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Abstract Background Osteoporosis and sarcopenia frequently occur in patients with end-stage renal disease undergoing hemodialysis (HD), and depression is also a common mental health issue in this population. Despite the prevalence of these conditions, the interrelationships among them remain poorly understood in HD patients. Methods In this multicenter cross-sectional study, 858 HD patients from 7 dialysis centers were recruited. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was calculated from body composition data obtained through multifrequency bioimpedance analysis (BIA), while handgrip strength (HGS) was measured with a dynamometer. Gait speed was evaluated with a 4-meter walk test, and depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Results Among the 858 participants (524 men, 334 women), 39.2% had osteoporosis. The prevalence of sarcopenia and depression was 18.9% and 42.1%, respectively. Logistic regression analysis showed that SMI was significantly associated with a decreased risk of osteoporosis (OR = 0.638, 95% CI = 0.494–0.823, P = 0.001), while HGS was not(OR = 0.990, 95% CI = 0.963–1.017, P = 0.449). HD patients with sarcopenia were 1.92 times more likely to have osteoporosis than those without sarcopenia. Most notably, after adjusting for both sarcopenia and SMI, the risk of osteoporosis in HD patients with depression was 1.45 times higher than in those without depression (OR = 1.452, 95% CI = 1.060–1.989, P = 0.020). Conclusions In HD patients, increased muscle mass, rather than muscle strength, is linked to a lower risk of osteoporosis. Notably, depression emerges as a significant risk factor for osteoporosis in this population, highlighting the need for mental health considerations in managing bone health.

Abstract Transgenic soybean [Glycine max(L.) Merrill] currently covers approximately 80% of the global crop area for this species, with the majority of transgenic plants being glyphosate resistant (Roundup Ready, GR or RR). However, there is significant concern regarding the potential effects of GM crops and their byproducts on soil microbial communities. During our research, we discovered a type of semiwild soybean that emerged due to genetic drift at a transgenic test site. Nevertheless, the ecological risk to soil rhizosphere microorganisms associated with planting semiwild soybean following genetic drift remains unclear. Therefore, we conducted a field experiment and collected soil samples at various stages of plant growth. Our results indicate that the species diversity of rhizosphere bacteria in transgenic glyphosate-resistant semiwild soybean was also not significantly different from that observed in other types of soybean. Additionally, Basidiomycota had beneficial effects on rhizosphere fungi during the flowering and maturation stages in transgenic glyphosate-tolerant semiwild soybean. These findings provide valuable insights into how genetic drift in transgenic soybean may impact the soil microenvironment.

Abstract The stereoselectivity of enzymes plays a central role in asymmetric biocatalytic reactions, but there remains a dearth of evolution-driven biochemistry studies investigating the evolutionary trajectory of this vital property. Imine reductases (IREDs) are one such enzyme that possesses excellent stereoselectivity, and stereocomplementary members are pervasive in the family. However, the regulatory mechanism behind stereocomplementarity remains cryptic. Herein, we reconstruct a panel of active ancestral IREDs and trace the evolution of stereoselectivity from ancestors to extant IREDs. Combined with coevolution analysis, we reveal six historical mutations capable of recapitulating stereoselectivity evolution. An investigation of the mechanism with X-ray crystallography shows that they collectively reshape the substrate-binding pocket to regulate stereoselectivity inversion. In addition, we construct an empirical fitness landscape and discover that epistasis is prevalent in stereoselectivity evolution. Our findings emphasize the power of ASR in circumventing the time-consuming large-scale mutagenesis library screening for identifying mutations that change functions and support a Darwinian premise from a molecular perspective that the evolution of biological functions is a stepwise process.

This paper aims to examine Confucian thesis of moral politics. By comparing three types of administration, Confucius’ thoughts on the problematics of moral politics are analyzed in more detail, highlighting the inner tension between the moral and the political. The difficulty of the concept is shown by discussing its development so that the validity question can be brought to the fore. In order to conduct a comprehensive analysis of the moral politics, it is necessary to first address three distinct approaches to its development. We call the consanguinity-based system of administration of the Western Zhou feudal system Lĭ-Chìh (禮治). This implies using the rites (禮) as the primary means of state governance. Comparatively speaking, the morality-governed administrative method is known as Dé-Chìh (德治). The third, Fă-Chìh (法治), denotes that laws are the basis for state governance. The interdependence of rites, morals, and law makes it impossible to simply divide the three modes of administration. The theory of moral politics offers new avenues for development since China adopted the democratic system. A group of Chinese academics known as the New Confucians attempted to integrate this theory with the democratic system in the early 20th century in an attempt to find a fresh approach to the theory’s application issue. This theory still revolves around Dé-Chìh. Fă-Chìh’s authenticity is amply verified. The New Confucians regard the conflict between Dé-Chíh and Dé-Chìh as a dialectical evolution.

