Genome-wide identification of GATA transcription factors in tetraploid potato and expression analysis in differently colored potato flesh.

The GATA gene family belongs to a kind of transcriptional regulatory protein featuring a zinc finger motif, which is essential for plant growth and development. However, the identification of the GATA gene family in tetraploid potato is still not performed. In the present research, a total of 88 GATA genes in the tetraploid potato C88.v1 genome were identified by bioinformatics methods. These StGATA genes had an uneven distribution on 44 chromosomes, and the corresponding StGATA proteins were divided into four subfamilies (I-IV) based on phylogenetic analysis. The cis-elements of StGATA genes were identified, including multiple cis-elements related to light-responsive and hormone-responsive. The collinearity analysis indicates that segmental duplication is a key driving force for the expansion of GATA gene family in tetraploid potato, and that the GATA gene families of tetraploid potato and Arabidopsis share a closer evolutionary relationship than rice. The transcript profiling analysis showed that all 88 StGATA genes had tissue-specific expression, indicating that the StGATA gene family members participate in the development of multiple potato tissues. The RNA-seq analysis was also performed on the tuber flesh of two potato varieties with different color, and 18 differentially expressed GATA transcription factor genes were screened, of which eight genes were validated through qRT-PCR. In this study, we identified and characterized StGATA transcription factors in tetraploid potato for the first time, and screened differentially expressed genes in potato flesh with different color. It provides a theoretical basis for further understanding the StGATA gene family and its function in anthocyanin biosynthesis.

Hemorrhage profile associated with immune checkpoint inhibitors: a systematic review and a real-world study based on the FAERS database.

OBJECTIVES: To investigate the risk of hemorrhage associated with Immune Checkpoint Inhibitors (ICIs) and characterize its clinical features. METHODS: We systematically reviewed randomized clinical trials (RCTs) of hemorrhage related to ICIs and calculated odds ratios (ORs) with 95% confidence intervals (CIs). Pharmacovigilance studies were conducted by collecting ICIs-related hemorrhage cases from the FAERS database and assessing disproportionalities by reporting odds ratios (RORs) and information components (ICs). RESULTS: A total of 79 RCTs involving 45,100 patients were finally included in the systematic review, with four published RCTs (n = 1965) and 75 unpublished RCTs (n = 43135). The primary analysis showed no significant difference in ICIs compared to the control group (OR 1.18 [95% CI 1.00-1.38], p = 0.05). In subgroup analyses, anti-PD-L1 combined with anti-CTLA-4 increased the risk of hemorrhage (OR 1.95, p = 0.03), and anti-CTLA-4 increased the risk of hemorrhage in the gastrointestinal system (OR 2.23, p = 0.04). 3555 cases of hemorrhage from the FAERS database were included in the disproportionate analysis, and the result suggested that ICIs increased the risk of hemorrhage (IC025 = 0.23). CONCLUSION: Our study suggests that ICIs increase the risk of hemorrhage, and in particular, anti-CTLA-4 significantly increases the risk of hemorrhage in the gastrointestinal system.

Non-linear relationship between the body roundness index and metabolic syndrome: data from National Health and Nutrition Examination Survey (NHANES) 1999-2018.

Obesity is an important characteristic manifestation of metabolic syndrome (MetS), and body roundness index (BRI) is one of the anthropometric indicators associated with obesity. However, studies on the relationship between BRI and MetS risk are limited. We aimed to explore the relationship between baseline BRI and MetS in the USA population. Our study used data from the National Health and Nutrition Examination Survey from 1999 to 2018, ultimately enrolling and analysing 47 303 participants. Data-driven tertiles were used to categorise BRI levels, and multivariate logistic regression models were fitted to investigate the association of BRI with MetS in adults. In addition, receiver operating characteristic curve analysis was used to assess the ability of BRI to predict MetS. The distribution of BRI was different across ethnic groups with a gradual decrease in the proportion of non-Hispanic Whites and other races. In addition, BRI was significantly associated with traditional cardiovascular risk factors. Univariate regression analysis indicated BRI to be a moderate risk factor for MetS, and multivariate logistic regression analysis found that BRI remained an independent risk factor for MetS. After adjusting for confounding variables, a non-linear relationship was found between BRI levels and the prevalence of MetS. More importantly, BRI predicted MetS with the largest AUC among anthropometric measures. In summary, elevated baseline BRI levels are independently associated with the development of MetS, and baseline BRI may assist in identifying patients at risk for MetS, leading to early and optimal treatment to improve their outcomes.

