between the T and TMG groups and the TMG-low and TMG-high subgroups were determined. NSMBCs and SMBCs were compared in TME and PB. Type B thymoma was more likely to develop into MG, with types B2 and B3 being especially associated with MG worsening. The percentage of CD19+ B cells in PB gradually increased, whereas the percentage of CD20+ B cells and the CD19/CD20 ratio were not altered. The (Bm2 + Bm2′)/(eBm5 + Bm5) index was significantly higher in the TMG-high than in thymoma group. The difference between SMBC/CD19+ and NSMBC/CD19+ B cell ratios was significantly lower in the thymoma than TMG group. NSMBCs assembled around tertiary lymphoid tissue in thymomas of patients with TMG. Few NSMBCs were observed in patients with thymoma alone, with these cells being diffusely distributed. MG severity in patients with TMG can be determined by measuring CD19+ B cells and Bm1-Bm5 in PB. The CD19/CD20 ratio is a marker of disease severity in TMG patients. Differences between NSMBCs and SMBCs in PB and TME of thymomas can synergistically determine MG severity in patients with TMG.

Abstract Introduction Anti-mitosis has been a key strategy of anti-cancer therapies, targeting at a fundamental property of cancer cells, their non-controllable proliferation due to overactive mitotic divisions. For improved anti-cancer therapies, it is important to find out whether cancer cells can proliferate independent of mitosis and become resistant to anti-mitotic agents. Results In this study, live-cell imaging was applied to both primary-cultures of tumor cells, and immortalized cancer cell lines, to detect aberrant proliferations. Cells isolated from various malignant tumors, such as Grade-III hemangiopericytoma, atypical meningioma, and metastatic brain tumor exhibit distinct cellular behaviors, including amoeboid sequestration, tailing, tunneling, nucleic DNA leakage, as well as prokaryote-like division such as binary fission and budding-shedding, which are collectively referred to and reported as ‘non-mitotic proliferation’ in this study. In contrast, benign tumors including Grade-I hemangiopericytoma and meningioma were not obvious in such behaviors. Moreover, when cultured in medium free of any anti-cancer drugs, cells from a recurrent Grade-III hemangiopericytoma that had been subjected to pre-operation adjuvant chemotherapy gradually shifted from non-mitotic proliferation to abnormal mitosis in the form of daughter number variation (DNV) and endomitosis, and eventually regular mitosis. Similarly, when treated with the anti-cancer drugs Epirubicin or Cisplatin, the cancer cell lines HeLa and A549 showed a shift from regular mitosis to abnormal mitosis, and further to non-mitosis as the dominant mode of proliferation with increasing drug concentrations. Upon removal of the drugs, the cells reversed back to regular mitosis with only minor occurrences of abnormal mitosis, accompanied by increased expression of the stem cell markers ALDH1, Sox, Oct4 and Nanog. Conclusions The present study revealed that various types of malignant, but not benign, cancer cells exhibited cellular behaviors indicative of non-mitotic proliferation such as binary fission, which was typical of prokaryotic cell division, suggesting cell level atavism. Moreover, reversible transitions through the three modes of proliferation, i.e., mitosis, abnormal mitosis and non-mitosis, were observed when anticancer drug concentrations were grossly increased inducing non-mitosis or decreased favoring mitosis. Potential clinical significance of non-mitotic proliferation in cancer drug resistance and recurrence, and its relationship with cancer stem cells are worthy of further studies.

Abstract Background Although both preclinical and clinical studies have shown the great application potential of MSCs (mesenchymal stem/stromal cells) in treating many kinds of diseases, therapeutic inconsistency resulting from cell heterogeneity is the major stumbling block to their clinical applications. Cell population diversity and batch variation in the cell expansion medium are two major inducers of MSC heterogeneity. Methods Cell population diversity was investigated through single-cell RNA sequencing analysis of human MSCs derived from the umbilical cord and expanded with fully chemically defined medium in the current study. Then, the MSC subpopulation with enhanced anti-inflammatory effects was studied in vitro and in vivo. Results Our data showed that MSCs contain different populations with different functions, including subpopulations with enhanced functions of exosome secretion, extracellular matrix modification and responses to stimuli (regeneration and immune response). Among them, CD317+ MSCs have improved differentiation capabilities and enhanced immune suppression activities. Underlying mechanism studies showed that higher levels of TSG6 confer enhanced anti-inflammatory functions of CD317+ MSCs. Conclusions Thus, CD317+ MSCs might be a promising candidate for treating immunological disorder-related diseases.

Abstract Background Virtual simulation and face-to-face simulation are effective for clinical judgment training. Rare studies have tried to improve clinical judgment ability by applying virtual simulation and face-to-face simulation together. This study aimed to evaluate the effect of an integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program on enhancing nursing students’ clinical judgment ability and understanding of nursing students’ experiences of the combined simulation. Methods A sequential exploratory mixed-methods study was conducted in a nursing simulation center of a university in Central China. Third-year nursing students (n = 122) taking clinical training in ICUs were subsequentially assigned to the integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program arm (n = 61) or the face-to-face simulation-only arm (n = 61) according to the order in which they entered in ICU training. Clinical judgment ability was measured by the Lasater Clinical Judgment Rubric (LCJR). Focus group interviews were conducted to gather qualitative data. Results Students in both arms demonstrated significant improvement in clinical judgment ability scores after simulation, and students in the integrated arm reported more improvement than students in the face-to-face simulation-only arm. The qualitative quotes provided a context for the quantitative improvement measured by the LJCR in the integrated arm. Most of the quantitative findings were confirmed by qualitative findings, including the domains and items in the LJCR. The findings verified and favored the effect of the combination of non-immersive virtual simulation and high-fidelity face-to-face simulation integrated program on enhancing nursing students’ clinical judgment ability. Conclusions The integrated virtual simulation and face-to-face simulation program was feasible and enhanced nursing students’ self-reported clinical judgment ability. This integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program may benefit nursing students and newly graduated nurses in the ICU more than face-to-face simulation only.

