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Abstract Deep phenotyping the right ventricle (RV) is essential for understanding the mechanisms of adaptive and maladaptive RV responses to pulmonary hypertension (PH). In this study, feature selection coupled with machine learning classification/ranking of specific cardiac magnetic resonance imaging (MRI) features from cine-MRI, flow-sensitized, and extracellular-volume techniques were used to assess RV remodelling in monocrotaline (MCT) and Sugen hypoxia (SuHx) PH rats. Early physiological changes associated with RV adaptation were detected along with prediction of RV maladaptive outcomes. Key adaptation features included haemodynamic alterations of pulmonary blood flow ejection and wave reflection, mild RV dilatation, progressive RV hypertrophy with subtle extracellular volume growth of RV wall. A dominant component of maladaptation was the extracellular matrix increase at RV insertion points and septum, observations compatible with histopathologic and RNA-sequencing results. The upregulation of mammalian target of rapamycin (mTOR) paralleled by AMP-activated protein kinase (AMPK) deactivation was seen at 4-week MCT and 8-week SuHx, along with reduced sarcoplasmic/endoplasmic reticulum Ca2+ATPase (SERCA2) expression, strongly associated with the RV systolic malfunction seen at this stage in vivo. The here established MRI features can serve as potential imaging biomarkers to evaluate PH treatment efficacy in preclinical studies and build up translational markers for the PH clinic.

Phages are the most diverse and abundant biological entities on earth. In recent years, the proliferation of high-throughput sequencing technology has led to a surge in research on the composition and functions of phages in diverse ecological niches. Particularly, phages in fermented foods have been receiving increasing attention from researchers, which interact with their bacterial hosts through the lytic and lysogenic life cycles, playing important ecological roles and influencing the succession of microbial communities. Additionally, phages also exhibit potential auxiliary metabolic functions, which in turn affects the formation of flavor substances in fermented foods to a certain extent. This paper provides a comprehensive review of the present status and hot topics of research on phages in fermented foods, with a specific focus on the composition, diversity, genomic DNA extraction techniques and auxiliary metabolic functions of phages as well as their interactions with the host and the underlying mechanism (e.g., clustered regularly interspaced short palindromic repeats (CRISPR) and binding receptors). Finally, this review concludes with a discussion of future research directions, aiming to provide a reference for further research and application of phages in fermented foods.

Abstract Background Glycated albumin (GA) levels have been considered as a promising biomarker for estimating glycemic control during pregnancy, but the relationship between GA levels and the incidence of adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains unclear. Our study aimed to investigate the relationship between GA levels during the third trimester and 13 different adverse pregnancy-related outcomes among women with GDM in China. Methods We retrospectively extracted clinical data from the medical records of 819 pregnant women with GDM who underwent prenatal examinations and child delivery at the Affiliated Hospital of Qingdao University between January 2022 and October 2022. The cohort was divided into GA-high (GA-H) and GA-low (GA-L) groups based on the median GA level of 10.6%. Then, the incidence rates of 13 specific adverse pregnancy outcomes were compared between the two groups. Furthermore, we estimated the mean GA levels in pregnant GDM women with or without specific adverse outcomes. Multivariate logistic regression analysis was performed to assess whether the GA levels (high or low) were independent risk factors for specific adverse outcomes in pregnant women with GDM. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of GA levels for the adverse pregnant outcomes in women with GDM. E-value for sensitivity analysis was performed to assess the robustness of the findings to unmeasured confoundings. Results We included 819 pregnant women with GDM, whose average age was 33.09 ± 4.47 years, average pre-pregnancy BMI was 23.51 ± 3.67 kg/m2, and the average gestational week in which GDM diagnosed was 24.80 ± 1.79 weeks. The analysis showed that 80.71% (661/819) pregnant women with GDM were associated with adverse pregnancy-related outcomes. Pregnant women in the GA-L group showed higher incidence of the premature rupture of membranes (PROM), whereas those in the GA-H group showed higher incidence of neonatal hypoglycemia. The GA levels showed acceptable clinical performance for predicting neonatal hypoglycemia with an area under the ROC curve (AUC) value of 0.700 (P = 0.010), sensitivity of 71.4%, and specificity of 70.2%. The optimal cut off value for GA was 11.55%. Conclusions This study demonstrated that GA levels were significantly associated with specific adverse pregnancy outcomes, especially PROM and neonatal hypoglycemia. Furthermore, GA levels in the third trimester showed acceptable clinical performance for predicting neonatal hypoglycemia among pregnant women with GDM. In the future, the potential role of GA as a predictor of adverse pregnancy outcomes need to be further confirmed and explored in GDM women.

