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Abstract Background Muscle-invasive bladder carcinoma (MIBC) is a serious and more advanced stage of bladder carcinoma. N6-Methyladenosine (m6A) is a dynamic and reversible modifications that primarily affects RNA stability and alternative splicing. The dysregulation of m6A in MIBC can be potential target for clinical interventions, but there have been limited studies on m6A modifications in MIBC and their associations with post-transcriptional regulatory processes. Methods Paired tumor and adjacent-normal tissues were obtained from three patients with MIBC following radical cystectomy. The additional paired tissues for validation were obtained from patients underwent transurethral resection. Utilizing Nanopore direct-RNA sequencing, we characterized the m6A RNA methylation landscape in MIBC, with a focus on identifying post-transcriptional events potentially affected by changes in m6A sites. This included an examination of differential transcript usage, polyadenylation signal sites, and variations in poly(A) tail length, providing insights into the broader impact of m6A alterations on RNA processing in MIBC. Results The prognostic-related m6A genes and m6A-risk model constructed by machine learning enables the stratification of high and low-risk patients with precision. A novel m6A modification site in the 3’ untranslated region (3’UTR) of IGLL5 gene were identified, characterized by a lower m6A methylation ratio, elongated poly(A) tails, and a notable bias in transcript usage. Furthermore, we discovered two particular transcripts, VWA1-203 and CEBPB-201. VWA1-203 displayed diminished m6A methylation levels, a truncated 3’UTR, and an elongated poly(A) tail, whereas CEBPB-201 showed opposite trends, highlighting the complex interplay between m6A modifications and RNA processing. Source code was provided on GitHub ( https://github.com/lelelililele/Nanopore-m6A-analysis ). Conclusions The state-of-the-art Nanopore direct-RNA sequencing and machine learning techniques enables comprehensive identification of m6A modification and provided insights into the potential post-transcriptional regulation mechanisms on the development and progression in MIBC.

Abstract Background TMJ morphology/position and trabecular structure are influenced by various factors. The role of the interincisal angle, an indicator of the anterior occlusal relationship, on TMJ remains unclear. This study aims to investigate the morphology, trabecular bone structure, and position of the condyle, as well as the glenoid fossa’s morphology in skeletal class II populations with different interincisal angles. Materials and methods A total of 150 adult patients with normodivergent facial types and skeletal class II malocclusions were selected and divided into three groups based on their interincisal angles: normal, small, and large angle groups. The indexes of TMJ were measured using cone-beam computed tomography (CBCT) data and analyzed using Dolphin Imaging, Mimics, and ImageJ. Results The small angle group had the smallest anteroposterior diameter (APD), while the large angle group had a greater mediolateral diameter (MLD). The large angle group exhibited significantly the largest maximum axial area, bone surface area, and bone volume (P

Abstract The liver plays a vital role in lipid synthesis and metabolism in poultry. To study the functional genes more effectively, it is essential to screen of reliable reference genes in the chicken liver, including females, males, embryos, as well as the Leghorn Male Hepatoma (LMH) cell line. Traditional reference gene screening involves selecting commonly used housekeeping genes (HKGs) for RT-qPCR experiments and using different algorithms to identify the most stable ones. However, this approach is limited in selecting the best reference gene from a small pool of HKGs. High-throughput sequencing technology may offer a solution to this limitation. This study aimed to identify the most consistently expressed genes by utilizing multiple published RNA-seq data of chicken liver and LMH cells. Subsequently, the stability of the newly identified reference genes was assessed in comparison to previously validated stable poultry liver expressed reference genes and the commonly employed HKGs using RT-qPCR. The findings indicated that there is a higher degree of similarity in stable expression genes between female and male liver (such as LSM14A and CDC40). In embryonic liver, the optimal new reference genes were SUDS3, TRIM33, and ERAL1. For LMH cells, the optimal new reference genes were ALDH9A1, UGGT1, and C21H1orf174. However, it is noteworthy that most HKGs did not exhibit stable expression across multiple samples, indicating potential instability under diverse conditions. Furthermore, RT-qPCR experiments proved that the stable expression genes identified from RNA-seq data outperformed commonly used HKGs and certain validated reference genes specific to poultry liver. Over all, this study successfully identified new stable reference genes in chicken liver and LMH cells using RNA-seq data, offering researchers a wider range of reference gene options for RT-qPCR in diverse situations.

Abstract Objectives This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). Methods This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. Result The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. Conclusions CSVDs are associated with increased exposure to elevated BP later in life.

China’s Chang'e-5 spacecraft successfully collected 1731 g of Lunar regolith and returned it to Earth on December 17, 2020. In this paper, Chang'e-5 simulated Lunar regolith is used as the main material to form stable and dense solid Lunar soil structures by adding different amounts of an inorganic curing agent and water. The internal morphology, failure morphology under uniaxial compression, and stress–strain relationship of the Lunar regolith solidified samples (L-R-S-Ss) are then investigated. The damage constitutive model of the Lunar regolith cured body is analyzed according to the stress–strain curves, with the following results found. (1) Scanning electron microscopy indicates that the L-R-S-Ss contain more microvoids and microfractures, which are the main factors that lead to destruction. (2) The uniaxial failure mode of the L-R-S-Ss is primarily split failure, with both vertical and oblique cracks, with the angle between the main crack and the vertical axis being less than 30°. (3) The content of the curing agent and the amount of water are important factors affecting the L-R-S-S strength. As the water content increases, the L-R-S-S compressive strength tends to decrease. The L-R-S-S strength increases with increasing amount of cementitious material. (4) A cubic polynomial and a rational fraction are used to fit the ascending and descending sections of the L-R-S-S stress–strain curves, respectively, and a piecewise constitutive model of the L-R-S-S specimens is proposed. The calculated results of the model are in good agreement with the experimental curves.

Magnitude estimation is a critical task in seismology, and conventional methods usually require dense seismic station arrays to provide data with sufficient spatiotemporal distribution. In this context, we propose the Earthquake Graph Network (EQGraphNet) to enhance the performance of single-station magnitude estimation. The backbone of the proposed model consists of eleven convolutional neural network layers and ten RCGL modules, where a RCGL combines a Residual Connection and a Graph convolutional Layer capable of mitigating the over-smoothing problem and simultaneously extracting temporal features of seismic signals. Our work uses the STanford EArthquake Dataset for model training and performance testing. Compared with three existing deep learning models, EQGraphNet demonstrates improved accuracy for both local magnitude and duration magnitude scales. To evaluate the robustness, we add natural background noise to the model input and find that EQGraphNet achieves the best results, particularly for signals with lower signal-to-noise ratios. Additionally, by replacing various network components and comparing their estimation performances, we illustrate the contribution of each part of EQGraphNet, validating the rationality of our approach. We also demonstrate the generalization capability of our model across different earthquakes occurring environments, achieving mean errors of ±0.1 units. Furthermore, by demonstrating the effectiveness of deeper architectures, this work encourages further exploration of deeper GNN models for both multi-station and single-station magnitude estimation.