Abstract Biomarkers are not only of significant importance for cancer diagnosis and selection of treatment plans but also recently increasingly used for the evaluation of malignancy development and tumor heterogeneity. Large-size tumors from clinical patients can be unique and valuable sources for the study of cancer progression, particularly to the extent of intratumoral heterogeneity. In the present study, we obtained a series of post-surgery puncture samples from a breast cancer patient with a 4 × 3.5 × 2 cm tumor in its original size. Immunohistochemistry for Ki-67, COX-2, and CA IX was performed and the expression levels within the breast cancer tumor mass were evaluated in the reconstructed 3D models. To further evaluate the intratumoral heterogeneity, we performed high throughput whole transcriptome sequencing of 12 samples from different spatial positions within the tumor tissue. Comparing the reconstructed 3D distribution of biomarkers with projected tumor growth models, asymmetric and heterogeneous expansion of tumor mass was found to be possibly influenced by factors such as blood supply, inflammation and/or hypoxia stimulations, as suggested from the correlation between the results of Ki-67 and CA IX or COX-2 staining. Furthermore, high-throughput RNA sequencing data provided additional information for profiling the intratumoral heterogeneity and expanded the understanding of cancer progression. Digital technology for medical imaging once properly integrated with molecular pathology examinations will become particularly helpful in dissecting out in-depth information for precision medicine. We prospect that this approach, facilitated by rapidly advancing artificial intelligence, could provide new insights for clinical decision-making in the future. Strategies for the continuous development from the present study for better performance and application were discussed.

Abstract Tobacco bacterial wilt is a major limiting factor for tobacco production and development, and it is more likely to occur under perennial single cropping of tobacco. In recent years, the rotation of tobacco-radish has gradually become popular. Therefore, we studied the effects of years of tobacco–radish rotation on tobacco bacterial wilt occurrence and rhizosphere microorganisms. The results indicated that both SY and TY could significantly reduce the risk of tobacco bacterial wilt occurrence, and SY had the lowest disease index. The rotation of radish plants significantly increased the soil pH but decreased the contents of alkali-hydrolysed nitrogen and organic matter in the soil. Alkali-hydrolysed nitrogen and pH are the key factors affecting the composition of the bacterial community. Furthermore, radish rotation changed the composition of the soil microbial community, increased the diversity of the bacterial community, and significantly altered the bacterial community structure. At the genus level, the abundance of Sphingomonas species negatively correlated with Ralstonia increased significantly, while the relative abundance of Rhodanobacter species positively correlated with Ralstonia decreased significantly. Disease index, pH and available phosphorus were the main factors affecting the variation in different bacterial genera. The network analysis results showed that Ralstonia was less connected in the network than in the CK group, and the SY treatment group had a more complex bacterial network structure. Overall, 2 years of tobacco and radish rotation improved the bacterial community structure of the rhizosphere soil and alleviated the harm caused by tobacco bacterial wilt, which is highly important for the stability and health of the rhizosphere soil ecosystem.

Abstract The Equilibrium Optimiser (EO) has been demonstrated to be one of the metaheuristic algorithms that can effectively solve global optimisation problems. Balancing the paradox between exploration and exploitation operations while enhancing the ability to jump out of the local optimum are two key points to be addressed in EO research. To alleviate these limitations, an EO variant named adaptive elite‐guided Equilibrium Optimiser (AEEO) is introduced. Specifically, the adaptive elite‐guided search mechanism enhances the balance between exploration and exploitation. The modified mutualism phase reinforces the information interaction among particles and local optima avoidance. The cooperation of these two mechanisms boosts the overall performance of the basic EO. The AEEO is subjected to competitive experiments with state‐of‐the‐art algorithms and modified algorithms on 23 classical benchmark functions and IEE CEC 2017 function test suite. Experimental results demonstrate that AEEO outperforms several well‐performing EO variants, DE variants, PSO variants, SSA variants, and GWO variants in terms of convergence speed and accuracy. In addition, the AEEO algorithm is used for the edge server (ES) placement problem in mobile edge computing (MEC) environments. The experimental results show that the author’s approach outperforms the representative approaches compared in terms of access latency and deployment cost.

Ultrafast, high-intensity X-ray free-electron lasers can perform diffraction imaging of single protein molecules. Various algorithms have been developed to determine the orientation of each single-particle diffraction pattern and reconstruct the 3D diffraction intensity. Most of these algorithms rely on the premise that all diffraction patterns originate from identical protein molecules. However, in actual experiments, diffraction patterns from multiple different molecules may be collected simultaneously. Here, we propose a predicted model-aided one-step classification–multireconstruction algorithm that can handle mixed diffraction patterns from various molecules. The algorithm uses predicted structures of different protein molecules as templates to classify diffraction patterns based on correlation coefficients and determines orientations using a correlation maximization method. Tests on simulated data demonstrated high accuracy and efficiency in classification and reconstruction.