This paper employs statistical methods to analyze the relationship between vegetation and climatology variables.Additionally， it quantitatively assesses vegetation feedback over East Asia using the equilibrium feedback assessment （EFA） method.The study reveals a significant correlation between vegetation and climate variables， including temperature and precipitation.In middle and high latitudes， positive feedback is observed between vegetation and temperature， while negative feedback is identified between vegetation and precipitation.In middle and low latitudes， positive feedback is observed between vegetation and precipitation， while negative feedback is identified between vegetation and temperature.In high latitudes， the positive vegetation anomaly tends to reduce the albedo by shading effect， leading to increased energy absorption and warming air during winter and spring.The analysis highlights that in low latitudes， the correlation between leading vegetation and precipitation is highly sensitive.It is mainly because the high year-round temperature in this area leads to the vegetation being dominated by precipitation signals.The study also finds a positive correlation between leading vegetation and precipitation in low latitudes.The increased vegetation stimulates moisture convergence and enhances evapotranspiration， resulting in more precipitation.The vegetation feedback parameter for temperature is positive in regions around the Da Hinggan Mountains and Baikal Lake， predominantly covered by evergreen needle-leaf forests.The feedback parameter in this area is approximately 1 to 2 ℃·(0. 1FPAR ) -1.The positive feedback parameter is identified in the southern part of China， ranging from 0.2 to 1 ℃·(0. 1FPAR ) -1.Regarding precipitation， the feedback parameter exhibits significant noise， making it challenging to distinguish signals except for the positive signal around the North China Plain.In the North China Plain， the feedback parameter for precipitation is approximately 1.5 cm·mon-1 ·(0. 1FPAR ) -1.

Abstract GPUs are increasingly playing vital roles in the modern technology industry. Improving the GPU performance involves optimizing its architectural design and fine-tuning its software code. However, to achieve this, engineers must investigate codes from as many GPU-related applications as possible to identify code portions that need fine-tuning. Moreover, this effort requires engineers to have good domain knowledge, and their work is made more arduous because the source codes of applications are normally confidential. To this end, we introduce ShaderAnalyzer, a solution leveraging graph mining and machine learning to analyze GPU-executed low-level machine codes and identify their fine-tuning opportunities. Our approach includes representing machine code with graph structure and subsequently identifying frequently occurring substructures within the codes. Optimizing the execution of these substructures can enhance the overall performance of the GPU. In addition, our model leverages these frequent patterns to further facilitate engineers’ tasks by selecting representative patterns to predict and investigate low-efficiency ones. We conduct comprehensive experiments to evaluate the performance of our solution, and the results have been validated by our industry partners. ShaderAnalyzer is an end-to-end framework that helps engineers identify code segments with the highest potential for performance gains after fine-tuning and offers valuable insights for hardware architects in future products design.

Abstract Persistent macrophage activation and cytokine storms are critical causes for the rapid disease progression and high mortality rate of Secondary Hemophagocytic lymphohistiocytosis (sHLH). Identification of key regulatory factors that govern the activation of macrophages is vital. Plasma exosomal circular RNAs (circRNAs) are considered important biomarkers and potential therapeutic targets for various diseases, however, their function in sHLH is still unclear. In this study, we demonstrated for the first time that circMETTL3, derived from METTL3, is upregulated in sHLH patient plasma exosomes, which may plays an important role in the diagnosis of sHLH. Significantly, we also revealed that a novel peptide encoded by circMETTL3, METTL3-156aa, is an inducer of M1 macrophage polarization, which is responsible for the development of cytokine storms during sHLH. We then identified that METTL3-156aa binding with lactate dehydrogenase A (LDHA) and promotes M1 macrophage polarization by enhancing macrophage glycolysis. Additionally, the glycolysis metabolite lactate upregulates the cleavage factor SRSF10 expression by lactylation. This results in increased splicing of the pre-METTL3 mRNA, leading to an enchance in the production of cirMETTL3. Therefore, our results suggest that the circMETTL3/METTL3-156aa/LDHA/Lactate/SRSF10 axis forms a positive feedback loop and may be a novel therapeutic target for the treatment of sHLH.