Abstract Despite the widespread adoption of emergency coronary reperfusion therapy, reperfusion‐induced myocardial injury remains a challenging issue in clinical practice. Following myocardial reperfusion, S100A8/A9 molecules are considered pivotal in initiating and regulating tissue inflammatory damage. Effectively reducing the S100A8/A9 level in ischemic myocardial tissue holds significant therapeutic value in salvaging damaged myocardium. In this study, HA (hemagglutinin)‐ and RAGE (receptor for advanced glycation end products)‐ comodified macrophage membrane‐coated siRNA nanoparticles (MMM/RNA NPs) with siRNA targeting S100A9 (S100A9‐siRNA) are successfully prepared. This nanocarrier system is able to target effectively the injured myocardium in an inflammatory environment while evading digestive damage by lysosomes. In vivo, migration of MMM/RNA NPs to myocardial injury lesions is confirmed in a myocardial ischemia‐reperfusion injury (MIRI) mouse model. Intravenous injection of MMM/RNA NPs significantly reduced S100A9 levels in serum and myocardial tissues, further decreasing myocardial infarction area and improving cardiac function. Targeted reduction of S100A8/A9 by genetically modified macrophage membrane‐coated nanoparticles may represent a new therapeutic intervention for MIRI.

ABSTRACT: The in ovo feeding (IOF) of L-arginine (L-Arg) to chick embryos is a viable method for improving early intestinal development, subsequently leading to an acceleration in growth rate during the posthatch stage. However, the liver, being the pivotal organ for energy metabolism in poultry, the precise effects and mechanisms of L-Arg on the liver development and metabolism remain unclear. To elucidate these, the present study injected 2 doses of L-Arg (10 mg/egg and 15 mg/egg) into the embryos of Hongyao chickens at 17.5 d of incubation, subsequently incubating them until d 19 for further analysis. IOF of 15 mg L-Arg/egg significantly increased the organ indices of liver and small intestine, as well as the duodenal villus height/crypt depth. RNA-Seq analysis of liver tissues showed that the metabolism of xenobiotics, amino acid metabolism, and the fatty acid metabolism were significantly enriched in L-Arg injection group. The core differentially expressed genes (DEGs) were primarily involved in cell proliferation and fatty acid metabolism. The CCK8 assays revealed that supplemental L-Arg significantly enhanced the proliferation of primary embryo hepatocytes and leghorn male hepatoma (LMH) cells. Upregulation of core DEGs, including HBEGF, HES4, NEK3, EGR1, and USP2, significantly promoted the proliferation of liver cells. Additionally, analysis of triglyceride and total cholesterol content, as well as oil red O staining, indicated that supplemental L-Arg effectively reduced lipid accumulation. Overall, L-Arg supplementation in late chick embryos may promote early liver and small intestine development by reducing liver lipid deposition and enhancing energy efficiency, necessitating further experimental validation. This study provides profound insights into the molecular regulatory network of L-Arg in promoting the development of chicken embryos. The identified DEGs that promote cell proliferation and lipid metabolism can serve as novel targets for further developing methods to enhance early development of chicken embryos.

Abstract In order to provide suitable material selection for such fluid–solid coupling model tests, orthogonal experimental studies were conducted using iron concentrate powder and barite powder as aggregates, cement as cementitious materials, and gypsum and clay as modifiers. This research showed: (1) The ATC plays a dominant role in controlling the strength indexes and water absorption of the material, and these indexes show a significant decrease with the increase of the bone adhesive ratio. For each level of ATC increase, the compressive strength decreases by 0.2 MPa, the elastic modulus decreases by 10–20 MPa, and the cohesion decreases by 25–45 kPa. (2) Mixing gypsum and cement cannot jointly promote strength growth. (3) With the increase of GTC, the water absorption rate of the material increases, while the softening coefficient and permeability coefficient decrease obviously. Gypsum, which accounts for 4–16% of cement content, can be suitable for studying the hydraulic properties of similar materials for most sedimentary rock. Based on Weibull statistical damage theory, a damage constitutive model for the entire process of rock triaxial compression under the combined action of rainwater infiltration and load was established. Due to the influence of internal pores, the experimental and theoretical results have a certain deviation, the higher the confining pressure, the more obvious the deviation. In addition, the higher the rock strength, the less obvious the deviation caused by pores. This damage model can better describe the progressive failure process of rocks after rainwater infiltration, and can provide theoretical reference for the study of slope stability caused by rainwater infiltration.

Abstract Background Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue “tracking” labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs. Results In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced. Conclusion Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.

Abstract The adaptability of cultured fish to complex flow conditions is crucial for their survival after being released into the wild. Running water in natural environments poses significant challenges for the proliferation and release of cultured fish. This study aimed to investigate the effects of flow stimulation on the adjustment capacity of cultured fish to cope with running water. The target fish were cultured grass carp. An annular flume was used to conduct tests on training and control groups. The results demonstrated an enhancement in the adjustment capacity of cultured fish following appropriate flow stimulation training. (1) The trained fish exhibited a heightened preference for low-velocity areas. (2) The trained fish displayed the ability to select a route characterized by low energy consumption, predominantly following the periphery of the low-velocity area. This suggested that an appropriate flow velocity could improve the sensitivity of training fish to water flow information, and their adjustment capacity to cope with running water improved to a certain extent. A higher adjustment capacity allowed them to process flow rate information rapidly and identify a migration strategy with lower energy consumption. This study provides a useful reference for enhancing the survival rate of grass carp through stock enhancement initiatives and contributes to the sustainability of freshwater ecosystems.

Abstract Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research. Graphical abstract

Abstract The development of the electric vehicle industry has spurred demand for secondary batteries capable of rapid‐charging and slow‐discharging. Among them, sodium‐ion batteries (SIBs) with layered oxide as the cathode exhibit competitive advantages due to their comprehensive electrochemical performance. However, to meet the requirements of rapid‐charging and slow‐discharging scenarios, it is necessary to further enhance the rate performance of the cathode material to achieve symmetrical capacity at different rates. Simultaneously, minimizing lattice strain during asymmetric electrochemical processes is also significant in alleviating strain accumulation. In this study, the ordered distribution of transition metal layers and the diffusion pathway of sodium ions are optimized through targeted K‐doping of sodium layers, leading to a reduction of the diffusion barrier and endowment of prominent rate performance. At a 20C rate, the capacity of the cathode can reach 94% of that at a 0.1C rate. Additionally, the rivet effect of the sodium layers resulted in a global volume strain of only 0.03% for the modified cathode during charging at a 10C rate and discharging at a 1C rate. In summary, high‐performance SIBs, with promising prospects for rapid‐charging and slow‐discharging capability, are obtained through the regulation of sodium layers, opening up new avenues for commercial applications.

