A retrotransposon insertion in the Mao1 promoter results in erect pubescence and higher yield in soybean.

Adaptive changes in crops contribute to the diversity of agronomic traits, which directly or indirectly affect yield. The change of pubescence form from appressed to erect is a notable feature during soybean domestication. However, the biological significance and regulatory mechanism underlying this transformation remain largely unknown. Here, we identified a major-effect locus, PUBESCENCE FORM 1 (PF1), the upstream region of Mao1, that regulates pubescence form in soybean. The insertion of a Ty3/Gypsy retrotransposon in PF1 can recruit the transcription factor GAGA-binding protein to a GA-rich region, which up-regulates Mao1 expression, underpinning soybean pubescence evolution. Interestingly, the proportion of improved cultivars with erect pubescence increases gradually with increasing latitude, and erect-pubescence cultivars have a higher yield possibly through a higher photosynthetic rate and photosynthetic stability. These findings open an avenue for molecular breeding through either natural introgression or genome editing toward yield improvement and productivity.

Tandemly duplicated MYB genes are functionally diverged in the regulation of anthocyanin biosynthesis in soybean.

Gene duplications have long been recognized as a driving force in the evolution of genes, giving rise to novel functions. The soybean (Glycine max) genome is characterized by a large number of duplicated genes. However, the extent and mechanisms of functional divergence among these duplicated genes in soybean remain poorly understood. In this study, we revealed that 4 MYB genes (GmMYBA5, GmMYBA2, GmMYBA1, and Glyma.09g235000)-presumably generated by tandem duplication specifically in the Phaseoleae lineage-exhibited a stronger purifying selection in soybean compared to common bean (Phaseolus vulgaris). To gain insights into the diverse functions of these tandemly duplicated MYB genes in anthocyanin biosynthesis, we examined the expression, transcriptional activity, induced metabolites, and evolutionary history of these 4 MYB genes. Our data revealed that Glyma.09g235000 is a pseudogene, while the remaining 3 MYB genes exhibit strong transcriptional activation activity, promoting anthocyanin biosynthesis in different soybean tissues. GmMYBA5, GmMYBA2, and GmMYBA1 induced anthocyanin accumulation by upregulating the expression of anthocyanin pathway-related genes. Notably, GmMYBA5 showed a lower capacity for gene induction compared to GmMYBA2 and GmMYBA1. Metabolomics analysis further demonstrated that GmMYBA5 induced distinct anthocyanin accumulation in Nicotiana benthamiana leaves and soybean hairy roots compared to GmMYBA2 and GmMYBA1, suggesting their functional divergence leading to the accumulation of different metabolites accumulation following gene duplication. Together, our data provide evidence of functional divergence within the MYB gene cluster following tandem duplication, which sheds light on the potential evolutionary directions of gene duplications during legume evolution.

Nucleoporin Nup98 is an essential factor for ipo4 dependent protein import.

Nucleocytoplasmic transport of macromolecules is essential in eukaryotic cells. In this process, the karyopherins play a central role when they transport cargoes across the nuclear pore complex. Importin 4 belongs to the karyopherin ß family. Many studies have focused on finding substrates for importin 4, but no direct mechanism studies of its precise transport function have been reported. Therefore, this paper mainly aimed to study the mechanism of nucleoporins in mediating nuclear import and export of importin 4. To address this question, we constructed shRNAs targeting Nup358, Nup153, Nup98, and Nup50. We found that depletion of Nup98 resulted in a shift in the subcellular localization of importin 4 from the cytoplasm to the nucleus. Mutational analysis demonstrated that Nup98 physically and functionally interacts with importin 4 through its N-terminal phenylalanine-glycine (FG) repeat region. Mutation of nine of these FG motifs to SG motifs significantly attenuated the binding of Nup98 to importin 4, and we further confirmed the essential role of the six FG motifs in amino acids 121-360 of Nup98 in binding with importin 4. In vitro transport assay also confirmed that VDR, the substrate of importin 4, could not be transported into the nucleus after Nup98 knockdown. Overall, our results showed that Nup98 is required for efficient importin 4-mediated transport. This is the first study to reveal the mechanism of importin 4 in transporting substrates into the nucleus.

Sex-determining region Y gene promotes liver fibrosis and accounts for sexual dimorphism in its pathophysiology.

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.

Global, regional and national temporal trends in prevalence for musculoskeletal disorders in women of childbearing age, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease Study 2019.