Abstract Congenital heart defects are leading causes of neonatal mortality and are often associated with placental abnormalities, but mechanisms linking placenta and heart development are poorly understood. Herein, we investigated a potential signaling network connecting the placenta and nascent heart in mice. We found that fetal hearts exposed to media conditioned by placental tissue or differentiated wild-type trophoblast stem (TS) cells, but not undifferentiated TS cells, showed increased heart rate and epicardial cell outgrowth. This effect was not observed when hearts were exposed to media from TS cells lacking OVO-Like 2, a transcription factor required for trophoblast differentiation and placental development. Trophoblasts released abundant extracellular vesicles into media, and these vesicles were sufficient to mediate cardio-promoting effects. Our findings provide a potential mechanism whereby the placenta communicates with the fetal heart to promote cardiac morphogenesis, and offers insight into the link between poor placentation and a higher incidence of heart defects.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2',7'-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosisrelated genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions: Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Abstract Background Low levels of the essential amino acid lysine in maize endosperm is considered to be a major problem regarding the nutritional quality of food and feed. Increasing the lysine content of maize is important to improve the quality of food and feed nutrition. Although the genetic basis of quality protein maize (QPM) has been studied, the further exploration of the quantitative trait loci (QTL) underlying lysine content variation still needs more attention. Results Eight maize inbred lines with increased lysine content were used to construct four double haploid (DH) populations for identification of QTLs related to lysine content. The lysine content in the four DH populations exhibited continuous and normal distribution. A total of 12 QTLs were identified in a range of 4.42–12.66% in term of individual phenotypic variation explained (PVE) which suggested the quantitative control of lysine content in maize. Five main genes involved in maize lysine biosynthesis pathways in the QTL regions were identified in this study. Conclusions The information presented will allow the exploration of candidate genes regulating lysine biosynthesis pathways and be useful for marker-assisted selection and gene pyramiding in high-lysine maize breeding programs.

Abstract Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53–75 and 85–107) directly interacts with the C-terminal region of TAK1 (amino acids 1–300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.

Numerical models have risen to prominence as indispensable tools for the in-depth study of the water cycle and these extreme hydrological phenomena， gaining widespread application across the globe.To delve into the spatiotemporal evolution patterns of global terrestrial water circulation against the backdrop of climate change and to decipher the intricate feedback mechanisms among atmospheric， land， and hydrological systems， the exploration of coupled atmospheric-land-hydrological models has emerged as a pivotal area of focus in the international research landscape dedicated to atmospheric and hydrological studies.This paper embarks on its journey by meticulously reviewing and delineating the evolution of coupled models， shedding light on the distinct advantages of the Weather Research and Forecasting Model Hydrological （WRF-Hydro） modeling system.It methodically dissects the primary sensitivity parameters of the WRF-Hydro model， while extensively covering its applications in analyzing surface runoff， soil moisture， the energy-water cycle， and the intertwined atmospheric and hydrological processes.The discourse culminates in a forward-looking exploration of the future directions in the development of the WRF-Hydro coupled model.Emphasizing strategic advancements， the paper advocates for a concerted effort towards the creation of robust scale conversion schemes， the refinement of parameterization methods， and the execution of high-resolution simulations.These simulations are crucial for accurately mapping the spatial and temporal dynamics of atmospheric and hydrological variables within basins， thereby significantly enhancing the model's capacity to intricately depict the interactions among atmospheric conditions， land surface phenomena， and hydrological processes.This comprehensive approach underlines the imperative to deepen our understanding and improve our modeling capabilities， aiming at a more effective prediction and management of the impacts arising from climate change and extreme hydrometeorological events.

Abstract Purpose Bone metastases occur in 50-70% of patients with breast cancer (BC) and result in high mortality. Platelet distribution width (PDW), a commonly used parameter of activated platelets, has been associated with a poor prognosis in BC. We aim to investigate the prognostic role of PDW for bone metastasis in BC patients. Methods 515 patients who received BC surgery in the Harbin Medical University Cancer Hospital from July 1, 2016, to December 31, 2017, were reviewed. Patients’ characteristics and platelet indices upon enrollment in this study were collected. The Kaplan-Meier method was used to estimate the 5-year bone metastasis incidence. The univariate and multivariate Cox regression analyses were utilized to identify risk factors associated with bone metastasis. Results The patients with bone metastases exhibited lower PDW levels than the patients without bone metastases. Moreover, decreased PDW was significantly correlated with histologic type, multifocal disease, and lymph node status. In addition, the patients with reduced PDW levels were more likely to develop bone metastasis. Multivariate analysis showed that PDW was an independent predictor for bone metastasis. Conclusion PDW is an independent predictor of bone metastasis in BC. Further research is warranted.

