A novel anti-inflammatory strategy for myocardial ischemia-reperfusion in rats with cinnamamide derivative compound 7.

Reperfusion after myocardial ischemia would aggravate myocardial structural and functional damage, known as myocardial ischemia-reperfusion (MI/R) injury. Cinnamamide derivatives have been reported to exert cardioprotective effects, and we have previously reported that compound 7 played a role in cardioprotection against MI/R via anti-inflammatory effect. However, exact mechanism underlying such beneficial action of compound 7 is still unclear. The protective effect of compound 7 was determined in H9c2 cells under H2O2 stimulation with or without nigerin (NLRP3 activator). Electrocardiogram, echocardiography, myocardial infarction size, histopathology and serum biochemical assay were performed in MI/R rats. Metabolomics in vivo and mRNA or protein levels of NLRP3, ASC, cleaved caspase-1 and its downstream IL-18 and IL-1ß were detected both in vitro and in vivo. Compound 7 significantly ameliorate H2O2-induced cardiomyocyte damage, which was supported by in vivo data determined by improved left ventricular systolic function and histopathological changes, reduced myocardial infarction area and cellular apoptosis in heart tissue. Cardiac differential metabolites demonstrated that compound 7 indeed altered the cardiac reprogramming of inflammation-related metabolites, which was evidenced by down-regulated cardiac inflammation by compound 7. Additionally, compound 7 alleviated myocardial injury by inhibiting the NLRP3 pathway rather than other members of the inflammasome both in vitro and in vivo, which was further evidenced by CETSA assay. Whereas, nigerin blocked the inhibitory activity of compound 7 against NLRP3. Cinnamamide derivative compound 7 ameliorated MI/R injury by inhibiting inflammation via NLRP3.

Cardioprotective effect of Cinnamamide derivative compound 10 against myocardial ischemia-reperfusion through regulating cardiac autophagy via Sirt1.

BACKGROUND AND PURPOSE: Our previous research discovered that cinnamamide derivatives are a new type of potential cardioprotective agents myocardial ischemia-reperfusion (MIR) injury, among which Compound 10 exhibits wonderful beneficial action in vitro. However, the exact mechanism of Compound 10 still needs to be elucidated. EXPERIMENTAL APPROACH: The protective effect of Compound 10 was determined by detecting the cell viability and LDH leakage rate in H9c2 cells subjected to H2O2. Alterations of electrocardiogram, echocardiography, cardiac infarct area, histopathology and serum myocardial zymogram were tested in MIR rats. Additionally, the potential mechanism of Compound 10 was explored through PCR. Network pharmacology and Western blotting was conducted to monitor levels of proteins related to autophagic flux and mTOR, autophagy regulatory substrate, induced by Compound 10 both in vitro and in vivo, as well as expressions of Sirtuins family members. KEY RESULTS: Compound 10 significantly ameliorated myocardial injury, as demonstrated by increased cell viability, decreased LDH leakage in vitro, and declined serum myocardial zymogram, ST elevation, cardiac infarct area and improved cardiac function and microstructure of heart tissue in vivo. Importantly, Compound 10 markedly enhanced the obstruction of autophagic flux and inhibited excessive autophagy initiation against MIR by decreased ATG5, Rab7 and increased P-mTOR and LAMP2. Furthermore, Sirt1 knockdown hindered Compound 10's regulation on mTOR, leading to interrupted cardiac autophagic flux. CONCLUSIONS AND IMPLICATIONS: Compound 10 exerted cardioprotective effects on MIR by reducing excessive autophagy and improving autophgic flux blockage. Our work would take a novel insight in seeking effective prevention and treatment strategies against MIR injury.

Non-centrosymmetric topological phase probed by non-linear Hall effect.