Resveratrol (RSV) has been shown to prevent epithelial-mesenchymal transition (EMT) in different diseases by modulating several signaling pathways, and RSV can prevent EMT by modulating the signaling of the TGF-β/Smad axis. In the development of renal ischemia‒reperfusion injury (RIRI), RSV and MSC-derived exosomes could ameliorate RIRI via different signaling pathways. In this study, we aimed to investigate the effect of RSV plus MSC-derived exosomes on the prognosis of RIRI. Quantitative real-time polymerase chain reaction (PCR) was performed to measure the expression of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA in TCMK-1 cells and mice under various conditions. HE and Masson staining were used to evaluate kidney injury and fibrosis in mice under various conditions. RSV effectively maintained the TGF-β- and AA-induced upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in TCMK-1 cells. Moreover, MSC-derived exosomes effectively reinforced the effect of RSV on reducing the TGF-β- and AA-induced upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in TCMK-1 cells. Furthermore, MSC-derived exosomes enhanced the capability of RSV to maintain the RIRI-induced increases in Cr and BUN, as well as the upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in mice. In addition, MSC-derived exosomes enhanced the capability of RSV to decrease RIRI-induced kidney injury and fibrosis in mice. Our findings showed that the administration of MSC-derived exosomes and RSV could suppress the TGF-β-induced epithelial-mesenchymal transition. This suppressive effect was promoted by the coadministration of MSC-derived exosomes and RSV.

ABSTRACT: Utilizing publicly available RNA-seq data to screen for ideal reference genes is more efficient and accurate than traditional methods. Previous studies have identified optimal reference genes in various chicken tissues, but none have specifically focused on the oviduct (including the infundibulum, magnum, isthmus, uterus, and vagina), which is crucial for egg production. Identifying stable reference genes in the oviduct is essential for improving research on gene expression levels. This study investigated genes with consistent expression patterns in the chicken oviduct, encompassing both individual oviduct tract tissues and the entire oviduct, by utilizing multiple RNA-seq datasets. The screening results revealed the discovery of 100 novel reference genes in each segment of oviduct tissues, primarily associated with cell cycle regulation and RNA binding. Moreover, the majority of housekeeping genes (HKGs) showed inconsistent expression levels across distinct samples, suggesting their lack of stability under varying conditions. The stability of the newly identified reference genes was assessed in comparison to previously validated stable reference genes in chicken oviduct and commonly utilized HKGs, employing traditional reference gene screening methods. HERPUD2, CSDE1, VPS35, PBRM1, LSM14A, and YWHAB were identified to be suitable novel reference gene for different parts of the oviduct. HERPUD2 and YWHAB were reliable for gene expression normalization throughout the oviduct tract. Furthermore, overexpression and interference assays in DF1 cells showed LSM14A and YWHAB play a crucial role in cell proliferation, highlighting the importance of these newly reference genes for further research. Overall, this study has expanded the options for reference genes in RT-qPCR experiments in different segments of the chicken oviduct and the entire oviduct.

Due to the diversity of postpartum depression (PPD) patients and the complexity of associated pathophysiological changes, most current animal models cannot accurately simulate PPD-like symptoms. In this study, we established a reliable animal model for PPD by inducing chronic unpredictable mild stress (CUMS) at different stages (pre-pregnancy, pregnancy, or postnatal) in female mice, followed by maternal separation (MS) from day 2–21 after delivery. The results for female mice subjected to pre-pregnancy stress were not statistically significant due to a lower conception rate. However, female mice exposed to CUMS during either the gestational or postnatal stage, followed by MS, successfully exhibited PPD-like symptoms. The models were deemed effective based on observed behavioral abnormalities, impaired hippocampal neuron functioning, and reduced serum concentrations of neurotransmitters (5-HT, GABA, and NE). Additionally, mice that underwent gestational CUMS followed by MS displayed a more dysfunctional hypothalamic-pituitary-adrenal (HPA) axis and more severe uterine inflammation. The study also investigated the impact of PPD on the behavior and neurodevelopment of adolescent offspring through behavioral tests, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, and western blotting (WB). The results indicated that adolescent offspring of mothers with PPD exhibited behavioral and neurodevelopmental disorders, with male offspring being more susceptible than females. Female mice exposed to both CUMS and MS during the postnatal period had more severe adverse effects on their offspring compared to the other model groups.

Abstract The compound drought‐extreme precipitation event (CDEP) is one of the most impactful successive compound events that shift from drought to extreme precipitation in the same location within a short period. Due to its dual characteristics of drought and flood, CDEP tends to be more destructive than the impact of individual drought or flood. Yet few studies have analyzed the likelihood of CDEP at different time intervals and their potential variations under global warming. In this study, we assessed the coincidence rate between droughts and extreme precipitation events at 1‐month (CDEP‐1), 2‐month (CDEP‐2), and 3‐month (CDEP‐3) intervals, as well as their potential changes in a 1.5 and 2°C warming world (under both SSP2‐4.5 and SSP5‐8.5 scenarios). Our results suggest that global droughts and extreme precipitation events have coincided more frequently at 1‐month interval than at 2‐ and 3‐month intervals during the period 1985–2014. The global average coincidence rates of CDEP‐1, CDEP‐2, and CDEP‐3 are 24%, 10%, and 7%, respectively. Notably, the coincidence rate of CDEP‐1 exceeded 40% in Eastern Asia, north‐eastern North America, and India, indicating that more than 40% of droughts have been followed by extreme precipitation events in the next month after drought termination. Under both SSP2‐4.5 and SSP5‐8.5 scenarios, climate warming will increase the coincidence rate of CDEP‐1, CDEP‐2, and CDEP‐3, especially will lead to higher values in the coincidence rate of CDEP‐1. This study contributes to a better understanding of the patterns of CDEP and helps to develop more targeted risk management strategies.

Introduction: Tripterygium species have been traditionally used in Chinese medicine for treating various conditions. The aim of the study was to construct a drug-modified renal infarction targeting liposome (rTor-LIP) containing Tripterygium in order to improve the therapeutic effect on renal injury.Methods: rTor-LIP was prepared using the extruder method containing Tripterygium solution. The preparation was characterized by transmission electron microscopy, Marvin laser particle size analyzer, and Western blotting. In vitro experiments were conducted to verify the biocompatibility of rTor-LIP, and in vivo experiments were conducted to verify the therapeutic effect of rTor- LIP on renal injury.Results and discussion: The surface of rTor-LIP was regular and oval. In vitro results showed that after co-incubation with rTor-LIP, endothelial cells did not show significant apoptosis, and there were no significant abnormalities in the mitochondrial metabolism. The in vivo results showed that the morphology of endothelial cells in the rTor-LIP group was uniform and the cytoplasmic striations were clear, but the local striations had disappeared. Thus, rTor-LIP nano-targeted liposomes can effectively target hypoxic kidney tissue, providing a new idea for the treatment of renal infarction.