Abstract Background Treatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients. Methods Cancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed. Results Fifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P

Abstract Background The current clinical management of carotid atherosclerosis is based on the control of risk factors and medicine. However, the risk of adverse events associated with the medicine resulting in concerns and low medication compliance makes it necessary to seek a safer alternative therapy. This study assessed the effectiveness and safety of acupuncture as a treatment for carotid atherosclerosis. Methods In this randomized controlled trial, patients with carotid atherosclerotic plaques were included and randomly assigned (1:1) to receive real acupuncture or sham acupuncture for 12 weeks. The follow-up period was 12 weeks. The primary outcome included carotid intima-media thickness (cIMT), plaque score (PS), plaque volume (PV) and grey-scale median (GSM). Secondary outcome was pulse wave velocity (PWV). Adverse events results were recorded as safety outcomes. Results From January 2021 to February 2022, 60 eligible patients were included. 55 patients (91.7%) completed the intervention and the 12-week follow-up and there was no statistical difference in demographics between the groups. At the end of treatment, the real acupuncture group had significantly reduced PS (P = 0.002), PV (P = 0.000), and improved GSM (P = 0.044). There was no significant difference in the reduction in cIMT (Left cIMT: P = 0.338, Right cIMT: P = 0.204) and PWV between the groups (the left BS: P = 0.429; the left ES: P = 0.701; the right BS: P = 0.211; the right ES: P = 0.083). Three mild adverse reactions occurred during the study. Conclusion This study found that acupuncture had a certain effect on reducing the thickness and volume of carotid plaque and improving the stability of plaque with minor side effects. These findings suggest that acupuncture may be a potential alternative therapy for carotid atherosclerosis. Trial registration This trial has been registered at ClinicalTrials.gov (ChiCTR2100041762). Submitted 30 December 2020, Registered 4 January 2021 Prospectively registered.

Highlights A novel cascade strategy is proposed to construct Pd-NiCo2O4 electrocatalyst. First time discovery that Ni incorporation together with Pd loading is able to balance the competitive adsorption of OH– and 5-hydroxymethylfurfural. Pd–NiCo2O4 promotes both the indirect and direct synergistic oxidation process. Pd–NiCo2O4 catalyst exhibits extraordinary current density and excellent Faradaic Efficiency at a low potential.

Abstract Pyroptosis, a lytic form of cell death mediated by the gasdermin family, is characterized by cell swelling and membrane rupture. Inducing pyroptosis in cancer cells can enhance antitumor immune responses and is a promising strategy for cancer therapy. However, excessive pyroptosis may trigger the development of inflammatory diseases due to immoderate and continuous inflammatory reactions. Nanomaterials and nanobiotechnology, renowned for their unique advantages and diverse structures, have garnered increasing attention owing to their potential to induce pyroptosis in diseases such as cancer. A nano-delivery system for drug-induced pyroptosis in cancer cells can overcome the limitations of small molecules. Furthermore, nanomedicines can directly induce and manipulate pyroptosis. This review summarizes and discusses the latest advancements in nanoparticle-based treatments with pyroptosis among inflammatory diseases and cancer, focusing on their functions and mechanisms and providing valuable insights into selecting nanodrugs for pyroptosis. However, the clinical application of these strategies still faces challenges owing to a limited understanding of nanobiological interactions. Finally, future perspectives on the emerging field of pyroptotic nanomaterials are presented. Graphical abstract