Introduction: Depression is a common psychiatric problem in maintenance hemodialysis (MHD) patients. Recent studies have begun to explore the relationship between body composition and depression. Phase angle (PhA), a core parameter for assessing body composition, has been observed to be associated with frailty and cognitive dysfunction. The aim of this study was to investigate the association between PhA and depression in MHD patients. Methods: This multicenter, cross-sectional study included 843 MHD patients from seven dialysis centers in Shanghai, China. Depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ-9), with a score of ≥10 indicating depression. PhA was measured by bioelectrical impedance analysis. Nutritional status was assessed by malnutrition inflammation score (MIS). Multivariable logistic regression models were used to investigate the association between PhA and depression. Restricted cubic spline (RCS) analysis was utilized to examine the association. Receiver operating characteristic curve was used to identify the cut-off value of PhA for depression. Results: A total of 15.2% of patients (62.8% male, median age 66 years) had depression. Median PhA level (interquartile range) of depressed patients was 4.4° (3.9–4.9°) for males and 3.9° (3.2–4.7°) for females. There was a significant decrease in the prevalence of depression with increasing quartiles of PhA levels. In multivariable logistic regression analyses, after adjusting for age, sex, education level, spKt/V, dialysis vintage, Charlson comorbidity index, hemoglobin, and serum albumin, lower PhA levels (lowest quartile group) were significantly associated with depressive symptoms (adjusted odds ratio, 2.19; 95% confidence interval, 1.07 to 4.48), compared to higher PhA levels (highest quartile group). RCS analysis showed a relatively inverse linear association between PhA and depression. The optimal cut-off value of PhA for depression was 4.9° for males and 3.5° for females. Subgroup analyses validated the findings across patient characteristics, including age, sex, diabetes, education, and malnutrition. Conclusion: Our findings indicated an inverse association between PhA and depressive symptoms in Chinese MHD patients, suggesting that PhA could serve as a valuable indicator for assessing the risk of depression in this population. Further studies are needed to explore the potential of PhA as a prognostic tool and its implications for intervention strategies.

This study investigates the narrative development and main characteristics of primary school students in grades 2-5 in mainland China. Data from 120 primary school students were collected using indicators of narrative development and self-designed narrative ability tests. According to the findings from the analyses, primary school students of different grades demonstrated different performances in terms of macrostructure (completeness, profundity) and microstructure (productivity, elaboration, normative). These results demonstrate that the narrative development of Mandarin-speaking children from grades 2 to 5 in mainland China can be divided into two stages: the grade 2 is the spoken words writing stage and grades 3 to 5 is the transition stage, which means the age effect is significant. Furthermore, the main characteristics of Mandarin-speaking children's spoken words writing stage in mainland China are as follows: They can use language description and psychological activities to describe and record characters, but the structure of story is incomplete; they tended to end a story with an objective ending, while the narrative is insufficient and narrative accuracy is not high. While the children in the transition stage can have a more complete story structure and use longer language descriptions and psychological activities to record things; they tend to use different endings to express themselves and have more precise narratives.

IntroductionNative endophytic microorganisms in tobacco seeds are closely related to their resistance to Ralstonia solanacearum (R. solanacearum) infections. However, the role of the native seed core microbiome in the suppression of bacterial wilt disease (BWD) remains underexplored.MethodsThe characteristics of endophytic bacterial communities in both resistant and susceptible tobacco varieties were characterized using high-throughput sequencing technology.ResultsThis study found Paenibacillus as a potential microbial antagonist against BWD based on its significantly greater presence in BWD-resistant tobacco varieties, with a relative abundance that was 83.10% greater in the seeds of resistant tobacco than in those of susceptible varieties. Furthermore, a Paenibacillus strain identified as Paenibacillus odorifer 6036-R2A-26 (P. odorifer 26) was isolated from the seeds of the resistant variety. Following irrigation treatment with P. odorifer 26, the BWD index was reduced by 51.08%. Additionally, this strain exhibited significant growth-promoting effects on tobacco. It significantly increased the fresh weight of the tobacco plants by 30.26% in terms of aboveground weight, 37.75% in terms of underground weight, and 33.97% in terms of aboveground dry weight. This study highlights the critical role of Paenibacillus in tobacco seeds in the suppression of BWD, which may result from its antagonistic and growth-promoting properties.DiscussionThe results of this study revealed differences in the structural characteristics of endophytic bacterial communities between resistant and susceptible tobacco varieties, with groups such as Paenibacillus potentially playing significant roles in resisting BWD. These findings highlight the superiority of seed endophytic microorganisms. In the context of declining plant disease resistance and the spread of bacterial wilt, core endophytic microorganisms in seeds may emerge as a viable option for enhancing the productivity of agricultural ecosystems.

