Oxidative stress disrupts vascular microenvironmental homeostasis affecting the development of atherosclerosis.

Atherosclerosis is primarily an inflammatory reaction of the cardiovascular system caused by endothelial damage, leading to progressive thickening and hardening of the vessel walls, as well as extensive necrosis and fibrosis of the surrounding tissues, the most necessary pathological process causing cardiovascular disease. When the body responds to harmful internal and external stimuli, excess oxygen free radicals are produced causing oxidative stress to occur in cells and tissues. Simultaneously, the activation of inflammatory immunological processes is followed by an elevation in oxygen free radicals, which directly initiates the release of cytokines and chemokines, resulting in a detrimental cycle of vascular homeostasis abnormalities. Oxidative stress contributes to the harm inflicted upon vascular endothelial cells and the decrease in nitric oxide levels. Nitric oxide is crucial for maintaining vascular homeostasis and is implicated in the development of atherosclerosis. This study examines the influence of oxidative stress on the formation of atherosclerosis, which is facilitated by the vascular milieu. It also provides an overview of the pertinent targets and pharmaceutical approaches for treating this condition.

Association between single and multiple cardiometabolic diseases and all-cause mortality among Chinese older adults: A prospective, nationwide cohort study.

BACKGROUND AND AIM: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population. METHODS AND RESULTS: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001). CONCLUSIONS: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs.

Ca(H2PO4)2 and MgSO4 activated nitrogen-related bacteria and genes in thermophilic stage of compost.

This study was conducted to investigate the effects of Ca(H2PO4)2 and MgSO4 on the bacterial community and nitrogen metabolism genes in the aerobic composting of pig manure. The experimental treatments were set up as control (C), 1% Ca(H2PO4)2 + 2% MgSO4 (CaPM1), and 1.5% Ca(H2PO4)2 + 3% MgSO4 (CaPM2), which were used at the end of composting for potting trials. The results showed that Ca(H2PO4)2 and MgSO4 played an excellent role in retaining nitrogen and increasing the alkali-hydrolyzed nitrogen (AN), available phosphorus (AP), and available potassium (AK) contents of the composts. Adding Ca(H2PO4)2 and MgSO4 changed the microbial community structure of the compost. The microorganisms associated with nitrogen retention were activated. The complexity of the microbial network was enhanced. Genetic prediction analysis showed that the addition of Ca(H2PO4)2 and MgSO4 reduced the accumulation of nitroso-nitrogen and the process of denitrification. At the same time, despite the reduction of genes related to nitrogen fixation, the conversion of ammonia to nitrogenous organic compounds was promoted and the stability of nitrogen was increased. Mantel test analysis showed that Ca(H2PO4)2 and MgSO4 can affect nitrogen transformation-related bacteria and thus indirectly affect nitrogen metabolism genes by influencing the temperature, pH, and organic matter (OM) of the compost and also directly affected nitrogen metabolism genes through PO43- and Mg2+. The pot experiment showed that composting with 1.5% Ca(H2PO4)2 + 3% MgSO4 produced the compost product that improved the growth yield and nutrient content of cilantro and increased the fertility of the soil. In conclusion, Ca(H2PO4)2 and MgSO4 reduces the loss of nitrogen from compost, activates nitrogen-related bacteria and genes in the thermophilic phase of composting, and improves the fertilizer efficiency of compost products. KEY POINTS: • Ca(H2PO4)2 and MgSO4 reduced the nitrogen loss and improved the compost effect • Activated nitrogen-related bacteria and altered nitrogen metabolism genes • Improved the yield and quality of cilantro and fertility of soil.

[Mechanism of Fuzheng Huayu Tablets against hepatic fibrosis based on transcriptome and single-cell sequencing].

This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Developing Thermally Stable Defect-Assisted Phosphors of BaSc2Ge3O10:Bi3+ for Pc-UV-LEDs Applications.