Abstract Background The association between the triglyceride-glucose (TyG) index and clinical outcomes in patients with both coronary artery disease (CAD) and psoriasis is unclear. This study investigated the association between the TyG index and major adverse cardiovascular events (MACE) in patients with both CAD and psoriasis. Methods This retrospective cohort study included patients diagnosed with both CAD and psoriasis who underwent coronary angiography at the Fuwai Hospital, Beijing, China, between January 2017 and May 2022. The study endpoint was the occurrence of MACE or end of follow-up time. Multivariate Cox proportional analysis and restricted cubic splines (RCS) were used to determine the association between the TyG index and MACE. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold value of the TyG index for predicting MACE. Results This study enrolled 293 patients with both CAD and psoriasis, including 258 (88.1%) males with a mean age of 58.89 ± 9.61 years. Patients were divided into four groups based on the TyG quartiles: Q1 (N = 74), Q2 (N = 73), Q3 (N = 73), and Q4 (N = 73). After adjusting for the potential confounders, the TyG index was independently associated with MACE, both as a continuous variable (HR = 1.53, 95% CI = 1.03–2.28, P = 0.035) and as a categorical variable (Q1: reference; Q2: HR = 1.85, 95% CI = 0.88–3.87, P = 0.105; Q3: HR = 2.39, 95% CI = 1.14-5.00, P = 0.021; Q4: HR = 2.19, 95% CI = 1.001–4.81, P = 0.0497; P for trend = 0.039). RCS analysis showed an linear association between the TyG index and MACE (P-overall = 0.027, P-non-linear = 0.589). ROC curve analysis showed that the TyG index of ≥ 8.73 was the optimal threshold value (area under the ROC curve = 0.60, 95% CI 0.53–0.67). TyG index ≥ 8.73 was significantly associated with MACE (HR = 2.10, 95% CI = 1.32–3.34, P = 0.002). After adjustment for confounders, the TyG index showed independent association with MACE (HR = 2.00, 95% CI = 1.17–3.42, P = 0.011). Conclusions The TyG index showed a positive linear correlation with MACE in patients with both CAD and psoriasis. The TyG index of ≥ 8.73 might be the optimal threshold for predicting MACE. Graphical Abstract

Abstract Background Multiple vaccinations have received approval for the prevention of the coronavirus illness. Nevertheless, the sluggish vaccination rate is mostly attributed to the general population’s limited understanding and unwillingness to accept the use of vaccinations. Thus, it is important to investigate the Rwandan population’s knowledge, attitudes, and perceptions toward COVID-19 vaccines. Methods A cross-sectional survey was conducted among 370 participants from 11th to 17th February 2023. Demographic information was gathered, and knowledge, attitudes, and perceptions of COVID-19 vaccinations were assessed. A binary logistic regression analysis was undertaken to determine the parameters that determine the perception of COVID-19 vaccinations. Results This study included 370 participants. Among them, 85% had good knowledge about COVID-19 vaccines, and 84% had a positive attitude towards them. Additionally, the study had a diverse group, with half of the participants being female and nearly half falling between the ages of 30 and 39. Several key findings emerged through logistic regression analysis. Those aged 30–39 had 1.39 times higher odds of positive perception than 18–28 (OR = 1.39, 95% CI = 1.08–3.24). Participants with a university education were twice as likely to have a positive perception compared to those without an education level (OR = 2.43, 95% CI = 1.30–6.20). Additionally, single individuals were three times more likely to have a positive perception than their married counterparts (OR = 3.39, 95% CI = 1.28–9.09). Vaccinated individuals had twice the odds of positive perception than non-vaccinated individuals (OR = 2.89, 95% CI = 1.01–8.89). Those receiving information from government health institutions were three times more likely to have a positive perception than those who received the information from friends (OR = 3.19, 95% CI = 1.02–12.7). Moreover, employed participants were four times more likely to have a positive perception non-employed individuals (OR = 4.21, 95% CI = 1.48–13.6). Besides, gender and COVID-19 diagnosis did not significantly correlate with positive COVID-19 vaccine perception. Conclusion The results indicate that the general public in Rwanda has good knowledge, positive attitudes, and a positive perception toward the COVID-19 vaccination, however, some of the participants had some misconceptions towards COVID-19. The findings of this study will be valuable for policymakers and healthcare authorities working to improve vaccination rates.

Abstract Rapid urbanization increases psychological stress among pedestrians, potentially heightening mental health disorders. This study examines the role of street walls' visual and textural characteristics in stress recovery, using Qingdao as a case study. Virtual reality is employed to simulate five distinct street walls: yellow mortar, brown stone, red brick, green plant, and white mortar. The stress recovery effectiveness of these walls was evaluated through psychological and physiological indicators from 48 young college students. Results indicated that street walls with warm tones, particularly brown stone, significantly aid stress recovery. Psychologically, Restorative Components Scale was highest for brown stone at 1.13. Physiologically, it was linked with notable reductions in diastolic and pulse pressure (decreases of 2.95 mmHg and 2.27 mmHg, respectively), and enhanced parasympathetic activity, as evidenced by the fastest decrease in low frequency/high frequency ratio (LF/HF), and increases in pNN50 and RR (0.14–2.01% and 1.57–11.81 ms, respectively). For urban design, the incorporation of warm-toned materials and natural elements like stone is recommended for their superior restorative benefits.

