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We aimed to explore and analyse the dietary intake patterns of 3-6 year-old children left behind by one or both parents and to assess their associations with body mass index (BMI) and the prevalence of childhood anaemia in rural Anhui, eastern China. We used random cluster sampling to recruit rural children aged 3-6 years in two rural areas in Anhui province. Sociodemographic information and dietary intake were collected by self-reported questionnaires. Height, weight and prevalence of anaemia were measured by trained nurses blinded to parental migration status. Factor analysis was applied to determine that major dietary patterns, binary logistic regression and generalised linear regression were used to explore the associations between anaemia and BMI Z-score with dietary patterns. Of 1720 children aged 3-6 years, 236 were left by both parents and 388 were left by a single parent. The prevalence of stunting and underweight among left-behind children with migration of both parents (BLBC) was significantly higher than that of non-left-behind children (NLBC). Three dietary patterns-"grain-vegetable," "meat-egg" and "fast food-sweet"-were identified in our study, and the total variance explained was 46.9%. The meat-egg dietary pattern was associated with a decreased risk of anaemia after adjustment for confounding factors in the left-behind children with migration of both parents (BLBC), left-behind children with single parent migration (SLBC) and non-left-behind children (NLBC) groups. After adjusting for confounding factors, the fast food-sweet dietary pattern was found to be associated with an increased risk of anaemia (OR [95% CI]: Q 4 : 2.21 [1.14, 4.57], p = 0.034). In addition, children with obesity had a lower intake of vegetables and fruits (β = -0.08, 95% CI: -0.13, -0.02) compared with children with a normal weight. In conclusion, there are correlations between different types of parental migration and children's nutritional status in rural Anhui. The meat-egg dietary pattern may have a preventive effect on anaemia in comparison with other dietary patterns, irrespective of whether children are left behind or not. Children with overweight and obesity had a higher intake of pork and red meat and snacks compared with children with normal BMI., (© 2024 British Nutrition Foundation.)