Non-centrosymmetric topological material has attracted intense attention due to its superior characteristics as compared with the centrosymmetric one, although probing the local quantum geometry in non-centrosymmetric topological material remains challenging. The non-linear Hall (NLH) effect provides an ideal tool to investigate the local quantum geometry. Here, we report a non-centrosymmetric topological phase in ZrTe5, probed by using the NLH effect. The angle-resolved and temperature-dependent NLH measurement reveals the inversion and ab-plane mirror symmetries breaking at <30 K, consistently with our theoretical calculation. Our findings identify a new non-centrosymmetric phase of ZrTe5 and provide a platform to probe and control local quantum geometry via crystal symmetries.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

Colorectal ALOX15 as a host factor determinant of EPA and DHA effects on colorectal carcinogenesis.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 polyunsaturated fatty acids (ω-3 PUFAs) derived from fish oil, are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. However, studies investigating the effects of EPA and DHA on colorectal carcinogenesis (CRC) have yielded conflicting results. The factors that determine these discrepant results remain unknown. Resolvins, oxidative metabolites of EPA and DHA, inhibit key pro-tumorigenic cytokine and chemokine signaling of colorectal cancer (e.g., IL-6, IL-1ß, and CCL2). 15-lipoxygenase-1 (ALOX15), a critical enzyme for resolvin generation is commonly lost during human CRC. Whether ALOX15 expression, as a host factor, modulates the effects of EPA and DHA on CRC remains unknown. Therefore, we evaluated the effects of ALOX15 transgenic expression in colonic epithelial cells on resolvin generation by EPA and DHA and CRC in mouse models representative of human CRC. Our results revealed that 1) EPA and DHA effects on CRC were diverse, ranging from suppressive to promotive, and these effects were occasionally altered by the formulations of EPA and DHA (free fatty acid, ethyl ester, triglyceride); 2) EPA and DHA uniformly suppressed CRC in the presence of intestinal ALOX15 transgenic expression, which induced the production of resolvins, decreased colonic CCL3-5 and CXCL-5 expression and tumor associated macrophages while increasing CD8 T cell abundance in tumor microenvironment; and 3) RvD5, the predominant resolvin produced by ALOX15, inhibited macrophage generation of pro-tumorigenic cytokines. These findings demonstrate the significance of intestinal ALOX15 expression as a host factor in determining the effects of EPA and DHA on CRC. Significance: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. Studies of EPA and DHA effects on colorectal carcinogenesis (CRC) have revealed inconsistencies; factors determining the direction of their impact on CRC have remained unidentified. Our data show that EPA and DHA effects on CRC were divergent and occasionally influenced by their formulations. More importantly, intestinal 15-lipoxgenase-1 (ALOX15) expression modulated EPA and DHA effects on CRC, leading to their consistent suppression of CRC. ALOX15 promoted EPA and DHA oxidative metabolism to generate resolvins, which inhibited key pro-tumorigenic inflammatory cytokines and chemokines, including IL-6. IL-1ß, and CCL2. ALOX15 is therefore an important host factor in determining EPA and DHA effects on CRC.

The multifaceted role of RNA-based regulation in plant stress memory.

Plants have evolved interconnected regulatory pathways which enable them to respond and adapt to their environments. In plants, stress memory enhances stress tolerance through the molecular retention of prior stressful experiences, fostering rapid and robust responses to subsequent challenges. Mounting evidence suggests a close link between the formation of stress memories and effective future stress responses. However, the mechanism by which environmental stressors trigger stress memory formation is poorly understood. Here, we review the current state of knowledge regarding the RNA-based regulation on stress memory formation in plants and discuss research challenges and future directions. Specifically, we focus on the involvement of microRNAs (miRNAs), small interfering RNAs (siRNAs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) in stress memory formation. miRNAs regulate target genes via post-transcriptional silencing, while siRNAs trigger stress memory formation through RNA-directed DNA methylation (RdDM). lncRNAs guide protein complexes for epigenetic regulation, and AS of pre-mRNAs is crucial to plant stress memory. Unraveling the mechanisms underpinning RNA-mediated stress memory formation not only advances our knowledge of plant biology but also aids in the development of improved stress tolerance in crops, enhancing crop performance and global food security.