ObjectiveTo develop a nomogram model based on the albumin-bilirubin (ALBI) score for predicting the 90-day prognosis of patients with acute-on-chronic liver failure (ACLF) and to evaluate its predictive efficacy.MethodsClinical data of 290 ACLF patients at the Third People’s Hospital of Nantong City, collected from December 2020 to December 2023, were analyzed. The data were divided into a training set (n = 200) and a validation set (n = 90), with August 2022 as the cut-off date. Patients in the training set were categorized into an improvement group (n = 133) and a mortality group (n = 67) based on their 90-day outcomes. The predictive power of baseline parameters was assessed using univariate and multivariate logistic regression to construct model. Model performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA) and the Hosmer-Lemeshow test.ResultsCreatinine (CR) [odds ratio (OR) = 1.013, 95% confidence interval (CI): 1.004–1.022], ALBI (OR = 10.831, 95% CI: 4.009–33.247), Gender (OR = 1.931, 95% CI: 0.973–3.870) and ascites (OR = 3.032, 95% CI: 1.249–8.178) were identified as independent prognostic factors. The prognostic model formula was derived as prognostic index (PI) = –0.591 + 0.658 × Gender + 1.109 × ascites + 0.012 × CR + 2.382 × ALBI. The area under the curve (AUC) was 0.804 (95% CI: 0.741–0.866), with a specificity of 85.0% and a sensitivity of 65.7% at a cut-off of 0.425. The AUC of the validation set was 0.811 (95% CI: 0.697–0.926). The Hosmer-Lemeshow test indicated a good model fit with a p-value of 0.287 for the training set and 0.423 for the validation set. Calibration curves demonstrated the accuracy of the model, and DCA results suggested that the model was clinically useful when the threshold was below 0.6.ConclusionThe nomogram model incorporating ALBI with CR, Gender and ascites can predict the 90-day prognosis of ACLF patients, potentially helping to optimize treatment strategies and improve patient outcomes.

Abstract Antimicrobial peptides (AMPs) have become a viable source of novel antibiotics that are effective against human pathogenic bacteria. In this study, we construct a bank of culturable marine biofilm bacteria constituting 713 strains and their nearly complete genomes and predict AMPs using ribosome profiling and deep learning. Compared with previous approaches, ribosome profiling has improved the identification and validation of small open reading frames (sORFs) for AMP prediction. Among the 80,430 expressed sORFs, 341 are identified as candidate AMPs with high probability. Most potential AMPs have less than 40% similarity in their amino acid sequence compared to those listed in public databases. Furthermore, these AMPs are associated with bacterial groups that are not previously known to produce AMPs. Therefore, our deep learning model has acquired characteristics of unfamiliar AMPs. Chemical synthesis of 60 potential AMP sequences yields 54 compounds with antimicrobial activity, including potent inhibitory effects on various drug‐resistant human pathogens. This study extends the range of AMP compounds by investigating marine biofilm microbiomes using a novel approach, accelerating AMP discovery.

ABSTRACT Coral microbiomes play a crucial role in maintaining the health and functionality of holobionts. Disruption in the equilibrium of holobionts, including bacteria, fungi, and archaea, can result in the bleaching of coral. However, little is known about the viruses that can infect holobionts in coral, especially bacteriophages. Here, we employed a combination of amplicon and metagenomic analyses on Acropora muricata and Galaxea astreata to investigate the diversity and functionality of viruses in healthy and bleached corals. Analysis showed that the alpha diversity of holobionts (bacteria, eukaryotes, zooxanthellae, and lysogenic and lytic viruses) was higher in bleached corals than that in healthy corals. Meanwhile, bleached corals exhibited a relatively higher abundance of specific viral classes, including Revtraviricetes, Arfiviricetes, Faserviricetes, Caudoviricetes, Herviviricetes, and Tectiliviricetes; moreover, we found that the expression levels of functional genes involved in carbon and sulfur metabolism were enriched. An increase in Vibrio abundance has been reported as a notable factor in coral bleaching; our analysis also revealed an increased abundance of Vibrio in bleached coral. Finally, bleached corals contained a higher abundance of Vibrio phages and encoded more virulence factor genes to increase the competitiveness of Vibrio after coral bleaching. In conclusion, we attempted to understand the causes of coral bleaching from the perspective of phage–bacteria–coral tripartite interaction.IMPORTANCEViruses, especially bacteriophages, outnumber other microorganisms by approximately 10-fold and represent the most abundant members of coral holobionts. Corals represent a model system for the study of symbiosis, the influence of viruses on organisms inhabiting healthy coral reef, the role of rapid horizontal gene transfer, and the expression of auxiliary metabolic genes. However, the least studied component of coral holobiont are viruses. Therefore, there is a critical need to investigate the viral community of viruses, and their functionality, in healthy and bleached coral. Here, we compared the composition and functionality of viruses in healthy and bleached corals and found that viruses may participate in the induction of coral bleaching by enhancing the expression of virulence genes and other auxiliary metabolic functions.