OBJECTIVES: To provide an overview and in-depth analysis of temporal trends in prevalence of musculoskeletal (MSK) disorders in women of childbearing age (WCBA) at global, regional and national levels over the last 30 years, with a special focus on their associations with age, period and birth cohort. METHODS: Estimates and 95% uncertainty intervals (UIs) for MSK disorders prevalence in WCBA were extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. An age-period-cohort model was adopted to estimate the overall annual percentage change of prevalence (net drift, % per year), annual percentage change of prevalence within each age group (local drift, % per year), fitted longitudinal age-specific rates adjusted for period deviations (age effects) and period/cohort relative risks (period/cohort effects) from 1990 to 2019. RESULTS: In 2019, the global number of MSK disorders prevalence in WCBA was 354.57 million (95% UI: 322.64 to 387.68). Fifty countries had at least one million prevalence, with India, China, the USA, Indonesia and Brazil being the highest accounting for 51.03% of global prevalence. From 1990 to 2019, a global net drift of MSK disorders prevalence in WCBA was -0.06% (95% CI: -0.07% to -0.05%) per year, ranging from -0.09% (95% CI: -0.10% to -0.07%) in low-middle sociodemographic index (SDI) region to 0.10% (95% CI: 0.08% to 0.12%) in high-middle SDI region, with 138 countries presenting increasing trends, 24 presenting decreasing trends and 42 presenting relatively flat trends. As reflected by local drift, higher SDI regions had more age groups showing rising prevalence whereas lower SDI regions had more declining prevalence. Globally, an increasing occurrence of MSK disorders prevalence in WCBA beyond adolescent and towards the adult stage has been prominent. Age effects illustrated similar patterns across different SDI regions, with risk increasing with age. High SDI region showed generally lower period risks over time, whereas others showed more unfavourable period risks. High, high-middle and middle SDI regions presented unfavourable prevalence deteriorations, whereas others presented favourable prevalence improvements in successively birth cohorts. CONCLUSIONS: Although a favourable overall temporal trend (net drift) of MSK disorders prevalence in WCBA was observed over the last 30 years globally, there were 138 countries showing unfavourable rising trends, coupled with deteriorations in period/cohort risks in many countries, collectively raising concerns about timely realisation of the Targets of Sustainable Development Goal. Improvements in the MSK disorders-related prevention, management and treatment programmes in WCBA could decline the relative risk for successively younger birth cohorts and for all age groups over period progressing.

The macrophage-associated prognostic gene ANXA5 promotes immunotherapy resistance in gastric cancer through angiogenesis.

Gastric cancer (GC) remains a predominant form of malignant tumor globally, necessitating innovative non-surgical therapeutic approaches. This investigation aimed to delineate the expression landscape of macrophage-associated genes in GC and to evaluate their prognostic significance and influence on immunotherapeutic responsiveness. Utilizing the CellMarker2.0 database, we identified 69 immune cell markers with prognostic relevance in GC, including 12 macrophage-specific genes. A Weighted Gene Co-Expression Network Analysis (WGCNA) isolated 3,181 genes correlated with these macrophage markers. The Cancer Genome Atlas (TCGA-STAD) dataset was employed as the training set, while data from the GSE62254 served as the validation cohort. 13 genes were shortlisted through LASSO-Cox regression to formulate a prognostic model. Multivariable Cox regression substantiated that the calculated risk score serves as an imperative independent predictor of overall survival (OS). Distinct macrophage infiltration profiles, pathway associations, treatment susceptibilities, and drug sensitivities were observed between high- and low-risk groups. The preliminary validation of ANXA5 in predicting the survival rates of GC patients at 1 year, 3 years, and 5 years, as well as its expression levels were higher and role in promoting tumor angiogenesis in GC through immunohistochemistry and angiogenesis experiments. In summary, macrophage-related genes were potentially a novel crosstalk mechanism between macrophages and endothelial cells in the tumor microenvironment, and the interplay between inflammation and angiogenesis might have also offered new therapeutic targets, providing a new avenue for personalized treatment interventions.

Targeting the macrophage immunocheckpoint: a novel insight into solid tumor immunotherapy.