Abstract Background Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM. Methods DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023. Results Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (

ObjectiveRetroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibroinflammatory tissue that surrounds the abdominal aorta and the iliac arteries and often entraps the ureters. Hydronephrosis is a common complication of RPF, however, its clinical features and outcomes have not been well elucidated.MethodsA total of 115 RPF-related hydronephrosis patients have been recruited from 9 clinical centers in China since March 2010. They were followed up until death or September 2021, whichever came first.ResultsThe mean age at diagnosis was 58.83 ± 12.13 years, and 80 patients (69.57%) were men. The median disease duration was 3.00 (1.00, 9.00) months. Renal impairment was observed in 88.35% of the patients, and 49.57% showed bilateral ureteral involvement. Elevated ESR and CRP were presented in 80.28 and 62.02% of the patients, respectively. Overall, 28.21% (11/39) of the patients had increased IgG4 levels, and 41.38% (12/29) showed positive pathological IgG4 staining (IgG4+/IgG+ ≥ 40% or IgG4+ ≥ 10/HPF). Among them, three patients were diagnosed as IgG4RD. After 60.43 ± 34.53 months of follow-up, 36 patients had poor prognosis, which was associated with severe kidney impairment, bilateral hydronephrosis and inflammation status (elevated ESR and IgG) at diagnosis by case–control study. eGFR and creatinine were independent risk factors after adjusting for all other significant associations (p = 0.002 and p = 0.067, respectively). Glucocorticoid-based therapy could reduce the time of stenting, decrease the need for long-term ureteral stenting/percutaneous nephrostomy (PNS)/ureterolysis, increase the rate of mass shrinkage, and reduce the new requirement of hemodialysis compared to surgery-only strategy for RPF-related hydronephrosis patients in need of renal drainage, but did not reduce new-onset renal atrophy.ConclusionSeverity of kidney dysfunction and inflammation status were related to the poor prognosis of hydronephrosis induced by RPF. More efficient interventions and strategies are needed to further improve outcomes.

BackgroundThe application of neoadjuvant immunotherapy in the treatment of esophageal cancer needs further exploration. This study aimed to investigate the safety and effectiveness of tislelizumab, an anti-PD-1 antibody, combined with chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC).MethodsIn this phase II study, patients with clinical stages of II-IVA (T3-T4 and/or node positive) potentially resectable LA-ESCC were enrolled. Patients received neoadjuvant tislelizumab and chemotherapy every 3 weeks for 4 cycles before surgery and adjuvant tislelizumab for 9 months. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy.ResultsThe study included 30 patients. 25 patients completed neoadjuvant chemoimmunotherapy and underwent surgery, 96% with R0 resection. The pCR and MPR rate was 44% and 52%. The 6-month and 1-year DFS rate was 100% and 75.3%. 43.3% patients experienced severe (grade 3-4) treatment-related adverse events (TRAEs) and 5 patients developed severe immune-related adverse events (irAEs). Further exploration found that a group of peripheral lymphocyte subsets increased significantly after 2 cycles of neoadjuvant therapy in patients who achieved pCR, suggesting the importance of dynamic monitoring of circulating lymphocyte.ConclusionsThe combination of perioperative tislelizumab and neoadjuvant chemotherapy has achieved an encouraging pCR rate and demonstrated a manageable safety profile in patients with potentially resectable ESCC.Clinical Trial Registrationhttps://www.chictr.org.cn/, identifier ChiCTR2100043772.

The mechanical degradation mechanism of T91 ferrite/martensite steel at 500 °C and 316NG austenitic steel at both 500 °C and 600 °C in supercritical carbon dioxide were investigated in detail by slow strain rate tensile tests and first-principles calculations of the adsorption and dissociation of CO2. In high-temperature CO2 atmosphere, CO2 could spontaneously dissociate into CO and O, and the spontaneously and partially dissociated O atoms exhibited a strong interaction with Cr. As the temperature was increased to 600 °C, the partial dissociation of CO2 occurred more rapidly and the ultimate tensile strength and total elongation of 316NG steel decreased significantly as well. Furthermore, a composite failure mode with intergranular brittle fracture and ductile fracture was investigated.

