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Abstract The N6-methyladenosine (m6A) modification serves as an essential epigenetic regulator in eukaryotic cells, playing a significant role in tumorigenesis and cancer progression. However, the detailed biological functions and underlying mechanisms of m6A regulation in gastric cancer (GC) are poorly understood. Our research revealed that the m6A demethylase ALKBH5 was markedly downregulated in GC tissues, which was associated with poor patient prognosis. Functional studies demonstrated that suppressing ALKBH5 expression enhanced GC cell proliferation, migration, and invasion. Mechanistically, ALKBH5 removed m6A modifications from the 5’ uncapped and polyadenylated transcripts (UPTs) of WRAP53. This demethylation decreased WRAP53 stability and translation efficiency. The lower level of WRAP53 disrupts the interaction between USP6 and RALBP1 protein, promoting RALBP1 degradation and thereby suppressing the PI3K/Akt/mTOR signaling cascade, ultimately attenuating the progression of GC. These findings highlight the pivotal role of ALKBH5-mediated m6A demethylation in inhibiting GC progression and the potential role of ALKBH5 as a promising biomarker and therapeutic target for GC intervention.

Abstract Background As the inflorescence of wheat, spike architecture largely determines grain productivity. Dissecting the genetic basis for the spike morphology of wheat can contribute to the designation of ideal spike morphology to improve grain production. Results The present study characterizes a dense spike1 (ds1) mutant, derived from Nongda3753, induced by EMS treatment, which exhibits a dense spike and reduced plant height. Through bulked segregant analysis sequencing (BSA-Seq) of two segregating populations, ds1 was mapped to the short arm of chromosome 7B. Further genotypic and phenotypic analyses of the residual heterozygous lines from F3 to F6 of Yong3002×ds1 revealed that there was a 0-135 Mb deletion in chromosome 7B associated with the dense spike phenotype. The reads count analysis of the two bulks in BSA-Seq, along with the cytological analysis of ds1, ND3753, NIL-ds1 and NIL-Y3002, confirmed that the partial unidirectional translocation of 5AL (543–713 Mb) to 7BS (0-135 Mb) exists in ds1. This translocation led to an increase in both copy number and expression of the Q gene, which is one of the reasons for the dense spike phenotype observed in ds1. Conclusion Partial unidirectional translocation from 5AL to 7BS was identified in the EMS-induced mutant ds1, which exhibits dense spike phenotype. This research illustrates the effect of one chromosome structure variation on wheat spike morphology, and provides new materials with several chromosome structure variations for future wheat breeding.

AimProgrammed cell death (PCD) critically influences the tumor microenvironment (TME) and is intricately linked to tumor progression and patient prognosis. This study aimed to develop a novel prognostic indicator and marker of drug sensitivity in patients with gastric cancer (GC) based on PCD.MethodsWe analyzed genes associated with 14 distinct PCD patterns using bulk transcriptome data and clinical information from TCGA-STAD for model construction with univariate Cox regression and LASSO regression analyses. Microarray data from GSE62254, GSE15459, and GSE26901 were used for validation. Single-cell transcriptome data from GSE183904 were analyzed to explore the relationship between TME and the newly constructed model, named PCD index (PCDI). Drug sensitivity comparisons were made between patients with high and low PCDI scores.ResultsWe developed a novel twelve-gene signature called PCDI. Upon validation, GC patients with higher PCDI scores had poorer prognoses. A high-performance nomogram integrating the PCDI with clinical features was also established. Additionally, single-cell transcriptome data analysis suggested that PCDI might be linked to critical components of the TME. Patients with high PCDI scores exhibited resistance to standard adjuvant chemotherapy and immunotherapy but might benefit from targeted treatments with NU7441, Dasatinib, and JQ1.ConclusionThe novel PCDI model shows significant potential in predicting clinical prognosis and drug sensitivity of GC, thereby facilitating personalized treatment strategies for patients with GC.

Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions induced by inflammatory responses, in which cell-free DNA (cfDNA) plays a pivotal role. This study investigated the therapeutic potential of biodegradable cationic nanoparticles (cNPs) in alleviating ALI. Using a mouse model of lipopolysaccharide-induced ALI, we examined the impact of intravenously administered cNPs. Our findings indicate that cNPs possess robust DNA binding capability, enhanced accumulation in inflamed lungs, and a favorable safety profile in vivo. Furthermore, cNPs attenuate the inflammatory response in LPS-induced ALI mice by scavenging cfDNA, mainly derived from neutrophil extracellular traps, and activating the macrophage-mediated cGAS-STING pathway. The findings suggest a potential treatment for ALI by targeting cfDNA with cNPs. This approach has demonstrated efficacy in mitigating lung injury and merits further exploration.

Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are key components in immune checkpoint studies across various tumors, including those in the urinary tract. The utilization of PD-1/PD-L1 inhibitors in urinary tract tumors is on the rise. This study provides a comprehensive overview of PD-1/PD-L1 research in urinary tract tumors through bibliometric analysis. A search was conducted in the Web of Science Core Collection (WoSCC) database for academic papers on PD-1/PD-L1 in urinary tract tumors published between January 1, 1999, and September 3, 2022. Tools such as VOSviewer, CiteSpace, and an online bibliometric platform, were used for an in-depth analysis covering countries, institutions, authors, journals, references, and keywords. A total of 1,711 articles on PD-1/PD-L1 in urinary tract tumors were analyzed. The United States led in article contributions, followed by China and Japan. Harvard University was the top institution in this research area. With notable conctributions from Choueiri TK, who authored 48 related articles. The Journal for Immunotherapy of Cancer was the top publisher, and Topalian SL’s 2012 publication in The New England Journal of Medicine was the most cited article. Key author keywords included “immunotherapy,” “PD-L1,” “renal cell carcinoma,” “bladder cancer,” and “immune checkpoint inhibitors.” Notably, research on the role of PD-1/PD-L1 in kidney and bladder cancer has garnered significant attention.