A recurrent positional encoding circular attention mechanism network for biomedical image segmentation.

Deep-learning-based medical image segmentation techniques can assist doctors in disease diagnosis and rapid treatment. However, existing medical image segmentation models do not fully consider the dependence between feature segments in the feature extraction process, and the correlated features can be further extracted. Therefore, a recurrent positional encoding circular attention mechanism network (RPECAMNet) is proposed based on relative positional encoding for medical image segmentation. Multiple residual modules are used to extract the primary features of the medical images, which are thereafter converted into one-dimensional data for relative positional encoding. The recursive former is used to further extract features from medical images, and decoding is performed using deconvolution. An adaptive loss function is designed to train the model and achieve accurate medical-image segmentation. Finally, the proposed model is used to conduct comparative experiments on the synapse and self-constructed kidney datasets to verify the accuracy of the proposed model for medical image segmentation.

Harnessing microbial interactions with rice: Strategies for abiotic stress alleviation in the face of environmental challenges and climate change.

Rice, which feeds more than half of the world's population, confronts significant challenges due to environmental and climatic changes. Abiotic stressors such as extreme temperatures, drought, heavy metals, organic pollutants, and salinity disrupt its cellular balance, impair photosynthetic efficiency, and degrade grain quality. Beneficial microorganisms from rice and soil microbiomes have emerged as crucial in enhancing rice's tolerance to these stresses. This review delves into the multifaceted impacts of these abiotic stressors on rice growth, exploring the origins of the interacting microorganisms and the intricate dynamics between rice-associated and soil microbiomes. We highlight their synergistic roles in mitigating rice's abiotic stresses and outline rice's strategies for recruiting these microorganisms under various environmental conditions, including the development of techniques to maximize their benefits. Through an in-depth analysis, we shed light on the multifarious mechanisms through which microorganisms fortify rice resilience, such as modulation of antioxidant enzymes, enhanced nutrient uptake, plant hormone adjustments, exopolysaccharide secretion, and strategic gene expression regulation, emphasizing the objective of leveraging microorganisms to boost rice's stress tolerance. The review also recognizes the growing prominence of microbial inoculants in modern rice cultivation for their eco-friendliness and sustainability. We discuss ongoing efforts to optimize these inoculants, providing insights into the rigorous processes involved in their formulation and strategic deployment. In conclusion, this review emphasizes the importance of microbial interventions in bolstering rice agriculture and ensuring its resilience in the face of rising environmental challenges.

The different role of adversity before and after birth in adolescent depression.

BACKGROUND: Early adversity is strongly linked to adolescent depression, but there is limited research on the impact of indirect exposure to adversity before birth and the distinct role of adversity before and after birth. METHODS: A total of 1911 Chinese adolescents (48.8 % males; ages 11 to 19, Mean = 13.96) reported early adversities before and after birth, depression, negative self-cognition and perceived school climate. Structural equation model was used to test the association between early adversity before/after birth and adolescent depression, with negative self-cognition serving as a mediator and school climate as a moderator. RESULTS: Adversity before birth was related to adolescent depression through the full mediating role of negative self-cognition. Furthermore, it was more associated with negative self-cognition in schools with a more favorable climate. Adversity after birth was related to adolescent depression through the partial mediating role of negative self-cognition, and school climate played a nonsignificant moderating role in the mediating path. LIMITATIONS: Early adversity was measured through adolescent reports, possibly generating recall bias. The cross-sectional design should be taken into consideration when drawing conclusions about causality. CONCLUSIONS: Adversities before and after birth are associated with adolescent depression in distinct ways. The more association between adversity before birth and negative self-cognition in a favorable school climate supports the "healthy context paradox." Interventions that target depression should focus on promoting a positive school climate and helping adolescents who have experienced early adversity bolster positive self-cognition.