Tumor immunotherapy, which targets immune checkpoints, presents a promising strategy for the treatment of various cancer types. However, current clinical data indicate challenges in its application to solid tumors. Recent studies have revealed a significant correlation between the degree of immune response in immunotherapy and the tumor microenvironment, particularly with regard to tumor-infiltrating immune cells. Among these immune cells, macrophages, a critical component, are playing an increasingly vital role in tumor immunotherapy. This review focuses on elucidating the role of macrophages within solid tumors and provides an overview of the progress in immunotherapy approaches centered around modulating macrophage responses through various immune factors. Video Abstract.

Global burden of liver cirrhosis and other chronic liver diseases caused by specific etiologies from 1990 to 2019.

BACKGROUND: This study aimed to assess the global, regional, and national burden of liver cirrhosis and other chronic liver diseases between 1990 and 2019, considering five etiologies (hepatitis B, hepatitis C, alcohol use, NAFLD and other causes), age, gender, and sociodemographic index (SDI). METHODS: Data on liver cirrhosis and other chronic liver diseases mortality, incidence, and disability-adjusted life years (DALYs) were collected from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2019. RESULTS: In 2019, liver cirrhosis and other chronic liver diseases accounted for 1,472,011 (95% UI 1,374,608-1,578,731) deaths worldwide, compared to 1,012,975 (948,941-1,073,877) deaths in 1990. Despite an increase in absolute deaths, the age-standardized death rate declined from 24.43 (22.93-25.73) per 100,000 population in 1990 to 18.00 (19.31-16.80) per 100,000 population in 2019. Eastern sub-Saharan Africa exhibited the highest age-standardized death rate (44.15 [38.47-51.91] per 100,000 population), while Australasia had the lowest rate (5.48 [5.05-5.93] deaths per 100,000 population in 2019). The age-standardized incidence rate of liver cirrhosis and other chronic liver diseases attributed to hepatitis B virus has declined since 1990, but incidence rates for other etiologies have increased. Age-standardized death and DALYs rates progressively decreased with higher SDI across different GBD regions and countries. Mortality due to liver cirrhosis and other chronic liver diseases increased with age in 2019, and the death rate among males was estimated 1.51 times higher than that among females globally. CONCLUSION: Liver cirrhosis and other chronic liver diseases continues to pose a significant global public health challenge. Effective disease control, prevention, and treatment strategies should account for variations in risk factors, age, gender, and regional disparities.

Assessment of the Diagnostic Performance of Clinical Examinations and High-Frequency Ultrasound in Patients With Pigmented Skin Tumors.

OBJECTIVES: To investigate whether the integration of high-frequency ultrasound (HFUS) to routine clinical examinations could improve diagnostic performance and management decision for pigmented skin tumors. METHODS: Three general practitioners trained previously and a dermatologist independently assessed pigmented skin tumors and rendered management decision based on clinical examinations alone or clinical examinations integrating HFUS. RESULTS: After integrating HFUS, the diagnostic area under the curve (AUC) (0.658-0.693 versus 0.848, all P < .05) and specificity (46.6-58.6% versus 89.7%, all P < .05) for pigmented skin malignancies were improved for general practitioners, meanwhile unnecessary biopsy rate reduced (42.9-53.6% versus 10.7%, P < .001). To the dermatologist, the diagnostic AUC (0.822 versus 0.949, P < .001), sensitivity (81.7% versus 96.7%, P = .012) and specificity (0.828 versus 0.931, P = .031) improved significantly, meanwhile both missed biopsy rate (14.5% versus 4.8%, P = .031) and unnecessary biopsy rate (19.6% versus 7.1%, P = .016) decreased. Additionally, the diagnostic performance of the general practitioner with integrating HFUS could be comparable with the dermatologist based on clinical examinations alone (all P > .05). CONCLUSIONS: As a complementary tool of clinical examinations, HFUS could help physicians differentiate pigmented skin malignancies and manage decision.

The GZnC1 variant from common wild rice influences grain Zn content.

