Risk for Donor-Derived Syphilis after Kidney Transplantation, China, 2007-2022.

To evaluate the risk of acquiring syphilis from a donated kidney, we evaluated kidney transplantation pairs from West China Hospital, Sichuan, China, during 2007-2022. Donor-derived syphilis was rare. Risk may be higher if donors have active syphilis and may be reduced if recipients receive ceftriaxone.

Nanofluidic Membrane-Assisted Organic Electrochemical Transistors for Bioinspired Gustatory Sensation Based on Selective Cation Transport.

Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

Active strong coupling of exciton and nanocavity based on GSST-WSe2 hybrid nanostructures.

The strong coupling between optical resonance microcavity and matter excitations provides a practical path for controlling light-matter interactions. However, conventional microcavity, whose functions are fixed at the fabrication stage, dramatically limits the modulation of light-matter interactions. Here, we investigate the active strong coupling of resonance mode and exciton in GSST-WSe2 hybrid nanostructures. It is demonstrated that significant spectral splitting is observed in single nanostructures, tetramers, and metasurfaces. We further confirm the strong coupling by calculating the enhanced fluorescence spectra. The coupling effect between the excited resonance and exciton is dramatically modulated during the change of GSST from amorphous to crystalline, thus realizing the strong coupling switching. This switching property has been fully demonstrated in several systems mentioned earlier. Our work is significant in guiding the study of actively tunable strong light-matter interactions at the nanoscale.

Enhancement of vitamin B6 production driven by omics analysis combined with fermentation optimization.

BACKGROUND: Microbial engineering aims to enhance the ability of bacteria to produce valuable products, including vitamin B6 for various applications. Numerous microorganisms naturally produce vitamin B6, yet the metabolic pathways involved are rigorously controlled. This regulation by the accumulation of vitamin B6 poses a challenge in constructing an efficient cell factory. RESULTS: In this study, we conducted transcriptome and metabolome analyses to investigate the effects of the accumulation of pyridoxine, which is the major commercial form of vitamin B6, on cellular processes in Escherichia coli. Our omics analysis revealed associations between pyridoxine and amino acids, as well as the tricarboxylic acid (TCA) cycle. Based on these findings, we identified potential targets for fermentation optimization, including succinate, amino acids, and the carbon-to-nitrogen (C/N) ratio. Through targeted modifications, we achieved pyridoxine titers of approximately 514 mg/L in shake flasks and 1.95 g/L in fed-batch fermentation. CONCLUSION: Our results provide insights into pyridoxine biosynthesis within the cellular metabolic network for the first time. Our comprehensive analysis revealed that the fermentation process resulted in a remarkable final yield of 1.95 g/L pyridoxine, the highest reported yield to date. This work lays a foundation for the green industrial production of vitamin B6 in the future.

Patterns of antibiotic administration in Chinese neonates: results from a multi-center, point prevalence survey.

OBJECTIVES: In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization's (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China. METHODS: One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019. RESULTS: Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group. CONCLUSION: Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates.

Genome-Wide Mapping of Plasma IgG N-Glycan Quantitative Trait Loci Identifies a Potentially Causal Association between IgG N-Glycans and Rheumatoid Arthritis.

Observational studies highlight associations of IgG N-glycosylation with rheumatoid arthritis (RA); however, the causality between these conditions remains to be determined. Standard and multivariable two-sample Mendelian randomization (MR) analyses integrating a summary genome-wide association study for RA and IgG N-glycan quantitative trait loci (IgG N-glycan-QTL) data were performed to explore the potentially causal associations of IgG N-glycosylation with RA. After correcting for multiple testing (p < 2 × 10-3), the standard MR analysis based on the inverse-variance weighted method showed a significant association of genetically instrumented IgG N-glycan (GP4) with RA (odds ratioGP4 = 0.906, 95% confidence interval = 0.857-0.958, p = 5.246 × 10-4). In addition, we identified seven significant associations of genetically instrumented IgG N-glycans with RA by multivariable MR analysis (p < 2 × 10-3). Results were broadly consistent in sensitivity analyses using MR_Lasso, MR_weighted median, MR_Egger regression, and leave-one-out analysis with different instruments (all p values <0.05). There was limited evidence of pleiotropy bias (all p values > 0.05). In conclusion, our MR analysis incorporating genome-wide association studies and IgG N-glycan-QTL data revealed that IgG N-glycans were potentially causally associated with RA. Our findings shed light on the role of IgG N-glycosylation in the development of RA. Future studies are needed to validate our findings and to explore the underlying physiological mechanisms in the etiology of RA.