Current ultraviolet (UV) light sources are dominated by blacklights that contain mercury vapor. Improper disposal or accidental breakage of these lamps can lead to serious pollution. Phosphor-converted light-emitting diodes (pc-UV-LEDs) have the potential to replace these mercury-containing lamps, making them more environmentally friendly. To improve the adjustability of the UV emission and reduce production cost, a series of UV-emitting phosphors were developed by introducing Bi3+ in BaSc2Ge3O10 (BSGO) which has a broad bandgap of 5.88 eV. The phosphor exhibits a negative thermal quenching effect that results from thermally activated defects. Despite this, the emission intensity of the phosphor sustains up to 107% at 353 K and 93% at 473 K compared to the intensity at 298 K. The internal quantum efficiency and the external quantum efficiency reach 81.0 and 49.32%, respectively, under 305 nm excitation. A pc-UV-LEDs were fabricated by combining the phosphor with a chip. The resulting device emits a broad band ranging from 295 nm to 450 nm, covering part of the UVB (280 nm ∼ 315 nm) and UVA (315-400 nm) regions. Our work has the potential to promote the replacement of current blacklights, including high-pressure mercury lamps and fluorescent low-pressure mercury lamps, by pc-UV-LEDs in applications such as bug zappers and tanning beds. Moreover, the phosphor exhibits desirable long persistent luminescence, which extends its prospect of applications.

Potential roles of the rhizospheric bacterial community in assisting Miscanthus floridulus in remediating multi-metal(loid)s contaminated soils.

Phytoremediation technology is an important approach applied to heavy metal remediation, and how to improve its remediation efficiency is the key. In this study, we compared the rhizospheric bacterial communities and metals contents in Miscanthus floridulus (M. floridulus) of four towns, including Huayuan Town (HY), Longtan Town (LT), Maoer Village (ME), and Minle Town (ML) around the lead-zinc mining area in Huayuan County, China. The roles of rhizospheric bacterial communities in assisting the phytoremediation of M. floridulus were explored. It was found that the compositions of the rhizospheric bacterial community of M. floridulus differed in four regions, but majority of them were heavy metal-resistant bacteria that could promote plant growth. Results of bioconcentration factors showed the enrichment of Cu, Zn, and Pb by M. floridulus in these four regions were significantly different. The Zn enrichment capacity of ML was the strongest for Cu and stronger than LT and ME for Pb. The enrichment capacity of LT and ML was stronger than HY and ME. These bacteria may influence the different heavy metals uptake of M. floridulus by altering the soil physiochemical properties (e.g., soil peroxidase, pH and moisture content). In addition, co-occurrence network analysis also showed that LT and ML had higher network stability and complexity than HY and ME. Functional prediction analysis of the rhizospheric bacterial community showed that genes related to protein synthesis (e.g., zinc-binding alcohol dehydrogenase/oxidoreductase, Dtx R family transcriptional regulators and ACC deaminase) also contributed to phytoremediation in various ways. This study provides theoretical guidance for selecting suitable microorganisms to assist in the phytoremediation of heavy metals.

Endophytic Fungus Talaromyces sp. MR1 Promotes the Growth and Cadmium Uptake of Arabidopsis thaliana L. Under Cadmium Stress.

Endophytes play essential roles in plant growth under metal(loid)s stress. An endophytic fungus strain MR1 was isolated from the roots of Miscanthus floridulus collected from a lead-zinc mining area (Huayuan, China), which could produce indole-3-acetic acid and have Cadmium (Cd) tolerance. Further 18S rRNA sequencing analysis showed that it was highly similar (99.83%) to Talaromyces pinophilus. In pot experiments, we explored the effects of strain MR1 on the growth and Cd uptake of a wide-type Arabidopsis thaliana under low (LC) and high (HC) Cd concentrations. The results showed that MR1 effectively increased the dry weight of aboveground and underground tissues by 25.95-107.21% in both LC and HC groups. Due to MR1 inoculation, the Cd content in the underground tissues was significantly (p < 0.05) decreased by 39.28% under low Cd concentration, while it was significantly (p < 0.05) increased by 28.28% under high Cd concentration. Besides, MR1 inoculations significantly (p < 0.05) increased the total content of removed Cd (17.080 µg) and BCF (0.064) by 129.77% and 153.95% under high Cd concentration. Therefore, we speculated that MR1 might be selected as the effective microbial agent to increase crop yield and control Cd content in the crop in light Cd-contaminated soil. Besides, MR1 could potentially enhance the phytoremediation efficiency of extremely Cd-contaminated soil.

The relationship of maternal polymorphisms of genes related to meiosis and DNA damage repair with fetal chromosomal stability.

