Accurate and affordable detection of rifampicin and isoniazid resistance in Tuberculosis sputum specimens by multiplex PCR-multiple probes melting analysis.

BACKGROUND: Escalating cases of multidrug-resistant tuberculosis (MDR-TB) pose a major challenge to global TB control efforts, necessitating innovative diagnostics to empower decentralized detection of gene mutations associated with resistance to rifampicin (RIF) and isoniazid (INH) in Mycobacterium tuberculosis (M. tuberculosis) in resource-constrained settings. METHODS: Combining multiplex fluorescent PCR and Multiple Probes Melting Analysis, we identified mutations in the rpoB, katG, ahpC and inhA genes from sputum specimens. We first constructed a reference plasmid library comprising 40 prevalent mutations in the target genes' resistance determining regions and promoters, serving as positive controls. Our assay utilizes a four-tube asymmetric PCR method with specifically designed molecular beacon probes, enabling simultaneous detection of all 40 mutations. We evaluated the assay's effectiveness using DNA isolated from 50 clinically confirmed M. tuberculosis sputum specimens, comparing our results with those obtained from Sanger sequencing and retrospective validation involving bacteriological culture and phenotypic drug susceptibility testing (pDST). We also included the commercial Xpert MTB/RIF assay for accuracy comparison. RESULTS: Our data demonstrated remarkable sensitivity in detecting resistance to RIF and INH, achieving values of 93.33% and 95.24%, respectively, with a specificity of 100%. The concordance between our assay and pDST was 98.00%. Furthermore, the accuracy of our assay was comparable to both Sanger sequencing and the Xpert assay. Importantly, our assay boasts a 4.2-h turnaround time and costs only $10 per test, making it an optimal choice for peripheral healthcare settings. CONCLUSION: These findings highlight our assay's potential as a promising tool for rapidly, accurately, and affordably detecting MDR-TB.

Silencing LINC00987 ameliorates adriamycin resistance of acute myeloid leukemia via miR-4458/HMGA2 axis.

BACKGROUND: Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML. METHODS: In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML. RESULTS: We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells. CONCLUSIONS: Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.

CRISPR/Cas13a-based supersensitive circulating tumor DNA assay for detecting EGFR mutations in plasma.

Despite recent technological advancements in cell tumor DNA (ctDNA) mutation detection, challenges persist in identifying low-frequency mutations due to inadequate sensitivity and coverage of current procedures. Herein, we introduce a super-sensitivity and specificity technique for detecting ctDNA mutations, named HiCASE. The method utilizes PCR-based CRISPR, coupled with the restriction enzyme. In this work, HiCASE focuses on testing a series of EGFR mutations to provide enhanced detection technology for non-small cell lung cancer (NSCLC), enabling a detection sensitivity of 0.01% with 40 ng cell free DNA standard. When applied to a panel of 140 plasma samples from 120 NSCLC patients, HiCASE exhibits 88.1% clinical sensitivity and 100% specificity with 40 µL of plasma, higher than ddPCR and Super-ARMS assay. In addition, HiCASE can also clearly distinguish T790M/C797S mutations in different positions at a 1% variant allele frequency, offering valuable guidance for drug utilization. Indeed, the established HiCASE assay shows potential for clinical applications.

Regulatory mechanism and molecular genetic dissection of rice (Oryza sativa L.) grain size.

With the sharp increase of the global population, adequate food supply is a great challenge. Grain size is an essential determinant of rice yield and quality. It is a typical quantitative trait controlled by multiple genes. In this paper, we summarized the quantitative trait loci (QTL) that have been molecularly characterized and provided a comprehensive summary of the regulation mechanism and genetic pathways of rice grain size. These pathways include the ubiquitin-proteasome system, G-protein, mitogen-activated protein kinase, phytohormone, transcriptional factors, abiotic stress. In addition, we discuss the possible application of advanced molecular biology methods and reasonable breeding strategies, and prospective on the development of high-yielding and high-quality rice varieties using molecular biology techniques.

Rice Seed Protrusion Quantitative Trait Loci Mapping through Genome-Wide Association Study.