Lithium-rich layered oxides (LROs) are considered as promising cathodes in building next-generation lithium-ion batteries (LIBs) with superior charge-discharge capacity. Nevertheless, LROs are confronted with irreversible oxygen loss accompanied with surface-to-bulk degradation upon cycling. To inhibit the oxygen release and to increase the lifespan of LROs, we report on an innovative strategy to rapidly construct an ultrathin oxygen-deficient shell layer covering the surface of LROs’ particles via a sparking plasma sintering (SPS) technique. It is demonstrated that the inner structure of the LROs’ particles is maintained, whereas the surface of the particles forms a thin shell (∼5 nm) consisting of a considerable amount of oxygen vacancies. Benefitting from the existence of an oxygen-deficient shell, the cathode activation is facilitated and the oxygen loss is suppressed, leading to enhanced capacity and prominent cyclability under long cycling. The modified LRO exhibits outstanding electrochemical performance, delivering a maximum capacity of 187.67 mAh g−1 and a capacity retention of 95.71% after 200 cycles at 250 mA g−1. Our work evidences that SPS is a fast and effective approach to construct oxygen-deficient shell on LRO cathodes for high-performance LIBs.

Abstract Near‐infrared (NIR) chiroptical response has been less explored because it is challenging to achieve both chirality and NIR absorption/emission. Herein, we describe the design of heterohelicene‐type β‐isoindigo‐based boron‐dipyrromethene (BODIPY) analogs (β‐IBs), which shift the absorption peak to 800 nm and produce significant Cotton effects (127.8 M−1 cm−1) and absorbance dissymmetry factors (|gabs| = 3.5 × 10−3). The luminescence dissymmetry factor (glum) and circularly polarized luminescence (CPL) brightness (BCPL) of up to 1.24 × 10−3 and 1.78 M−1 cm−1 were realized beyond 800 nm. These β‐IBs are the first examples of helicene‐type compounds with the highest gabs in the NIR region and CPL beyond 800 nm. Theoretical calculations demonstrate that the strong chiroptical activities are triggered by their large transition magnetic dipole moments. This study not only provides a new approach to the synthesis of a larger variety of unprecedented helicene‐type BODIPY analogs but also demonstrates excellent NIR chiroptical properties.

Research on hepatic steatosis in animal husbandry has been a prominent area of study. Developing an appropriate in vitro cellular steatosis model is crucial for comprehensively investigating the mechanisms involved in liver lipid deposition in poultry and for identifying potential interventions to address abnormalities in lipid metabolism. The research on the methods of in vitro liver steatosis in chickens, particularly the effects of different fat mixtures, is still lacking. In this study, LMH cells were utilized to investigate the effects of OA, SO, PA, SP, and their pairwise combinations on steatosis development, with the aim of identifying the optimal conditions for inducing steatosis. Analysis of triglyceride (TG) content in LMH cells revealed that OA and SP had limited efficacy in increasing TG content, while a combination of SO and PA in a 1:2 ratio exhibited the highest TG content. Moreover, Oil Red O staining results in LMH cells demonstrated that the combination treatment had a more pronounced induction effect compared to 0.375 mM SO. Additionally, RNA-seq analysis showed that 0.375 mM SO significantly influenced the expression of genes associated with fatty acid metabolism compared to the control group, whereas the combination of SO and PA led to an enrichment of key GO terms associated with programmed cell death. These findings suggest that varying conditions of cellular steatosis could lead to distinct disruptions in gene expression. The optimal conditions for inducing steatosis in LMH cells were also tested on chicken embryonic liver cells and embryos. TG detection and Oil Red O staining assays showed that the combination of SO and PA successfully induced steatosis. However, the gene expression pattern differed from that of LMH cells. This study lays the foundations for further investigations into avian hepatic steatosis.

Abstract The heart is a muscular organ that pumps blood throughout the body and is one of the most vital organs in human body. While cardiomyocytes are essential for maintaining the normal function of the heart, a variety of cardiovascular diseases such as coronary artery occlusion, arrhythmia, and myocarditis can lead to cardiomyocyte death, resulting in deterioration of heart function. The adult mammalian heart is incapable of regenerating sufficient cardiomyocytes following cardiac injuries, eventually leading to heart failure and death. Cardiac macrophages are ubiquitously distributed in the healthy heart and accumulated at the site of injury. Macrophages play essential roles in regulating homeostasis and proliferation of cardiomyocyte, promoting electrical conduction, and removing dead cardiomyocytes and debris through direct and indirect cell–cell crosstalk. In this review, we summarize the latest insights into the role of macrophages in maintaining cardiac homeostasis and the macrophage-cardiomyocyte crosstalk in both healthy and injured scenarios. Video Abstract

In this paper, a pole-changing (PC) flux reversal permanent magnet (FRPM) motor is proposed for obtaining a wide speed range. According to the general air-gap field modulation theory, the permanent magnet (PM) magnetic field is modulated into a series of harmonics with different pole numbers by rotor teeth. By introducing an especial PM arrangement, two groups of working harmonics with different pole-pair numbers are generated in the proposed 12-7 PC-FRPM motor due to the modulation of rotor teeth. Based on the calculated slot pitch angles of these harmonics, two winding connections can be obtained for PC operation to achieve two operating modes. The electromagnetic performance of PC-FRPM motor before and after PC are analyzed using finite element analysis and verified by the experimental test results.

Background: Many researchers have investigated the use of Chinese herbs to delay the progression of chronic kidney disease (CKD) through their effects on colonic microflora and microbiota-derived metabolites. However, whether FuZhengHuaYuJiangZhuTongLuo (FZHY) has effects that are similar to those of AST-120 on CKD needs to be elucidated. Methods: In this study, we compared the effects of FZHY and AST-120 on the colonic microbiota and plasma metabolites in the CKD rat model. We developed a unilateral ureteral obstruction (UUO)-induced CKD rat model and then administered FZHY and AST-120 to these model rats. Non-targeted metabolomic LC-MS analysis, 16S rRNA sequencing, and histopathological staining were performed on plasma, stool, and kidney tissues, respectively, and the joint correlation between biomarkers and metabolites of candidate bacteria was analyzed. Results: Our results showed that administering FZHY and AST-120 effectively ameliorated UUO-induced abnormal renal function and renal fibrosis and regulated the composition of microbiota and metabolites. Compared to the UUO model group, the p_Firmicutes and o_Peptostreptococcales_Tissierellales were increased, while 14 negative ion metabolites were upregulated and 21 were downregulated after FZHY treatment. Additionally, 40 positive ion metabolites were upregulated and 63 were downregulated. On the other hand, AST-120 treatment resulted in an increase in the levels of g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, as well as 12 upregulated and 23 downregulated negative ion metabolites and 56 upregulated and 63 downregulated positive ion metabolites. Besides, FZHY increased the levels of candidate bacterial biomarkers that were found to be negatively correlated with some poisonous metabolites, such as 4-hydroxyretinoic acid, and positively correlated with beneficial metabolites, such as l-arginine. AST-120 increased the levels of candidate bacterial biomarkers that were negatively correlated with some toxic metabolites, such as glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid. Conclusion: FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD.