Small Transjugular Intrahepatic Portosystemic Shunt Plus Variceal Embolization for Gastric Varices: A Multicenter Cohort Study.

BACKGROUND AND AIMS: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs. METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at seven medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality. RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% versus 13.6%, P=0.005) and OHE (31.0% versus 39.4%, P=0.02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% versus 9.7%, P=0.42). In patients with GOV2 and IGV1, TIPS+E reduced both rebleeding (GOV2: 7.8% versus 25.1%, P=0.01; IGV1: 5.6% versus 30.8%, P=0.03) and OHE (GOV2: 31.8% versus 51.5%, P=0.008; IGV1: 11.6% versus 38.5%, P=0.04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% versus 8.7%, P=0.37) or OHE (33.1% versus 35.3%, P=0.60). CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

miR-200b-3p relieved inflammation in patients with heart failure by regulating ZEB1 expression.

BACKGROUND: MicroRNA-200b-3p (miR-200b-3p) plays a pivotal role in inflammatory responses and is implicated in various inflammatory disorders. In this study, we aim to explore the role of miR-200b-3p in the inflammatory response in heart failure (HF). METHODS: Patients diagnosed with heart failure and age-matched healthy controls were studied. Peripheral blood samples from participants were collected for RNA-seq analysis to explore the expression profile of miR-200b-3p. The predictive value of miR-200b-3p and ZEB1 in the prognosis of heart failure was evaluated by analyzing the receiver operating characteristic (ROC) curve. Bioinformatics analysis and double luciferase reporter gene analysis were used to confirm the interaction between miR-200b-3p and ZEB1. Real-time quantitative polymerase chain reaction (QRT-PCR) was used to detect the expression levels of miR-200b-3p and ZEB1 in cardiopulmonary bypass. Additionally, the effects of miR-200b-3p on myocardial cell line (H9c2) injury were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the extracardiac circulation of HF patients, miR-200b-3p expression was significantly reduced, while ZEB1 levels were notably elevated. Analysis of the ROC curve revealed that miR-200b-3p and ZEB1 have predictive value in the prognosis of HF patients. The double luciferase reporter experiment demonstrated that miR-200b-3p binds to ZEB1 and inhibits its expression. Overexpression of miR-200b-3p demonstrated a remarkable ability to alleviate inflammation and inhibit the damage to myocardial cells in vivo. CONCLUSION: MiR-200b-3p can target and inhibit ZEB1, reducing the inflammatory reaction of myocardial cells. The miR-200b-3p/ZEB1 network may be helpful in preventing and treating HF.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

A long non-coding RNA functions as a competitive endogenous RNA to modulate TaNAC018 by acting as a decoy for tae-miR6206.

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.

The close association of micronutrients with COVID-19.

Objectives: The present study was conducted to explore the performance of micronutrients in the prediction and prevention of coronavirus disease 2019 (COVID-19). Methods: This is an observational case-control study. 149 normal controls (NCs) and 214 COVID-19 patients were included in this study. Fat-soluble and water-soluble vitamins were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and inorganic elements were detected by inductively coupled plasma-mass spectrometry (ICP-MS) analysis. A logistic regression model based on six micronutrients were constructed using DxAI platform. Results: Many micronutrients were dysregulated in COVID-19 compared to normal control (NC). 25-Hydroxyvitamin D3 [25(OH)D3], magnesium (Mg), copper (Cu), calcium (Ca) and vitamin B6 (pyridoxic acid, PA) were significantly independent risk factors for COVID-19. The logistic regression model consisted of 25(OH)D3, Mg, Cu, Ca, vitamin B5 (VB5) and PA was developed, and displayed a strong discriminative capability to differentiate COVID-19 patients from NC individuals [area under the receiver operating characteristic curve (AUROC) = 0.901]. In addition, the model had great predictive ability in discriminating mild/normal COVID-19 patients from NC individuals (AUROC = 0.883). Conclusions: Our study showed that micronutrients were associated with COVID-19, and our logistic regression model based on six micronutrients has potential in clinical management of COVID-19, and will be useful for prediction of COVID-19 and screening of high-risk population.