BackgroundHeart rate variability (HRV) is an important marker of autonomic nervous system function and cardiovascular health. Holter monitoring is a crucial method for evaluating HRV, but the procedure and result analysis are relatively complex. This study aims to develop a simplified diagnostic index for predicting HRV decline in newly diagnosed non-small cell lung cancer (NSCLC) patients and evaluate its prognostic value.MethodsThis retrospective cross-sectional study included 131 newly diagnosed NSCLC patients. Baseline characteristics were compared between normal HRV group and declined HRV group. Univariate and multivariate logistic regression analyses identified significant predictors of HRV decline. A diagnostic index was developed based on resting heart rate (RHR), serum sodium, and interleukin-6 (IL-6) and externally validated. Kaplan-Meier survival analysis assessed the prognostic value of the index.ResultsPatients with declined HRV had higher median RHR (84 b.p.m. vs. 70 b.p.m., p < 0.001), lower serum sodium (136.3 mmol/L vs. 138.7 mmol/L, p < 0.001), lower serum albumin (39 g/L vs. 41 g/L, p = 0.031), higher lactate dehydrogenase (LDH) (202 U/L vs. 182 U/L, p = 0.010), and higher IL-6 (11.42 pg/ml vs. 5.67 pg/ml, p < 0.001). Multivariate analysis identified RHR (OR = 3.143, p = 0.034), serum sodium (OR = 6.806, p < 0.001), and IL-6 (OR = 3.203, p = 0.033) as independent predictors of HRV decline. The diagnostic index, with an area under the curve (AUC) of 0.849, effectively predicted HRV decline. ROC analysis of the external validation data demonstrated an AUC of 0.788. Survival analysis showed that patients with a diagnostic index > 2 had significantly worse overall survival (log-rank p < 0.001).ConclusionsThe study identified key clinical parameters that predict HRV decline in newly diagnosed NSCLC patients. The developed diagnostic index, based on RHR, serum sodium, and IL-6, effectively stratifies patients by HRV status and has significant prognostic value, aiding in early identification and management of high-risk patients.

Apoptosis repressor with caspase recruitment domain (ARC) is a highly potent and multifunctional suppressor of various types of programmed cell death (PCD) (e.g. apoptosis, necroptosis, and pyroptosis) and plays a key role in determining cell fate. Under physiological conditions, ARC is predominantly expressed in terminally differentiated cells, such as cardiomyocytes and skeletal muscle cells. Its expression and activity are tightly controlled by a complicated system consisting of transcription factor (TF), non-coding RNA (ncRNA), and post-translational modification (PTM). ARC dysregulation has been shown to be closely associated with many chronic diseases, including cardiovascular disease, cancer, diabetes, and neurodegenerative disease. However, the detailed mechanisms of ARC involved in the progression of these diseases remain unclear to a large extent. In this review, we mainly focus on the regulatory mechanisms of ARC expression and activity and its role in PCD. We also discuss the underlying mechanisms of ARC in health and disease and highlight the potential implications of ARC in the clinical treatment of patients with chronic diseases. This information may assist in developing ARC-based therapeutic strategies for patients with chronic diseases and expand researchers’ understanding of ARC.

Euphorbia species are widely distributed plants, many of which are used in folk medicine. Over the past twenty years, they have received considerable phytochemical and biological attention. Their diterpenoid constituents, especially those with abietane, tigliane, ingenane skeletons, are thought to be the main toxicant and bioactive factors. In this work, the utility of 13C-NMR spectroscopy for the structural elucidation of these compounds is briefly discussed.

Abstract Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. “Organs-on-chips: Intestine” is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024. This standard specifies the scope, terminology, definitions, technical requirements, detection methods, and quality control in building the human intestinal model on a chip. The publication of this group standard will guide the institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of intestine-on-a-chip for translational applications.

Abstract The wave equation revealing the wave propagation in chiral phononic crystals, established through force equilibrium law, conceals the underlying physical information, such as the essence of the motion coupling and the inertial amplification effect. This has led to a controversy over the bandgap mechanism. In this article, we theoretically unveil the reason for this controversy, and put forward an alternative approach from wave behavior to formulate the wave equation, offering an alternative pathway to articulate the bandgap physics directly. Based on the physics revealed by our theory method, we identify the obstacles in coupled acoustic and optic branches to widen and lower the bandgap. Then we introduce an approach based on spherical hinges to decrease the barriers, for customizing the bandgap frequency and width. Finally, we validate our proposal through numerical simulation and experimental demonstration.