A polymeric nanocarrier that eradicates breast cancer stem cells and delivers chemotherapeutic drugs.

BACKGROUND: Drug nanocarriers can markedly reduce the toxicities and side effects of encapsulated chemotherapeutic drugs in the clinic. However, these drug nanocarriers have little effect on eradicating breast cancer stem cells (BCSCs). Although compounds that can inhibit BCSCs have been reported, these compounds are difficult to use as carriers for the widespread delivery of conventional chemotherapeutic drugs. METHODS: Herein, we synthesize a polymeric nanocarrier, hyaluronic acid-block-poly (curcumin-dithiodipropionic acid) (HA-b-PCDA), and explore the use of HA-b-PCDA to simultaneously deliver chemotherapeutic drugs and eradicate BCSCs. RESULTS: Based on molecular docking and molecular dynamics studies, HA-b-PCDA delivers 35 clinical chemotherapeutic drugs. To further verify the drug deliver ability of HA-b-PCDA, doxorubicin, paclitaxel, docetaxel, gemcitabine and camptothecin are employed as model drugs to prepare nanoparticles. These drug-loaded HA-b-PCDA nanoparticles significantly inhibit the proliferation and stemness of BCSC-enriched 4T1 mammospheres. Moreover, doxorubicin-loaded HA-b-PCDA nanoparticles efficiently inhibit tumor growth and eradicate approximately 95% of BCSCs fraction in vivo. Finally, HA-b-PCDA eradicates BCSCs by activating Hippo and inhibiting the JAK2/STAT3 pathway. CONCLUSION: HA-b-PCDA is a polymeric nanocarrier that eradicates BCSCs and potentially delivers numerous clinical chemotherapeutic drugs.

Facial palsy induced by immune checkpoint blockade: A systematic analysis of clinical trials and a pharmacovigilance study of postmarketing data.

BACKGROUND: To estimate the risk of facial nerve palsy (FP) associated with immune checkpoint inhibitors (ICIs), and to describe its clinical features. METHODS: Data from randomized controlled trials (RCTs) and FDA Adverse Event Reporting System (FAERS) database were included. The primary outcome was the risk of FP events associated with ICIs. For data from RCTs, pooled analysis was performed by using risk ratios (RRs) with 95%CIs. In a separate retrospective pharmacovigilance study of FAERS, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC). RESULTS: A total of 21 RCTs (193,05 patients) were included, ICIs were associated with increased risk of FP (OR = 3.07, 95%CI:1.43-6.58). Results of subgroup analysis indicated that OR of ICI-related FP did not vary significantly by tumor type, ICIs treatment schedule, case of events, study design, median PFS and publication status. FAERS pharmacovigilance data identified 274 cases of FP related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of FP (ROR = 3.03, 95%CI:2.69-3.42; IC = 1.56, 95%CI:1.38-1.76). The median onset time of FP was 5.5 weeks, drug interruption was recorded in 78.0% of cases, with a positive dechallenge in 82.8 % of cases, and 71.7% of cases were recovered or recovering. CONCLUSIONS: These data suggest that ICIs were significantly associated with increased risk of FP in both trial settings and in clinical practice.

ZFP541 and KCTD19 regulate chromatin organization and transcription programs for male meiotic progression.

The successful progression of meiosis prophase I requires integrating information from the structural and molecular levels. In this study, we show that ZFP541 and KCTD19 work in the same genetic pathway to regulate the progression of male meiosis and thus fertility. The Zfp541 and/or Kctd19 knockout male mice show various structural and recombination defects including detached chromosome ends, aberrant localization of chromosome axis components and recombination proteins, and globally altered histone modifications. Further analyses on RNA-seq, ChIP-seq, and ATAC-seq data provide molecular evidence for the above defects and reveal that ZFP541/KCTD19 activates the expression of many genes by repressing several major transcription repressors. More importantly, we reveal an unexpected role of ZFP541/KCTD19 in directly modulating chromatin organization. These results suggest that ZFP541/KCTD19 simultaneously regulates the transcription cascade and chromatin organization to ensure the coordinated progression of multiple events at chromosome structural and biochemical levels during meiosis prophase I.

Risk factors for malnutrition in patients with nasopharyngeal carcinoma.