Background: Carotenoids play key roles in photosynthesis and are widely used in foods as natural pigments, antioxidants, and health-promoting compounds. Enhancing carotenoid production in microalgae via biotechnology has become an important area of research., Results: We knocked out the Na + /Ca 2+ antiporter gene slr0681 in Synechocystis sp. PCC 6803 via homologous recombination and evaluated the effects on carotenoid production under normal (NL) and high-light (HL) conditions. On day 7 of NL treatment in calcium ion (Ca 2+ )-free medium, the cell density of Δslr0681 decreased by 29% compared to the wild type (WT). After 8 days of HL treatment, the total carotenoid contents decreased by 35% in Δslr0681, and the contents of individual carotenoids were altered: myxoxanthophyll, echinenone, and β-carotene contents increased by 10%, 50%, and 40%, respectively, while zeaxanthin contents decreased by ~40% in Δslr0681 versus the WT. The expression patterns of carotenoid metabolic pathway genes also differed: ipi expression increased by 1.2- to 8.5-fold, whereas crtO and crtR expression decreased by ~90% and 60%, respectively, in ∆slr0681 versus the WT. In addition, in ∆slr0681, the expression level of psaB (encoding a photosystem I structural protein) doubled, whereas the expression levels of the photosystem II genes psbA2 and psbD decreased by ~53% and 84%, respectively, compared to the WT., Conclusion: These findings suggest that slr0681 plays important roles in regulating carotenoid biosynthesis and structuring of the photosystems in Synechocystis sp. This study provides a theoretical basis for the genetic engineering of microalgae photosystems to increase their economic benefits and lays the foundation for developing microalgae germplasm resources with high carotenoid contents. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Coal gasification is an effective way to use coal cleanly and efficiently, and coal gasification fine slag is a by-product of coal gasification with high carbon content, large specific surface area, developed pore structure and large output during production. At present, combustion has become an effective way to dispose of coal gasification fine slag on a large scale, and the coal gasification fine slag after combustion treatment can be further used for construction raw materials. In this paper, the emission characteristics of gas-phase pollutants and particulate matter under different combustion temperatures (900 °C, 1100 °C, 1300 °C) and combustion atmosphere (5%, 10%, 21% O 2 concentration) are studied with the drop tube furnace experimental system. By co-firing different proportions of coal gasification fine slag (10%, 20%, 30%) and raw coal, the pollutants formation law under co-firing conditions is studied. Scanning electron microscopy-energy spectroscopy (SEM-EDS) is used to characterize the apparent morphology and elemental composition of particulate samples. The measurement results of gas-phase pollutants show that the increase of furnace temperature and O 2 concentration can effectively promote combustion and improve burnout characteristics, but the emission of gas-phase pollutants increases. A certain proportion (10%-30%) of coal gasification fine slag is added to the raw coal, which reduces the total emission of gas-phase pollutants (NO x and SO x ). Studies on the characteristics of particulate matter formation show that co-firing with coal gasification fine slag in raw coal can effectively reduce submicron particle emission, and the lower fine particle emission is also detected at lower furnace temperature and oxygen concentration. The element analysis of particulate matter formation shows that the Fe, Si and S elements content of submicron particle generated by YL (the coal gasification fine slag generated by water slurry furnace in of Shaanxi Extended China Coal Yulin Energy Chemical Co., Ltd) sample increases significantly with the increase of furnace temperature and O 2 concentration, which is the main influencing factor for the increase of submicron particle. With the increase of the mixing ratio of YL sample, the content of major elements such as Fe, K and Mg of submicron particle decreases significantly, which is an important reason why the amount of the submicron particle decreases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This study was aimed at assessing the risk factors for hypertension (HTN) and prehypertension (PHT) in order to clarify the role of lipid accumulation product (LAP) in the development of HTN among nondiabetic individuals. A large cross-sectional study was conducted in community health service centers in urban Bengbu, Anhui Province, China. All participants completed an interview questionnaire and procedures to obtain physical measurements and biochemical indicators. Multivariate logistic regression was used to test for the prevalence of HTN and PHT in relation to each quartile increase in LAP level and family history of HTN. The resulting interaction effects were evaluated by relative excess risk of interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). A total of 7733 subjects were enrolled in the study. The overall prevalence rates of PHT and HTN were 37.1% and 24.8%, respectively. After adjusting for confounding factors, multinomial logistic regression analysis showed that compared with subjects in LAP quartile 1, those in quartile 3 (OR, 1.257; 95% CI, 1.062-1.494) and quartile 4 (OR, 1.323; 95% CI, 1.101-1.592) had a significantly higher risk for HTN (p for trend < .001). A significant interaction was observed between LAP and family history of HTN in men (AP, 0.1661; 95% CI, 0.0024-0.3296; SI, 1.4037; 95% CI, 1.0599-1.8593) and in women (RERI, 1.4111; 95% CI, 0.1458-2.9678; AP, 0.1662; 95% CI, 0.0085-0.3237; SI, 1.3886; 95% CI, 1.0568-1.8247). The results demonstrated that the interactive effects of LAP with family history of HTN may influence the development of HTN synergistically., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: The triglyceride glucose (TyG) index has been regarded as an effective proxy of Insulin resistance (IR). Studies on the TyG index, obesity and the risk of prehypertension (PHT) in elderly people are not apparent currently. The study sought to investigate the predictive value of TyG index and the associations with PHT risk and obesity., Methods: A community-based cross-sectional study was conducted in Bengbu City, Anhui province, China. Participants older than 65 years accepted questionnaire surveys, physical examinations and blood biochemistry tests. Based on the testing results, indicators including BMI (body mass index), WC (waist circumference), WHtR (waist-to-height-ratio), LAP(Lipid accumulation products) and TyG were calculated. Residents were classified into quartiles by their TyG indexes. Receiver operating characteristic curve (ROC) analysis was carried out to predict obesity indices for PHT. The three additive interaction indicators, RERI (relative excess risk due to interaction), AP (attributable proportion due to interaction) and S (synergy index) were used to assess the interaction impacts., Results: Two thousand six hundred sixty-six eligible elderly people were included in study and the prevalence of PHT was 71.04% (n = 1894). With increasing TyG index quartile, PHT became more prevalent. After adjusting for confounding factors, the prevalence of PHT risk with TyG levels in the fourth quartile (Q4, male: 2.83, 95%CI: 1.77-4.54; female: 2.75, 95%CI:1.91-3.97) was greater than that in the first quartile (Q1:ref). TyG index (AUC: 0.626, 95%CI: 0.602 to 0.650) was superior than BMI (AUC: 0.609, 95%CI: 0.584 to 0.633) in predicting PHT among females. Eventually, there were significant interactions of TyG index with obesity in males (General obesity: AP = 0.87, 95%CI: 0.72 to 1.02, S = 10.48, 95%CI: 3.43 to 31.97; Abdominal obesity: AP = 0.60,95%CI: 0.38 to 0.83, S = 3.53, 95%CI: 1.99 to 6.26) and females (General obesity: AP = 0.89, 95%CI: 0.79 to 0.98, S = 12.46, 95%CI: 5.61 to 27.69; Abdominal obesity: AP = 0.66, 95%CI: 0.51 to 0.82, S = 3.89, 95%CI:2.54 to 5.98)., Conclusion: TyG index and PHT risk are tightly correlated. The risk of chronic disease in the elderly can be decreased by early detection of PHT utilizing the TyG index. In this research, the TyG index was more predictable than other indicators of obesity., (© 2023. The Author(s).)