Joint EURADOS-EANM initiative for an advanced computational framework for the assessment of external dose rates from nuclear medicine patients.

BACKGROUND: In order to ensure adequate radiation protection of critical groups such as staff, caregivers and the general public coming into proximity of nuclear medicine (NM) patients, it is necessary to consider the impact of the radiation emitted by the patients during their stay at the hospital or after leaving the hospital. Current risk assessments are based on ambient dose rate measurements in a single position at a specified distance from the patient and carried out at several time points after administration of the radiopharmaceutical to estimate the whole-body retention. The limitations of such an approach are addressed in this study by developing and validating a more advanced computational dosimetry approach using Monte Carlo (MC) simulations in combination with flexible and realistic computational phantoms and time activity distribution curves from reference biokinetic models. RESULTS: Measurements of the ambient dose rate equivalent H*(10) at 1 m from the NM patient have been successfully compared against MC simulations with 5 different codes using the ICRP adult reference computational voxel phantoms, for typical clinical procedures with 99mTc-HDP/MDP, 18FDG and Na131I. All measurement data fall in the 95% confidence intervals, determined for the average simulated results. Moreover, the different MC codes (MCNP-X, PHITS, GATE, GEANT4, TRIPOLI-4®) have been compared for a more realistic scenario where the effective dose rate E of an exposed individual was determined in positions facing and aside the patient model at 30 cm, 50 cm and 100 cm. The variation between codes was lower than 8% for all the radiopharmaceuticals at 1 m, and varied from 5 to 16% for the face-to face and side-by-side configuration at 30 cm and 50 cm. A sensitivity study on the influence of patient model morphology demonstrated that the relative standard deviation of H*(10) at 1 m for the range of included patient models remained under 16% for time points up to 120 min post administration. CONCLUSIONS: The validated computational approach will be further used for the evaluation of effective dose rates per unit administered activity for a variety of close-contact configurations and a range of radiopharmaceuticals as part of risk assessment studies. Together with the choice of appropriate dose constraints this would facilitate the setting of release criteria and patient restrictions.

Perioperative versus adjuvant S-1 plus oxaliplatin chemotherapy for stage II/III resectable gastric cancer (RESONANCE): a randomized, open-label, phase 3 trial.

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361).

Associations between waist circumference, central obesity, and the presence of non-valvular atrial fibrillation patients with heart failure.

Background: Reportedly, there is a clear correlation between waist circumference (WC) and atrial fibrillation (AF). However, there is no specific discussion about the relationship between WC and non-valvular AF (NVAF) patients with heart failure. Our main purpose was to study the relationship between WC, central obesity (CO), and NVAF patients with heart failure. Methods: This is a retrospective cohort study. A total of 3,435 patients with NVAF in the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2017 were enrolled. The targeted independent variable and the dependent variable were WC and CO and the presence of NVAF with heart failure, respectively. Univariate, multiple regression, and subgroup analyses were used to analyze their relationship. We used the receiver operating characteristic (ROC) curve to choose the better predictor of NVAF with heart failure between WC and CO and calculated the proposed cut-off value of WC in males and female separately. Results: The identified risk factors of NVAF with heart failure were sex, height, WC, CO, body mass index (BMI), fasting blood glucose (FBG), homocysteine (HCY), triglyceride (TG), low-density lipoprotein cholesterol (LDLC), hypertension, diabetes mellitus (DM), stroke, vascular disease, and plaque. Then, a binary logistic regression model indicated that the occurrence of NVAF patients with heart failure increased 10% with WC increasing 1 cm and had a 2.8-fold increased risk with CO compared to those without. The predictive value [area under the ROC curve (AUC)], specificity, sensitivity, and accuracy of WC for the disease risk of NVAF with heart failure were higher than those of CO. The proposed cut-off value of WC was 91.85 cm for males and 93.15 cm for females. The diagnostic value of WC for NVAF with heart failure was higher for females than it was for males. Conclusions: Our research found that WC is related to the presence of heart failure in the patients with NYAF and can predict the presence of NVAF with heart failure. Our findings may help to improve the treatment and care strategies of NVAF individuals with abdominal obesity.

