Dyslipidemia characterized by low density lipoprotein cholesterol and risk of preterm Birth: A Mendelian randomization study.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality worldwide, and dyslipidemia is associated with preterm birth in observational studies. We use Mendelian randomization (MR) analyses to uncover the causal association between blood lipid levels and preterm birth. METHODS: We extracted uncorrelated (R2 < 0.001) single-nucleotide polymorphisms strongly associated (p < 5 × 10-8) with blood lipids from genome wide association studies of FinnGen database and UK Biobank participants. Inverse variance weighted method was the main MR analysis. Sensitivity analyses including genetic pleiotropy, heterogeneity, and directionality of causality were conducted. RESULTS: The study included 115,082 participants with lipid measurements, 8,507 patients with preterm birth. Increasing apolipoprotein B (odds ratio (OR), 1.12[95 % CI, 1.02-1.23]; p = 0.019), low-density lipoprotein cholesterol (OR, 1.11[95 % CI, 1.00-1.22]; p = 0.040), non-high-density lipoprotein cholesterol (OR, 1.12[95 % CI, 1.01-1.24]; p = 0.026), remnant cholesterol (OR, 1.11[95 % CI, 1.00-1.23]; p = 0.047) and total free cholesterol (OR, 1.11[95 % CI, 1.01-1.23]; p = 0.037) were associated with increased risk of preterm delivery. Moreover, triglycerides in low-density lipoprotein were causally associated with the risk of PTB. Our sensitivity analysis yielded robust results, uncovering no evidence of horizontal pleiotropy or reverse causal relationships. CONCLUSION: Our investigation unveils the adverse impact of dyslipidemia on preterm birth, with a particular emphasis on the detrimental effect of elevated low-density lipoprotein cholesterol.

The novel HLA-DRB1 allele, HLA-DRB1*09:54 was identified in a Chinese individual.

HLA-DRB1*09:54 shows a substitution G to A at position 449 when compared with HLA-DRB1*09:01:02:01.

INT-1B3, an LNP formulated miR-193a-3p mimic, promotes anti-tumor immunity by enhancing T cell mediated immune responses via modulation of the tumor microenvironment and induction of immunogenic cell death.

microRNAs (miRNAs) are small, non-coding RNAs that regulate expression of multiple genes. MiR-193a-3p functions as a tumor suppressor in many cancer types, but its effect on inducing specific anti-tumor immune responses is unclear. Therefore, we examined the effect of our lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on anti-tumor immunity. INT-1B3 inhibited distant tumor metastasis and significantly prolonged survival. INT-1B3-treated animals were fully protected against challenge with autologous tumor cells even in absence of treatment indicating long-term immunization. Protection against autologous tumor cell challenge was hampered upon T cell depletion and adoptive T cell transfer abrogated tumor growth. Transfection of tumor cells with our miR-193a-3p mimic (1B3) resulted in tumor cell death and apoptosis accompanied by increased expression of DAMPs. Co-culture of 1B3-transfected tumor cells and immature DC led to DC maturation and these mature DC were able to stimulate production of type 1 cytokines by CD4+ and CD8+ T cells. CD4-CD8- T cells also produced type 1 cytokines, even in response to 1B3-transfected tumor cells directly. Live cell imaging demonstrated PBMC-mediated cytotoxicity against 1B3-transfected tumor cells. These data demonstrate for the first time that miR-193a-3p induces long-term immunity against tumor development via modulation of the tumor microenvironment and induction of immunogenic cell death.

Mapping of long interspersed element-1 (L1) insertions by TIPseq provides information about sub chromosomal genetic variation in human embryos.