BACKGROUND: Malnutrition is a common complication in patients with nasopharyngeal carcinoma (NPC). However, there are few studies on risk factors for malnutrition in NPC patients. Our aims were to identify the risk factors for malnutrition in NPC patients. METHODS: NPC patients were recruited in this cross-sectional study, and they were divided into well-nourished and malnourished groups according to the Global Leadership Initiative on Malnutrition (GLIM). Potential risk factors were initially screened using univariate analysis (p < 0.1), and the selected ones were analyzed by logistic regression analysis (p < 0.05) to identify the risk factors for malnutrition in NPC patients. RESULTS: In total, 305 NPC patients meeting eligibility criteria were enrolled. Multivariate logistic regression analysis revealed that low body mass index (BMI) (OR = 0.596, 95% CI 0.520-0.683, p < 0.001), the high total radiation dose received (OR = 1.046, 95% CI 1.023-1.069, p < 0.001), appetite loss (OR = 2.839, 95% CI 1.269-6.353, p = 0.011), and low PA (OR = 0.993, 95% CI 0.988-0.998, p = 0.008) were risk factors for malnutrition in NPC patients. CONCLUSIONS: The low BMI, the high total radiation dose received, appetite loss, and low prealbumin were risk factors for malnutrition in NPC patients.

Cadmium-absorptive Bacillus vietnamensis 151-6 reduces the grain cadmium accumulation in rice (Oryza sativa L.): Potential for cadmium bioremediation.

Microbial bioremediation of heavy metal-polluted soil is a promising technique for reducing heavy metal accumulation in crops. In a previous study, we isolated Bacillus vietnamensis strain 151-6 with a high cadmium (Cd) accumulation ability and low Cd resistance. However, the key gene responsible for the Cd absorption and bioremediation potential of this strain remains unclear. In this study, genes related to Cd absorption in B. vietnamensis 151-6 were overexpressed. A thiol-disulfide oxidoreductase gene (orf4108) and a cytochrome C biogenesis protein gene (orf4109) were found to play major roles in Cd absorption. In addition, the plant growth-promoting (PGP) traits of the strain were detected, which enabled phosphorus and potassium solubilization and indole-3-acetic acid (IAA) production. Bacillus vietnamensis 151-6 was used for the bioremediation of Cd-polluted paddy soil, and its effects on growth and Cd accumulation in rice were explored. The strain increased the panicle number (114.82%) and decreased the Cd content in rice rachises (23.87%) and grains (52.05%) under Cd stress, compared with non-inoculated rice in pot experiments. For field trials, compared with the non-inoculated control, the Cd content of grains inoculated with B. vietnamensis 151-6 was effectively decreased in two cultivars (low Cd-accumulating cultivar: 24.77%; high Cd-accumulating cultivar: 48.85%) of late rice. Bacillus vietnamensis 151-6 encoded key genes that confer the ability to bind Cd and reduce Cd stress in rice. Thus, B. vietnamensis 151-6 exhibits great application potential for Cd bioremediation.

Thromboembolism profiles associated with cyclin-dependent kinase 4/6 inhibitors: a real-world pharmacovigilance study and a systematic review.

BACKGROUND: Thrombosis is the second leading cause of mortality in cancer patients. This study aimed to investigate the association between cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and thrombosis. RESEARCH DESIGN AND METHODS: A retrospective pharmacovigilance analysis based on real-world data combined with a systematic review was used to explore the thrombotic risk profiles of CDK4/6i. The study has been registered with Prospero (CRD42021284218). RESULT: In the pharmacovigilance analysis, CDK4/6i showed a higher rate of reported venous thromboembolism (VTE) (ROR = 2.78, 95% CI = 2.64-2.92), with the highest signal for trilaciclib (ROR = 27.55, 95% CI = 13.43-56.52) but only 9 cases, followed by abemaciclib (ROR = 3.73, 95% CI = 3.19-4.37). For arterial thromboembolism (ATE), only ribociclib increased the reporting rate (ROR = 2.14, 95% CI = 1.91-2.41). In the meta-analysis, palbociclib, abemaciclib, and trilaciclib all increased the risk of VTE (OR = 2.23, 3.17, and 3.90). In the subgroup analysis, only abemaciclib increased the risk of ATE (OR = 2.11, 95% CI = 1.12-3.99)    . CONCLUSIONS: CDK4/6i had different profiles of thromboembolism. Palbociclib, abemaciclib, or trilaciclib increased the risk of VTE. Ribociclib and abemaciclib showed a weak association with the risk of ATE.