Objective The aim of this study was to conduct a comprehensive evaluation of the rehydration efficacy of QSBYD and elucidate its potential underlying mechanism.Design 38 participants were randomly assigned to receive either QSBYD or placebo before and after exercise and heat-induced dehydration. Hydration indicators were measured over time. Blood tests assessed cellular anaerobic respiration metabolites, serum inflammatory markers, and coagulation markers. Perceptual measures of thirst, fatigue, and muscular soreness were also taken.Results QSBYD consumption resulted in lower urine volume (Control vs. QSBYD: 260.83 ± 167.99 ml vs. 187.78 ± 141.34 ml) and smaller decrease in percentage of nude body weight change from baseline (Control vs. QSBYD: −0.52 ± 0.89% vs. −0.07 ± 0.52%). Although no significant differences in urine specific gravity, QSBYD resulted in reduced urine volume at 120 min, suggesting improved fluid retention. Furthermore, QSBYD resulted in lower levels of IL-1β (Control vs. QSBYD: 2.40 ± 0.68 vs. 1.33 ± 0.66 pg/mL), suggesting QSBYD may provide benefits beyond hydration.Conclusion Further investigation into the underlying mechanisms and long-term effects of QSBYD on hydration is warranted. QSBYD may be an effective alternative to commercial sports drinks in mitigating dehydration effects.

The continual emergence of tick-borne rickettsioses has garnered widespread global attention. Candidatus Rickettsia barbariae (Candidatus R. barbariae), which emerged in Italy in 2008, has been detected in humans from northwestern China. However, the lack of Candidatus R. barbariae genome and isolated strains limits the understanding of its biological characteristics and genomic features. Here, we isolated the Rickettsia for the first time from eggs of Rhipicephalus turanicus in northwestern China, and assembled its whole genome after next-generation sequencing, so we modified the proposed name to Rickettsia barbariae (R. barbariae) to conform to the International Code of Nomenclature of Prokaryotes. Phylogenetic analysis based on the whole genome revealed that it was most closely related to the pathogenic Rickettsia parkeri and Rickettsia africae. All virulence factors, present in the pathogenic spotted fever group rickettsiae, were identified in the R. barbariae isolate. These findings highlight the pathogenic potential of R. barbariae and the necessity for enhanced surveillance of the emerging Rickettsia in the human population.

ABSTRACTThe emergence of Anaplasma bovis or A. bovis-like infection in humans from China and the United States of America has raised concern about the public health importance of this pathogen. Although A. bovis has been detected in a wide range of ticks and mammals in the world, no genome of the pathogen is available up to now, which has prohibited us from better understanding the genetic basis for its pathogenicity. Here we describe an A. bovis genome from metagenomic sequencing of an infected goat in China. Anaplasma bovis had the smallest genome of the genus Anaplasma, and relatively lower GC content. Phylogenetic analysis of single-copy orthologue sequence showed that A. bovis was closely related to A. platys and A. phagocytophilum, but relatively far from intraerythrocytic Anaplasma species. Anaplasma bovis had 116 unique orthogroups and lacked 51 orthogroups in comparison to other Anaplasma species. The virulence factors of A. bovis were significantly less than those of A. phagocytophilum, suggesting less pathogenicity of A. bovis. When tested by specific PCR assays, A. bovis was detected in 23 of 29 goats, with an infection rate up to 79.3% (95% CI: 64.6% ∼94.1%). The phylogenetic analyses based on partial 16S rRNA, gltA and groEL genes indicated that A. bovis had high genetic diversity. The findings of this study lay a foundation for further understanding of the biological characteristics and genetic diversity of A. bovis, and will facilitate the formulation of prevention and control strategies.

AbstractOver the past two decades, extensive research has been conducted on the rhetorical structure of research articles (RAs) from the English for Specific Purposes (ESP) genre approach. However, RA configuration from the Systemic Functional Linguistic (SFL) genre perspective remains under-investigated, particularly in the Traditional Chinese Medicine (TCM) field. This study aimed to examine the deployment of SFL elemental genres to construct the TCM RAs. To this end, 40 empirical articles published from 2020 to 2021 were selected from five high-impact TCM journals for the analysis. The findings showed that report, recount, argument, and explanation were employed to construct the TCM RAs. Under these broad genre families, 13 elemental genres were identified, for instance, descriptive report, procedural recount, exposition and factorial explanation. Regarding the frequency, report and recount played a major role in configuring the TCM RAs whereas argument and explanation played a supplementary role. Moreover, the ESP genre held that the macro-structure of RA is shaped like an hourglass, which was also attested by the present SFL elemental genres in terms of the generic complexity. Such deconstruction of a macrogenre into elemental genres serving as building blocks of text promises pedagogical implications for English for Academic Purposes (EAP) teachers and graduate students.