Zinc (Zn) deficiency, caused by inadequate Zn intake in the human diet, has serious health implications. Rice (Oryza sativa) is the staple food in regions with a high incidence of Zn deficiency, so raising Zn levels in rice grain could help alleviate Zn deficiency. The wild relatives of cultivated rice vary widely in grain Zn content and thus are suitable resources for improving this trait. However, few loci underlying grain Zn content have been identified in wild rice relatives. Here, we identified a major quantitative trait locus for grain Zn content, Grain Zn Content 1 (qGZnC1), from Yuanjiang common wild rice (Oryza rufipogon Griff.) using map-based cloning. Down-regulating GZnC1 expression reduced the grain Zn content, whereas the presence of GZnC1 had the opposite effect, indicating that GZnC1 is involved in grain Zn content in rice. Notably, GZnC1 is identical to a previously reported gene, EMBRYO SAC ABORTION 1 (ESA1), involved in seed setting rate. The mutation in GZnC1/ESA1 at position 1819 (T1819C) causes delayed termination of protein translation. In addition, GZnC1 is specifically expressed in developing panicles. Several genes related to Zn-transporter genes were up-regulated in the presence of GZnC1. Our results suggest that GZnC1 activates Zn transporters to promote Zn distribution in panicles. Our work thus sheds light on the genetic mechanism of Zn accumulation in rice grain and provides a new genetic resource for improving Zn content in rice.

Impact of adjuvant therapy on outcomes after curative-intent resection for distal cholangiocarcinoma.

BACKGROUND: The benefit of adjuvant therapy (AT) after curative resection of distal cholangiocarcinoma (DCC) remains unclear. The objective of the current study was to investigate the impact of AT on long-term survival of patients who underwent curative-intent resection for DCC. METHODS: Patients who underwent curative-intent resection for DCC between 2000 and 2020 were identified from a multi-institutional database. The primary outcomes included overall (OS) and recurrence-free survival (RFS). RESULTS: Among 245 patients, 150 (61.2%) patients received AT (chemotherapy alone: n = 43; chemo- and radiotherapy: n = 107) after surgical resection, whereas 95 (38.8%) patients underwent surgery only. Patients who received AT were younger, and more likely to have an advanced tumor with the presence of perineural invasion (PNI), lymph node metastasis (LNM), lymph-vascular invasion, and higher T categories (all p < 0.05). Overall, there was no difference in OS (median, surgery + AT 25.5 vs. surgery alone 24.5 months, p = 0.27) or RFS (median, surgery + AT 15.8 vs. surgery alone 18.9 months, p = 0.24) among patients who did versus did not receive AT. In contrast, AT was associated with improved long-term survival among patients with PNI (median OS, surgery + AT 25.9 vs. surgery alone 17.8 months, p = 0.03; median RFS, surgery + AT 15.9 vs. surgery alone 11.9 months, p = 0.04) and LNM (median, surgery + AT 20.0 vs. surgery alone 17.8 months, p = 0.03), but not among patients with no PNI or LNM (all p > 0.1). CONCLUSIONS: AT was commonly utilized among patients with DCC. Patients with more advanced disease, including the presence of PNI or LNM, benefited the most from AT with improved long-term outcomes among this subset of patients.

Identification of an important QTL for seed oil content in soybean.

Seed oil content is one of the most important quantitative traits in soybean (Glycine max) breeding. Here, we constructed a high-density single nucleotide polymorphism linkage map using two genetically similar parents, Heinong 84 and Kenfeng 17, that differ dramatically in their seed oil contents, and performed quantitative trait loci (QTL) mapping of seed oil content in a recombinant inbred line (RIL) population derived from their cross. We detected five QTL related to seed oil content distributed on five chromosomes. The QTL for seed oil content explained over 10% of the phenotypic variation over two years. This QTL was mapped to an interval containing 20 candidate genes, including a previously reported gene, soybean RING Finger 1a (RNF1a) encoding an E3 ubiquitin ligase. Notably, two short sequences were inserted in the GmRNF1a coding region of KF 17 compared to that of HN 84, resulting in a longer protein variant in KF 17. Our results thus provide information for uncovering the genetic mechanisms determining seed oil content in soybean, as well as identifying an additional QTL and highlighting GmRNF1a as candidate gene for modulating seed oil content in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01384-2.

The global burden of alcoholic liver disease: a systematic analysis of the global burden of disease study 2019.