The germination of seeds is a prerequisite for crop production. Protrusion is important for seed germination, and visible radicle protrusion through seed covering layers is the second phase of the process of seed germination. Analyzing the mechanism of protrusion is important for the cultivation of rice varieties. In this study, 302 microcore germplasm populations were used for the GWAS of the protrusion percentage (PP). The frequency distribution of the PP at 48 h and 72 h is continuous, and six PP-associated QTLs were identified, but only qPP2 was detected repeatedly two times. The candidate gene analysis showed that LOC_Os02g57530 (ETR3), LOC_Os01g57610 (GH3.1) and LOC_Os04g0425 (CTB2) were the candidate genes for qPP2, qPP1 and qPP4, respectively. The haplotype (Hap) analysis revealed that Hap1 of ETR3, Hap1 and 3 of GH3.1 and Hap2 and 5 of CTB2 are elite alleles for the PP. Further validation of the germination phenotype of these candidate genes showed that Hap1 of ETR3 is a favorable allele for the germination percentage; Hap3 of GH3.1 is an elite allele for seed germination; and Hap5 of CTB2 is an elite allele for the PP, the germination percentage and the vigor index. The results of this study identified three putative candidate genes that provide valuable information for understanding the genetic control of seed protrusion in rice.

Correction: The impact of digital inclusive finance on SMEs' technological innovation activities-Empirical analysis based on the data of new third board enterprises.

[This corrects the article DOI: 10.1371/journal.pone.0293500.].

Comparative physiological and transcriptome analysis between potassium-deficiency tolerant and sensitive sweetpotato genotypes in response to potassium-deficiency stress.

BACKGROUND: Sweetpotato is a typical ''potassium (K+) favoring'' food crop, which root differentiation process needs a large supply of potassium fertilizer and determine the final root yield. To further understand the regulatory network of the response to low potassium stress, here we analyze physiological and biochemical characteristics, and investigated root transcriptional changes in two sweetpotato genotypes, namely, - K tolerant "Xu32" and - K susceptible"NZ1". RESULT: We found Xu32 had the higher capability of K+ absorption than NZ1 with better growth performance, higher net photosynthetic rate and higher chlorophyll contents under low potassium stress, and identified 889 differentially expressed genes (DEGs) in Xu32, 634 DEGs in NZ1, 256 common DEGs in both Xu32 and NZ1. The Gene Ontology (GO) term in molecular function enrichment analysis revealed that the DEGs under low K+ stress are predominately involved in catalytic activity, binding, transporter activity and antioxidant activity. Moreover, the more numbers of identified DEGs in Xu32 than that in NZ1 responded to K+-deficiency belong to the process of photosynthesis, carbohydrate metabolism, ion transport, hormone signaling, stress-related and antioxidant system may result in different ability to K+-deficiency tolerance. The unique genes in Xu32 may make a great contribution to enhance low K+ tolerance, and provide useful information for the molecular regulation mechanism of K+-deficiency tolerance in sweetpotato. CONCLUSIONS: The common and distinct expression pattern between the two sweetpotato genotypes illuminate a complex mechanism response to low potassium exist in sweetpotato. The study provides some candidate genes, which can be used in sweetpotato breeding program for improving low potassium stress tolerance.

Asymmetric nexus between pandemic uncertainty and public health spendings: Evidence from quantile estimation.

The COVID-19 pandemic has brought significant challenges to healthcare systems worldwide, prompting governments to allocate substantial resources toward public health spendings (PHS). However, the uncertainties surrounding the pandemic have raised questions about the effectiveness and sustainability of such expenditures. This research analyzes the nonlinear link between pandemic uncertainty (PNU) and PHS in countries with highest PNU (USA, India, France, Germany, UK, Saudi Arabia, South Korea, Indonesia, Japan, and China). Previous studies have employed panel data methodologies to establish consistent findings regarding the relationship between pandemics and health spendings, regardless of the fact that several countries have not autonomously recognized this connection. In contrast, this current research adopts a distinctive tool called "quantile-on-quantile," which enables the examination of time series dependency within each economy, providing both international and country-specific perspectives on the relationship between the variables. The estimations indicate that PNU leads to an increase in PHS in the vast majority of economies chosen by us, focusing on definite segments of the data distribution. Moreover, the data demonstrates that there are differences in the asymmetry between the variables across various nations. This underscores the need for policymakers to take careful deliberation when formulating policies related to health spendings and addressing the challenges posed by pandemic uncertainty.