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes, its therapeutic potential is compromised by its short half-life and narrow therapeutic index. Current long-acting insulin analogs, such as insulin-polymer conjugates, are mainly used to improve pharmacokinetics by reducing renal clearance. However, these conjugates are synthesized without sacrificing the bioactivity of insulin, thus retaining the narrow therapeutic index of native insulin, and exceeding the efficacious dose still leads to hypoglycemia. Here, we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated clearance. By impairing the binding affinity to the receptor and the activation of the receptor, di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly, increases its maximum tolerated dose 10-fold. The target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high dose. This work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events.

Abstract Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.

Summary: Prostate cancer (PCa) is one of the most prevalent urogenital malignancies. Bone metastasis from PCa reduces patient survival rates significantly. There currently exists no effective treatment for bone metastatic PCa, and the underlying mechanisms remain unclear. This study performed transcriptomic screening on PCa bone metastasis specimens and intersection analysis in public databases and identified SERPINH1 as a potential target for treatment. SERPINH1 was found to be upregulated in PCa bone metastases and with poor prognosis, high Gleason score, and advanced metastatic status. SERPINH1 induced PCa cells’ bone metastasis in vivo, promoted their proliferation, and mitigated apoptosis. Mechanistically, SERPINH1 bound to P62, reducing TRIM21-mediated K63-linked ubiquitination degradation of P62 and promoting proliferation and resistance to apoptosis of PCa. This study suggests the regulation of ubiquitination degradation of P62 by SERPINH1 that promotes PCa bone metastasis and can be considered as a potential target for treatment of bone metastatic PCa.

Abstract Ulcerative colitis (UC) is a complicated and recurrent intestinal disease. Currently available drugs for UC treatment are scarce, therefore, novel therapeutic drugs for the UC are urgently to be developed. Gingerenone A (GA) is a phenolic compound known for its anti‐inflammatory effect, but its effect on UC remains unknown. Here, it is shown that GA protects mice against UC, which is closely associated with inhibiting intestinal mucosal inflammation and enhancing intestinal barrier integrity in vivo and in vitro. Of note, RNA sequencing analysis demonstrates an evident correlation with IL‐17 signaling pathway after GA treatment, and this effect is further corroborated by Western blot. Mechanistically, GA directly interacts with IL‐17RA protein through pull‐down, surface plasmon resonance analysis and molecular dynamics simulation. Importantly, lentivirus‐mediated IL‐17RA/Act1 knock‐down or GA co‐treatment with brodalumab/ixekizumab significantly impairs the protective effects of GA against DSS‐induced inflammation and barrier dysfunction, suggesting a critical role of IL‐17RA signaling for GA‐mediated protection against UC. Overall, these results indicate that GA is an effective agent against UC mainly through the direct binding of IL‐17RA to inhibit inflammatory signaling activation.

Abstract Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI). The kidney is susceptible to IRI under several clinical conditions, including hypotension, sepsis, and surgical procedures, such as partial nephrectomy and kidney transplantation. Extensive research has been conducted on the mechanism and intervention strategies of renal IRI in past decades; however, the complex pathophysiology of IRI-induced AKI (IRI-AKI) is not fully understood, and there remains a lack of effective treatments for AKI. Renal IRI involves several processes, including reactive oxygen species (ROS) production, inflammation, and apoptosis. Mitochondria, the centers of energy metabolism, are increasingly recognized as substantial contributors to the early phases of IRI. Multiple mitochondrial lesions have been observed in the renal tubular epithelial cells (TECs) of IRI-AKI mice, and damaged or dysfunctional mitochondria are toxic to the cells because they produce ROS and release cell death factors, resulting in TEC apoptosis. In this review, we summarize the recent advances in the mitochondrial pathology in ischemic AKI and highlight promising therapeutic approaches targeting mitochondrial dysfunction to prevent or treat human ischemic AKI.

Abstract Transcription factor EB (TFEB), known as a major transcriptional regulator of the autophagy-lysosomal pathway, regulates target gene expression by binding to coordinated lysosomal expression and regulation (CLEAR) elements. TFEB are regulated by multiple links, such as transcriptional regulation, post-transcriptional regulation, translational-level regulation, post-translational modification (PTM), and nuclear competitive regulation. Targeted regulation of TFEB has been victoriously used as a treatment strategy in several disease models such as ischemic injury, lysosomal storage disorders (LSDs), cancer, metabolic disorders, neurodegenerative diseases, and inflammation. In this review, we aimed to elucidate the regulatory mechanism of TFEB and its applications in several disease models by targeting the regulation of TFEB as a treatment strategy.

The existing strawberry ripeness detection algorithm has the problems of a low precision and a high missing rate in real complex scenes. Therefore, we propose a novel model based on a hybrid attention mechanism. Firstly, a partial convolution-based compact inverted block is developed, which significantly enhances the feature extraction capability of the model. Secondly, an efficient partial hybrid attention mechanism is established, which realizes the remote dependence and accurate localization of strawberry fruit. Meanwhile, a multi-scale progressive feature pyramid network is constructed, and the fine-grained features of strawberry targets of different sizes are accurately extracted. Finally, a Focaler-shape-IoU loss function is proposed to effectively solve the problem of the difficulty imbalance between strawberry samples and the influence of the shape and size of the bounding box on the regression. The experimental results show that the model’s precision and mAP0.5 reach 92.1% and 92.7%, respectively, which are 2.0% and 1.7% higher than the baseline model. Additionally, our model is better in detection performance than most models with fewer parameters and lower FLOPs. In summary, the model can accurately identify the maturity of strawberry fruit under complex farmland environments and provide certain technical guidance for automated strawberry-picking robots.