Alcohol use is a major risk factor for the burden of mortality and morbidity. Alcoholic cirrhosis (AC) and alcoholic liver cancer (ALC) are most important and severe liver disease outcomes caused by alcohol use. The objectives of the current study were to investigate the global prevalence and burden of disease in disability-adjusted life years (DALYs) for AC and ALC, based on data from the Global Burden of Disease (GBD). Incidence, prevalence, death, and DALYs for GBDs in different locations, years, sex, and age groups were estimated using DisMod-MR 2.1 and a generic Cause of Death Ensemble Modeling approach. The correlations between the age-standardized incidence rate or age-standardized death rate and gender, sociodemographic index (SDI), and alcohol usage were conducted by Generalized Linear Models. Globally, the changes of age-standardized rates of indicators were not much significant over the 30-year period. However, the changes varied widely across regions. Central Asia and East Europe contributed the highest age-standardized incidence, prevalence, death, and DALYs and increased sharply by past 30 years. Generalized Linear Models (GLMs) showed male gender as a risk factor of AC, with the relative risk of incidence of 1.521 and relative risk of death of 1.503. Globally, there were improvements in overall health with regard to GBDs over the 30 years. However, the prevention of AC and ALC should be promoted in middle and middle-high SDI regions, especially Central Asia and East Europe, whereas more medical resources should be provided to improve treatment levels in low SDI region.

HSPA6, a novel prognostic and therapeutic biomarker, associated with Ming classification in gastric cancer.

OBJECTIVE: This study aimed to explore the clinical relevance of heat shock protein family A member 6 (HSPA6) in gastric cancer (GC) and its effect on GC cell proliferation. METHODS: HSPA6 mRNA and protein levels were analyzed by bioinformatics, RT-qPCR, western blot and immunohistochemistry. HSPA6 was correlated with clinicopathological variables by the Chi-square test. Kaplan-Meier survival analysis and the univariate and multivariate Cox models were used to assess the prognostic value of HSPA6. Nomogram was used to predict overall survival in patients with GC. Knockdown or over-expression of HSPA6 in GC cell lines was constructed by lentiviral transduction. EdU and CCK-8 assay were used to detect cell proliferation. In vivo mouse tumor models were performed to evaluate the effects of HSPA6 on GC growth. RESULTS: HSPA6 were significantly upregulated in the GC tissues compared to the normal stomach epithelium and were associated with Ming classification (p < 0.001) and tumor size (p = 0.002). Patients with high expression of HSPA6 showed worse survival compared to the low expression group. HSPA6 was identified to be an independent prognostic biomarker for GC. HSPA6 was functionally annotated with the cell cycle, G2M checkpoint and Hippo pathway. Knockdown of HSPA6 suppressed XGC-1 cell proliferation both in vitro and in vivo. Overexpression of HSPA6 in AGS cells increased proliferation rates, increased the levels of cyclinB1 and YAP and decreased that of phosphorylated YAP. HSPA6 knockdown in the NUGC2 cells had the opposite effect. CONCLUSIONS: HSPA6 promotes GC proliferation by the Hippo pathway, as a novel prognostic biomarker and potential therapeutic target.

Clinical pharmacy undergraduate education in China: a comparative analysis based on ten universities' training programs.

BACKGROUND: In recent years, the scale of personnel training for clinical pharmacy professionals in China has expanded increasingly, however, the shortage of clinical pharmacists is still prominent. In 2018, the Ministry of Education of China released national standards for the teaching quality of undergraduate majors at regular colleges and universities, which has developed a core policy for undergraduate clinical pharmacy training. To explore the training methods for clinical pharmacy professionals in China and to promote the healthy and sustainable development of the clinical pharmacy education system. This study comparatively analyzed the training programs for clinical pharmacy undergraduates in China's ten universities, discussed training programs suitable for clinical pharmacy professionals in China. METHODS: The clinical pharmacy education programs in these ten universities were obtained through official school websites or by interviewing relevant people, and then compared and analyzed. RESULTS: The school with the largest number of courses and the most class hours in general courses is University A1 (34 courses, 1316 class hours), and the school with the most credits is University B1 (75.5 credits). The schools with the largest number of courses and the most class hours in the basic courses are University A1 (50 courses, 1997 class hours), and the schools with the most credits are University B3 and University B1 (105.5 credits). The schools with the largest number of courses in the core courses are University C1 (23 courses), and the school with the most credits and class hours is University B2 (51 credits, 914 class hours). The school with the most class hours in practical teaching is University B6 (1406 class hours), and the schools with the longest internship time are University A1 and University B6 (52 weeks). CONCLUSIONS: There was substantial variation in programs. There remains a gap between the existing educational model and clinical training in pharmacy in China and developed countries. China should explore the most appropriate method for undergraduate education in clinical pharmacy based on studying foreign excellent educational models and the experience of China.