Pushing the Electrochemical Performance Limits of Polypyrrole Toward Stable Microelectronic Devices.

Conducting polymers have achieved remarkable attentions owing to their exclusive characteristics, for instance, electrical conductivity, high ionic conductivity, visual transparency, and mechanical tractability. Surface and nanostructure engineering of conjugated conducting polymers offers an exceptional pathway to facilitate their implementation in a variety of scientific claims, comprising energy storage and production devices, flexible and wearable optoelectronic devices. A two-step tactic to assemble high-performance polypyrrole (PPy)-based microsupercapacitor (MSC) is utilized by transforming the current collectors to suppress structural pulverization and increase the adhesion of PPy, and then electrochemical co-deposition of PPy-CNT nanostructures on rGO@Au current collectors is performed. The resulting fine patterned MSC conveyed a high areal capacitance of 65.9 mF cm-2 (at a current density of 0.1 mA cm-2), an exceptional cycling performance of retaining 79% capacitance after 10,000 charge/discharge cycles at 5 mA cm-2. Benefiting from the intermediate graphene, current collector free PPy-CNT@rGO flexible MSC is produced by a facile transfer method on a flexible substrate, which delivered an areal capacitance of 70.25 mF cm-2 at 0.1 mA cm-2 and retained 46% of the initial capacitance at a current density of 1.0 mA cm-2. The flexible MSC is utilized as a skin compatible capacitive micro-strain sensor with excellent electromechanochemical characteristics.

Corrigendum: Integrated analysis of small RNAs, transcriptome and degradome sequencing reveal the drought stress network in Agropyron mongolicum Keng.

[This corrects the article DOI: 10.3389/fpls.2022.976684.].

Immune checkpoint inhibitors increase the risk of kidney transplant rejection: a real-world pharmacovigilance study.

BACKGROUND: Kidney transplant recipients with cancer are at higher risk of kidney transplant rejection (KTR), and the safety of immune checkpoint inhibitors (ICIs) is unclear. The present study investigates the relationship between ICIs and KTR using data from the Food and Drug Administration Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: Case reports of KTR inducted by ICIs in FAERS from 1 January 2011, to 30 June 2021, were collected, and a disproportionate analysis was performed to assess the correlation between ICIs and KTR. RESULTS: A total of 99 cases of ICI-related KTR were reported in the FAERS database. Most of them were male patients (n = 63, 84.0%), and more than half of patients suffered from malignant melanoma (n = 46, 52.9%). The median onset time after the medication was 22 days, the withdrawal rates of ICIs were 78.0%, and the overall death rate was 29.3%. In general, there was a significant relevance between ICIs and KTR (ROR = 3.92[3.21-4.79] IC025 = 1.56), of which PD-1 was the most prominent (n = 81 ROR = 5.26[4.22-6.57] IC025 = 1.86). CONCLUSIONS: ICIs may increase the risk of KTR in organ transplant recipients with cancer.

A pharmacovigilance analysis of FDA adverse event reporting system events for romosozumab.

BACKGROUND: Romosozumab is a novel drug for the treatment of osteoporosis. The adverse reactions of romosozumab still need to be explored. The FDA Adverse Event Reporting System (FAERS) provides an enormous dataset for adverse events (AEs) analysis. RESEARCH DESIGN AND METHODS: AEs registered in FAERS between January 2019 and December 2020 were collected for this study. The reporting odds ratio (ROR) method was applied to analyze the AEs of romosozumab. The number of AEs ≥4 cases and ROR value 95% confidence interval (CI) lower limit >1 was considered statistically significant. RESULTS: A total of 4,413,695 AEs were collected for this study. There were 1,948 AEs related with romosozumab reported in FAERS. There are 1851 AEs including 17 system classifications after filtered. Injection site pain (ROR = 6.89, CI = 5.60, 8.48), cardiac failure (ROR = 12.62, CI = 9.85, 16.17), renal impairment (ROR = 9.11, CI = 6.98, 11.89), pneumonia (ROR = 1.53, CI = 1.10, 2.21), blood alkaline phosphatase increased (ROR = 14.60, CI = 9.28, 22.97) were possible AEs after romosozumab application. CONCLUSIONS: Our study provides an adverse reaction warning for the clinical application of romosozumab and provides a real-world disproportionality analysis data support for the possible AEs of romosozumab.