How to promote knowledge transfer within R&D team? An evolutionary game based on prospect theory.

Knowledge transfer is the basis for R&D teams and enterprises to improve innovation performance, win market competition and seek sustainable development. In order to explore the path to promote knowledge transfer within the R&D team, this study considers the bounded rationality and risk preference of individuals, incorporates prospect theory into evolutionary game, constructs a perceived benefits matrix distinct from the traditional benefits matrix, and simulates the evolutionary game process. The results show that, R&D personnel's knowledge transfer decisions depend on the net income difference among strategies; only if perceived cost is less than the sum of perceived synergy benefit, perceived organization reward value, and perceived organization punishment value, can knowledge be fully shared and transferred within the R&D team. Moreover, R&D personnel's knowledge transfer decisions are interfered by the irrational psychological factors, including overconfidence, reflection, loss avoidance, and obsession with small probability events. The findings help R&D teams achieve breakthroughs in improving the efficiency of knowledge transfer, thereby enhancing the capacity of enterprises for collaborative innovation.

Multi-attribute group decision-making based on Pythagorean fuzzy rough Aczel-Alsina aggregation operators and its applications to Medical diagnosis.

The fusion of information is a very hectic process whenever we analyze the information. Several frameworks have been introduced to reduce the uncertainty while fusing the information. Among those techniques, the Pythagorean fuzzy rough set (PyFRS), which is based on approximations is a key idea for dealing with uncertainty when data is taken from real-world circumstances. Furthermore, the most adaptable and flexible operational laws based on the parameters for fuzzy frameworks are Aczel-Alsina t-norm (AATNM) and Aczel-Alsina t-conorm (AATCNM). The major goal of this work is to introduce some methods for the basic operations of the information in the shape of Pythagorean fuzzy rough (PyFR) values (PyFRVs). Consequently, the PyFR Aczel-Alsina weighted geometric (PyFRAAWG), PyFR Aczel-Alsina ordered weighted geometric (PyFRAAOWG), and PyFR Aczel-Alsina hybrid weighted geometric (PyFRAAHWG) operators are developed in this article based on AATNM and AATCNM. Further, some basic properties of the developed operators are observed and discussed. Further, the developed approaches are applied to the problem of multi-attribute group decision-making (MAGDM). The obtained results from the MAGDM problem are observed at various values of the parameters involved by AATNM and AATCNM. Moreover, the results are also compared with already existing techniques for the significance of the developed approach.

The impact of digital inclusive finance on SMEs' technological innovation activities-Empirical analysis based on the data of new third board enterprises.

The landscape of financial technology is undergoing a continuous evolution, driven by the relentless advancement of information technology. In this transformative milieu, digital finance has emerged as a novel financial paradigm, offering a blueprint for fostering inclusive finance. With a particular emphasis on its implications for Small and Medium-sized Enterprises (SMEs), this article harnesses a comprehensive dataset spanning the years 2011 to 2021, encompassing digital inclusive finance and SMEs listed on the SME board. Employing fixed effects models, this study performs a regression analysis to verify the driving effect of digital inclusive finance on SMEs' innovation activities. The findings unequivocally affirm the potency of inclusive finance in ameliorating the longstanding financing constraints that have historically constrained the growth trajectory of SMEs. Furthermore, the study elucidated the nuanced nature of the promotional impact of digital inclusive finance on SMEs, contingent upon their distinct property rights and technological attributes. Specifically, the empirical findings unveil a discernible pattern wherein digital inclusive finance exerts a conspicuously stronger promotional effect on non-state-owned enterprises and high-tech SMEs' endeavors in technological innovation. The conclusions derived from this research furnish a salient point of reference for governmental authorities engaged in the formulation and advancement of digital inclusive finance strategies, thereby imparting strategic guidance for the cultivation of innovation and holistic development within the SME sector.

Effect of physical exercise on sleep quality in college students: Mediating role of smartphone use.