Abstract Objective To compare the computed tomography (CT) images of patients with locally advanced gastric cancer (GC) before and after neoadjuvant chemotherapy (NAC) in order to identify CT features that could predict pathological response to NAC. Methods We included patients with locally advanced GC who underwent gastrectomy after NAC from September 2016 to September 2021. We retrieved and collected the patients’ clinicopathological characteristics and CT images before and after NAC. We analyzed CT features that could differentiate responders from non-responders and established a logistic regression equation based on these features. Results We included 97 patients (69 [71.1%] men; median [range] age, 60 [26–75] years) in this study, including 66 (68.0%) responders and 31 (32.0%) non-responders. No clinicopathological variable prior to treatment was significantly associated with pathological response. Out of 16 features, three features (ratio of tumor thickness reduction, ratio of reduction of primary tumor attenuation in arterial phase, and ratio of reduction of largest lymph node attenuation in venous phase) on logistic regression analysis were used to establish a regression equation that demonstrated good discrimination performance in predicting pathological response (area under receiver operating characteristic curve 0.955; 95% CI, 0.911–0.998). Conclusion Logistic regression equation based on three CT features can help predict the pathological response of patients with locally advanced GC to NAC.

Gastric/gastroesophageal junction (G/GEJ) cancer represents a significant global health challenge. Radical surgery remains the cornerstone of treatment for resectable G/GEJ cancer. Supported by robust evidence from multiple clinical studies, therapeutic approaches, including adjuvant chemotherapy or chemoradiation, and perioperative chemotherapy, are generally recommended to reduce the risk of recurrence and enhance long-term survival outcomes post-surgery. In recent years, immune checkpoint inhibitors (ICIs) have altered the landscape of systemic treatment for advanced or metastatic G/GEJ cancer, becoming the standard first-line therapy for specific patients. Consequently, exploring the efficacy of ICIs in the adjuvant or neoadjuvant setting for resectable G/GEJ cancer is worthwhile. This review summarizes the current advances in the application of ICIs for resectable G/GEJ cancer.

Spelt (Triticum aestivum ssp. spelta) is an important wheat subspecies mainly cultivated in Europe before the 20th century that has contributed to modern wheat breeding as a valuable genetic resource. However, relatively little is known about the origins and maintenance of spelt populations. Here, using resequencing data from 416 worldwide wheat accessions, including representative spelt wheat, we demonstrate that European spelt emerged when primitive hexaploid wheat spread to the west and hybridized with pre-settled domesticated emmer, the putative maternal donor. Genomic introgression regions from domesticated emmer confer spelt’s primitive morphological characters used for species taxonomy, such as tenacious glumes and later flowering. We propose a haplotype-based “spelt index” to identify spelt-type wheat varieties and to quantify utilization of the spelt gene pool in modern wheat cultivars. This study reveals the genetic basis for the establishment of the spelt wheat subspecies in a specific ecological niche and the vital role of the spelt gene pool as a unique germplasm resource in modern wheat breeding.

Abstract TFE3 is a member of the MiT family of the bHLH-leucine zipper transcription factor. We previously focused on the role of TFE3 in autophagy and cancer. Recently, an increasing number of studies have revealed that TFE3 plays an important role in metabolic regulation. TFE3 participates in the metabolism of energy in the body by regulating pathways such as glucose and lipid metabolism, mitochondrial metabolism, and autophagy. This review summarizes and discusses the specific regulatory mechanisms of TFE3 in metabolism. We determined both the direct regulation of TFE3 on metabolically active cells, such as hepatocytes and skeletal muscle cells, and the indirect regulation of TFE3 through mitochondrial quality control and the autophagy–lysosome pathway. The role of TFE3 in tumor cell metabolism is also summarized in this review. Understanding the diverse roles of TFE3 in metabolic processes can provide new avenues for the treatment of some metabolism-related disorders.

Abstract Decoding human action intention prior to motion onset with surface electromyograms (sEMG) is an emerging neuroengineering topic with interesting clinical applications such as intelligent control of powered prosthesis/exoskeleton devices. Despite extensive prior works in the related fields, it remains a technical challenge due to considerable variability of complex multi-muscle activation patterns in terms of volatile spatio-temporal characteristics. To address this issue, we first hypothesize that the inherent variability of the idle state immediately preceding the motion initiation needs to be addressed explicitly. We therefore design a hierarchical dynamic Bayesian learning network model that integrates an array of Gaussian mixture model – hidden Markov models (GMM-HMMs), where each GMM-HMM learns the multi-sEMG processes either during the idle state, or during the motion initiation phase of a particular motion task. To test the hypothesis and evaluate the new learning network, we design and build a upper-limb sEMG-joystick motion study system, and collect data from 11 healthy volunteers. The data collection protocol adapted from the psychomotor vigilance task includes repeated and randomized binary hand motion tasks (push or pull) starting from either of two designated idle states: relaxed (with minimal muscle tones), or prepared (with muscle tones). We run a series of cross-validation tests to examine the performance of the method in comparison with the conventional techniques. The results suggest that the idle state recognition favors the dynamic Bayesian model over a static classification model. The results also show a statistically significant improvement in motion prediction accuracy by the proposed method (93.83±6.41%) in comparison with the conventional GMM-HMM method (89.71±8.98%) that does not explicitly account for the idle state. Moreover, we examine the progress of prediction accuracy over the course of motion initiation and identify the important hidden states that warrant future research.