IntroductionA growing body of research indicates that microorganisms play a crucial role in human health. Imbalances in microbial communities are closely linked to human diseases, and identifying potential relationships between microbes and diseases can help elucidate the pathogenesis of diseases. However, traditional methods based on biological or clinical experiments are costly, so the use of computational models to predict potential microbe-disease associations is of great importance.MethodsIn this paper, we present a novel computational model called MLFLHMDA, which is based on a Multi-View Latent Feature Learning approach to predict Human potential Microbe-Disease Associations. Specifically, we compute Gaussian interaction profile kernel similarity between diseases and microbes based on the known microbe-disease associations from the Human Microbe-Disease Association Database and perform a preprocessing step on the resulting microbe-disease association matrix, namely, weighting K nearest known neighbors (WKNKN) to reduce the sparsity of the microbe-disease association matrix. To obtain unobserved associations in the microbe and disease views, we extract different latent features based on the geometrical structure of microbes and diseases, and project multi-modal latent features into a common subspace. Next, we introduce graph regularization to preserve the local manifold structure of Gaussian interaction profile kernel similarity and add Lp,q-norms to the projection matrix to ensure the interpretability and sparsity of the model.ResultsThe AUC values for global leave-one-out cross-validation and 5-fold cross validation implemented by MLFLHMDA are 0.9165 and 0.8942+/−0.0041, respectively, which perform better than other existing methods. In addition, case studies of different diseases have demonstrated the superiority of the predictive power of MLFLHMDA. The source code of our model and the data are available on https://github.com/LiangzheZhang/MLFLHMDA_master.

Background: The structural brain alterations for subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are poorly defined. We sought to characterize grey matter volume (GMV) and cortical thickness associated with SCD and MCI among rural-dwelling older adults in China. Methods: This population-based cross-sectional study included 1072 dementia-free participants from the brain MRI sub-study of MIND-China (2018–2020). We defined MCI following the Petersen’s criteria, and SCD as the self-rated Ascertain Dementia 8-item Questionnaire score ≥ 2. Data were analyzed using voxel-based morphometry (VBM), surface-based morphometry analysis (SBM), and logistic regression models. Results: SCD was defined in 243 persons and MCI in 246 individuals. The VBM analysis showed that MCI (vs. normal cognition) was significantly associated with reduced GMV in brain regions such as the bilateral parahippocampus, bilateral hippocampus, and bilateral fusiform (P 0.05). The ROI-wise SBM analysis revealed that SCD was significantly associated with cortical thinning in the right paracentral sulcus, left caudal middle frontal gyrus, and left entorhinal cortex (P

Abstract Aims Leukocyte telomere length (LTL), as a biomarker of biological aging, is associated with the prevalence and complications of diabetes. This study aims to investigate the associations between LTL and all‐cause and cause‐specific mortality in patients with type 2 diabetes. Methods All participants with baseline LTL records were included from the National Health and Nutrition Examination Survey 1999–2002. Death status and its causes were ascertained for National Death Index based on International Classification of Diseases, Tenth Revision code. Cox proportional hazards regression models were established to estimate the hazard ratios (HRs) of LTL associating with all‐cause and cause‐specific mortality. Results The study enrolled 804 diabetic patients with the mean follow‐up of 14.9 ± 2.59 years. There were 367 (45.6%) all‐cause deaths, 80 (10.0%) cardiovascular deaths, and 42 (5.2%) cancer‐related deaths. Longer LTL was associated with reduced all‐cause mortality, whereas this association disappeared after adjusting for other variables. Compared with the lowest tertiles of LTL, the multivariable‐adjusted hazard ratio of cardiovascular mortality was 2.11 (95% confidence interval [CI] 1.31–3.39; p

L-Arabinose isomerase (L-AI) has been commonly used as an efficient biocatalyst to produce D-tagatose via the isomerization of D-galactose. However, it remains a significant challenge to efficiently synthesize D-tagatose using the native (wild type) L-AI at an industrial scale. Hence, it is extremely urgent to redesign L-AI to improve its catalytic efficiency towards D-galactose, and herein a structure-based molecular modification of Lactobacillus plantarum CY6 L-AI (LpAI) was performed. Among the engineered LpAI, both F118M and F279I mutants showed an increased D-galactose isomerization activity. Particularly, the specific activity of double mutant F118M/F279I towards D-galactose was increased by 210.1% compared to that of the wild type LpAI (WT). Besides the catalytic activity, the substrate preference of F118M/F279I was also largely changed from L-arabinose to D-galactose. In the enzymatic production of D-tagatose, the yield and conversion ratio of F118M/F279I were increased by 81.2% and 79.6%, respectively, compared to that of WT. Furthermore, the D-tagatose production of whole cells expressing F118M/F279I displayed about 2-fold higher than that of WT cell. These results revealed that the designed site-directed mutagenesis is useful for improving the catalytic efficiency of LpAI towards D-galactose.

Ancient glass artifacts were susceptible to weathering from the environment, causing changes in their chemical composition, which pose significant obstacles to the identification of glass products. Analyzing the chemical composition of ancient glass has been beneficial for evaluating their weathering status and proposing measures to reduce glass weathering. The objective of this study was to explore the optimal machine learning algorithm for glass type classification based on chemical composition. A set of glass artifact data including color, emblazonry, weathering, and chemical composition was employed and various methods including logistic regression and machine learning techniques were used. The results indicated that a significant correlation (p < 0.05) could only observed between surface weathering and the glass types (high-potassium and lead–barium). Based on the random forest and logistic regression models, the primary chemical components that signify glass types and weathering status were determined using PbO, K2O, BaO, SiO2, Al2O3, and P2O5. The random forest model presented a superior ability to identify glass types and weathering status, with a global accuracy of 96.3%. This study demonstrates the great potential of machine learning for glass chemical component estimation and glass type and weathering status identification, providing technical guidance for the appraisal of ancient glass artifacts.

To address the lack of effective monitoring, evaluation, and prediction methods for water stress in citrus seedlings, we conducted 10 sets of water stress gradient experiments. Based on the experimental dataset, we constructed, trained, and improved an MLP classification model for citrus seedling water stress. In addition, we developed a monitoring, evaluation, and prediction system based on this model. The experiments demonstrated that 7 days of slight water stress can induce changes in overall root wilting and growth stagnation, and the chlorophyll content in the leaves can decrease by up to 11.78%. Furthermore, the optimal VWC for seedlings was [45%, 50%], the boundary of drought was [20%, 25%], and the boundary of waterlogging was [50%, 55%]. We validated the effectiveness of the system in assessing the growth status of seedlings over the past 7 days and predicting it after 7 days through testing sets and experiments on slight water stress. We found that the system achieved non-destructive remote monitoring, evaluation, and prediction of slight water stress in citrus seedlings, thus enhancing seedling quality. These research findings provide valuable insights into water stress management in citrus seedlings and other crops.