Auricularia heimuer is a gelatinous fungus with great edible and medicinal values. In September 2021, a suspected cobweb disease was found in some A. heimuer farms in Fujian Province, China. The disease caused white cottony mycelium to grow on the basal surface of the A. heimuer at the beginning of infection and gradually spread along the outer edge of the fruiting body, and eventually the white pathogen mycelium covered the entire fruiting body, which eventually led to the wilting and death of about 35% of A. heimuer . Two heavily infected tissues of A. heimuer were collected and two isolates were obtained by single spore isolation and purification technique. The pathogen colonies grew 10 to 12 mm per day on potato dextrose agar (PDA), and the colonies were initially white in color and gradually changed to yellowish brown with neat margins. Well-developed mycelium with septum, Conidiophores are bottle-stemmed and whorl-shaped branches, Conidia solitary, as ovoid, colorless singletons or doublets. The chlamydospores are yellowish, smooth surface, with 2-3 septa, size 9-22 μm × 30-38 μm. These morphological features are consistent with the Hypomyces mycophilus (Gea et al. 2019; Wang et al. 2021). For molecular identification, genomic DNA of the two isolates was obtained using an extraction kit (Biocolor, Shanghai, China), internal transcribed spacers (ITS) regions and 5SrRNA were amplified using ITS1 and ITS4 primers (White et al. 1990). A 590 bp DNA fragment was obtained and the sequences were deposited in GenBank (Accession Nos. OP715875 and OP782039), A BLAST search in GenBank revealed the highest similarity (≥99%) to H. mycophilus (GenBank Accession Nos. MH857567 and KU937111) . To fulfill Koch's postulates, the isolates cultured on PDA plates for 10 days were made into a spore suspension with sterile water at a concentration of 5 × 106 conidia/ml and sprayed onto twenty healthy fruiting bodies grown to about 2 cm in diameter, and another ten healthy fruiting bodies sprayed with sterile water as control, and incubated in an artificial climate chamber at 25℃ and relative humidity of 90%-95% (Back et al. 2012). After 4 days of inoculation, the pathogen started to germinate and slowly grew white mycelium, then the white mycelium multiplied at the base of the fruiting bodies and spread from the base to the periphery, and finally the fruiting bodies were completely covered by the pathogenic mycelium and gradually wilted. The symptoms were consistent with the natural disease symptoms under cultivation conditions, while the control group had normal growth of the seeds and no disease symptoms. H. mycophilus was reisolated and purified from symptomatic cotyledons and identified by the above method, and the results of the two experiments were consistent. To our knowledge, this is the first report of H. mycophilus causing cobweb disease in A. heimuer.

Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide; about 25% of NAFLD silently progress into steatohepatitis, in which some of them may develop into fibrosis, cirrhosis and liver failure. However, few drugs are available for NAFLD, partly because of an incomplete understanding of its pathogenic mechanisms. Here, using in vivo and in vitro gain- and loss-of-function approaches, we identified up-regulated DKK1 plays a pivotal role in high-fat diet-induced NAFLD and its progression. Mechanistic analysis reveals that DKK1 enhances the capacity of hepatocytes to uptake fatty acids through the ERK-PPARγ-CD36 axis. Moreover, DKK1 increased insulin resistance by activating the JNK signaling, which in turn exacerbates disorders of hepatic lipid metabolism. Our finding suggests that DKK1 may be a potential therapeutic and diagnosis candidate for NAFLD and metabolic disorder progression., (© 2022 Yang et al.)