OBJECTIVES: To evaluate the association between maternal polymorphisms of NANOS3 rs2016163, HELQ rs4693089, PRIM1 rs2277339, TLK1 rs10183486, ERCC6 rs2228526, EXO1 rs1635501, DMC1 rs5757133, and MSH5 rs2075789 and fetal chromosomal abnormality. METHODS: This retrospective case-control study included 571 women with fetal chromosome abnormalities (330 pregnant women diagnosed with fetal aneuploidy, 241 with fetal de novo structural chromosome pregnancy) and 811 healthy pregnant women between January 2018 and April 2022. All the above polymorphisms were tested using SNaPshot. RESULTS: All the eight polymorphisms were analyzed for genotypes, alleles, under dominant and recessive genetic models. Significant distribution differences of TLK1 rs10183486 in fetal chromosome structural abnormality were found between the case group and control subjects who were <35 years of age [Genotype: p=0.029; Dominant: OR (95 %CI)=0.46 (0.25-0.82), p=0.01 and allele: OR (95 %CI)=0.47 (0.27-0.82), p=0.01 respectively], while no difference was found in the recessive model [OR (95 %CI)=2.49 (0.31-20.40), p=0.39]. In advanced age subgroups for fetal aneuploidy, significant differences were found in genotypes analysis of PRIM1 rs2277339 (p=0.008), allele analysis of TLK1 rs10183486 [OR (95 %CI)=0.62 (0.42-0.91), p=0.02]. For the fetal chromosome structural abnormality population, HELQ rs4693089 revealed a significant distribution difference (p=0.01) but not in the allele, dominant and recessive genetic models analysis (p>0.05 individually). CONCLUSIONS: For older women, maternal PRIM1 rs2277339 and TLK1 rs10183486 polymorphisms may be associated with fetal aneuploidy, while HELQ rs4693089 may be associated with fetal chromosome structural abnormality. Also, carriers of T allele of TLK1 rs10183486 have a lower risk of fetal chromosome structural abnormality in younger women.

Thioredoxin-1 regulates IRE1α to ameliorate sepsis-induced NLRP3 inflammasome activation and oxidative stress in Raw 264.7 cell.

Objective: Sepsis is life-threatening organ dysfunction caused by the dysregulated host response to infection. Endoplasmic reticulum stress (ERS)-mediated inositol-requiring enzyme 1 α (IRE1α) inflammatory signaling pathway is involved in sepsis. NLRP3 inflammasome plays a key role in the activation of caspase-1 and the maturation of IL-1ß and IL-18, and finally enhances the inflammatory response. More and more evidences show that ERS is an endogenous trigger of NLRP3 inflammasome. Thioredoxin-1 (Trx-1) is a small ubiquitous thiol-1 protein with redox/inflammation modulatory properties relevant to sepsis pathogenesis. In this study, we investigated the role of Trx-1 in ERS mediated IRE1α/NLRP3 signaling pathway in Raw 264.7 cells.Methods: Raw 264.7 cells stimulated by LPS were used to construct an inflammation model of sepsis in vitro, and the expression of proteins related to the IRE1α/NLRP3 pathway was detected through using western blot and RT-PCR. The expression of IL-18 and IL-1ß in cell supernatant was also measured by ELISA, and caspase 1 activity and ROS expression in cells were detected by kits.Results: Our study shows that IRE1α signaling pathway related to endoplasmic reticulum stress in sepsis can activate inflammation related genes, and stimulate to produce a large number of pro-IL-1ß. At the same time, IRE1α can activate NLRP3 inflammasome and promote activation and maturation of pro-IL-1ß. Finally leads to excessive inflammatory response and ROS release, and promotes the progress of sepsis.Conclusions: Trx-1 may inhibit NLRP3 activity and pro-IL-Iß production by inhibit IRE1α pathway of ER stress. So as to inhibit inflammatory response and ROS of cells, and play a protective role in sepsis.

Reversibility of brain glucose kinetics in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by 1H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA1c normalise intracerebral glucose levels. METHODS: Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m2 and HbA1c 84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent 1H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist. RESULTS: Following the intervention, mean ± SD HbA1c decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (p=0.006), with minimal weight changes (p=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (p<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (p=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA1c (r = 0.71, p=0.048). CONCLUSION/INTERPRETATION: These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control. Trial registration ClinicalTrials.gov NCT03469492.