Bioinformatics and Functional Analysis of OsASMT1 Gene in Response to Abiotic Stress.

The study aimed to elucidate the functional characteristics of OsASMT1 gene under copper (Cu) or sodium chloride (NaCl) stress. Bioinformatics scrutiny unveiled that OsASMT1 is situated on chromosome 9. Its protein architecture, comprising dimerization and methyltransferase domains, showed significant similarities to OsASMT2 and OsASMT3. High expression in roots and panicles, along with abiotic stress putative cis-regulatory elements in the promoter, indicated potential stress responsiveness. Real-time quantitative PCR confirmed OsASMT1 induction under Cu and NaCl stress in rice. Surprisingly, yeast expressing OsASMT1 did not exhibit enhanced resistance to abiotic stresses. The results of subcellular localization analysis indicated that OsASMT1 plays a role in the cytoplasm. While OsASMT1 responded to Cu and NaCl stress in rice, its heterologous expression in yeast failed to confer abiotic stress resistance, highlighting the need for further investigation of its functional implications.

Efficacy of Ying-huang and San-ao Decoctions in Sepsis-Associated Acute Lung Injury.

Objective: The objective of this study was to evaluate the efficacy of the combined treatment of Ying-Huang Decoction and San-ao Decoction compared to conventional treatment alone in patients with sepsis-associated acute lung injury (S-ALI) and to assess its potential mechanisms for improving clinical symptoms, reducing inflammatory response, and promoting respiratory function recovery. Methods: We included 84 S-ALI patients admitted to our hospital between January 2021 and January 2023. The patients were divided into a control group and an observation group, with 42 patients in each group. The control group received conventional treatment, while the observation group received the combined treatment of Ying-Huang Decoction and San-ao Decoction in addition to conventional treatment. The study was conducted in accordance with the principles of the Helsinki Declaration and received ethical approval. The main outcome measures assessed included symptom scores, levels of inflammatory factors, lung injury scores (such as LIS scores), respiratory function parameters (such as PVPI and EVLWL levels), and the incidence of adverse reactions. Results: The observation group receiving the combined treatment of Ying-Huang Decoction and San-ao Decoction demonstrated favorable outcomes compared to the control group. Significant improvements were observed in the observation group's symptom scores compared to the control group (P < .05). Patients in the observation group experienced a notable alleviation of clinical symptoms associated with S-ALI. In terms of inflammatory response, the observation group showed significantly lower levels of inflammatory factors, including IL-6, CRP, and IL-17, compared to the control group (P < .01). This suggests that the combined decoction treatment effectively reduced the systemic inflammatory response in S-ALI patients. Lung injury scores, as assessed by the LIS, were significantly reduced in the observation group compared to the control group (P < .05). This indicates that the combined treatment contributed to the mitigation of lung tissue damage in S-ALI patients. Respiratory function parameters, such as PVPI and EVLWL levels, showed significant improvement in the observation group compared to the control group (P < .01), indicating enhanced respiratory function. Conclusion: The combined treatment of Ying-Huang Decoction and San-ao Decoction, in addition to conventional treatment, demonstrated beneficial effects in the management of S-ALI, leading to improved clinical symptoms, reduced inflammatory response, and enhanced respiratory function. These findings suggest the potential integration of traditional Chinese medicine approaches, such as Ying-Huang Decoction and San-ao Decoction, in the treatment of S-ALI, providing additional options for clinicians and potentially improving patient outcomes. It is important to acknowledge the limitations of this study, such as its retrospective design and the need for further research with larger sample sizes to validate the results and minimize potential biases.

Emodin Attenuates Sepsis-induced Intestinal Injury by Regulating TRPM7 Expression.