PURPOSE: Retrotransposons play important roles during early development when they are transiently de-repressed during epigenetic reprogramming. Long interspersed element-1 (L1), the only autonomous retrotransposon in humans, comprises 17% of the human genome. We applied the Single Cell Transposon Insertion Profiling by Sequencing (scTIPseq) to characterize and map L1 insertions in human embryos. METHODS: Sixteen cryopreserved, genetically tested, human blastocysts, were accessed from consenting couples undergoing IVF at NYU Langone Fertility Center. Additionally, four trios (father, mother, and embryos) were also evaluated. scTIPseq was applied to map L1 insertions in all samples, using L1 locations reported in the 1000 Genomes as controls. RESULTS: Twenty-nine unknown and unique insertions were observed in the sixteen embryos. Most were intergenic; no insertions were located in exons or immediately upstream of genes. The location or number of unknown insertions did not differ between euploid and aneuploid embryos, suggesting they are not merely markers of aneuploidy. Rather, scTIPseq provides novel information about sub-chromosomal structural variation in human embryos. Trio analyses showed a parental origin of all L1 insertions in embryos. CONCLUSION: Several studies have measured L1 expression at different stages of development in mice, but this study for the first time reports unknown insertions in human embryos that were inherited from one parent, confirming no de novo L1 insertions occurred in parental germline or during embryogenesis. Since one-third of euploid embryo transfers fail, future studies would be useful for understanding whether these sub-chromosomal genetic variants or de novo L1 insertions affect embryo developmental potential.

SFN promotes renal fibrosis via binding with MYH9 in chronic kidney disease.

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on CKD. First, we found that SFN was highly expressed in patients with CKD, as well as in CKD animal and cell models. Next, we induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes kidney fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.

Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306).

Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort. Results: In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM). Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Double Balloon Combined with Oxytocin in Labor Induction: Analysis of Multivariate Factors Affecting the Efficacy of Cervical Ripening.

Objective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction. Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups. Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257-2.112), fetal distress (OR = 1.371, 95% CI: 1.331-2.633), and the placement of cervical ripening balloon catheter for >12h (OR = 1.563, 95% CI: 1.231-3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455-0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for >12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714-0.811). Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.

An unusual colon mass.

A 55-year-old man came to our hospital for a colonoscopy due to periumbilical paroxysmal pain. The colonoscopy showed a huge mass near the ascending colon, with necrosis on the surface and unclear basal boundary. The structure of the residual and basal mucosa of the mass was similar to the normal intestinal mucosa. The biopsy pathology showed inflammatory cells infiltration. The patient underwent an appendectomy 30 years ago. In order to further clarify the nature of this mass, an abdominal enhanced computerized tomography (CT) was arranged for him. The CT showed segmental thickening of the ascending colon and "concentric circles" in the ileocecal part, which were consistent with intussusception like change. Then, we arranged a surgery for him. The intraoperative exploration revealed that the mass was located in the ileocecal part, about 5cm*4cm*3cm in size, soft in texture, and the intestinal tube was mildly edema. After opening the specimen, we found that the appendiceal stump had intratussed into the cecum and forming the granulomatous new tissue. Postoperative pathology showed proliferation of submucosal adipose tissue and granulation tissue, and infiltration of inflammatory cells with necrosis.

Persistent upper gastrointestinal symptoms after Helicobacter pylori eradication: malignant lymphoma following "chicken skin-like" gastritis.

A 37-year-old patient presented to our hospital for upper endoscopy with upper abdominal pain for 10 days. The gastroscopy showed food retention, a large ulcer from the corner of the stomach to the stomach body was seen, the bottom was obviously depressed, the surface was covered by white moss, and the edge of the ulcer presented as a "auricular" sign (Ear-shape appearance). Pathology showed malignant lymphoma. One and a half years prior, the patient underwent a gastroscopy at our hospital. At that time, the gastroscopy showed a large number of nodular protrusions in the gastric antrum, gastric angle, and some parts of the gastric body, presenting a "chicken skin like" change. At the same time, a superficial ulcer lesion was visible in the gastric angle. Pathology suggested gastritis and a small amount of necrotic tissue, as well as proliferation of lymphoid follicles. After receiving the treatment to eradicate Helicobacter pylori (HP), the patient's symptoms significantly improved and no further follow-up was conducted.

Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer.