ABSTRACT: The application of reverse transcription quantitative real-time PCR technology for the production of gene tissue expression profiles is a widely employed approach in molecular biology research. It is imperative to ascertain internal reference genes that exhibit stable expression across diverse tissues to ensure the precision of tissue gene expression profiles. While there have been studies documenting the most suitable reference genes for various tissues in chickens, there is a dearth of research on the identification of reference genes in the gastrointestinal (GI) tract of chickens. This study utilized 4 different algorithms (Delta CT, BestKeeper, NormFinder, and Genorm) to assess the stability of 19 internal reference genes in various GI tract tissues, including individual GI tract tissues, the anterior and posterior GI tract, and the entire GI tissue. The RefFinder software was employed to comprehensively rank these genes. The research findings successfully identified the most appropriate internal reference genes for each type of GI tissue. Furthermore, TBP, DNAJC24, Polr2b, RPL13, andAp2m exhibited stable expression in the entire and posterior GI tract, whereas HMBS, TBP, Ap2m, GUSB, DNAJC24, and RPL13 demonstrated stable expression in the anterior GI tract. However, the internal reference genes commonly utilized, namely β-Actin, 18s RNA, and ALB, exhibit poor stability and are not advised for future investigations concerning gene expression in the GI region. Consequently, MUC2 and CDX1, 2 genes that specifically express in the gut, were chosen for examination to ascertain the stability of the aforementioned internal reference genes in this particular study. In summary, this study presents a relatively stable set of internal reference genes that can be employed to enhance the precision of quantifying mRNA expression levels in functional genes within the chicken GI tract.

Vegetation restoration can reduce surface albedo and retain more heat on the land surface. This feedback would partially offset the cooling effect of vegetation by absorbing CO2. Ignoring the climate feedback from changes in albedo will lead us to overestimate the contribution of increased vegetation to warming mitigation. Utilizing remote sensing data and employing a radiative forcing algorithm, we quantified the climatic feedback associated with vegetation restoration on the Chinese Loess Plateau (CLP). The surface albedo on the CLP decreased from 2001 to 2017, correlating with increased vegetation greenness, resulting in positive radiative forcing (multi-year average: 1.58 W/m2, average growth rate: 0.125 W/m2/yr). The radiative feedback of reduced albedo due to vegetation restoration is equivalent to the warming effect of emitting 3.7 kgCO2/m2. Contrary to expectations, CLP vegetation restoration efforts lacked a significant cooling effect, potentially increasing surface warming risks from albedo changes. These results emphasize the dominant role of biogeophysical feedback mechanisms induced by vegetation restoration. It will contribute to a comprehensive assessment of the climate benefits of large-scale vegetation increases in temperate regions. Decision makers can provide diverse vegetation management and restoration strategies depending on the differences in climate feedback for vegetation restoration at different locations.

ABSTRACT: The main objectives of this study were to estimate genetic parameters for milk urea nitrogen (MUN) in Holstein cattle and to conduct a single-step (ss)GWAS to identify candidate genes associated with MUN. Phenotypic measurements from 24,435 Holstein cows were collected from March 2013 to July 2019 in 9 dairy farms located in the Beijing area, China. A total of 2,029 cows were genotyped using the Illumina 150K Bovine Bead Chip, containing 121,188 SNP. A single-trait repeatability model was used to evaluate the genetic background of MUN. We found that MUN is a trait with low heritability (0.06 ± 0.004) and repeatability (0.12). Considering similar milk production levels, a lower MUN concentration indicates higher nitrogen digestibility. The genetic correlations between MUN and milk yield, net energy concentration, fat percentage, protein percentage, and lactose percentage were positive and ranged from 0.02 to 0.26. The genetic correlation between MUN and somatic cell score (SCS) was negative (−0.18), indicating that animals with higher MUN levels tend to have lower SCS. Both ssGWAS and pathway enrichment analyses were used to explore the genetic mechanisms underlying MUN. A total of 18 SNP (located on BTA11, BTA12, BTA14, BTA17, and BTA18) were found to be significantly associated with MUN. The genes CFAP77, CAMSAP1, CACNA1B, ADGRB1, FARP1, and INTU are considered to be candidate genes for MUN. These candidate genes are associated with important biological processes such as protein and lipid metabolism and binding to specific proteins. This set of candidate genes, metabolic pathways, and their functions provide a better understanding of the genomic architecture and physiological mechanisms underlying MUN in Holstein cattle.

Data-driven prediction of time series is significant in many scientific research fields such as global climate change and weather forecast. For global monthly mean temperature series, considering the strong potential of deep neural network for extracting data features, this paper proposes a data-driven model, ResGraphNet, which improves the prediction accuracy of time series by an embedded residual module in GraphSAGE layers. The experimental results of a global mean temperature dataset, HadCRUT5, show that compared with 11 traditional prediction technologies, the proposed ResGraphNet obtains the best accuracy. The error indicator predicted by the proposed ResGraphNet is smaller than that of the other 11 prediction models. Furthermore, the performance on seven temperature datasets shows the excellent generalization of the ResGraphNet. Finally, based on our proposed ResGraphNet, the predicted 2022 annual anomaly of global temperature is 0.74722 °C, which provides confidence for limiting warming to 1.5 °C above pre-industrial levels.

Background To determine the effect of 131I treatment on postoperative parathyroid function and the timing of recovery of parathyroid function (RPF) in patients with protracted hypoPT. Methods 260 patients with papillary thyroid cancer (PTC) were retrospectively analyzed, including 166 patients treated with radioactive iodine-131 (131I) classified into the 131I group and 94 patients without 131I treatment classified into the control group. Data on clinicopathological characteristics, demographics, dose and interval time of 131I treatment, number of parathyroid glands remaining in situ (PGRIS), occurrence of hypoPT, duration of RPF, preoperative and postoperative levels of Ca and PTH were collected. Results The patients in the 131I group showed a higher persistent hypoPT rate than those in the control group (p = 0). The PGRIS and total number of PG were significantly higher in patients who recovered from protracted HypoPT (p = 0.02; p = 0.03). PGRIS and 131I treatment [1 ∼ 2 VS 0, p = 0.03, OR 3.19; 3 ∼ 4 VS 0, p = 0.02, OR3.62; p = 0.02, OR 1.98, respectively] were independent factors influencing postoperative persistent hypoPT. The timing of RPF differed significantly for patients in the control group compared to those in the 131I group [p = 0.00]. Conclusions We found that 131I treatment significantly prolonged the RPF of patients with protracted hypoPT and caused late RPF (even beyond 12 months). The diagnosis of “permanent” hypoPT should be cautiously made at least 12 months after surgery, especially in patients who receive 131I treatment.

Performance assessment of low carbon cities (LCCs) attracts great interest and attention from academia, industry, and government as an effective measure to promote urban low-carbon development. However, the efforts of LCCs could be misinterpreted without consideration of the fact that cities with different endowments face different challenges and assume different responsibilities, thus it is important that this fact is considered in assessing LCCs’ performance. This study develops the previous study by the research team, “dual perspective diagnosis method for assessing LCC performance”, by introducing a correction factor to take into account the impacts of local endowments and mitigate the ‘one-size-fits-all’ phenomenon when comparing LCC assessments between cities. The empirical case study presented in the paper indicates that the adoption of a correction factor has improved the accuracy of the assessment results by demonstrating actual management efforts in developing LCC performance. It is proposed that applying the correction factor can help to achieve more accurate assessments of the status of low-carbon city practice, based on which more effective low-carbon policies can be designed and implemented towards achieving carbon peaking and carbon neutrality goals.