Background: Sepsis is a potentially lethal organ immune dysfunction induced by infection, with the stomach being the first organ to be attacked. Emodin has anti-inflammatory and gastrointestinal functions, but its therapeutic effect on intestinal injury in sepsis remains unclear. This study sought to investigate the role of emodin in treating intestine damage brought on by sepsis. Methods: Between June 2021 and July 2023, Lipopolysaccharide (LPS) was used to stimulate human intestinal epithelial cells NCM460 to create a septic cell model, and treatment was regulated by rhodopsin. Transient receptor potential melastatin 7 (TRPM7) expression was used to check that the LPS induction conditions were acceptable. About the proliferation of the NCM460 cells, the effects of overexpressing TRPM7 and silencing TRPM7 were assessed. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide test. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 expression in the cells was detected using enzyme-linked immunosorbent assays. TRPM7 messenger RNA expression was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Western blot determined the levels of TRPM7, Bcl2-associated X (Bax), and B-cell lymphoma-2 (Bcl2) protein expression levels. The terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling (TUNEL) technique was used to measure the apoptosis rate. Results: The levels of the inflammatory factors and Bax expression in the cells and the cell apoptosis rate steadily increased as the LPS-induced concentration increased. In contrast, cell viability and the Bcl2 expression levels gradually decreased. In this study, we treated the cells with LPS at a concentration of 25 µg/mL for 12 hours. It was detected that the knockdown of TRPM7 expression decreased the effect of LPS induction, while boosting the expression of TRPM7 boosted the effectiveness. Treatment with emodin lowered TRPM7 expression, increasing cell survival, and Bcl2 expression levels while decreasing the apoptosis rate, inflammatory factors, and Bax expression levels. Conclusion: Emodin may alleviate sepsis-induced intestinal injury by down-regulating the TRPM7 gene. These findings suggest that emodin may hold promise as a therapeutic agent for treating intestinal injury in sepsis. If further validated through additional research and clinical trials, emodin or similar compounds could potentially be developed into safe and effective medications for sepsis patients.

Bidirectional Two-Sample Mendelian Randomization Study of Immunoglobulin G N-Glycosylation and Senescence-Associated Secretory Phenotype.

Observational studies revealed changes in Immunoglobulin G (IgG) N-glycosylation during the aging process. However, it lacks causal insights and remains unclear in which direction causal relationships exist. The two-sample bidirectional Mendelian randomization (MR) design was adopted to explore causal associations between IgG N-glycans and the senescence-associated secretory phenotype (SASP). Inverse variance weighted (IVW) and Wald ratio methods were used as the main analyses, supplemented by sensitivity analyses. Forward MR analyses revealed causal associations between the glycan peak (GP) and SASP, including GP6 (odds ratio [OR] = 0.428, 95% confidence interval [CI] = 0.189-0.969) and GP17 (OR = 0.709, 95%CI = 0.504-0.995) with growth/differentiation factor 15 (GDF15), GP19 with an advanced glycosylation end-product-specific receptor (RAGE) (OR = 2.142, 95% CI = 1.384-3.316), and GP15 with matrix metalloproteinase 2 (MMP2) (OR = 1.136, 95% CI =1.008-1.282). The reverse MR indicated that genetic liability to RAGE was associated with increased levels of GP17 (OR = 1.125, 95% CI = 1.003-1.261) and GP24 (OR = 1.222, 95% CI = 1.046-1.428), while pulmonary and activation-regulated chemokines (PARC) exhibited causal associations with GP10 (OR = 1.269, 95% CI = 1.048-1.537) and GP15 (OR = 1.297, 95% CI = 1.072-1.570). The findings provided suggested evidence on the bidirectional causality between IgG N-glycans and SASP, which might reveal potential regulatory mechanisms.

Endogenous Hormone Levels and Transcriptomic Analysis Reveal the Mechanisms of Bulbil Initiation in Pinellia ternata.