Abstract Background N4-acetylcytidine (ac4C), a widespread modification in human mRNAs that is catalyzed by the N-acetyltransferase 10 (NAT10) enzyme, plays an important role in promoting mRNA stability and translation. However, the biological functions and regulatory mechanisms of NAT10-mediated ac4C were poorly defined. Methods ac4C mRNA modification status and NAT10 expression levels were analyzed in gastric cancer (GC) samples and compared with the corresponding normal tissues. The biological role of NAT10-mediated ac4C and its upstream and downstream regulatory mechanisms were determined in vitro and in vivo. The therapeutic potential of targeting NAT10 in GC was further explored. Results Here, we demonstrated that both ac4C mRNA modification and its acetyltransferase NAT10 were increased in GC, and increased NAT10 expression was associated with disease progression and poor patient prognosis. Functionally, we found that NAT10 promoted cellular G2/M phase progression, proliferation and tumorigenicity of GC in an ac4C-depedent manner. Mechanistic analyses demonstrated that NAT10 mediated ac4C acetylation of MDM2 transcript and subsequently stabilized MDM2 mRNA, leading to its upregulation and p53 downregulation and thereby facilitating gastric carcinogenesis. In addition, Helicobacter pylori (Hp) infection contributed to NAT10 induction, causing MDM2 overexpression and subsequent p53 degradation. Further investigations revealed that targeting NAT10 with Remodelin showed anti-cancer activity in GC and augmented the anti-tumor activity of MDM2 inhibitors in p53 wild-type GC. Conclusions These results suggest the critical role of NAT10-mediated ac4C modification in GC oncogenesis and reveal a previously unrecognized signaling cascade involving the Hp-NAT10-MDM2-p53 axis during GC development.

Abstract Background The prognosis of patients with gastric cancer (GC) with gastric outlet obstruction (GOO) after gastrectomy is highly variable. In this study, we aimed to develop a nomogram to predict the prognosis of these patients. Patients and Methods Data from 218 GC patients with GOO who underwent gastrectomy at Sun Yat-sen University Cancer Center were retrospectively collected as a training cohort. The data of 59 patients with the same diagnosis who underwent gastrectomy at the First Affiliated Hospital of Guangxi Medical University were collected as an external verification cohort. A nomogram for the overall survival (OS) was developed using the Cox regression model in the training cohort, which was validated in a verification cohort. Results Multivariate analysis showed that the surgical procedure (P

Abstract Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy‐M‐Exo) is developed via fusing tumor‐derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T‐cell response. Moreover, the nanovaccine Hy‐M‐Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy‐M‐Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy.

A central paradigm in nanomedicine is that when synthetic nanoparticles (NPs) enter the body, they are immediately cloaked by a corona of macromolecules (mostly proteins) that mediates the role of the physico-chemical properties in the NP biological functions (the “coronation paradigm”). In this work, we focused on the assessment of the “coronation paradigm” for cationic NPs (cNPs) used as rheumatoid arthritis (RA) drugs due to their ability to scavenge cell-free DNA (cfDNA). We fabricated series of cNPs uniformly coated with single or di-hydroxyl groups and different types of amino groups and showed that hydroxylated nanoparticles displayed a prolonged retention in inflamed joints and greater anti-inflammatory effect in collagen-induced arthritis (CIA) rats than the non-hydroxylated analogues. Especially, the cNPs with secondary amines and a di-hydroxyl shell showed the best performance among the tested cNPs. Proteomic analysis showed that the cNPs with a di-hydroxyl shell adsorbed less opsonin proteins than the cNPs carrying mono hydroxyl groups and non-hydroxylated ones, which may provide a mechanistic explanation for the different biodistribution profiles of cNPs. Thus, this study suggests that the protein corona mediates the effects of the surface chemistry on the fate and functions of cNPs as anti-RA drugs.

Scar contraction frequently happens in patients with deep burn injuries. Hitherto, porcine dermal extracellular matrix (dECM) has supplied microenvironments that assist in wound healing but fail to inhibit scar contraction. To overcome this drawback, we integrate dECM into three-dimensional (3D)-printed dermal analogues (PDA) to prevent scar contraction. We have developed thermally gelled, non-rheologically modified dECM powder (dECMp) inks and successfully transformed them into PDA that was endowed with a micron-scale spatial structure. The optimal crosslinked PDA exhibited desired structure, good mechanical properties as well as excellent biocompatibility. Moreover, in vivo experiments demonstrated that PDA could significantly reduced scar contraction and improved cosmetic upshots of split thickness skin grafts (STSG) than the commercially available dermal templates and STSG along. The PDA has also induced an early, intense neovascularization, and evoked a type-2-like immune response. PDA's superior beneficial effects may attribute to their desired porous structure, the well-balanced physicochemical properties, and the preserved dermis-specific ECM cues, which collectively modulated the expression of genes such as Wnt11, ATF3, and IL1β, and influenced the crucial endogenous signalling pathways. The findings of this study suggest that PDA is a clinical translatable material that possess high potential in reducing scar contraction.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Rapid nondestructive testing of peanut seed vigor is of great significance in current research. Before seeds are sown, effective screening of high-quality seeds for planting is crucial to improve the quality of crop yield, and seed vitality is one of the important indicators to evaluate seed quality, which can represent the potential ability of seeds to germinate quickly and whole and grow into normal seedlings or plants. Meanwhile, the advantage of nondestructive testing technology is that the seeds themselves will not be damaged. In this study, hyperspectral technology and superoxide dismutase activity were used to detect peanut seed vigor. To investigate peanut seed vigor and predict superoxide dismutase activity, spectral characteristics of peanut seeds in the wavelength range of 400-1000 nm were analyzed. The spectral data are processed by a variety of hot spot algorithms. Spectral data were preprocessed with Savitzky-Golay (SG), multivariate scatter correction (MSC), and median filtering (MF), which can effectively to reduce the effects of baseline drift and tilt. CatBoost and Gradient Boosted Decision Tree were used for feature band extraction, the top five weights of the characteristic bands of peanut seed vigor classification are 425.48nm, 930.8nm, 965.32nm, 984.0nm, and 994.7nm. XGBoost, LightGBM, Support Vector Machine and Random Forest were used for modeling of seed vitality classification. XGBoost and partial least squares regression were used to establish superoxide dismutase activity value regression model. The results indicated that MF-CatBoost-LightGBM was the best model for peanut seed vigor classification, and the accuracy result was 90.83%. MSC-CatBoost-PLSR was the optimal regression model of superoxide dismutase activity value. The results show that the R2 was 0.9787 and the RMSE value was 0.0566. The results suggested that hyperspectral technology could correlate the external manifestation of effective peanut seed vigor.