The success of experimental phasing in macromolecular crystallography relies primarily on the accurate locations of heavy atoms bound to the target crystal. To improve the process of substructure determination, a modified phase-retrieval algorithm built on the framework of the relaxed alternating averaged reflection (RAAR) algorithm has been developed. Importantly, the proposed algorithm features a combination of the π-half phase perturbation for weak reflections and enforces the direct-method-based tangent formula for strong reflections in reciprocal space. The proposed algorithm is extensively demonstrated on a total of 100 single-wavelength anomalous diffraction (SAD) experimental datasets, comprising both protein and nucleic acid structures of different qualities. Compared with the standard RAAR algorithm, the modified phase-retrieval algorithm exhibits significantly improved effectiveness and accuracy in SAD substructure determination, highlighting the importance of additional constraints for algorithmic performance. Furthermore, the proposed algorithm can be performed without human intervention under most conditions owing to the self-adaptive property of the input parameters, thus making it convenient to be integrated into the structural determination pipeline. In conjunction with the IPCAS software suite, we demonstrated experimentally that automatic de novo structure determination is possible on the basis of our proposed algorithm.

Ultra-intense, ultra-fast X-ray free-electron lasers (XFELs) enable the imaging of single protein molecules under ambient temperature and pressure. A crucial aspect of structure reconstruction involves determining the relative orientations of each diffraction pattern and recovering the missing phase information. In this paper, we introduce a predicted model-aided algorithm for orientation determination and phase retrieval, which has been tested on various simulated datasets and has shown significant improvements in the success rate, accuracy and efficiency of XFEL data reconstruction.

Abstract To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P

Abstract CD320, which is a transmembrane protein responsible for facilitating the absorption of vitamin B12, plays a key role in this process. However, the relationships between CD320 and immune cell infiltration levels remain unclear, with limited studies investigating the diagnostic and prognostic significance of CD320 in hepatocellular carcinoma. We used various databases, including the TIMER, GEPIA, UALCAN and TCGA databases to investigate the expression levels of CD320 in hepatocellular carcinoma. Subsequently, we analyzed the prognosis of hepatocellular carcinoma patients with different expression levels of CD320. Furthermore, we also performed Western blot, immunohistochemistry, and immunofluorescence analyses to validate the results of the database analysis. Finally, the functions of CD320 in hepatocellular carcinoma were also confirmed via relevant cell experiments and angiogenesis assays. We found that CD320 expression was significantly upregulated in tumor vascular endothelial cells. Moreover, the knockdown of CD320 led to a reduction in angiogenesis in endothelial cells. Increased expression of CD320 was also correlated with a poor prognosis in patients with hepatocellular carcinoma, which suggested that CD320 may be a potential prognostic marker. Finally, TIMER analysis demonstrated that the infiltration of six immune cell types was significantly associated with high expression levels of CD320 in hepatocellular carcinoma. Herein, we demonstrated that CD320 may play an important role in angiogenesis in hepatocellular carcinoma. These findings suggested that CD320 may be a potential clinical prognostic marker and immunotherapy target for hepatocellular carcinoma.

Abstract The “hologenome” concept is an increasingly popular way of thinking about microbiome-host for marine organisms. However, it is challenging to track hologenome dynamics because of the large amount of material, with tracking itself usually resulting in damage or death of the research object. Here we show the simple and efficient holo-2bRAD approach for the tracking of hologenome dynamics in marine invertebrates (i.e., scallop and shrimp) from one holo-2bRAD library. The stable performance of our approach was shown with high genotyping accuracy of 99.91% and a high correlation of r > 0.99 for the species-level profiling of microorganisms. To explore the host-microbe association underlying mass mortality events of bivalve larvae, core microbial species changed with the stages were found, and two potentially associated host SNPs were identified. Overall, our research provides a powerful tool with various advantages (e.g., cost-effective, simple, and applicable for challenging samples) in genetic, ecological, and evolutionary studies.

Abstract Background Norepinephrine and phenylephrine are commonly used vasoactive drugs to treat hypotension during the perioperative period. The increased release of endogenous norepinephrine elicits prothrombotic changes, while parturients are generally in a hypercoagulable state. Therefore, this trial aims to investigate whether there is a disparity between equivalent doses of prophylactic norepinephrine infusion and phenylephrine infusion on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Methods Sixty-six eligible parturients will be recruited for this trial and randomly assigned to the norepinephrine or phenylephrine group. The “study drug” will be administered at a rate of 15 ml/h starting from the intrathecal injection. The primary outcome are plasma coagulation factor VIII activity (FVIII: C), fibrinogen, and D-dimer levels. The secondary outcomes include hemodynamic variables and umbilical artery blood pH value. Discussion Our study is the first trial comparing the effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Positive or negative results will all help us better understand the impact of vasoactive drugs on patients. If there are any differences, this trial will provide new evidence for maternal choice of vasoactive medications in the perioperative period. Trial registration Chinese Clinical Trial Registry ChiCTR2300077164. Registered on 1 November 2023. https://www.chictr.org.cn/ .