Metabolic engineering of Candida tropicalis for efficient 1,2,4-butanetriol production.

1,2,4-Butanetriol serves as a precursor in the manufacture of diverse pharmaceuticals and the energetic plasticizer 1,2,4-butanetriol trinitrate. The study involved further modifications to an engineered Candida tropicalis strain, aimed at improving the production efficiency of 1,2,4-butanetriol. Faced with the issue of xylonate accumulation due to the low activity of heterologous xylonate dehydratase, we modulated iron metabolism at the transcriptional level to boost intracellular iron ion availability, thus enhancing the enzyme activity by 2.2-fold. Addressing the NADPH shortfall encountered during 1,2,4-butanetriol biosynthesis, we overexpressed pivotal genes in the NADPH regeneration pathway, achieving a 1,2,4-butanetriol yield of 3.2 g/L. The introduction of calcium carbonate to maintain pH balance led to an increased yield of 4 g/L, marking a 111% improvement over the baseline strain. Finally, the use of corncob hydrolysate as a substrate culminated in 1,2,4-butanetriol production of 3.42 g/L, thereby identifying a novel host for the conversion of corncob hydrolysate to 1,2,4-butanetriol.

Explaining how childhood physical abuse and physical neglect influence adult depression: An analysis with multiple sequential mediators.

BACKGROUND: Substantial evidence indicates that experiencing physical abuse and neglect during childhood significantly elevates the likelihood of developing depression in adulthood. Nevertheless, there remains a dearth of understanding regarding the mechanisms underpinning this correlation. OBJECTIVE: In this study, we aimed to examine the associations of childhood physical abuse and physical neglect with depression using follow-up data from UK Biobank and quantified the contribution of smoking, insomnia, and BMI in these associations. PARTICIPANTS AND SETTINGS: This study included 144,704 participants (64,168 men and 80,536 women) from UK Biobank, most of whom were white (97 %). METHODS: Physical abuse and physical neglect were measured using two items of Childhood Trauma Screener (CTS). Data on the incidence of depression were obtained from primary care, hospital inpatient records, self-reported medical conditions, and death registries. We used a sequential mediation analysis based on the "g-formula" approach to explore the individual and joint effects of potential mediators. RESULTS: The depression incidence rate was 1.85 per 1000 person-years for men and 2.83 per 1000 person-years for women, respectively. Results of Cox proportional risk regression showed that physical abuse (HRs: 1.39-1.53, P < 0.001) and physical neglect (HRs: 1.43-1.60, P < 0.001) are associated with depression. Smoking, insomnia, and BMI together mediated 3 %-26 % of the associations. CONCLUSIONS: These findings contribute to our understanding of how physical abuse and physical neglect influence depression. Furthermore, a more effective reduction in the burden of depression can be achieved by managing modifiable mediators.

An injectable active hydrogel based on BMSC-derived extracellular matrix for cartilage regeneration enhancement.

Articular cartilage injury impairs joint function and necessitates orthopedic intervention to restore the structure and function of the cartilage. Extracellular matrix (ECM) scaffolds derived from bone marrow mesenchymal stem cells (BMSCs) can effectively promote cell adhesion, proliferation, and chondrogenesis. However, pre-shaped ECM scaffolds have limited applicability due to their poor fit with the irregular surface of most articular cartilage defects. In this study, we fabricated an injectable active ECM hydrogel from autologous BMSCs-derived ECM by freeze-drying, liquid nitrogen milling, and enzymatic digestion. Moreover, our in vitro and in vivo results demonstrated that the prepared hydrogel enhanced chondrocyte adhesion and proliferation, chondrogenesis, cartilage regeneration, and integration with host tissue, respectively. These findings indicate that active ECM components can provide trophic support for cell proliferation and differentiation, restoring the structure and function of damaged cartilage.