Anomaly detection tasks involving time-series signal processing have been important research topics for decades. In many real-world anomaly detection applications, no specific distributions fit the data, and the characteristics of anomalies are different. Under these circumstances, the detection algorithm requires excellent learning ability of the data features. Transformers, which apply the self-attention mechanism, have shown outstanding performances in modelling long-range dependencies. Although Transformer based models have good prediction performance, they may be influenced by noise and ignore some unusual details, which are significant for anomaly detection. In this paper, a novel temporal context fusion framework: Temporal Context Fusion Transformer (TCF-Trans), is proposed for anomaly detection tasks with applications to time series. The original feature transmitting structure in the decoder of Informer is replaced with the proposed feature fusion decoder to fully utilise the features extracted from shallow and deep decoder layers. This strategy prevents the decoder from missing unusual anomaly details while maintaining robustness from noises inside the data. Besides, we propose the temporal context fusion module to adaptively fuse the generated auxiliary predictions. Extensive experiments on public and collected transportation datasets validate that the proposed framework is effective for anomaly detection in time series. Additionally, the ablation study and a series of parameter sensitivity experiments show that the proposed method maintains high performance under various experimental settings.

ABSTRACT: Objectives: To determine tuberculosis (TB) recurrence in previously successfully treated patients in a routine program setting and baseline characteristics associated with TB recurrence. Methods: A prospective longitudinal study in Jiangxi Province, China. Patients, ≥14 years old, were consecutively registered and were followed up for seven years to assess TB recurrence against a patients’ individual baseline data that had been entered into a database at TB registration. Results: There were 800 TB patients registered at baseline, and 634 (79.2%) of them completed anti-TB treatments. Fifty-nine (9.3%) died, and 21 (3.3%) were lost to follow-up over the follow-up period. There were 96 patients with recurrent episodes (total incidence 15.2% or annual incidence 2,200/100,000). Of the recurrent cases, 53 (55.2%) happened within 2-year after completion of anti-TB treatments. After controlling confounding factors, the risk of TB recurrence was significantly higher in the age range 34-73 years (P

BackgroundProstate cancer (PCa) is the second most diagnosed cancer in men. Most PCa-related deaths result from metastatic disease. Metastases occur most often in the bones (90%). However, the current treatments for bone metastases in PCa are not very effective. Here we present an overview of the current research situation of bone metastases in PCa, focusing on hotspots and trends.MethodsWe searched the Web of Science Core Collection database for publications related to bone metastases in PCa published between 1999 and 2021. We used VOSviewer, CiteSpace, and a bibliometric online platform to perform a bibliometric analysis of countries, institutions, authors, journals, references, and keywords.ResultsA total of 4,832 related articles were included in the present study. The USA published the most articles in the field, followed by China and England. The University of Texas MD Anderson Cancer Center is the leading institution in the research field of bone metastases in PCa. Saad F, from Canada, has made great achievements in this area by publishing 91 related articles. Prostate is the journal which published most related articles, and Mundy GR, 2002, Nat Rev Cancer, is the most cited article in this field. Furthermore, the analysis of author keywords can be divided into five clusters: (1) diagnosis of PCa, (2) mechanism of bone metastasis, (3) drug treatments of bone metastases, (4) radiotherapy of bone metastases, and (5) treatments and prognosis of PCa.ConclusionsmCRPC has been the hottest topic in PCa in recent years. CT is the most common diagnostic method for bone metastases. Enzalutamide and radium-223, as important treatments for bone metastases in PCa, bring about widespread attention. Furthermore, the researchers focus on the tumor microenvironment and biomarkers to explore the mechanism and the therapeutic targets of bone metastases in PCa.

BackgroundAlthough TP53 and SPOP are frequently mutated in metastatic prostate cancer (PCa), their prognostic value is ambiguous, and large sample studies are lacking, especially when they co-occur with other genetic alterations.MethodsGenomic data and patients’ clinical characteristics in PCa were downloaded from the cBioPortal database. We extensively analyzed other gene alterations in different mutation status of TP53 and SPOP. We further subdivided TP53 and SPOP mutation into subgroups based on different mutation status, and then evaluated the prognostic value. Two classification systems for TP53 survival analysis were used.ResultsA total of 2,172 patients with PCa were analyzed in our study, of which 1,799 were metastatic PCa patients. The mutual exclusivity analysis showed that TP53 and SPOP mutation has a strong mutual exclusion (p

Abstract Background The relationship between gastric bare area adipose tissues invasion (GBAI) confirmed pathologically and the prognosis of gastric cancer (GC) patients is undefined. Till present, there has not been literature investigating this phenomenon. Here, we aimed at analyzing the implication of GBAI in GC. Methods The data of 1822 patients who underwent radical surgery between January 2000 and December 2013 at the Sun Yat-sen University Cancer Center were retrieved. Pathologically, tumor deposits (TDs) located > 5 mm from the leading edge of the primary tumor and the lymph nodes (LNs) station number 1, 2, 7, and 9 were considered GBAI. Kaplan-Meier method, log-rank test, and Cox’s proportional hazards model were employed to analyze. Results Two hundred and five (11.3%) patients were pathologically diagnosed with GBAI, which was more commonly found in proximal or linitis lastica than distal GC (P < 0.001). There was significant difference in 5-year survival between patients with and without GBAI for stages IIB, IIIA, IIIB, and IIIC, respectively (P < 0.009 for IIB, IIIA, and IIIB; P = 0.021 for IIIC). Among the 205 GBAI patients, 61 had detailed radiological follow-up data in which 26 (34.7%) were found to have retroperitoneal infiltration, 27 (36.0%) had peritoneal metastasis, 10 (13.3%) had hematogenous metastasis, 16 (21.3%) had lymphatic metastasis, and 16 (21.3%) had others. Conclusions GBAI was identified as a predictor of unfavorable prognosis for GC and was more commonly found in the proximal or linitis plastica of the stomach than in distal stomach. Retroperitoneal infiltration was one of the most commonly identified metastatic route for GC associated with GBAI after radical surgery.