OBJECTIVE: To investigate the effect of physical exercise on sleep quality and the mediating effect of smartphone use behavior in college students. METHODS: A cross-sectional study design was adopted. An online survey of 5,075 college students was conducted using the Physical Activity Rating Scale-3, the Pittsburgh Sleep Quality Index, and the Mobile Phone Addiction Tendency Scale. RESULTS: The sleep quality of college students was poor, and the proportion of college students with good sleep quality was 23.567%. A significant correlation existed between sleep quality and physical exercise (r = -0.159, P < 0.001) and mobile phone addiction (r = 0.355, P < 0.001). Physical exercise can predict sleep quality in college students (ß = -0.011, P < 0.001). Smartphone use plays a part in mediating the process by which physical exercise affects sleep quality. CONCLUSION: Chinese college students have poor sleep quality. Physical exercise and smartphone use behavior are important factors affecting the sleep quality of college students. Physical exercise can directly predict the sleep quality of college students and can predict the sleep quality of college students through the mediating effect of smartphone use behavior.

Spatial-temporal coupling coordination and interaction between digitalization and traditional industrial upgrading: a case study of the Yellow River Basin.

The realization of coupling coordination between digitalization and traditional industrial upgrading in the Yellow River Basin holds significant practical value for promoting high-quality industrial development in the region. In order to assess this coupling coordination, we utilized inter-provincial panel data from nine provinces in the Yellow River Basin, covering the period from 2011 to 2020. Through the application of a coupling coordination degree model, we calculated the degree of coupling coordination and relative development between digitalization and traditional industrial upgrading. Additionally, we conducted a spatial-temporal analysis to identify the characteristics and trends of digitalization and traditional industrial upgrading. Furthermore, we constructed a panel VAR model to examine the interactive relationship between these two factors. The findings are as follows: (1) overall, over the study period, the degree of coupling coordination between digitalization and traditional industrial upgrading in the Yellow River Basin transitioned from a disordered state to a run-in stage. The corresponding development type changed from a low steady state to a co-existence of low and medium steady states. Notably, the levels of digitalization, traditional industrial upgrading, and coupling coordination all exhibited a gradual increase, while the relative development degree declined. (2) The coupling coordination degree between digitalization and traditional industrial upgrading in the Yellow River Basin demonstrated significant regional variation. Provinces displaying a "high-high" agglomeration distribution and "low-low" agglomeration distribution were concentrated in the middle and lower reaches, as well as the upper reaches, of the Yellow River. Furthermore, there was a positive spatial autocorrelation between these regions. (3) Both digitalization and traditional industrial upgrading exhibit self-reinforcing mechanisms, and a long-term dynamic correlation exists between them.

Icariin as a potential anticancer agent: a review of its biological effects on various cancers.

Numerous chemical compounds used in cancer treatment have been isolated from natural herbs to address the ever-increasing cancer incidence worldwide. Therein is icariin, which has been extensively studied for its therapeutic potential due to its anti-inflammatory, antioxidant, antidepressant, and aphrodisiac properties. However, there is a lack of comprehensive and detailed review of studies on icariin in cancer treatment. Given this, this study reviews and examines the relevant literature on the chemopreventive and therapeutic potentials of icariin in cancer treatment and describes its mechanism of action. The review shows that icariin has the property of inhibiting cancer progression and reversing drug resistance. Therefore, icariin may be a valuable potential agent for the prevention and treatment of various cancers due to its natural origin, safety, and low cost compared to conventional anticancer drugs, while further research on this natural agent is needed.

Genome-Wide Analysis of the PHT Gene Family and Its Response to Mycorrhizal Symbiosis in Tomatoes under Phosphate Starvation Conditions.