Agricultural environments are usually characterized by height differences and tree shading, which pose challenges for communication in smart agriculture. This study focuses on optimizing the packet loss rate and power consumption of LoRa’s practical communication quality. The research includes the investigation of the PHY anti-frame loss mechanism, encompassing PHY frame loss detection and the response mechanism between gateways and nodes. By implementing a closed loop for transmission and reception, the study enhances the communication network’s resistance to interference and security. Theoretical performance calculations for the SX1278 radio frequency chip were conducted under different parameters to determine the optimal energy efficiency, reducing unnecessary energy waste. An experimental assessment of the packet loss rate was conducted to validate the practical efficacy of the research findings. The results show that the LoRa communication with the anti-frame loss mechanism and the optimal energy ratio parameter exhibits an adequate performance. In the presence of strong and weak interferences, the reception rates are maximally improved by 37.8% and 53.4%, with effective distances of 250 m and 600 m, corresponding to enhancements of 100 m and 400 m, respectively. This research effectively reduces LoRa energy consumption, mitigates packet loss, and extends communication distances, providing insights for wireless transmission in agricultural contexts.

ABSTRACT Microbial symbionts are of great importance for macroscopic life, including fish, and both collectively comprise an integrated biological entity known as the holobiont. Yet little is known as to how the normal balance within the fish holobiont is maintained and how it responds to biotic and/or abiotic influences. Here, through amplicon profiling, the genealogical relationship between artificial F1 hybrid pufferfish with growth heterosis, produced from crossing female Takifugu obscurus with male Takifugu rubripes and its maternal halfsibling purebred, was well recapitulated by their gut microbial community similarities, indicating an evident parallelism between host phylogeny (hybridity) and microbiota relationships therein. Interestingly, modest yet significant fish growth promotion and gut microbiota alteration mediated by hybrid-purebred cohabitation were observed, in comparison with their respective monoculture cohorts that share common genetic makeups, implying a certain degree of environmental influences. Moreover, the underlying assemblage patterns of gut microbial communities were found associated with a trade-off between variable selection and dispersal limitation, which are plausibly driven by the augmented social interactions between hybrid and purebred cohabitants differing in behaviors. Results from this study not only can enrich, from a microbial perspective, the sophisticated understanding of complex and dynamic assemblage of the fish holobiont, but will also provide deeper insights into the ecophysiological factors imposed on the diversity-function relationships thereof. Our findings emphasize the intimate associations of gut microbiota in host genetics-environmental interactions and would have deeper practical implications for microbial contributions to optimize performance prediction and to improve the production of farmed fishes. IMPORTANCE Microbial symbionts are of great importance for macroscopic life, including fish, and yet little is known as to how the normal balance within the fish holobiont is maintained and how it responds to the biotic and/or abiotic influences. Through gut microbiota profiling, we show that host intrageneric hybridization and cohabitation can impose a strong disturbance upon pufferfish gut microbiota. Moreover, marked alterations in the composition and function of gut microbiota in both hybrid and purebred pufferfish cohabitants were observed, which are potentially correlated with different metabolic priorities and behaviors between host genealogy. These results can enrich, from a microbial perspective, the sophisticated understanding of the complex and dynamic assemblage of the fish holobiont and would have deeper practical implications for microbial contributions to optimize performance prediction and to improve farmed fish production.

Abstract Background Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in adults. Metabolic reprogramming in tumors is closely related to the immune microenvironment. This study aimed to explore the interactions between metabolism-associated genes (MAGs) and DLBCL prognosis and their potential associations with the immune microenvironment. Methods Gene expression and clinical data on DLBCL patients were obtained from the GEO database. Metabolism-associated molecular subtypes were identified by consensus clustering. A prognostic risk model containing 14 MAGs was established using Lasso-Cox regression in the GEO training cohort. It was then validated in the GEO internal testing cohort and TCGA external validation cohort. GO, KEGG and GSVA were used to explore the differences in enriched pathways between high- and low-risk groups. ESTIMATE, CIBERSORT, and ssGSEA analyses were used to assess the immune microenvironment. Finally, WGCNA analysis was used to identify two hub genes among the 14 model MAGs, and they were preliminarily verified in our tissue microarray (TMA) using multiple fluorescence immunohistochemistry (mIHC). Results Consensus clustering divided DLBCL patients into two metabolic subtypes with significant differences in prognosis and the immune microenvironment. Poor prognosis was associated with an immunosuppressive microenvironment. A prognostic risk model was constructed based on 14 MAGs and it was used to classify the patients into two risk groups; the high-risk group had poorer prognosis and an immunosuppressive microenvironment characterized by low immune score, low immune status, high abundance of immunosuppressive cells, and high expression of immune checkpoints. Cox regression, ROC curve analysis, and a nomogram indicated that the risk model was an independent prognostic factor and had a better prognostic value than the International Prognostic Index (IPI) score. The risk model underwent multiple validations and the verification of the two hub genes in TMA indicated consistent results with the bioinformatics analyses. Conclusions The molecular subtypes and a risk model based on MAGs proposed in our study are both promising prognostic classifications in DLBCL, which may provide novel insights for developing accurate targeted cancer therapies.

Glycine, the most basic amino acid found in nature, is considered an essential amino acid for chicks. However, the precise understanding of high concentrations of glycine’s significance in promoting the growth performance of chicks, as well as its impact on intestinal development, re-mains limited. Consequently, the objective of this study was to investigate the effects of glycine supplementation in drinking water on growth performance, intestine morphology, and development in newly hatched chicks. In this study, 200 newly born chicks were selected and pro-vided with a supplementation of 0.5%, 1%, and 2% glycine in their drinking water during their first week of life. The results revealed that glycine supplementation in drinking water could significantly increase the average daily gain of chicks from days 7 to 14. Furthermore, a significant difference was observed between the group supplemented with 1% glycine and the control group. Concurrently, this glycine supplementation increased the villus height and the ratio of the villus height to crypt depth in jejunum on both day 7 and day 14. Glycine supplementation in drinking water significantly affected the mRNA expression level of the ZO-1, GCLM, and rBAT genes in jejunum, which may have certain effects on the mucosal immune defense, cellular antioxidant stress capacity, and amino acid absorption. Overall, the findings of this study indicate that glycine supplementation in drinking water can enhance the growth performance of chicks and promote their intestine development.