CXCR4 Expressed by Tumor-Infiltrating B Cells in Gastric Cancer Related to Survival in the Tumor Microenvironment: An Analysis Combining Single-Cell RNA Sequencing with Bulk RNA Sequencing.

According to the World Health Organization (WHO), gastric cancer (GC) is the fourth leading cause of tumor-related mortality globally and one of the most prevalent malignant tumors. To better understand the role of tumor-infiltrating B cells (TIBs) in GC, this work used single-cell RNA sequencing (scRNA-Seq) and bulk RNA sequencing (bulk RNA-Seq) data to identify candidate hub genes. Both scRNA-Seq and bulk RNA-Seq data for stomach adenocarcinoma (STAD) were obtained from the GEO and TCGA databases, respectively. Using scRNA-seq data, the FindNeighbors and FindClusters tools were used to group the cells into distinct groups. Immune cell clusters were sought in the massive RNA-seq expression matrix using the single-sample gene set enrichment analysis (ssGSEA). The expression profiles were used in Weighted Gene Coexpression Network Analysis (WGCNA) to build TCGA's gene coexpression networks. Next, univariate Cox regression, LASSO regression, and Kaplan-Meier analyses were used to identify hub genes in scRNA-seq data from sequential B-cell analyses. Finally, we examined the correlation between the hub genes and TIBs utilizing the TISIDB database. We confirmed the immune-related markers in clinical validation samples using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). 15 cell clusters were classified in the scRNA-seq database. According to the WGCNA findings, the green module is most associated with cancer and B cells. The intersection of 12 genes in two separate datasets (scRNA and bulk) was attained for further analysis. However, survival studies revealed that increased C-X-C motif chemokine receptor 4 (CXCR4) expression was linked to worse overall survival. CXCR4 expression is correlated with active, immature, and memory B cells in STAD were identified. Finally, RT-PCR and IHC assays verified that in GC, CXCR4 is overexpressed, and its expression level correlates with TIBs. We used scRNA-Seq and bulk RNA-Seq to study STAD's cellular composition. We found that CXCR4 is highly expressed by TIBs in GC, suggesting that it may serve as a hub gene for these cells and a starting point for future research into the molecular mechanisms by which these immune cells gain access to tumors and potentially identify therapeutic targets.

Disparities in the Outcomes of Acute Pulmonary Embolism in Hospitalized Patients with Hematologic Malignancy and Solid Tumor.

This study aimed to compare the clinical burden and healthcare utilization outcomes of hematologic versus solid malignancies in patients hospitalized with acute pulmonary embolism (PE). This population-based, retrospective study extracted and analyzed the discharge data from the 2016-2018 US National Inpatient Sample (NIS) of hospitalized patients with a primary diagnosis of acute PE and a subsequent diagnosis of hematologic malignancies or solid tumors. Prolonged length-of-stay (LOS) was defined as ≥75th percentile LOS of the study cohort. Unfavorable discharge was defined as discharged to nursing home or long-term facility. Univariate and multivariate regression analyses were conducted to determine associations between cancer type, presence of unstable PE, and in-hospital outcomes in acute PE patients. Patients with acute PE with solid tumors had higher rates of in-hospital deaths and unfavorable discharge than those with hematologic malignancies (6.4% versus 3.2%, P < 0.001; 14.0% versus 11.2%, P = 0.01, respectively). Acute PE patients with hematologic malignancies had a lower risk of in-hospital death (aOR: 0.43, 95% CI: 0.31-0.60), unfavorable discharge (aOR: 0.76, 95% CI: 0.63-0.92), and prolonged LOS (aOR: 0.83, 95% CI: 0.71-0.98) than those with solid tumors. Stratified analysis showed that male patients aged <60 years with hematologic malignancies had a lower risk of prolonged LOS (aOR: 0.70, 95% CI: 0.52-0.94; aOR: 0.85, 95% CI: 0.68-1.05) and unfavorable discharge (aOR: 0.40, 95% CI: 0.22-0.71; aOR: 0.65, 95% CI: 0.50-0.85) than those with solid tumors. In the comparison of the outcomes of acute PE with hematologic malignancies and solid tumors, patients with hematologic malignancy had a lower risk of in-hospital deaths, prolonged LOS, and unfavorable discharge than those with solid tumors.

Identification of ST1 reveals a selection involving hitchhiking of seed morphology and oil content during soybean domestication.