On the basis of the principles of simultaneous equilibrium, conservation of mass, and aqueous electronic charge neutrality and the correspondence principle of ion entropy, the high-temperature thermodynamics of the ZnO–NH4Cl–H2O system was studied to predict solubility and construct Zn species distribution. The model was constructed precisely by using the MATLAB program. The total Zn2+ concentration in the solution was affected significantly by temperature and total ammonium concentration. ZnNH3Cl3− was the predominant species in the ZnO–NH4Cl–H2O system. The solubility of zinc diammine chloride in NH4Cl solution (>2 mol·L−1) in the temperature range of 303–353 K was determined using equilibrium experiments, which had results that agreed well with the theoretical value. The data and high-temperature thermodynamic model used in this paper are reliable.

Mechanism of high altitude adaptation of wheat remains unknown. Here, the authors assemble the draft genome of a Tibetan semi-wild wheat accession and resequence 245 wheat accessions to reveal that Tibetan semi-wild wheat has been de-domesticated from local landraces to adapt to high altitude.

The shading board has a negative influence on window ventilation while it is blocking direct sunlight. Circle vents are designed in the shading board to decrease the negative ventilation effect because air can flow through vents to compensate for the obstruction effect of shading board in this study. The thickness and the diameter of vents are calculated precisely and the optimum size is obtained. Mathematical analysis and ANSYS simulation analysis of the micro ventilation in vents are performed at the same time. From the comparison and validation of this analysis, the relationship beyond air velocity, shading board thickness and vent diameter is concluded to supply reliable basis and good reference for shading design and window ventilation analysis in the building.

Background Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI.Methods We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography.Results Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p

Summary: Despite the success for targeted delivery in the body, the efficient release without side effects caused by residual drug remains a challenge. For reducing residual drug, the pH-responsive carriers were prepared by self-assembly from aromatic macrocycles, which were non-toxic and biocompatible. The inner surroundings of aromatic macrocycles could be protonated positively by acid inducing the separation of neighboring macrocycles. Thus, Dox-loaded carriers successfully inhibited the proliferation of carcinoma cells (HepG2 and 4T1) rather than normal cells (HL7702). The effects were further proved in vivo without systemic cytotoxicity. Notably, the responsive environment for drug release depended on the concentration of carriers. Particularly, drug release was promoted by carrier separation. Carrier 2 exhibited preferable anticancer efficacy than carrier 1 due to the efficient release of Dox by full separation of the carrier. Collectively, we have developed a novel strategy serving as a selective and controlled drug release platform for cancer therapeutics. : Drug Delivery System; Supramolecular Materials; Biomaterials Subject Areas: Drug Delivery System, Supramolecular Materials, Biomaterials

Gastric cancer is a malignant tumor with high morbidity and mortality worldwide. However, increasing evidences have revealed the correlation between the glycolysis process and tumorigenesis. This study is aim to develop a list of glycolysis-related genes for risk stratification in gastric cancer patients. We included 500 patients’ sample data from GSE62254 and GSE26942 datasets, and classified patients into training (n = 350) and testing sets (n = 150) at a ratio of 7: 3. Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value. Based on HALLMARK gene sets, we identified 9 glycolysis-related genes (BPNT1, DCN, FUT8, GMPPA, GPC3, LDHC, ME2, PLOD2, and UGP2). On the basis of risk score developed by the 9 genes, patients were classified into high- and low-risk groups. The survival analysis showed that the high-risk patients had a worse prognosis ( p < 0.001). Similar finding was observed in the testing cohort and 2 independent cohorts (GSE13861 and TCGA-STAD, all p < 0.001). The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for overall survival ( p < 0.001). Furthermore, we constructed a nomogram that integrated the risk score and tumor stage, age, and adjuvant chemotherapy. Through comparing the results of the receiver operating characteristic curves and decision curve analysis, we found that the nomogram had a superior predictive accuracy than conventional TNM staging system, suggesting that the risk score combined with other clinical factors (age, tumor stage, and adjuvant chemotherapy) can develop a robust prediction for survival and improve the individualized clinical decision making of the patient. In conclusion, we identified 9 glycolysis-related genes from hallmark glycolysis pathway. Based on the 9 genes, gastric cancer patients were separated into different risk groups related to survival.

Highly efficient and versatile natural motors play a pivotal role in biological processes. Inspired by these biological motors, researchers developed their synthetic counterparts that can convert various energies into locomotion. With the potential to revolutionize the biomedical treatment process, these micro/nanomotors have been attracting a booming research enthusiasm since the birth of the first micro/nanomotor 15 years ago (since 2004). First, typical motion mechanisms are elucidated and a detailed comparison is provided regarding their efficiency in a biological context. Next, cutting‐edge proof‐of‐concept biomedical applications of the motors are overviewed, including on‐demand drug dispensing, cell transporting, and precise microsurgery. Current achievements and remaining bottlenecks are discussed, to spur more collaboration among chemistry, nanoengineering, and the biomedical fields. With increasing attention and continuing innovation of the field, clinical translation of micro/nanomotors is possible in the next 15 years.

Influence maximization is the problem of finding a certain amount of seed nodes that can trigger the largest expected number of remaining nodes under a pre-defined influence propagation model. However, most studies in this field apply online social network analysis methods mechanically and take commodity marketing in a broad sense as the research background, whose models are relatively simple, lacking characterization of specific business situation. Membership is a kind of classical marketing method. By selling membership, the company provides differentiated services to members and ordinary users, stimulating the former to consume. In this paper, we focus on the membership business model and study the membership-based influence maximization problem. First, due to the models used by predecessors failing in meeting the particularity of the membership, a novel influence propagation model membership-based influence cascade (MBIC) is proposed. According to the characteristics of membership, the MBIC model divides the influence propagation process into two stages, the influence stage and the reference stage. At the same time, the concepts of activity and intimacy are introduced to better model real social networks. Then, we propose the influence-reference rank (MBIC) algorithm that quantifies the ability of nodes at each stage in the MBIC to solve the membership-based influence maximization problem. Finally, experiments using real-world dynamic social networks with up to 1.4 million edges are conducted. The experimental results show that the influence-reference rank (IRR) achieves a better performance than several alternative algorithms under acceptable complexity conditions under MBIC model.