Construction of ajmalicine and sanguinarine de novo biosynthetic pathways using stable integration sites in yeast.

Yeast cell factories have been increasingly employed for producing plant-derived natural products. Unfortunately, the stability of plant natural product biosynthetic pathway genes, particularly when driven by the same sets of promoters and terminators, remains one of the biggest concerns for synthetic biology. Here we profile genomic loci flanked by essential genes as stable integration sites in a genome-wide manner, for stable maintenance of multigene biosynthetic pathways in yeast. We demonstrate the application of our yeast integration platform in the construction of sanguinarine (24 expression cassettes) and ajmalicine (29 expression cassettes) de novo biosynthetic pathways for the first time. Moreover, we establish stable yeast cell factories that can produce 119.2 mg L-1 heteroyohimbine alkaloids (containing 61.4 mg L-1 ajmalicine) in shake flasks, representing the highest titer of monoterpene indole alkaloids (MIAs) ever reported and promising the complete biosynthesis of other high-value MIAs (such as vinblastine) for biotechnological applications.

Review: the role of GSDMD in sepsis.

PURPOSE: Gasdermin D (GSDMD) is a cytoplasmic protein that is encoded by the gasdermin family GSDMD gene and is the ultimate executor of pyroptosis. Pyroptosis is a mode of lysis and inflammation that regulates cell death, ultimately leading to cell swelling and rupture. In sepsis, a dysregulated host response to infection frequently results in hyperinflammatory responses and immunosuppression, eventually leading to multiple organ dysfunction. Pyroptosis regulates innate immune defenses and plays an important role in the process of inflammatory cell death, and the absence of any link in the entire pathway from GSDMD to pyroptosis causes bacterial clearance to be hampered. Under normal conditions, the process of pyroptosis occurs much faster than apoptosis, and the threat to the body is also much greater. MATERIALS AND METHODS: We conducted a systematic review of relevant reviews and experimental articles using the keywords sepsis, Gasdermin D, and Pyroptosis in the PubMed, Scopus, Google Scholar, and Web of Science databases. CONCLUSION: Combined with the pathogenesis of sepsis, it is not difficult to find that pyroptosis plays a key role in bacterial inflammation and sepsis. Therefore, GSDMD inhibitors may be used as targeted drugs to treat sepsis by reducing the occurrence of pyroptosis. This review mainly discusses the key role of GSDMD in sepsis.

The effect of stigma on social participation in community-dwelling Chinese patients with stroke sequelae: A cross-sectional study.

OBJECTIVE: To explore the effect of stigma on social participation in community-dwelling Chinese patients with stroke sequelae. DESIGN: A cross-sectional survey study. SETTING: The study was conducted in two community centres in Tianjin, China. SUBJECTS: Community-dwelling Chinese patients with stroke sequelae. MEASURES: Chinese version of Stigma Scale for Chronic Illness, Chinese version of Impact on Participation and Autonomy, Modified Barthel index, Self-Rating Depression Scale, Social Support Rating Scale, Medical Coping Modes Questionnaire, background and disease-related questions. Pearson's correlation coefficients were computed between stigma and social participation. The impact of stigma on social participation was estimated by hierarchical multiple regression analysis after controlling for demographic, physical and psychosocial characteristics. RESULTS: In total, 136 patients with stroke sequelae were included in this study, with a mean age of 67.8 years. The Chinese version of the Stigma Scale for Chronic Illness had a mean score of 48.4 (SD 16.9), and the Chinese version of the Impact on Participation and Autonomy was 67.1 (SD 21.1). Significant correlations were found between stigma and social participation. Pearson's correlation coefficient ranged from 0.354 to 0.605 (P < 0.01). Enacted stigma provided a significant explanation for the variance of social participation by 1.1% (P < 0.05). Felt stigma provided a significant explanation for the variance of social participation by 2.9% (P < 0.001). CONCLUSION: Felt stigma and enacted stigma have independent associations with social participation. Patients with stroke sequelae who reported higher stigma experienced a lower level of social participation.

SLC2A3 variants in familial and sporadic congenital heart diseases in a Chinese Yunnan population.