Phosphate is one of the essential mineral nutrients. Phosphate transporter genes (PHTs) play an important role in Pi acquisition and homeostasis in tomato plants. However, basic biological information on PHT genes and their responses of symbiosis with arbuscular mycorrhizal in the genome remains largely unknown. We analyzed the physiological changes and PHT gene expression in tomatoes (Micro-Tom) inoculated with arbuscular mycorrhizal (AM) fungi (Funneliformis mosseae) under different phosphate conditions (P1: 0 µM, P2: 25 µM, and P3: 200 µM Pi). Twenty-three PHT genes were identified in the tomato genomics database. Protein sequence alignment further divided the 23 PHT genes into three groups, with similar classifications of exons and introns. Good colonization of plants was observed under low phosphate conditions (25 µM Pi), and Pi stress and AM fungi significantly affected P and N accumulation and root morphological plasticity. Moreover, gene expression data showed that genes in the SlPHT1 (SlPT3, SlPT4, and SlPT5) gene family were upregulated by Funneliformis mosseae under all conditions, which indicated that these gene levels were significantly increased with AM fungi inoculation. None of the analyzed SlPHT genes in the SlPH2, SlPHT3, SlPHT4, and SlPHO gene families were changed at any Pi concentration. Our results indicate that inoculation with AM fungi mainly altered the expression of the PHT1 gene family. These results will lay a foundation for better understanding the molecular mechanisms of inorganic phosphate transport under AM fungi inoculation.

Immune-enhancing activity of polysaccharides and flavonoids derived from Phellinus igniarius YASH1.

Introduction: Phellinus igniarius (P. igniarius) (Sanghuang) is a widely used traditional Chinese medicine fungus, and its natural products have great potential for clinical application in immune enhancement. This study aimed to explore the immune-enhancing activity and underlying mechanisms of the polysaccharides and flavonoids derived from Phellinus igniarius (P. igniarius) and to provide a theoretical and experimental basis for the development of novel drugs. Methods: Wild P. igniarius YASH1 from the Loess Plateau in Yan'an region was collected, and polysaccharides and total flavonoids were extracted, isolated and identified from mycelium and sporophore. In vitro antioxidant activity was detected through the scavenging activity of hydroxyl radicals and total antioxidant capacity. Cell Counting Kit-8 and trypan blue detection kit were used to detect the effect of extract polysaccharides and flavonoids on the proliferation and phagocytosis ability of immune cells. To assess the effect of the drugs on cytokine secretion by immune cells and immune recovery in immunocompromised mice, the expression of interleukin (IL)-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were examined at the cellular and animal levels. The species composition, abundance of gut microbiota and the altered content of short-chain fatty acids in the feces were analyzed to elucidate the possible mechanisms of drugs by 16S ribosomal RNA (rRNA) amplifiers sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Both polysaccharides and flavonoids derived from mycelium or sporophore had antioxidant activity and may stimulate the expression and secretion of IL-2, IL-6, and IFN-γ in immune cells while inhibiting TNF-α expression and secretion and increasing IL-2, IL-6, and IFN- γ expression levels in mice. Furthermore, polysaccharides and flavonoids from mycelium and sporophore showed different effects on the metabolic response of intestinal short-chain fatty acids (SCFAs) in mice, and the use of these drugs remarkably changed the species composition and abundance of intestinal flora in mice. Discussion: Polysaccharides and flavonoids from P. igniarius YASH1 mycelium and sporophore have in vitro antioxidant activity, and they affect the promotion of cell proliferation, stimulation of IL-2, IL-6, and IFN-γ secretion, and inhibition of TNF-α expression in immune cells. Polysaccharides and flavonoids from P. igniarius YASH1 may enhance immunity in immunocompromised mice and remarkably affect the intestinal flora and content of SCFAs.

The Role of IAA in Regulating Root Architecture of Sweetpotato (Ipomoea batatas [L.] Lam) in Response to Potassium Deficiency Stress.

Plants can adapt to the spatial heterogeneity of soil nutrients by changing the morphology and architecture of the root system. Here, we explored the role of auxin in the response of sweetpotato roots to potassium (K+) deficiency stress. Two sweetpotato cultivars, Xushu 32 (low-K-tolerant) and Ningzishu 1 (low-K-sensitive), were cultured in low K+ (0.1 mmol L-1, LK) and normal K+ (10 mmol L-1, CK) nutrient solutions. Compared with CK, LK reduced the dry mass, K+ content, and K+ accumulation in the two cultivars, but the losses of Xushu 32 were smaller than those of Ningzishu 1. LK also affected root growth, mainly impairing the length, surface area, forks number, and crossings number. However, Xushu 32 had significantly higher lateral root length, density, and surface area than Ningzishu 1, closely related to the roots' higher indole-3-acetic acid (IAA) content. According to the qPCR results, Xushu 32 synthesized more IAA (via IbYUC8 and IbTAR2) in leaves but transported and accumulated in roots through polar transport (via IbPIN1, IbPIN3, and IbAUX1). It was also associated with the upregulation of auxin signaling pathway genes (IbIAA4 and IbIAA8) in roots. These results imply that IAA participates in the formation of lateral roots and the change in root architecture during the tolerance to low K+ stress of sweetpotato, thus improving the absorption of K+ and the formation of biomass.