Pinellia ternata is a medicinal plant that has important pharmacological value, and the bulbils serve as the primary reproductive organ; however, the mechanisms underlying bulbil initiation remain unclear. Here, we characterized bulbil development via histological, transcriptomic, and targeted metabolomic analyses to unearth the intricate relationship between hormones, genes, and bulbil development. The results show that the bulbils initiate growth from the leaf axillary meristem (AM). In this stage, jasmonic acid (JA), abscisic acid (ABA), isopentenyl adenosine (IPA), and salicylic acid (SA) were highly enriched, while indole-3-acetic acid (IAA), zeatin, methyl jasmonate (MeJA), and 5-dexoxystrigol (5-DS) were notably decreased. Through OPLS-DA analysis, SA has emerged as the most crucial factor in initiating and positively regulating bulbil formation. Furthermore, a strong association between IPA and SA was observed during bulbil initiation. The transcriptional changes in IPT (Isopentenyltransferase), CRE1 (Cytokinin Response 1), A-ARR (Type-A Arabidopsis Response Regulator), B-ARR (Type-B Arabidopsis Response Regulator), AUX1 (Auxin Resistant 1), ARF (Auxin Response Factor), AUX/IAA (Auxin/Indole-3-acetic acid), GH3 (Gretchen Hagen 3), SAUR (Small Auxin Up RNA), GA2ox (Gibberellin 2-oxidase), GA20ox (Gibberellin 20-oxidase), AOS (Allene oxide synthase), AOC (Allene oxide cyclase), OPR (Oxophytodienoate Reductase), JMT (JA carboxy l Methyltransferase), COI1 (Coronatine Insensitive 1), JAZ (Jasmonate ZIM-domain), MYC2 (Myelocytomatosis 2), D27 (DWARF27), SMAX (Suppressor of MAX2), PAL (Phenylalanine Ammonia-Lyase), ICS (Isochorismate Synthase), NPR1 (Non-expressor of Pathogenesis-related Genes1), TGA (TGACG Sequence-specific Binding), PR-1 (Pathogenesis-related), MCSU (Molybdenium Cofactor Sulfurase), PP2C (Protein Phosphatase 2C), and SnRK (Sucrose Non-fermenting-related Protein Kinase 2) were highly correlated with hormone concentrations, indicating that bulbil initiation is coordinately controlled by multiple phytohormones. Notably, eight TFs (transcription factors) that regulate AM initiation have been identified as pivotal regulators of bulbil formation. Among these, WUS (WUSCHEL), CLV (CLAVATA), ATH1 (Arabidopsis Thaliana Homeobox Gene 1), and RAX (Regulator of Axillary meristems) have been observed to exhibit elevated expression levels. Conversely, LEAFY demonstrated contrasting expression patterns. The intricate expression profiles of these TFs are closely associated with the upregulated expression of KNOX(KNOTTED-like homeobox), suggesting a intricate regulatory network underlying the complex process of bulbil initiation. This study offers a profound understanding of the bulbil initiation process and could potentially aid in refining molecular breeding techniques specific to P. ternata.

The Causality between Human Immunoglobulin G (IgG) N-Glycosylation and Aging: A Mendelian Randomization Study.

BACKGROUND: Immunoglobulin G (IgG) N-glycosylation is considered a potential biomarker for aging and various pathological conditions. However, whether these changes in IgG N-glycosylation are a consequence or a contributor to the aging process remains unclear. This study aims to investigate the causality between IgG N-glycosylation and aging using Mendelian randomization (MR) analysis. METHODS: We utilized genetic variants associated with IgG N-glycosylation traits, the frailty index (FI), and leukocyte telomere length (LTL) from a previous genome-wide association study (GWAS) on individuals of European ancestry. Two-sample and multivariable MR analyses were conducted, employing the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to assess potential confounding factors. RESULTS: Using the IVW method, we found suggestive evidence of a causal association between GP14 and FI (ß 0.026, 95% CI 0.003 to 0.050, p = 0.027) and LTL (ß -0.020, 95% CI -0.037 to -0.002, p = 0.029) in the two-sample MR analysis. In the multivariable MR analysis, suggestive evidence was found for GP23 and FI (ß -0.119, 95% CI -0.219 to -0.019, p = 0.019) and GP2 and LTL (ß 0.140, 95% CI 0.020 to 0.260, p = 0.023). CONCLUSIONS: In conclusion, our results supported a potentially causal effect of lower GP23 levels on an advanced aging state. Additional verification is required to further substantiate the causal relationship between glycosylation and aging.