BACKGROUND: Solute carrier family 2 member 3 (SLC2A3), is a member of a superfamily of transport protein genes. SLC2A3 played an important role in embryonic development. Previous research reported SLC2A3 duplication was reportedly associated with congenital syndromic heart defects. However, it is not clear whether the gene is associated with non-syndromic congenital heart disease. Our study aimed to elucidate the relationship between its variation and congenital heart disease. METHODS: Genomic DNA extracted from the peripheral blood leukocytes of two families with CHD were sequenced with whole-exome sequencing to identify variations, used Sanger sequencing to investigate SLC2A3 variants in 494 Chinese patients with CHD and 576 healthy unrelated individuals. RESULTS: In members from the two families, three with CHD had the SLC2A3 (rs3931701) C > T variant. Of the 494 patients with CHD, 394 had gene variants (86 had the TT type and 308 had the CT type). Of the 576 healthy controls, 272 participants had gene variants (36 had the TT type and 236 had the CT type). The TT type [p < 0.0001, odds ratio (OR) =7.262, 95% confidence interval (CI) =4.631-11.388] and CT type (p < 0.0001, OR =3.967, 95% CI =2.991-5.263) of SLC2A3 (rs3931701) significantly increased the risk of sporadic ASD in a Chinese Yunnan population. CONCLUSIONS: Single nucleotide variations of SLC2A3, particularly, the SLC2A3 (rs3931701) C > T variant increased the risk of CHD among the studied population.

Functional expression of eukaryotic cytochrome P450s in yeast.

Cytochrome P450 enzymes (P450s) are a superfamily of heme-thiolate proteins widely existing in various organisms. Due to their key roles in secondary metabolism, degradation of xenobiotics, and carcinogenesis, there is a great demand to heterologously express and obtain a sufficient amount of active eukaryotic P450s. However, most eukaryotic P450s are endoplasmic reticulum-localized membrane proteins, which is the biggest challenge for functional expression to high levels. Furthermore, the functions of P450s require the cooperation of cytochrome P450 reductases for electron transfer. Great efforts have been devoted to the heterologous expression of eukaryotic P450s, and yeasts, particularly Saccharomyces cerevisiae are frequently considered as the first expression systems to be tested for this challenging purpose. This review discusses the strategies for improving the expression and activity of eukaryotic P450s in yeasts, followed by examples of P450s involved in biosynthetic pathway engineering.

Detection of shallow anterior chamber depth from two-dimensional anterior segment photographs using deep learning.

BACKGROUND: The purpose of this study was to implement and evaluate a deep learning (DL) approach for automatically detecting shallow anterior chamber depth (ACD) from two-dimensional (2D) overview anterior segment photographs. METHODS: We trained a DL model using a dataset of anterior segment photographs collected from Shanghai Aier Eye Hospital from June 2018 to December 2019. A Pentacam HR system was used to capture a 2D overview eye image and measure the ACD. Shallow ACD was defined as ACD less than 2.4 mm. The DL model was evaluated by a five-fold cross-validation test in a hold-out testing dataset. We also evaluated the DL model by testing it against two glaucoma specialists. The performance of the DL model was calculated by metrics, including accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: A total of 3753 photographs (1720 shallow AC and 2033 deep AC images) were assigned to the training dataset, and 1302 photographs (509 shallow AC and 793 deep AC images) were held out for two internal testing datasets. In detecting shallow ACD in the internal hold-out testing dataset, the DL model achieved an AUC of 0.86 (95% CI, 0.83-0.90) with 80% sensitivity and 79% specificity. In the same testing dataset, the DL model also achieved better performance than the two glaucoma specialists (accuracy of 80% vs. accuracy of 74 and 69%). CONCLUSIONS: We proposed a high-performing DL model to automatically detect shallow ACD from overview anterior segment photographs. Our DL model has potential applications in detecting and monitoring shallow ACD in the real world. TRIAL REGISTRATION: http://clinicaltrials.gov , NCT04340635 , retrospectively registered on 29 March 2020.

Nkx2-5 Regulates the Proliferation and Migration of H9c2 Cells.