Elevated cell-free DNA (cfDNA) levels in the plasma and synovial fluid of rheumatoid arthritis (RA) patients are proposed to be pathologically relevant. However, direct evidence to support this perception is lacking, and molecular feature of the cfDNA molecules with assumed pathological function is not well characterized. Here, we confirm remarkably increased levels of total synovial fluid and plasma cfDNAs in a large cohort of patients with rheumatoid arthritis compared to the counterparts in osteoarthritis, and demonstrate the potent inflammatogenic effects of RA synovial fluid cfDNA on both human monocyte cell line and primary cells related to RA. Massively parallel sequencing identifies distinct molecular pattern of cfDNA in RA, as characterized by enriching CpG-motif containing sequences. Importantly, these identified CpG-motif-rich sequences are hypomethylated in RA patients and induce severe inflammatory responses both in vitro and in vivo. Our data demonstrate the pathological role of global and specific cfDNA molecules in RA, thereby identifying novel therapeutic target candidate and potential biomarker for RA.

Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here the authors use ~40 nm cationic nanoparticles to scavenge cfDNA, and demonstrate the potential for nanomedicine to relieve debilitating RA symptoms.

Abstract Background The images of different flower species had small inter-class variations across different classes as well as large intra-class variations within a class. Flower classification techniques are mainly based on the features of color, shape and texture, however, the procedure always involves too many heuristics as well as manual labor to tweak parameters, which often leads to datasets with poor qualitative and quantitative measures. The current study proposed a deep architecture of convolutional neural network (CNN) for the purposes of improving the accuracy of identifying the white flowers of Fragaria × ananassa from other three wild flower species of Androsace umbellata (Lour.) Merr., Bidens pilosa L. and Trifolium repens L. in fields. Results The explored CNN architecture consisted of eightfolds of learnable weights including 5 convolutional layers and 3 fully connected layers, which received a true color 227 × 227 pixels flower image as its input. The developed CNN detector was able to classify the instances of flowers at overall average accuracies of 99.2 and 95.0% in the training and test procedure, respectively. The state-of-the-art CNN model was compared with the classical models of the scale-invariant feature transform (SIFT) features and the pyramid histogram of orientated gradient (PHOG) features combined with the multi-class support vector machine (SVM) algorithm. The proposed model turned out to be much more accurate than the traditional models of SIFT + SVM at overall average accuracies of 82.9 and 55.6% in the training and test procedure and PHOG + SVM at overall average accuracies of 78.3 and 63.1%, respectively. Conclusions The proposed state-of-the-art CNN method demonstrates that artificial intelligence is capable of precise classification of the white flower images, whose accuracy is comparable to traditional algorithms. The presented algorithm can be further used for the discrimination of white wild flowers in fields.

Abstract Background The prognostic value of preoperative controlling nutritional status (CONUT) has been reported in many malignancies. In present study, we aimed to clarify the prognostic impact of CONUT in gastric cancer (GC) receiving curative resection and adjuvant chemotherapy. Methods We retrospectively reviewed 697 consecutive patients undergoing curative surgery followed by adjuvant chemotherapy for Stage II-III GC between November 2000 and September 2012. Patients were classified into high (≥3) and low (≤2) CONUT groups according to the receiver operating characteristic (ROC) analysis. Results Of the included patients, 217 (31.1%) belonged to the high CONUT group. The high CONUT group had a significantly lower 5-year cancer-specific survival (CSS) rate than the low CONUT group (39.3 vs. 55.5%, P

The co-precipitation thermodynamics of the Li+–Fe2+/Fe3+–Al3+–F−–SO42−–PO43−–H2O system at 298 K is studied, aiming to understand the precipitation characteristics. Based on the principle of simultaneous equilibrium and the mass action law, the missing Ksp values of AlF3 and FeF3 were estimated. The results of thermodynamic calculation demonstrate that Al3+ and F− in the sulfuric acid leachate could be preferentially precipitated in the form of AlPO4 and FeF3 by the precise adjustment of the final pH value. Only a small amount of P and Fe was lost by the precipitation of Fe3(PO4)2·8H2O, FePO4, and Fe(OH)3 during the purification process. Controlling the oxidation of ferrous ions effectively is of critical significance for the loss reduction of P and Fe. Precipitation experiments at different pH value indicated that the concentration of Al3+ and F− in the leachate decreased as the final pH value rose from 3.05 to 3.90. When the final pH value was around 3.75, aluminum and fluoride ion impurities could be deeply purified, and the loss rate of phosphate ions and iron ions could be reduced as much as possible. Relevant research results can provide theoretical guidance for the purification of leachate in the wet recycling process of lithium-ion batteries.