Seed morphology and quality of cultivated soybean (Glycine max) have changed dramatically during domestication from their wild relatives, but their relationship to selection is poorly understood. Here, we describe a semi-dominant locus, ST1 (Seed Thickness 1), affecting seed thickness and encoding a UDP-D-glucuronate 4-epimerase, which catalyses UDP-galacturonic acid production and promotes pectin biosynthesis. Interestingly, this morphological change concurrently boosted seed oil content, which, along with up-regulation of glycolysis biosynthesis modulated by ST1, enabled soybean to become a staple oil crop. Strikingly, ST1 and an inversion controlling seed coat colour formed part of a single selective sweep. Structural variation analysis of the region surrounding ST1 shows that the critical mutation in ST1 existed in earlier wild relatives of soybean and the region containing ST1 subsequently underwent an inversion, which was followed by successive selection for both traits through hitchhiking during selection for seed coat colour. Together, these results provide direct evidence that simultaneously variation for seed morphology and quality occurred earlier than variation for seed coat colour during soybean domestication. The identification of ST1 thus sheds light on a crucial phase of human empirical selection in soybeans and provides evidence that our ancestors improved soybean based on taste.

LncRNA H19 acts as miR-301a-3p sponge to alleviate lung injury in mice with sepsis by regulating Adcy1.

BACKGROUND: The abnormal expression of long non-coding RNA (lncRNA) is closely related to disease progression. However, the role and mechanism of lncRNA H19 (lncH19) in sepsis-induced lung injury remain to be elucidated. METHODS: Cercal ligation and puncture (CLP) mice models and lipopolysaccharide (LPS)-induced cell injury model was used to construct sepsis-induced lung injury in vivo and in vitro. The expression of lncH19, microRNA (miR)-301a-3p, and adenylate cyclase 1 (Adcy1) mRNA was assessed using quantitative real-time PCR. The concentrations of inflammatory factors were determined by ELISA assay. Cell proliferation and apoptosis were determined using cell counting kit 8 assay, EdU staining, and flow cytometry. The protein expression of apoptosis markers and Adcy1 was examined by western blot analysis. Oxidative stress was assessed by detecting the contents of oxidative stress markers. The interaction between miR-301a-3p and lncH19 or Adcy1 was confirmed using RNA pull-down assay, dual-luciferase reporter assay, and RIP assay. RESULTS: LncH19 was lowly expressed in CLP mice models and LPS-induced cell injury models. Overexpressed lncH19 could alleviate CLP-induced lung injury in mice, as well as LPS-induced cell apoptosis, inflammation, and oxidative stress. MiR-301a-3p could be sponged by lncH19, and its overexpression could reverse the inhibition of lncH19 on LPS-induced cell injury. Adcy1 was a target of miR-301a-3p, and its expression was upregulated by lncH19. Silencing of Adcy1 could abolish the suppressive effect of the miR-301a-3p inhibitor on LPS-induced cell injury. CONCLUSION: LncH19 might inhibit sepsis-induced lung injury by acting as a sponge of miR-301a-3p to upregulate Adcy1. HIGHLIGHTSLncH19 overexpression relieves CLP-induced lung injury and LPS-induced cell injury.LncH19 directly sponges miR-301a-3p.MiR-301a-3p targets Adcy1.

MALE STERILITY 3 encodes a plant homeodomain-finger protein for male fertility in soybean.

Male-sterile plants are used in hybrid breeding to improve yield in soybean (Glycine max (L.) Merr.). Developing the capability to alter fertility under different environmental conditions could broaden germplasm resources and simplify hybrid production. However, molecular mechanisms potentially underlying such a system in soybean were unclear. Here, using positional cloning, we identified a gene, MALE STERILITY 3 (MS3), which encodes a nuclear-localized protein containing a plant homeodomain (PHD)-finger domain. A spontaneous mutation in ms3 causing premature termination of MS3 translation and partial loss of the PHD-finger. Transgenetic analysis indicated that MS3 knockout resulted in nonfunctional pollen and no self-pollinated pods, and RNA-seq analysis revealed that MS3 affects the expression of genes associated with carbohydrate metabolism. Strikingly, the fertility of mutant ms3 can restore under long-d conditions. The mutant could thus be used to create a new, more stable photoperiod-sensitive genic male sterility line for two-line hybrid seed production, with significant impact on hybrid breeding and production.