Background: Lipid accumulation product (LAP) is considered to be a new convenient useful indicator to assess the visceral fat. Therefore, we aimed to evaluate the risk factors of impaired fasting glucose (IFG) and diabetes, and explore the possible interacting influences of LAP with other factors on the risk of IFG and diabetes among Chinese normotension adults., Methods: A multistage stratified cluster sampling method was conducted to select urban residents in Bengbu, China. For each eligible participant, data on questionnaire survey, anthropometric measurements and laboratory tests were obtained. The effects of body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR) and LAP for predicting IFG and diabetes were performed by multiple logistic regressions and receiver operating characteristic (ROC) analyses. The interaction effects were evaluated by relative excess risk of interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI)., Results: Six thousand, four hundred sixty-seven normotension subjects (2695 men and 3772 women) were enrolled in our study, the prevalence of IFG and diabetes were 9.37% and 14.33%, respectively. When assessed using ROC curve analysis, LAP exhibited higher diagnostic accuracy for identifying IFG and diabetes than BMI, the area under the AUC curve was 0.650 (95% CI: 0.637 to 0.662). After adjustment for age, sex, educational level and other confounding factors, multivariate logistic regression analyses indicated that subjects with the fourth quartile of LAP were more likely to develop IFG (adjusted OR: 2.735, 95% CI: 1.794-4.170) and diabetes (adjusted OR: 1.815, 95% CI: 1.297-2.541) than those with the first quartile. A significant interaction between LAP and family history of diabetes was observed in participants (RERI = 1.538, 95%CI: 0.167 to 3.612; AP = 0.375, 95%CI: 0.118 to 0.631; SI = 1.980, 95%CI: 1.206 to 3.251). However, a significant interaction between LAP and abdominal obesity was indicated by the value of RERI (1.492, 95%CI: 0.087 to 3.723) and AP (0.413, 95%CI: 0.014 to 0.756), but not the value of SI (1.824, 95%CI: 0.873 to 3.526)., Conclusion: Our results demonstrated that there might be synergistic effect between LAP and family history of diabetes on the risk of IFG and diabetes., (© 2022. The Author(s).)

Multiple endocrine neoplasia type 1 (MEN1) is an inherited disease caused by mutations in the MEN1 gene encoding a nuclear protein menin. Among those different endocrine tumors of MEN1, the pancreatic neuroendocrine tumors (PNETs) are life-threatening and frequently implicated. Since there are uncertainties in genotype and phenotype relationship and there are species differences between humans and mice, it is worth it to replenish the mice model with human cell resources. Here, we tested whether the patient-origin induced pluripotent stem cell (iPSC) lines could phenocopy some defects of MEN1. In vitro β-cell differentiation revealed that the percentage of insulin-positive cells and insulin secretion were increased by at least two-fold in MEN1-iPSC derived cells, which was mainly resulted from significantly higher proliferative activities in the pancreatic progenitor stage (Day 7-13). This scenario was paralleled with increased expressions of prohormone convertase1/3 (PC1/3), glucagon-like peptide-1 (GLP-1), GLP-1R, and factors in the phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway, and the GLP-1R was mainly expressed in β-like cells. Blockages of either GLP-1R or PI3K significantly reduced the percentages of insulin-positive cells and hypersecretion of insulin in MEN1-derived cells. Furthermore, in transplantation of different stages of MEN1-derived cells into immune-deficient mice, only those β-like cells produced tumors that mimicked the features of the PNETs from the original patient. To the best of our knowledge, this was the first case using patient-origin iPSCs modeling most phenotypes of MEN1, and the results suggested that GLP-1R may be a potential therapeutic target for MEN1-related hyperinsulinemia.

Background: Various methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable., Methods: We dissect small-molecule combinations and identify the ideal cocktails to achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation., Results: We demonstrated that small-molecule cocktail CIP (including CHIR99021, IDE1, and PD0332991) efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-β/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification. The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas. Thus, we established a stepwise strategy with complete small molecules for efficiently producing scalable HBs and functionally matured HLCs. The small-molecule-derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo., Conclusion: Our current small-molecule-based hepatic generation protocol presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery using., (© 2022. The Author(s).)