MiR-652-3p promotes malignancy and metastasis of cancer cells via inhibiting TNRC6A in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) was one of the most prevalent life-threatening cancers. Metastasis is the leading cause of cancer-related death in HCC. MiRNAs play essential roles in cancer metastasis. METHODS: Expression of miR-652-3p in HCC was assessed. Function experiments of miR-652-3p and trinucleotide repeat-containing gene 6A protein (TNRC6A) were performed both in vitro and in vivo. mRNA sequencing, PCR, and western blot were performed to verify the target genes and pathway of miR-652-3p. The lung metastasis and xenograft cancer model in nude mice was established to investigate the effects of the miR-652-3p and TRNC6A on tumor metastasis in vivo. The relationship between the expression of the miR-652-3p, TNRC6A and the prognosis of HCC patients was analyzed. RESULTS: Upregulated miR-652-3p was found in the tumor tissues of HCC, especially in metastatic HCC patients. Overexpression of miR-652-3p promoted and knockdown of miR-652-3p suppressed HCC metastasis both in vitro and in vivo. MiR-652-3p promoted HCC metastasis via regulating the EMT pathway. TNRC6A was identified as a direct target of miR-652-3p, and the knockdown of TNRC6A restored repressed EMT and HCC metastasis caused by the inhibition of miR-652-3p. Clinical results revealed that high expression of miR-652-3p and low expression of TNRC6A were positively correlated to shortened overall survival and disease-free survival in HCC patients. CONCLUSIONS: MiR-652-3p promotes EMT and HCC metastasis by inhibiting TNRC6A expression in HCC. MiR-652-3p and TNRC6A may serve as potential biomarkers to predict prognosis in HCC patients with metastasis.

Glucagon-like peptide-1 receptor agonists and diabetic retinopathy: nationwide cohort and Mendelian randomization studies.

BACKGROUND: The ability of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to decrease certain microvascular events has called for the investigation of GLP-1 RAs against diabetic retinopathy (DR), but the evidence is limited. By combining data from observational and Mendelian randomization (MR) studies, we aimed to investigate whether GLP-1 RAs decrease the risk of DR. METHODS: We combined data from several Swedish Registers and identified patients with incident type 2 diabetes being treated with GLP-1 RAs between 2006 and 2015, and matched them to diabetic patients who did not use GLP-1 RAs as the comparisons. The Cox proportional hazards models were applied to assess the risk of DR. We further performed the summary-data-based MR (SMR) analyses based on the Genotype-Tissue Expression databases and the Genome-Wide Association Study of DR from the FinnGen consortium. RESULTS: A total of 2390 diabetic patients were treated with GLP-1 RAs and the incidence of DR was 5.97 per 1000 person-years. Compared with diabetic patients who did not use GLP-1 RAs having an incidence of 12.85 per 1000 person-years, the adjusted hazard ratio (HR) of DR was 0.42 [95% confidence interval (CI), 0.29-0.61]. Genetically-predicted GLP1R expression (the target of GLP-1 RAs) showed an inverse association with background [odds ratio (OR)=0.83, 95% CI, 0.71-0.97] and severe nonproliferative DR (OR=0.72, 95% CI, 0.53-0.98), and a non-significant association with overall (OR=0.97, 95% CI, 0.92-1.03) and proliferative DR (OR=0.98, 95% CI, 0.91-1.05). CONCLUSIONS: Both observational and mendelian randomization analyses showed a significantly lower risk of DR for patients treated with GLP-1 RAs, which calls for further studies to validate these findings.

Time spent in a better cardiovascular health and risk of cardiovascular diseases and mortality: a prospective cohort study.

BACKGROUND: The protective effect of a higher ideal cardiovascular health (CVH) score on cardiovascular diseases (CVDs) and mortality is well recognized. However, little is known regarding the length of favorable CVH status associated with CVDs and mortality. This study aimed to examined whether the duration of better (ideal or intermediate) CVH is associated with risk of developing CVDs and mortality. METHODS: This prospective cohort study used data from 83,536 individuals from 2006 to 2020 who were enrolled in the Kailuan Study. The CVH scores of individuals were assessed at visits 1, 2, 3, and 4, respectively. The years spent in better CVH were estimated for each individual as the number of examination cycles (0-4) in which the participant was in that CVH score ≥ 8 multiplied by 2 (the mean year interval of each visit). The primary outcomes are CVD events and all-cause mortality. RESULTS: After a median follow-up period of 7.48 years, 5486 (7.07%) cases of incident CVD events and 7669 (9.18%) deaths occurred. Compared with participants in " ≤ 4 years" group, those who maintained for > 4 years had less likely to develop adverse outcomes (CVD events: hazard ratio (HR): 0.60, 95% confidence interval (CI 0.56-0.63; all-cause mortality: HR: 0.77, 95% CI 0.74-0.81). The number of years spent in better CVH was nonlinearly correlated with CVD events or mortality (all Ps for nonlinear < 0.05). The results indicated that maintaining more than 6 years in a better CVH status was associated with a decreased risk of CVD events or mortality. CONCLUSION: Our study indicates that individuals maintaining more than 6 years in better CVH could increase cardiometabolic benefits and a lower risk of all-cause mortality.