Abstract Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-Seq, and host-virus proteins or protein/RNA interactome. This study uncovers many host factors that are currently underappreciated, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulate viral entry and/or replication. The cohesin complex is also identified as an anti-viral pathway, suggesting an important role of three-dimensional chromatin organization in mediating host-viral interaction. Furthermore, we discover another anti-viral regulator KLF5, a transcriptional factor involved in sphingolipid metabolism, which is up-regulated, and harbors genetic variations linked to COVID-19 patients with severe symptoms. Anti-viral effects of three identified candidates (DAZAP2/VTA1/KLF5) are confirmed individually. Molecular characterization of DAZAP2/VTA1/KLF5-knockout cells highlights the involvement of genes related to the coagulation system in determining the severity of COVID-19. Together, our results provide further resources for understanding the host anti-viral network during SARS-CoV-2 infection and may help develop new countermeasure strategies.

Traditional mode conversion ultrasonic motors are typically composed of the superposition of multiple vibration modes, making them more complex than single-mode ultrasonic motors. This complexity makes it difficult to miniaturize. A micro radial-torsional vibration mode ultrasonic motor is proposed and tested in this work. It is excited by a single-phase excitation signal. The proposed motor utilizes the radial in-plane vibration mode of the stator to convert the torsional vibration mode of the inner ring through the beams. The torsional vibration of the inner ring causes the rotor to rotate due to the friction force between the inner ring and the rotor. Based on the designed structure and verified using the finite element method, a prototype motor with a mass of 2.6 g and overall dimensions of Ô20 mm in diameter and 15 mm in height is fabricated and characterized. During the mechanical output performance test, the prototype achieved a maximum no-load speed of 3300 r/min and a stall torque of 0.2 mN $\cdot $ m at the driving voltage of 100 V $_{\mathrm {p-p}}$ .

Deconvolution is a commonly employed technique for enhancing image quality in optical imaging methods. Unfortunately, its application in optical coherence tomography (OCT) is often hindered by sensitivity to noise, which leads to additive ringing artifacts. These artifacts considerably degrade the quality of deconvolved images, thereby limiting its effectiveness in OCT imaging. In this study, we propose a framework that integrates numerical random phase masks into the deconvolution process, effectively eliminating these artifacts and enhancing image clarity. The optimized joint operation of an iterative Richardson-Lucy deconvolution and numerical synthesis of random phase masks (RPM), termed as Deconv-RPM, enables a 2.5-fold reduction in full width at half-maximum (FWHM). We demonstrate that the Deconv-RPM method significantly enhances image clarity, allowing for the discernment of previously unresolved cellular-level details in nonkeratinized epithelial cells ex vivo and moving blood cells in vivo.

Abstract Background To compare the early clinical efficacy of percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and modified posterior lumbar interbody fusion (MPLIF) in the treatment of lumbar degenerative disease (LDD). Methods A total of 37 patients who underwent PE-PLIF and 58 patients who underwent MPLIF from March 2019 to January 2022 were retrospectively reviewed. The operation time, intraoperative blood loss, post-operative hospitalization time, and post-operative bedrest time were recorded. The visual analogue scale (VAS) scores of leg pain and low back pain, Japanese Orthopaedic Association (JOA) scores, and the Oswestry Disability Index (ODI) scores were evaluated and compared before the operation, 3 days after the operation, 1 week after the operation, 1 month after the operation, 6 months after the operation and at the last follow-up. The modified MacNab’s criteria were applied at the last follow-up. The fusion rate and surgical-related complications during follow-up were recorded. Results The average operation time in the PE-PLIF group was highly significant longer than that in the MPLIF group (P

Backgroud Bronchopulmonary dysplasia (BPD) is one of the most important complications plaguing neonates and can lead to a variety of sequelae. the ability of the HIF-1α/VEGF signaling pathway to promote angiogenesis has an important role in neonatal lung development.Method Newborn rats were exposed to 85% oxygen. The effects of hyperoxia exposure on Pleomorphic Adenoma Gene like-2 (PLAGL2) and the HIF-1α/VEGF pathway in rats lung tissue were assessed through immunofluorescence and Western Blot analysis. In cell experiments, PLAGL2 was upregulated, and the effects of hyperoxia and PLAGL2 on cell viability were evaluated using scratch assays, CCK-8 assays, and EDU staining. The role of upregulated PLAGL2 in the HIF-1α/VEGF pathway was determined by Western Blot and RT–PCR. Apoptosis and ferroptosis effects were determined through flow cytometry and viability assays.Results Compared with the control group, the expression levels of PLAGL2, HIF-1α, VEGF, and SPC in lung tissues after 3, 7, and 14 days of hyperoxia exposure were all decreased. Furthermore, hyperoxia also inhibited the proliferation and motility of type II alveolar epithelial cells (AECII) and induced apoptosis in AECII. Upregulation of PLAGL2 restored the proliferation and motility of AECII and suppressed cell apoptosis and ferroptosis, while the HIF-1α/VEGF signaling pathway was also revived.Conclusions We confirmed the positive role of PLAGL2 and HIF-1α/VEGF signaling pathway in promoting BPD in hyperoxia conditions, and provided a promising therapeutic targets.

CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.

Background The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN.Methods 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman’s correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission.Results In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766.Conclusions FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

AbstractMicrofluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.