Introduction Smoking cessation should be part of tuberculosis (TB) treatment, but a cessation service is not available as part of a routine TB service in most low- and middle-income countries. WHO and The International Union Against Tuberculosis and Lung Disease (The Union) issued a guideline and China implemented a pilot project 5 years ago. This study aimed to determine changes in smoking status among TB patients at 5 years after completion of anti-TB treatment to observe long-term outcome of a smoking cessation project whose baseline characteristics were associated with a relapse of smoking behavior. Methods A prospective longitudinal study was conducted 5 years after completion of anti-TB treatment to assess changes in patient smoking status against individual baseline data that were entered into a database at the time of TB registration. The patients were tracked by trained village doctors and validated by township health staff. Their smoking status was assessed and entered into the database and analysed. Results Of the 800 TB patients registered at baseline, 650 (81.2%) were tracked. Ninety-one (11.4%) patients died and 59 (7.4%) were lost to follow-up. The rates of remaining non-smoking after 5 years were 82.0%, 63.0%, 49.6%, 43.5% and 30.0%, respectively for non-smokers, ex-smokers, current smokers who received cessation intervention, recent quitters, and current smokers not on a cessation intervention. The odds of smoking relapse were significantly higher for those aged ≥65 years (p=0.003) and registered in Xingguo County (p=0.025). Conclusions Findings from this study confirmed that non-smokers, ex-smokers and current smokers who received cessation intervention at baseline maintained higher non-smoking rates compared with those who did not receive the intervention. To prevent relapse, intensive cessation support should be given to TB patients aged ≥65 years. TB programme managers need to ensure integration and provision of smoking cessation advice and smoke-free policy in routine TB services.

Background and purpose Stroke is the leading cause of mortality and disability in China. Precise aetiological classification, imaging and biological markers may predict the prognosis of stroke. The Third China National Stroke Registry (CNSR-III), a nationwide registry of ischaemic stroke or transient ischaemic attack (TIA) in China based on aetiology, imaging and biology markers, will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke.Methods Between August 2015 and March 2018, the CNSR-III recruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China. Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews. Patients were followed for clinical outcomes at 3 months, 6 months and 1–5 year annually. Brain imaging, including brain MRI and CT, were completed at baseline. Blood samples were collected and biomarkers were tested at baseline.Results A total of 15 166 stroke patients were enrolled, among which 31.7% patients were women with the average age of 62.2±11.3 years. Ischaemic stroke was predominant (93.3%, n=14 146) and 1020 (6.7%) TIAs were enrolled.Conclusions CNSR-III is a large scale nationwide registry in China. Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.

In order to identify a volatile metallo-organic precursor for the deposition of hafnium oxide (HfO2) films for atomic layer deposition (ALD) applications, the evaporative properties of hafnium alkoxides (hafnium isopropoxide, hafnium n-propoxide and hafnium n-butoxide) were investigated using thermogravimetric analysis. These hafnium alkoxide samples were synthesized by the electrochemical method and characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance and inductively coupled plasma analysis techniques. The characterization results indicated that the products were 99.997% high-purity hafnium alkoxides and could meet the requirement of purity considering the usage of making HfO2 gate oxide by ALD. Synthesized samples were subjected to a simultaneous thermogravimetric–differential thermal analysis unit at 10 K min−1 in a dry nitrogen atmosphere flowing at 100 ml min−1. Benzoic acid was used to calculate a calibration constant, which could then be inserted into a modified Langmuir equation to calculate vapour pressure curves for hafnium isopropoxide and hafnium n-propoxide. Detailed vapour pressure data for the HfO2 precursor hafnium alkoxides were determined. The vapour pressure curve of hafnium isopropoxide was constructed within the first stage, and calculated to be lnp = 31.157 (±0.200)−13130.57 (±56.50)/T. Hafnium n-propoxide and hafnium n-butoxide were simultaneously undergoing evaporation and decomposition, thus making calculations invalid.

We previously demonstrated that transient receptor potential vanilloid subfamily 5 (TRPV5) expression was decreased in renal cell carcinoma (RCC) compared with that in normal kidney tissues, a finding that was correlated with vitamin D receptor (VDR) expression, but further investigations is warranted. The aim of this study was to elucidate whether VDR could regulate the expression of TRPV5 and affect proliferation and metastasis in RCC. In this study, we used lentivirus to conduct the model of VDR overexpression and knockdown caki-1 and 786-O RCC cell lines in vitro. The results demonstrated that VDR overexpression significantly inhibited RCC cells proliferation, migration and invasion, and promoted apoptosis by the MTT, transwell cell migration/invasion and flow cytometry assays, respectively. However, VDR knockdown in RCC cells had the opposite effect. The RNA-sequence assay, which was assessed in caki-1 cells after VDR overexpression and knockdown, also indicated that significantly differentially expressed genes were associated with cell apoptotic, differentiation, proliferation and migration. RT-PCR and western blot analysis showed that VDR knockdown increased TRPV5 expression and VDR overexpression decreased TRPV5 expression in caki-1 cells. Furthermore, knockdown of TRPV5 expression suppressed the VDR knockdown-induced change in the proliferation, migration and invasion in caki-1 cells. Taken together, these findings confirmed that VDR functions as a tumour suppressor in RCC cells and suppresses the proliferation, migration and invasion of RCC through regulating the expression of TRPV5.

To effectively manage a river system, systematic tracking and diagnosing the change and risks of a river system are essentially required to efficiently conserve or restore its conditions. Hence, this study focuses on how to integrate current status assessment, trend prediction, and cause diagnosis in river health to guide early warning decision-making in river protection and management. This study has presented a three-phase approach by coupling spatial with nonspatial information in a highly systematic and reliable way, and an early warning system has been designed. In phase I, the current health status is assessed and nowcasted by using the order degree of each indicator. In phase II, health predictors, including the single perspective-based health index (HI) (e.g., water quality index (WQI) and index of biotic integrity (IBI)) and multi-perspective-based health index, have been forecasted under normal conditions or emerging conditions using predictive models. In phase III, key causal factors threatening the river health have been identified to enable early notification and to address unexpected events before occurrence. Although different modeling methods can be used in each phase to demonstrate this concept, we tested the model of partial least square regression (PLSR) associated with time series. Additionally, the three-phase approach has been integrated with geographic information system (GIS) and a decision support system (DSS) to develop a river health prediction and early warning system (RHP-EWS), an automatic prediction and decision-making tool. This tool was implemented to deal with the landing of typhoon “Maria” in 2018 into the Shanxi River watershed in China. Because of the timely responses and decisions, the drinking water supply was not influenced. However, the models should be extended to other river systems for testing and improvement at different temporal or spatial scales.