Genetic association and causal inference between lung function and venous thromboembolism.

BACKGROUND: Previous studies have indicated that lower lung function is related to a higher risk of venous thromboembolism (VTE). However, causal inferences may be affected by confounders, coheritability or reverse causality. We aimed to explore the causal association between lung function and VTE. METHODS: Summary data from public genome-wide association studies (GWAS) for lung function and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly related to exposure were filtered as proxy instruments. We adopted linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (MR) analyses to infer the genetic backgrounds and causal associations between different lung functions and VTE events. RESULTS: LDSC showed a genetic correlation between forced expiratory volume in one second (FEV1) and deep vein thrombosis (DVT) (rg = - 0.189, P = 0.005). In univariate MR (UVMR), there was suggestive evidence for causal associations of genetically predicted force vital capacity (FVC) with DVT (odds ratio (OR) 0.774; 95% confidence interval (CI) 0.641-0.934) via forwards analysis and genetically predicted pulmonary embolism (PE) with FVC (OR 0.989; 95% CI 0.979-0.999) via reverse analysis. Multivariate MR (MVMR) analyses of lung function-specific SNPs suggested no significant direct effects of lung function on VTE, and vice versa. Of note is the borderline causal effect of PE on FEV1 (OR 0.921; 95% CI 0.848-1.000). CONCLUSIONS: Our findings identified a coheritability of FEV1 (significant) and FVC (suggestive) with DVT. There was no convincing causal relationship between lung function and the risk of VTE events. The borderline causal effect of PE on FEV1 and the significant genetic correlation of FEV1 with DVT may have clinical implications for improving the quality of existing prevention and intervention strategies.

Expanding the donor pool: Kidney transplantation from serum HBV DNA or HBeAg-positive donors to HBsAg-negative recipients.

BACKGROUND & AIMS: HBsAg-positive (HBsAg[+]) donors are rarely accepted for kidney transplantation (KT), especially when the donor is also HBV DNA-positive (HBV DNA[+]) or HBeAg-positive (HBeAg[+]) serologically. This study aimed to report kidney transplant outcomes from HBsAg(+) donors to HBsAg(-) recipients. METHODS: Consecutive cases were retrospectively identified from 1 July 2017 to 31 December 2020. KTs from HBsAg(-)/HBcAb-positive (HBcAb[+]) donors to HBcAb(-) recipients were selected as the control group. The primary outcomes were de novo HBV infection (DNH), graft and patient survival. RESULTS: We identified 105 HBsAg(-) recipients who received HBsAg(+) kidneys and 516 HBcAb(-) recipients who received HBcAb(+) kidneys. A higher DNH rate was observed after receiving HBsAg(+) kidneys than after receiving HBcAb(+) kidneys after a median follow-up of 23.0 months (4/105[3.8%] vs. 2/516[0.4%], p = .009). All four infected recipients receiving HBsAg(+) kidneys had HBsAg clearance after treatment. Graft and patient survival were comparable between the groups (p = .630, p = .910). The DNH rates were 0/22(0%), 3/70(4.3%) and 1/13(7.7%) after receiving HBsAg(+), HBV DNA(+) and HBeAg(+) kidneys, respectively (p = .455). The DNH rate was lower if the donor had received antiviral treatment (4/42[9.5%] vs. 0/63[0%], p = .023). HBsAb(-) recipients had a higher DNH incidence than HBsAb(+) recipients (3/25[12.0%] vs. 1/80[1.3%], p = .041). CONCLUSIONS: The use of HBsAg(+) donors contributed to comparable graft and patient survival, but HBV DNA(+) or HBeAg(+) donors and HBsAb(-) recipients maybe associated with a higher risk of HBV infection. These findings help expand the donor pool and emphasize the role of donor antiviral treatment and recipient HBV immunity in establishing optimal prophylactic regimens.

Prediction differences and implications of acute kidney injury with and without urine output criteria in adult critically ill patients.