Prussian blue analogues (PBAs) are considered as promising cathode materials for capacitive deionization (CDI) technology due to their 3D open‐frame structure and tunable redox active sites. However, the inevitably high content of [Fe(CN)6] vacancies in the crystal structure results in a low salt adsorption capacity (SAC) and poor recycling performance. Herein, a high‐salt nano‐reaction system is established by mechanochemical ball milling, enabling the preparation of a variety of highly crystallized PBAs (metal hexacyanoferrate, MHCF‐B‐170, M = Ni, Co, or Cu) with low vacancies (0.05–0.06 per formula unit). The reduction of vacancies in the PBAs lattice not only strengthens the conductivity and promotes the rapid transfer of electrons, but also reduces the migration energy barrier and accelerates the fast and reversible diffusion of Na+ ions. The structural characterization method and theoretical simulation demonstrates the excellent reversibility and crystal structure stability of MHCF‐B‐170 during the CDI process. Impressively, the NiHCF‐B‐170 exhibits excellent CDI performance, characterized by an exceptionally high SAC of up to 101.4 mg g−1 at 1.2 V, and demonstrates remarkable cycle stability with no significant degradation observed even after 100 cycles. This PBAs with low Fe(CN)6 vacancies are expected to be a competitive candidate material for CDI electrodes.

It is well established that hearing loss can lead to widespread plasticity within the central auditory pathway, which is thought to contribute to the pathophysiology of audiological conditions such as tinnitus and hyperacusis. Emerging evidence suggests that hearing loss can also result in plasticity within brain regions involved in higher-level cognitive functioning like the prefrontal cortex; findings which may underlie the association between hearing loss and cognitive impairment documented in epidemiological studies. Using the 40-Hz auditory steady state response to assess sound-evoked gamma oscillations, we previously showed that noise-induced hearing loss results in impaired gamma phase coherence within the prefrontal but not the auditory cortex. To determine whether region-specific structural or molecular changes accompany this differential plasticity following hearing loss, in the present study we utilized Golgi-Cox staining to assess dendritic organization and synaptic density, as well as Western blotting to measure changes in synaptic signaling proteins in these cortical regions. We show that following noise exposure, impaired gamma phase coherence within the prefrontal cortex is accompanied by alterations in pyramidal cell dendritic morphology and decreased expression of proteins involved in GABAergic (GAD65) and glutamatergic (NR2B) neurotransmission; findings that were not observed in the auditory cortex, where gamma phase coherence remained unchanged post-noise exposure. In contrast to the noise-induced effects we observed in the prefrontal cortex, plasticity in the auditory cortex was characterized by an increase in NR2B suggesting increased excitability, as well as increases in the synaptic proteins PSD95 and synaptophysin within the auditory cortex. Overall, our results highlight the disparate effect of noise-induced hearing loss on auditory and higher-level brain regions as well as potential structural and molecular mechanisms by which hearing loss may contribute to impaired cognitive and sensory functions mediated by the prefrontal and auditory cortices.

Chirality plays a crucial function in the regulation of normal physiological processes and is widespread in organisms. Chirality can be imparted to nanomaterials, whether they are natural or manmade, through the process of asymmetric assembly and/or grafting of molecular chiral groups or linkers. Chiral inorganic nanomaterials possess unique physical and chemical features that set them apart from regular nanomaterials. They also have the ability to interact with cells and tissues in a specific manner, making them useful in various biomedical applications, particularly in the treatment of tumors. Despite the growing amount of research on chiral inorganic nanomaterials in the tumor microenvironment (TME) and their promising potential applications, there is a lack of literature that comprehensively summarizes the intricate interactions between chiral inorganic nanomaterials and TME. In this review, we introduce the fundamental concept, classification, synthesis methods, and physicochemical features of chiral inorganic nanomaterials. Next, we briefly outline the components of TME, such as T cells, macrophages, dendritic cells, and weak acids, and then discuss the anti-tumor effects of several chiral inorganic nanoparticles targeting these components and their potential for possible application during cancer therapy. Finally, the present challenges faced by chiral inorganic nanomaterials in cancer treatment and their future areas of investigation are disclosed.