BACKGROUND The protein NKX2-5 affects mammalian heart development. In mice, the disruption of Nkx2-5 has been associated with arrhythmias, abnormal myocardial contraction, abnormal cardiac morphogenesis, and death. However, the details of the mechanisms are unclear. This study was designed to investigate them. MATERIAL AND METHODS Rat cardiomyocytes from the H9c2 cell line were used in our study. First, we knocked down Nkx2-5 in the H9c2 cells and then validated consequent changes in cell proliferation and migration. We then used RNA sequencing to determine the changes in transcripts. Finally, we validated these results by quantitative reverse transcription-polymerase chain reaction. RESULTS We confirmed that Nkx2-5 regulates the proliferation and migration of H9c2 cells. In our experiments, Nkx2-5 regulated the expression of genes related to proliferation, migration, heart development, and disease. Based on bioinformatics analysis, knockdown of Nkx2-5 caused differential expression of genes involved in cardiac development, calcium ion-related biological activity, the transforming growth factor (TGF)-ß signaling pathway, pathways related to heart diseases, the MAPK signaling pathway, and other biological processes and signaling pathways. CONCLUSIONS Nkx2-5 may regulate proliferation and migration of the H9c2 cells through the genes Tgfb-2, Bmp10, Id2, Wt1, Hey1, and Cacna1g; rno-miR-1-3p; the TGF­ß signaling pathway; the MAPK signaling pathway; as well as other genes and pathways.

Exercise alone and exercise combined with education both prevent episodes of low back pain and related absenteeism: systematic review and network meta-analysis of randomised controlled trials (RCTs) aimed at preventing back pain.

OBJECTIVES: We aimed to investigate which prevention strategies for low back pain (LBP) are most effective. DESIGN: We completed a Bayesian network meta-analysis to summarise the comparative effectiveness of LBP prevention strategies. The primary outcomes were an episode of LBP and LBP-associated work absenteeism represented as ORs with associated 95% credibility intervals (CrIs). We ranked all prevention strategies with surface under the cumulative ranking curve (SUCRA) analysis. DATA SOURCES: PubMed, EMBASE and CENTRAL databases were searched along with manual searches of retrieved articles. We only included randomised controlled trials (RCTs) that reported an episode of LBP and/or LBP-associated work absenteeism evaluating LBP prevention strategies were included. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Data were independently extracted by two investigators, and RCT quality was assessed using the Cochrane Risk of Bias tool. RESULTS AND SUMMARY: Forty RCTs were included. Exercise combined with education (OR: 0.59, CrI: 0.41 to 0.82) and exercise alone (OR: 0.59, CrI: 0.36 to 0.92) both prevented LBP episodes; exercise combined with education and education alone both had large areas under the curve (SUCRA: 81.3 and 79.4, respectively). Additionally, exercise (OR: 0.04, CrI: 0.00 to 0.34) prevented LBP-associated work absenteeism, with exercise and the combination of exercise and education ranking highest (SUCRA: 99.0 and 60.2, respectively). CONCLUSIONS: Exercise alone and exercise combined with education can prevent episodes of LBP and LBP-related absenteeism. TRIAL REGISTRATION NUMBER: PROSPERO 42017056884.

Functional MRS with J-edited lactate in human motor cortex at 4 T.

While functional MRI (fMRI) localizes regions of brain activation, functional MRS (fMRS) provides insights into metabolic underpinnings. Previous fMRS studies detected task-induced lactate increase using short echo-time non-edited 1H-MRS protocols, where lactate changes depended on accurate exclusion of overlapping lactate and lipid/macromolecule signals. Because long echo-time J-difference 1H-MRS detection of lactate is less susceptible to this shortcoming, we posited if J-edited fMRS protocol could reliably detect metabolic changes in the human motor cortex during a finger-tapping paradigm in relation to a reliable measure of basal lactate. Our J-edited fMRS protocol at 4T was guided by an fMRI pre-scan to determine the 1H-MRS voxel placement in the motor cortex. Because lactate and ß-hydroxybutyrate (BHB) follow similar J-evolution profiles we observed both metabolites in all spectra, but only lactate showed reproducible task-induced modulation by 0.07 mM from a basal value of 0.82 mM. These J-edited fMRS results demonstrate good sensitivity and specificity for task-induced lactate modulation, suggesting that J-edited fMRS studies can be used to investigate the metabolic underpinning of human cognition by measuring lactate dynamics associated with activation and deactivation fMRI paradigms across brain regions at magnetic field lower than 7T.