BACKGROUND: Gastric cancer is one of the most common malignant tumors in the world, and its occurrence and development involve complex biological processes. Iron death, as a new cell death mode, has attracted wide attention in recent years. However, the regulatory mechanism of iron death in gastric cancer and its effect on lipid peroxidation metabolism remain unclear. AIM: To explore the role of iron death in the development of gastric cancer, reveal its relationship with lipid peroxidation, and provide a new theoretical basis for revealing the molecular mechanism of the occurrence and development of gastric cancer. METHODS: The process of iron death in gastric cancer cells was simulated by cell culture model, and the occurrence of iron death was detected by fluorescence microscopy and flow cytometry. The changes of gene expression related to iron death and lipid peroxidation metabolism were analyzed by high-throughput sequencing technology. In addition, a mouse model of gastric cancer was established, and the role of iron death in vivo was studied by histology and immunohistochemistry, and the level of lipid peroxidation was detected. These methods comprehensively and deeply reveal the regulatory mechanism of iron death on lipid peroxidation metabolism in the occurrence and development of gastric cancer. RESULTS: Iron death was significantly activated in gastric cancer cells, and at the same time, associated lipid peroxidation levels increased significantly. Through high-throughput sequencing analysis, it was found that iron death regulated the expression of several genes related to lipid metabolism. In vivo experiments demonstrated that increased iron death in gastric cancer mice was accompanied by a significant increase in lipid peroxidation. CONCLUSION: This study confirmed the important role of iron death in regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer. The activation of iron death significantly increased lipid peroxidation levels, revealing its regulatory mechanism inside the cell.

Effect of osmanthus hydrolat on the aroma quality and volatile components of osmanthus black tea.

Osmanthus fragrans is an evergreen shrub with a pleasant fragrance and a wide range of applications in many fields. The condensed hydrolat obtained during the drying process of its fresh flowers was collected in a low-temperature vacuum environment and its sensory evaluation and volatile components were studied. The main aroma compounds in Osmanthus fragrans were dihydro-ß-ionone, nonanal, ß-cyclocitral, ß-ionone, benzaldehyde, α-ionone, and 6-methyl-5-hepten-2-one, whose contents were used as the main evaluation criteria, and the hydrolats obtained under different scenting and drying times were compared. This process can effectively collect the aroma components in Osmanthus fragrans and the optimal drying conditions were 50 °C for 5 h. The hydrolat was used to provide the scent of osmanthus black tea, which had a fresher and mellower taste, while the fragrance of osmanthus was abundant. These results show that osmanthus hydrolat can be used to provide the scent of floral black tea. Chemical compounds studied in this article: (-)-Catechin (PubChem CID: 1203); (-)-epigallocatechin gallate (PubChem CID: 65064); (-)-epicatechin gallate (PubChem CID: 367141); (-)-epigallocatechin (PubChem CID: 72277); (-)-epicatechin (PubChem CID: 72276); (-)-gallocatechin gallate (PubChem CID: 199472); (-)-catechin gallate (PubChem CID: 6419835); (-)-gallocatechin (PubChem CID: 9882981).

NIR-II-Responsive Versatile Nanozyme Based on H2O2 Cycling and Disrupting Cellular Redox Homeostasis for Enhanced Synergistic Cancer Therapy.

Disturbing cellular redox homeostasis within malignant cells, particularly improving reactive oxygen species (ROS), is one of the effective strategies for cancer therapy. The ROS generation based on nanozymes presents a promising strategy for cancer treatment. However, the therapeutic efficacy is limited due to the insufficient catalytic activity of nanozymes or their high dependence on hydrogen peroxide (H2O2) or oxygen. Herein, we reported a nanozyme (CSA) based on well-defined CuSe hollow nanocubes (CS) uniformly covered with Ag nanoparticles (AgNPs) to disturb cellular redox homeostasis and catalyze a cascade of intracellular biochemical reactions to produce ROS for the synergistic therapy of breast cancer. In this system, CSA could interact with the thioredoxin reductase (TrxR) and deplete the tumor microenvironment-activated glutathione (GSH), disrupting the cellular antioxidant defense system and augmenting ROS generation. Besides, CSA possessed high peroxidase-mimicking activity toward H2O2, leading to the generation of various ROS including hydroxyl radical (•OH), superoxide radicals (•O2-), and singlet oxygen (1O2), facilitated by the Cu(II)/Cu(I) redox and H2O2 cycling, and plentiful catalytically active metal sites. Additionally, due to the absorption and charge separation performance of AgNPs, the CSA exhibited excellent photothermal performance in the second near-infrared (NIR-II, 1064 nm) region and enhanced the photocatalytic ROS level in cancer cells. Owing to the inhibition of TrxR activity, GSH depletion, high peroxidase-mimicking activity of CSA, and abundant ROS generation, CSA displays remarkable and specific inhibition of tumor growth.