Abstract Background This study aimed to investigate clinical features and treatment strategies for intracranial aneurysm (IA) associated with pituitary adenoma (PA). Methods We enrolled patients with lesions in the sellar region and age-matched general population who were confirmed with IA from two hospitals. Four types of treatment strategies were performed, which included Type I (both IA and PA were treated with surgery), Type II (IA was treated with surgery and PA was performed by non-surgical treatment), Type III (PA was performed with surgery and observation was available for IA) and Type IV (both IA and PA were performed with non-surgical treatment). Results The incidence of IA was 2.2% in the general population, 6.1% in patients with PA, 4.3% in patients with Rathke cleft cyst, 2.8% in patients with meningioma and none were found with IA in patients with craniopharyngioma. Age over 50 years (OR, 2.69; 95% CI, 1.20–6.04; P = 0.016), female (OR, 3.83, P = 0.003), and invasive tumor (OR, 3.26, P = 0.003) were associated with a higher incidence of IA in patients with PA. During the mean follow-up of 49.2 months, no patients experienced stroke, and recurrence of aneurysms and aneurysms treated with observation were stable. Of four patients with recurrence of PA, three patients were treated for type I and one patient for type III. Conclusions Preoperative evaluation for aneurysm screening is necessary due to the high incidence of IA in PA patients. Our current treatment strategies may provide a benefit for these patients.

Abstract Unmanned aerial vehicles (UAVs) have become the focus of current research because of their practicability in various scenarios. However, current local path planning methods often result in trajectories with numerous sharp or inflection points, which are not ideal for smooth UAV flight. This paper introduces a UAV path planning approach based on distance gradients. The key improvements include generating collision-free paths using collision information from initial trajectories and obstacles. Then, collision-free paths are subsequently optimized using distance gradient information. Additionally, a trajectory time adjustment method is proposed to ensure the feasibility and safety of the trajectory while prioritizing smoothness. The Limited-memory BFGS algorithm is employed to efficiently solve optimal local paths, with the ability to quickly restart the trajectory optimization program. The effectiveness of the proposed method is validated in the Robot Operating System simulation environment, demonstrating its ability to meet trajectory planning requirements for UAVs in complex unknown environments with high dynamics. Moreover, it surpasses traditional UAV trajectory planning methods in terms of solution speed, trajectory length, and data volume.

The forging stage of rail flash welding has a decisive influence on joint strength, and the study of the temperature distribution in the process has an important role in further improving joint strength. In this paper, three calculation methods for the temperature field are given. First, the finite element model of the temperature field before forging rail flash welding is established by using the transient heat module of Ansys software and verified by infrared temperature measurement. Second, the temperature distribution of different parts of the rail before flash welding is obtained by using infrared thermal imaging equipment. Third, Matlab software is used to calculate the temperature of the non-measured part. Finally, the temperature distribution function along the rail axis is fitted through the temperature measurement data. The temperature distribution before the top forging of the rail flash welding can be used to analyze the joint and heat-affected zone organization and properties effectively and to guide the parameter setting and industrial production.

ObjectiveThe Triglyceride-glucose Index (TyG) index is a dependable metric for assessing the degree of insulin resistance, serving as a standalone predictor of ischemic stroke risk, but its precise relationship with early neurological deterioration (END) remains incompletely expounded within the context of acute mild ischemic stroke patients. This research is to examine the correlation of the TyG index with END among patients experiencing acute mild ischemic stroke in China.MethodsThis retrospective analysis was conducted to systematically gather data regarding patients experiencing their maiden episode of acute mild ischemic stroke and hospitalized at the Neurology Department of Nanjing Meishan Hospital, located in Nanjing, Jiangsu Province, China, over the period extending from January 2020 to December 2022. The severity of stroke was determined through the utilization of the National Institutes of Health Stroke Scale (NIHSS) scores upon their admission. Demographic characteristics were collected, and measurements of fasting blood glucose, blood lipids, and glycosylated hemoglobin Alc levels were taken. END was defined as a one-point rise in the motor item function score on the NIHSS or a two-point increase in the overall score during the initial 72 h of hospitalization. For evaluating the correlation of the TyG index with END, a multivariate logistic regression analysis was carried out. To investigate whether there is a nonlinear relationship between the TyG index and END, smoothed curves were utilized.ResultsThe study included 402 patients diagnosed with acute mild ischemic stroke, with a mean age of 66.15 ± 10.04 years. Within this population, 205 were males (51.00%) and 197 were females (49.00%). Among these patients, 107 (26.62%) experienced END within 72 h of admission. Patients who developed END showed higher levels of the TyG index in comparison to those who remained stable (9.18 ± 0.46 vs. 8.87 ± 0.46, p

Objective To evaluate the efficacy of the combined application of platelet-rich plasma (PRP) and negative pressure wound therapy (NPWT) in cavitary infected wounds, in addition to the parameter settings of NPWT. Methods The outcomes of patients with cavitary wounds who received debridement with either PRP plus NPWT (PRP group) or NPWT alone (controls) as part of their treatment protocol were retrospectively compared by examining preoperative and postoperative data on high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, neutrophil percentage, bacterial cultures, pain (measured using visual analogue scale [VAS] scores), postoperative hospitalization duration, and effective hospitalization days. Results A total of 24 patients were included (11 who received PRP plus NPWT and 13 who received NPWT alone). Postoperative hs-CRP levels, ESR, VAS scores, and effective hospitalization days were found to be significantly reduced in the PRP group versus controls. Moreover, the PRP group exhibited a significantly elevated rate of bacterial culture conversion at postoperative day 3. Conclusions The integration of surgical debridement with PRP and NPWT in the management of infected cavitary wounds may expedite infection containment and bacterial eradication, stimulate granulation tissue formation, and facilitate cavity closure, offering a novel and uncomplicated approach to wound healing.