Corrigendum: Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

[This corrects the article DOI: 10.3389/fpsyt.2024.1354999.].

Feasibility of Using Magnetic Resonance Spectroscopy Test Biomarkers to Diagnose Alzheimer's Disease: Systematic Evaluation and Meta-Analysis.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, resulting in impairments in memory, cognition, decision-making, and social skills. Thus, accurate preclinical diagnosis of Alzheimer's disease is paramount. The identification of biomarkers for Alzheimer's disease through magnetic resonance spectroscopy (MRS) represents a novel adjunctive diagnostic approach. OBJECTIVE: This study conducted a meta-analysis of the diagnostic results of this technology to explore its feasibility and accuracy. METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched without restrictions, with the search period extending up to July 31, 2022. The search strategy employed a combination of subject headings and keywords. All retrieved documents underwent screening by two researchers, who selected them for meta-analysis. The included literature was analyzed using Review Manager 5.4 software, with corresponding bias maps, forest plots, and summary receiver operating characteristic (SROC) curves generated and analyzed. RESULTS: A total of 344 articles were retrieved initially, with 11 articles meeting the criteria for inclusion in the analysis. The analysis encompassed data from approximately 1766 patients. In the forest plot, both sensitivity (95% CI) and specificity (95% CI) approached 1. Examining the true positive rate, false positive rate, true negative rate, and false negative rate, all studies on the summary receiver operating characteristic (SROC) curve clustered in the upper left quadrant, suggesting a very high accuracy of biomarkers detected by MRS for diagnosing Alzheimer's disease. CONCLUSION: The detection of biomarkers by MRS demonstrates feasibility and high accuracy in diagnosing AD. This technology holds promise for widespread adoption in the clinical diagnosis of AD in the future.

Effect of traditional Chinese medicine on metabolism disturbance in ischemic heart diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic heart diseases (IHD), characterized by metabolic dysregulation, contributes majorly to the global morbidity and mortality. Glucose, lipid and amino acid metabolism are critical energy production for cardiomyocytes, and disturbances of these metabolism lead to the cardiac injury. Traditional Chinese medicine (TCM), widely used for treating IHD, have been demonstrated to effectively and safely regulate the cardiac metabolism reprogramming. AIM OF THE REVIEW: This study discussed and analyzed the disturbed cardiac metabolism induced by IHD and development of formulas, extracts, single herb, bioactive compounds of TCM ameliorating IHD injury via metabolism regulation, with the aim of providing a basis for the development of clinical application of therapeutic strategies for TCM in IHD. MATERIALS AND METHODS: With "ischemic heart disease", "myocardial infarction", "myocardial ischemia", "metabolomics", "Chinese medicine", "herb", "extracts" "medicinal plants", "glucose", "lipid metabolism", "amino acid" as the main keywords, PubMed, Web of Science, and other online search engines were used for literature retrieval. RESULTS: IHD exhibits a close association with metabolism disorders, including but not limited to glycolysis, the TCA cycle, oxidative phosphorylation, branched-chain amino acids, fatty acid ß-oxidation, ketone body metabolism, sphingolipid and glycerol-phospholipid metabolism. The therapeutic potential of TCM lies in its ability to regulate these disturbed cardiac metabolisms. Additionally, the active ingredients of TCM have depicted wonderful effects in cardiac metabolism reprogramming in IHD. CONCLUSION: Drawing from the principles of TCM, we have pinpointed specific herbal remedies for the treatment of IHD, and leveraged advanced metabolomics technologies to uncover the effect of these TCMs on metabolomics alteration. In the future, further clinical experimental studies should be included to explore whether more TCM medicines can play a therapeutic role in IHD by reversing cardiac metabolism disorders; multi-omics would be conducted to explore more pathways and genes targeting such metabolism reprogramming by TCMs, and to seek more TCM therapies for IHD.