Synergy of surface adsorption and intracellular accumulation for removal of uranium with Stenotrophomonas sp: Performance and mechanisms.

Uranium is well-known to have serious adverse effects on the ecological environment and human health. Bioremediation stands out among many remediation methods owing to its being economically feasible and environmentally friendly. This study reported a great promising strategy for eliminating uranium by Stenotrophomonas sp. CICC 23833 in the aquatic environment. The bacterium demonstrated excellent uranium adsorption capacity (qmax = 392.9 mg/g) because of the synergistic effect of surface adsorption and intracellular accumulation. Further analysis revealed that hydroxyl, carboxyl, phosphate groups and proteins of microorganisms were essential in uranium adsorption. Intracellular accumulation was closely related to cellular activity, and the efficiency of uranium processing by the permeabilized bacterial cells was significantly improved. In response to uranium stress, the bacterium was found to release multiple ions in conjunction with uranium adsorption, which facilitates the maintenance of bacterial life activities and the conversion of uranyl to precipitates. These above results indicated that Stenotrophomonas sp. Had great potential application value for the remediation of uranium.

Expression pattern of peritoneum IL-6 is associated with baseline peritoneal transport function in uremic patients before dialysis.

OBJECTIVE: This study aimed to investigate the biological factors associated with baseline peritoneal transport in uremic patients before dialysis. METHODS: Thirty patients with uremia were grouped according to their peritoneal dialysate creatinine/serum creatinine ratio (D/P) as high-transport (H, 16 cases) with D/P>0.65 and low-transport (L, 14 cases) with D/P≤0.65 one month after continuous ambulatory peritoneal dialysis treatment. Multi-inflammatory levels such as serum IL-6 and albumin, peritoneal IL-6 level, and microvessel density (MVD) of visceral peritoneal were compared and correlated between the two groups to determine the associated factors. RESULTS: There were no significant differences in clinical parameters between the two groups (p < 0.05). There were no significant differences in serum IL-6 and albumin between the two groups. However, peritoneal IL-6 and MVD in group H were significantly higher than group L (p=0.012, p=0.044), and they were positively correlated (r=0.368, p=0.045). Furthermore, baseline D/P was positively correlated with IL-6 expressions (r=0.640, p=0.000) and peritoneal MVD (r=0.476, p=0.008), and independently associated with peritoneal IL-6 expression (p=0.004). CONCLUSIONS: The baseline peritoneal transport performance is associated with peritoneal IL-6 expression and MVD but not circulatory IL-6.

Engineering Vacancies at the 2D Nanocrystals for Robust Bifunctional Electrocatalysts.

Hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) through water decomposition are feasible methods to produce green and clean energy. Herein, we report a facile two-step strategy for the preparation of non-noble metal defect-rich nanosheets by an electrochemical process at room temperature. First-principle calculations are used to study the bifunctional catalytic reaction mechanism of defect engineering in transition-metal dichalcogenides (TMDs); from the first-principle calculations, we predicted that the rich S vacancies on the nanosheet promoted electron transfer and reduced the energy barrier of electrocatalysis. As a substantiation, we conducted HER/OER electrochemical characterizations and found that the defect-rich atomic-thick tantalum sulfide is a kind of dual-function electrocatalyst with enhanced comprehensive properties of Tafel slope (39 mV/dec for HER, 38 mV/dec for OER) and low overpotential (0.099 V for HER, 0.153 V for OER) in acidic and alkaline environments, respectively. Likewise, the defect-rich catalysts exhibit high stability in acidic and alkaline solutions, which have potential applications as electrocatalysts for the large-scale production of hydrogen and oxygen.