Abstract Background Doxorubicin (DOX) has limited chemotherapy application for malignancies due to cardiotoxicity. The pathogenesis of DOX-induced cardiomyopathy (DiCM) is yet to be elucidated. Increasing studies proved that activation of AKT prevented cardiomyocyte apoptosis and cardiac dysfunction in response to DOX insult. Our previous studies indicated that major vault protein (MVP) deficiency was accompanied by suppressed phosphorylation of AKT in metabolic diseases. This study aimed to investigate the role and underlying mechanism of MVP on cardiomyocyte apoptosis in DiCM. Methods Mice were intraperitoneally injected with DOX 5 mg/kg, once a week for 5 weeks, the total cumulative dose was 25 mg/kg. Cardiomyocyte-specific MVP overexpression was achieved using an adeno-associated virus system under the cTnT promoter after the fourth DOX injection. Cardiac function was examined by echocardiography followed by euthanasia. Tissue and serum were collected for morphology analysis and biochemical examination. Results Herein, we found that MVP expression was upregulated in DOX-treated murine hearts. Cardiac-specific MVP overexpression alleviated DOX-induced cardiac dysfunction, oxidative stress and fibrosis. Mechanistically, MVP overexpression activated AKT signaling and decreased cardiomyocyte apoptosis in DiCM. Conclusions Based on these findings, we supposed that MVP was a potential therapeutic agent against DiCM.

Summary Environmental bacteria have a great impact on fish gut microbiota, yet little is known as to where fish acquire their gut symbionts, and how gut microbiota response to the disturbance from environmental bacteria. Through the integrative analysis by community profiling and source tracking, we show that feed‐associated bacteria can impose a strong disturbance upon the hindgut microbiota of cultured fugu. Consequently, marked alterations in the composition and function of gut microbiota in slow growth fugu were observed, implying a reduced stability upon bacterial disturbance from feed. Moreover, quantitative ecological analyses indicated that homogeneous selection and dispersal limitation largely contribute to the community stability and partial variations among hosts in the context of lower degree of disturbance. While the disturbance peaked, variable selection leads to an augmented interaction within gut microbiota, entailing community unstability and shift. Our findings emphasized the intricate linkage between feed and gut microbiota and highlighted the importance of resolving the feed source signal before the conclusion of comparative analysis of microbiota can be drawn. Our results provide a deeper insight into aquaculture of fugu and other economically important fishes and have further implications for an improved understanding of host–microbe interactions in the vertebrate gastrointestinal tract.

Abstract Background Dilated cardiomyopathy (DCM) is one of the common causes of heart failure. Myocardial injury triggers an inflammatory response and recruits immune cells into the heart. High expression of Krüppel-like factor 2 (KLF2) in endothelial cells (ECs) potentially exerts an anti-inflammatory effect. However, the role of extracellular vesicles (EVs) from KLF2-overexpressing ECs (KLF2-EVs) in DCM remains unclear. Methods and results EVs were separated from the supernatant of KLF2-overexpressing ECs by gradient centrifugation. Mice were repeatedly administered low-dose doxorubicin (DOX) and then received KLF2-EVs through an intravenous injection. Treatment with KLF2-EVs prevented doxorubicin-induced left ventricular dysfunction and reduced the recruitment of Ly6high Mo/Mø in the myocardium. We used flow cytometry to detect Ly6high monocytes in bone marrow and spleen tissues and to elucidate the mechanisms underlying this beneficial effect. KLF2-EVs increased the retention of Ly6Chigh monocytes in the bone marrow but not in the spleen tissue. KLF2-EVs also significantly downregulated C–C chemokine receptor 2 (CCR2) protein expression in cells from the bone marrow. Conclusions EVs derived from KLF2-overexpressing ECs reduced cardiac inflammation and ameliorated left ventricular dysfunction in DCM mice by targeting the CCR2 protein to inhibit Ly6Chigh monocyte mobilization from the bone marrow. Graphical Abstract

Robust Principal Component Analysis (RPCA) offers a powerful tool for recovering a low-rank matrix from highly corrupted data, with growing applications in computational biology. Biological processes commonly form intrinsic hierarchical structures, such as tree structures of cell development trajectories and tumor evolutionary history. The rapid development of single-cell sequencing (SCS) technology calls for the recovery of embedded tree structures from noisy and heterogeneous SCS data. In this study, we propose RobustTree, a unified framework to reconstruct the inherent topological structure underlying high-dimensional data with noise. By extending RPCA to handle tree structure optimization, RobustTree leverages data denoising, clustering, and tree structure reconstruction. It solves the tree optimization problem with an adaptive parameter selection scheme that we proposed. In addition to recovering real datasets, RobustTree can reconstruct continuous topological structure and discrete-state topological structure of underlying SCS data. We apply RobustTree on multiple synthetic and real datasets and demonstrate its high accuracy and robustness when analyzing high-noise SCS data with embedded complex structures. The code is available at https://github.com/ucasdp/RobustTree.

The Sulige tight gas field is presently the largest gas field in China. Owing to the ultralow permeability and strong heterogeneity of the reservoirs in Sulige, the number of production wells has exceeded 3,000, keeping the stable gas supply in the decade. Thus, the daily production prediction of gas wells is significant for monitoring production and for implementing and evaluating stimulation measures. Therefore, on the basis of the three data-driven time series approaches, the daily production of 1692 wells over 10 years was mining for the daily production prediction of wells in Sulige. The jointed deep long short-term memory and fully connected neural network (DLSTM-FNN) model was proposed by introducing the recurrent neural network's sequential expression ability and was compared with random forest (RF) and support vector regression (SVR). After the daily production predictions of thousands of wells in Sulige, the proposed DLSTM-FNN model significantly improved the time series prediction accuracy and efficiency in the short training samples and had strong availability and practicability in the Sulige tight gas field.

A lanthanum modified sludge biochar chitosan (La-SBC-CS) microsphere was successfully synthesized by dropping sludge biochar (BC) and chitosan into a lanthanum chloride solution. Batch adsorption experiments were conducted to investigate the adsorption kinetics and isotherm. Application of continuous phosphate removal was achieved via lab-scale column reactors. The phosphate adsorption equilibrium data of the La-SBC-CS fitted well with the Freundlich isotherm, with a maximum adsorption amount of 81.54 mg p/g at 25 °C. Characterization of the adsorbent using scanning electron microscopy analysis (SEM), X-ray energy spectrum analysis (EDS), X-ray diffraction analysis (XRD) and Fourier infrared analysis (FTIR) techniques suggested that the possible adsorption mechanisms were electrostatic interaction, ligand exchange and complexation. The La-SBC-CS kept 76.37% phosphate removal efficiency after eight recycles. The results of continuous column reactor experiment demonstrated that the breakthrough time increased with an increase in adsorbent filling height, while it decreased with an increase in initial phosphate concentration or flow velocity. The Yoon model was applied to the continuous experimental data to predict breakthrough curves and determined the characteristic adsorption parameters for process design. This study indicated the potential for the practical application of La-SBC-CS in phosphate removal from wastewater. HIGHLIGHTS Adsorbent is prepared by loading lanthanum onto biochar, blending with chitosan.; The maximum adsorption capacity for La-SBC-CS was 81.54 mg/g.; The La-SBC-CS kept 76.37% phosphate removal efficiency after eight recycles.; La-SBC-CS has a good research prospect for the wastewater phosphorus removal.;