Transcriptomics Identifies Differentially Expressed Genes Inducing Tuber Formation in Early- and Late-Maturing Potatoes.

The timing of potato tuberization is affected by potato ripeness, environmental factors, and polygene regulation. The accurate control of the transition to tuberization has both scientific and practical production value, but the key factors regulating this transition remain unclear. This study grafted an early-maturing potato variety (Favorita) scion to the late-maturing Qingshu 9 variety and demonstrated that a heterologous early-maturing scion can induce early potato formation on a late-maturing rootstock. The transcriptome of functional leaves and stolons of grafted plants was comprehensively analyzed and 593 differentially expressed genes (DEGs) were identified, including 38 transcription factors. Based on gene molecular function analysis and previous reports, we propose that PIF5, bHLH93, CBF3, ERF109, TCP19, and YABBY1 are the key DEGs that induce tuber formation in early- and late-maturing potatoes. The YABBY1 gene was subjected to functional verification. The leaf area of StYABBY1-overexpressing plants was smaller than the wild type and no potato tubercles were formed, while an RNA interference plant line showed no change in leaf area and formed tubers, indicating that StYABBY1 has a role in leaf size regulation and tuber formation.

A disposable electrochemical magnetic immunosensor for the rapid and sensitive detection of 5-formylcytosine and 5-carboxylcytosine in DNA.

5-formylcytosine (5 fC) and 5-carboxylcytosine (5caC) serve as key intermediates in DNA demethylation process with significant implications for gene regulation and disease progression. In this study, we introduce a novel electrochemical sensing platform specifically designed for the sensitive and selective detection of 5 fC and 5caC in DNA. Protein A-modified magnetic beads (ProtA-MBs) coupled with specific antibodies facilitate the immunorecognition and enrichment of these modified bases. Signal amplification is achieved through several chemical reactions involving the interaction between N3-kethonaxl and guanine, copper-free click chemistry for the attachment of dibenzocyclooctyne (DBCO)-Biotin, and the subsequent recognition by streptavidin-conjugated horseradish peroxidase (SA-HRP). The assay's readout is performed on a disposable laser-induced graphene (LIG) electrode, modified with the bead-antibody-DNA complex in a magnetic field, and analyzed using differential pulse voltammetry in a system employing hydroquinone (HQ) as the redox mediator and H2O2 as the substrate. This immunosensor displayed excellent sensitivity, with detection limits of 14.8 fM for 5 fC across a 0.1-1000 pM linear range and 87.4 fM for 5caC across a 0.5-5000 pM linear range, and maintained high selectivity even in the presence of interferences from other DNA modifications. Successful application in quantifying 5 fC and 5caC in genomic DNA from cell extracts, with recovery rates between 97.7% to 102.9%, underscores its potential for clinical diagnostics. N3-kethoxal was used for the first time in an electrochemical sensor. This work not only broadens the toolkit for detecting DNA modifications but also provides a fresh impetus for the development of point-of-care testing (POCT) technologies.

Electrochemical chiral sensor for recognition of amino acid enantiomers with cyclodextrin-based microporous organic networks.