A theoretical model of factors influencing online consumer purchasing behavior through electronic word of mouth data mining and analysis.

The coronavirus disease 2019 pandemic has impacted and changed consumer behavior because of a prolonged quarantine and lockdown. This study proposed a theoretical framework to explore and define the influencing factors of online consumer purchasing behavior (OCPB) based on electronic word-of-mouth (e-WOM) data mining and analysis. Data pertaining to e-WOM were crawled from smartphone product reviews from the two most popular online shopping platforms in China, Jingdong.com and Taobao.com. Data processing aimed to filter noise and translate unstructured data from complex text reviews into structured data. The machine learning based K-means clustering method was utilized to cluster the influencing factors of OCPB. Comparing the clustering results and Kotler's five products level, the influencing factors of OCPB were clustered around four categories: perceived emergency context, product, innovation, and function attributes. This study contributes to OCPB research by data mining and analysis that can adequately identify the influencing factors based on e-WOM. The definition and explanation of these categories may have important implications for both OCPB and e-commerce.

Cross-domain Nuclei Detection in Histopathology Images using Graph-based Nuclei Feature Alignment.

As powerful tools deep neural networks have been successfully adopted for nuclei detection in histopathology images, whereas require the same probability distribution between training and testing data. However, domain shift among histopathology images widely exists in real-world applications and severely deteriorates the detection performance of deep neural networks. Despite encouraging results of existing domain adaptation methods, there remain challenges for cross-domain nuclei detection task. First, in view of the tiny size of nuclei, it is actually very difficult to obtain sufficient nuclei features, thus leading to a negative influence for feature alignment. Second, due to unavailable annotations in target domain, some extracted features contain background pixels and are thereby indiscriminative, which can largely confuse the alignment procedure. To address these challenges, in this paper, we propose an end-to-end graph-based nuclei feature alignment (GNFA) method for boosting cross-domain nuclei detection. Concretely, sufficient nuclei features are generated from nuclei graph convolutional network (NGCN) by aggregating information of adjacent nuclei upon construction of nuclei graph for successful alignment. In addition, importance learning module (ILM) is designed to further select discriminative nuclei features for mitigating negative influence of background pixels in target domain during alignment. By utilizing sufficient and discriminative node features generated from GNFA, our method can successfully perform feature alignment and effectively alleviate domain shift problem for nuclei detection. Extensive experiments of multiple adaptation scenarios reveal that our method achieves state-of-the-art performance in cross-domain nuclei detection compared with existing domain adaptation methods.

The gut microbiota: A new perspective for tertiary prevention of hepatobiliary and gallbladder diseases.

The gut microbiota is a complex ecosystem that has coevolved with the human body for hundreds of millions of years. In the past 30 years, with the progress of gene sequencing and omics technology, the research related to gut microbiota has developed rapidly especially in the field of digestive system diseases and systemic metabolic diseases. Mechanical, biological, immune, and other factors make the intestinal flora form a close bidirectional connection with the liver and gallbladder, which can be called the "gut-liver-biliary axis." Liver and gallbladder, as internal organs of the peritoneum, suffer from insidious onset, which are not easy to detect. The diagnosis is often made through laboratory chemical tests and imaging methods, and intervention measures are usually taken only when organic lesions have occurred. At this time, some people may have entered the irreversible stage of disease development. We reviewed the literature describing the role of intestinal flora in the pathogenesis and biotherapy of hepatobiliary diseases in the past 3-5 years, including the dynamic changes of intestinal flora at different stages of the disease, as well as the signaling pathways involved in intestinal flora and its metabolites, etc. After summarizing the above contents, we hope to highlight the potential of intestinal flora as a new clinical target for early prevention, early diagnosis, timely treatment and prognosis of hepatobiliary diseases. GRAPHICAL ABSTRACT.