IntroductionFusarium wilt disease (FWD) of tobacco is a destructive disease caused by Fusarium spp. in tobacco-growing regions worldwide. The Fusarium spp. infection may alter the composition and structure of the tobacco root microbial community; however, the relationship between these factors under large-scale geographical conditions in China remains underexplored.MethodsIn the context of this investigation, soil samples from the rhizosphere of tobacco plants were procured from fields afflicted with FWD and those devoid of the disease in the Hanzhong region of Shaanxi province, as well as in the Sanmenxia and Nanyang regions of Henan province. These regions are recognized for the commercial cultivation of tobacco. The examination focused on discerning the influence of tobacco FWD on the composition and configuration of the rhizosphere microbial community, along with their co-occurrence patterns. This scrutiny was underpinned by targeted PCR amplification and high-throughput sequencing (amplicon sequencing) of the 16S rRNA gene and the ITS1 region.ResultsThe amplicon data analyses showed that FWD influenced the microbial structure and composition of the tobacco rhizosphere soil. FWD had a greater impact on the microbiome of the tobacco fungal community than on the microbiome of the bacterial community. Healthy plants had the ability to recruit potential beneficial bacteria. Diseased plants were more susceptible to colonization by other pathogenic fungi, but they still had the capacity to recruit potential beneficial bacteria. The analysis of microbial intra- and inter-kingdom networks further indicated that FWD destabilized microbial networks. In the overall microbial interaction, microorganisms primarily interacted within their boundaries, but FWD increased the proportion of interactions occurring across boundaries. In addition, FWD could disrupt the interactions within microbial network modules.DiscussionThis study provides evidence that FWD can cause changes in the composition and network of microbial communities, affecting the interactions among various microorganisms, including bacteria and fungi. These findings contribute to our understanding of how plant microbiomes change due to disease. Furthermore, they add to our knowledge of the mechanisms that govern the assembly and interactions of microbial communities under the influence of FWD.

Wind energy is a cornerstone for enhancing grid stability and augmenting energy storage solutions, especially through its synergy with green hydrogen production. While substantial research has analyzed the economic dynamics of offshore wind and green hydrogen, the impact of offshore distances on hydrogen production costs remains underexplored. This study introduces a novel, globally applicable modeling framework for the Levelized Cost of Hydrogen (LCOH), illustrated using the strategically significant Taiwan Strait as a case study. By employing net present value analysis, we compare centralized, distributed, and onshore hydrogen production scenarios, documenting the lowest current LCOH values at $10.27, $10.31, and $11.32 per kg of hydrogen respectively. These findings highlight the cost-effectiveness of the centralized configuration and emphasize the significant costs linked to transmission infrastructure in onshore setups. Looking ahead to 2035, our framework predicts substantial reductions in LCOH, with low-cost scenarios forecasting profitability at just $9 per kilogram of hydrogen. Powered by the universally accessible ERA5 reanalysis dataset, our approach supports analogous assessments worldwide, thereby aiding strategic planning and the deployment of renewable technologies. In-depth sensitivity and Monte Carlo analyses further enhance our understanding of the impacts of offshore distance and other key factors, bolstering the economic evaluation of green hydrogen production. This comprehensive methodology not only assesses present capabilities but also facilitates broad application, fostering the strategic development of renewable technologies globally.

Breast cancer is a major public health concern worldwide, being the most commonly diagnosed cancer among women and a leading cause of cancer-related deaths. Recent studies have highlighted the significance of non-histone methylation in breast cancer, which modulates the activity, interaction, localization, and stability of target proteins. This regulation affects critical processes such as oncogenesis, tumor growth, proliferation, invasion, migration, and immune responses. This review delves into the enzymes responsible for non-histone methylation, such as protein arginine methyltransferases (PRMTs), lysine methyltransferases (KMTs), and demethylases, and explores their roles in breast cancer. By elucidating the molecular mechanisms and functional consequences of non-histone methylation, this review aims to provide insights into novel therapeutic strategies targeting these pathways. The therapeutic potential of targeting non-histone methylation to overcome drug resistance and enhance treatment efficacy in breast cancer is also discussed, highlighting promising avenues for future research and clinical applications.