BACKGROUND: Chirality is a ubiquitous phenomenon in nature, but enantiomers exhibit different pharmacological activities and toxicological effects. Therefore, Chiral recognition plays a pivotal role in various fields such as life sciences, chemical synthesis, drug development, and materials science. The synthesis of novel chiral composites with well-defined loading capabilities and ordered structures holds significant potential for electrochemical chiral recognition applications. However, the design of selective and stable electrochemical chiral recognition materials remains a challenging task. RESULT: In this work, we construct a simple and rapid electrochemical sensing platform for tryptophan (Trp) enantiomer recognition using cyclodextrin-modified microporous organic network as chiral recognition agent. CD-MON with chiral microenvironment was prepared by Sonogashira-Hagihara coupling reaction of the chiral molecule heptyl-6-iodo-6-deoxyß-cyclodextrin and 1, 4-Diethynylbenzene. The adhesion of BSA makes CD-MON firmly fixed on the electrode surface, and as a chiral protein, it can improve the chiral recognition ability through synergistic effect. Chiral amino acids are in full contact with the chiral microenvironment during pore conduction of MON, and L-Trp is more stably bound to CD-MON/BSA due to steric hindrance, host-guest recognition and hydrogen bonding. Therefore, the electrochemical sensor can effectively identify tryptophan enantiomers (IL-Trp/ID-Trp = 2.02), and it exhibits a detection limit of 2.6 µM for L-Trp. UV-Vis spectroscopy confirmed the adsorption capacity of CD-MON towards tryptophan enantiomers in agreement with electrochemistry results. SIGNIFICANCE: The prepared chiral sensor has excellent stability, reproducibility (RSD = 3.7%) and selectivity, realizes the quantitative detection of single isomer in tryptophan racemic and quantitative analysis in real samples with 94.0%-101.0% recovery. This work represents the first application of MON in chiral electrochemistry which expands the application scope of chiral sensors and holds great significance in separation science and electrochemical sensing.

Wheel-Running Exercise Alleviates Anxiety-Like Behavior via Down-Regulating S-Nitrosylation of Gephyrin in the Basolateral Amygdala of Male Rats.

Physical exercise has beneficial effect on anxiety disorders, but the underlying molecular mechanism remains largely unknown. Here, it is demonstrated that physical exercise can downregulate the S-nitrosylation of gephyrin (SNO-gephyrin) in the basolateral amygdala (BLA) to exert anxiolytic effects. It is found that the level of SNO-gephyrin is significantly increased in the BLA of high-anxiety rats and a downregulation of SNO-gephyrin at cysteines 212 and 284 produced anxiolytic effect. Mechanistically, inhibition of SNO-gephyrin by either Cys212 or Cys284 mutations increased the surface expression of GABAAR γ2 and the subsequent GABAergic neurotransmission, exerting anxiolytic effect in male rats. On the other side, overexpression of neuronal nitric oxide synthase in the BLA abolished the anxiolytic-like effects of physical exercise. This study reveals a key role of downregulating SNO-gephyrin in the anxiolytic effects of physical exercise, providing a new explanation for protein post-translational modifications in the brain after exercise.

Predicting risk of the subsequent early pregnancy loss in women with recurrent pregnancy loss based on preconception data.

BACKGROUND: For women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data. METHODS: A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features. RESULTS: In the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer-Lemeshow test was 7.427, and P = 0.505. CONCLUSIONS: Predicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.

First-trimester hemoglobin, haptoglobin genotype, and risk of gestational diabetes mellitus in a retrospective study among Chinese pregnant women.

BACKGROUND: This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. METHODS: This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. RESULTS: Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. CONCLUSION: Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.

Comparative physiological and transcriptomic analyses provide induction resistance mechanisms of Bacillus tequilensis against Colletotrichum fructicola in Camellia oleifera.

Bacillus tequilensis DZY 6715 was isolated from healthy leaves in Camellia oleifera, and the strain DZY 6715 significantly inhibited anthracnose disease resulting from Colletotrichum fructicola in C. oleifera, besides, its associated mechanism of disease resistance was explored. B. tequilensis DZY 6715 treatment controlled mycelial growth of C. fructicola in C. oleifera, and significantly decreased C. oleifera anthracnose incidence and disease index compared with the control group. B. tequilensis DZY 6715 has strong biofilm forming ability, and also secretes extracellular ß-1, 3-glucanase and chitinase, which could cause cell membranes damage and increased cellular compound leakage. C.oleifera treated with DZY 6715 also effectively enhanced enzyme activities and stimulated the synthesis the substances related to phenylpropane metabolism and reactive oxygen metabolism. Moreover, transcript profiling analysis revealed more differentially expressed genes related to phenylpropanoid pathway metabolism and antioxidant system inducing by DZY 6715 compared with the control in C. oleifera. Thus, it can be concluded that B. tequilensis DZY 6715 is a suitable bio-control agent to control anthracnose disease in C. oleifera.