BACKGROUND: Due to the convenience of serum creatinine (SCr) monitoring and the relative complexity of urine output (UO) monitoring, most studies have predicted acute kidney injury (AKI) only based on SCr criteria. This study aimed to compare the differences between SCr alone and combined UO criteria in predicting AKI. METHODS: We applied machine learning methods to evaluate the performance of 13 prediction models composed of different feature categories on 16 risk assessment tasks (half used only SCr criteria, half used both SCr and UO criteria). The area under receiver operator characteristic curve (AUROC), the area under precision recall curve (AUPRC) and calibration were used to assess the prediction performance. RESULTS: In the first week after ICU admission, the prevalence of any AKI was 29% under SCr criteria alone and increased to 60% when the UO criteria was combined. Adding UO to SCr criteria can significantly identify more AKI patients. The predictive importance of feature types with and without UO was different. Using only laboratory data maintained similar predictive performance to the full feature model under only SCr criteria [e.g. for AKI within the 48-h time window after 1 day of ICU admission, AUROC (95% confidence interval) 0.83 (0.82, 0.84) vs 0.84 (0.83, 0.85)], but it was not sufficient when the UO was added [corresponding AUROC (95% confidence interval) 0.75 (0.74, 0.76) vs 0.84 (0.83, 0.85)]. CONCLUSIONS: This study found that SCr and UO measures should not be regarded as equivalent criteria for AKI staging, and emphasizes the importance and necessity of UO criteria in AKI risk assessment.

The H3K27 demethylase controls the lateral line embryogenesis of zebrafish.

BACKGROUND: Kdm6b, a specific histone 3 lysine 27 (H3K27) demethylase, has been reported to be implicated in a variety of developmental processes including cell differentiation and cell fate determination and multiple organogenesis. Here, we regulated the transcript level of kdm6bb to study the potential role in controlling the hearing organ development of zebrafish. METHODS: A morpholino antisense oligonucleotide (MO) strategy was used to induce Kdm6b deficiency; immunohistochemical staining and in situ hybridization analysis were conducted to figure out the morphologic alterations and embryonic mechanisms. RESULTS: Kdm6bb is expressed in the primordium and neuromasts at the early stage of zebrafish embryogenesis, suggesting a potential function of Kdm6b in the development of mechanosensory organs. Knockdown of kdm6bb severely influences the cell migration and proliferation in posterior lateral line primordium, abates the number of neuromasts along the trunk, and mRNA-mediated rescue test can partially renew the neuromasts. Loss of kdm6bb might be related to aberrant expressions of chemokine genes encompassing cxcl12a and cxcr4b/cxcr7b in the migrating primordium. Moreover, inhibition of kdm6bb reduces the expression of genes in Fgf signaling pathway, while it increases the axin2 and lef1 expression level of Wnt/ß-catenin signaling during the migrating stage. CONCLUSIONS: Collectively, our results revealed that Kdm6b plays an essential role in guiding the migration of primordium and in regulating the deposition of zebrafish neuromasts by mediating the gene expression of chemokines and Wnt and Fgf signaling pathway. Since histone methylation and demethylation are reversible, targeting Kdm6b may present as a novel therapeutic regimen for hearing disorders.

Causality assessment of circulating Vitamin D level on venous thromboembolism: A Mendelian randomization study.

BACKGROUND AND AIMS: The associations of vitamin D level with venous thromboembolism (VTE) reported in observational studies, whereas these causal associations were uncertain in European population. Therefore, we used Mendelian randomization (MR) method to explore the causal associations between 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of VTE and its subtypes [including deep vein thrombosis (DVT) and pulmonary embolism (PE)]. METHODS AND RESULTS: We used three kinds of genetic instruments to proxy the exposure of 25(OH)D, including genetic variants significantly associated with 25(OH)D, expression quantitative trait loci of 25(OH)D target genes, and genetic variants within or nearby 25(OH)D target genes. MR analyses did not provide any evidence for the associations of 25(OH)D levels with VTE and its subtypes (p > 0.05). The summary-data-based MR (SMR) analyses indicated that elevated expression of VDR was associated with decreased risk of VTE (OR = 0.81; 95% CI, 0.65-0.998; p = 0.047) and PE (OR = 0.67; 95% CI, 0.50-0.91; p = 0.011), and expression of AMDHD1 was associated with PE (OR = 0.93; 95% CI, 0.88-0.99; p = 0.027). MR analysis provided a significant causal effect of 25(OH)D level mediated by gene AMDHD1 on PE risk (OR = 0.09; 95% CI, 0.01-0.60; p = 0.012). CONCLUSION: Our MR analysis did not support causal association of 25(OH)D level with the risk of VTE and its subtypes. In addition, the expression of VDR and AMDHD1 involved in vitamin D metabolism showed a strong association with VTE or PE and might represent targets for these conditions.