Oxide semiconductors are key materials in many technologies from flat-panel displays，solar cells to transparent electronics. However, many potential applications are hindered by the lack of high mobility p-type oxide semiconductors due to the localized O-2p derived valence band (VB) structure. In this work, the VB structure modulation is reported for perovskite Ba 2 BiMO 6 (M = Bi, Nb, Ta) via the Bi 6s 2 lone pair state to achieve p-type oxide semiconductors with high hole mobility up to 21 cm 2 V -1 s -1 , and optical bandgaps widely varying from 1.5 to 3.2 eV. Pulsed laser deposition is used to grow high quality epitaxial thin films. Synergistic combination of hard x-ray photoemission, x-ray absorption spectroscopies, and density functional theory calculations are used to gain insight into the electronic structure of Ba 2 BiMO 6 . The high mobility is attributed to the highly dispersive VB edges contributed from the strong coupling of Bi 6s with O 2p at the top of VB that lead to low hole effective masses (0.4-0.7 m e ). Large variation in bandgaps results from the change in the energy positions of unoccupied Bi 6s orbital or Nb/Ta d orbitals that form the bottom of conduction band. P-N junction diode constructed with p-type Ba 2 BiTaO 6 and n-type Nb doped SrTiO 3 exhibits high rectifying ratio of 1.3 × 10 4 at ±3 V, showing great potential in fabricating high-quality devices. This work provides deep insight into the electronic structure of Bi 3+ based perovskites and guides the development of new p-type oxide semiconductors., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Wide bandgap oxide semiconductors constitute a unique class of materials that combine properties of electrical conductivity and optical transparency. They are being widely used as key materials in optoelectronic device applications, including flat-panel displays, solar cells, OLED, and emerging flexible and transparent electronics. In this article, an up-to-date review on both the fundamental understanding of materials physics of oxide semiconductors, and recent research progress on design of new materials and high-performing thin film transistor (TFT) devices in the context of fundamental understanding is presented. In particular, an in depth overview is first provided on current understanding of the electronic structures, defect and doping chemistry, optical and transport properties of oxide semiconductors, which provide essential guiding principles for new material design and device optimization. With these principles, recent advances in design of p-type oxide semiconductors, new approaches for achieving cost-effective transparent (flexible) electrodes, and the creation of high mobility 2D electron gas (2DEG) at oxide surfaces and interfaces with a wealth of fascinating physical properties of great potential for novel device design are then reviewed. Finally, recent progress and perspective of oxide TFT based on new oxide semiconductors, 2DEG, and low-temperature solution processed oxide semiconductor for flexible electronics will be reviewed., (© 2021 Wiley-VCH GmbH.)

A population genetic study identified that the asialoglycoprotein receptor 1 (ASGR1) mutation carriers had substantially lower non-HDL-cholesterol (non-HDL-c) levels and reduced risks of cardiovascular diseases. However, the mechanism behind this phenomenon remained unclear. Here, we established Asgr1-knockout mice that represented a plasma lipid profile with significantly lower non-HDL-c and triglyceride (TG) caused by decreased secretion and increased uptake of VLDL/LDL. These 2 phenotypes were linked with the decreased expression of microsomal triglyceride transfer protein and proprotein convertase subtilisin/kexin type 9, 2 key targeted genes of sterol regulatory element-binding proteins (SREBPs). Furthermore, there were fewer nuclear SREBPs (nSREBPs) on account of more SREBPs being trapped in endoplasmic reticulum, which was caused by an increased expression of insulin-induced gene 1 (INSIG1), an anchor of SREBPs. Overexpression and gene knockdown interventions, in different models, were conducted to rescue the ASGR1-deficient phenotypes, and we found that INSIG1 knockdown independently reversed the ASGR1-mutated phenotypes with increased serum total cholesterol, LDL-c, TG, and liver cholesterol content accompanied by restored SREBP signaling. ASGR1 rescue experiments reduced INSIG1 and restored the SREBP network defect as manifested by improved apolipoprotein B secretion and reduced LDL uptake. Our observation demonstrated that increased INSIG1 is a critical factor responsible for ASGR1 deficiency-associated lipid profile changes and nSREBP suppression. This finding of an ASGR1/INSIG1/SREBP axis regulating lipid hemostasis may provide multiple potential targets for lipid-lowering drug development.

Pressurized oxy-combustion is an emerging and more efficient technology for carbon capture, utilization, and storage than the first generation (atmospheric) oxy-combustion. NO x is a major conventional pollutant produced in pressurized oxy-combustion. In pressurized oxy-combustion, the utilization of latent heat from moisture and removal of acid gases (NOx and SOx) are mainly conducted in an integrated direct-contact wash column. Recent studies have shown that NOx particular inlet concentration should be maintained before direct contact wash column to remove NOx and SOx efficiently. As a result, minimizing NOx for environmental reasons, avoiding corrosion in carbon capture, utilization, and storage, and achieving effective NOx and SOx removal in direct contact wash columns are crucial. Reburning is a capable and affordable technology for NO x reduction; however, this process is still less studied at elevated pressure, particularly in pressurized oxy-combustion. In this paper, the kinetic evaluation and optimization study on NO x reduction by reburning under pressurized oxy-combustion was conducted. First, the most suitable mechanism was selected by comparing the results of different kinetic models with the experimental data in literature at atmospheric and elevated pressures. Based on the validated mechanism, a variety of parameters were studied at high pressure, i.e., comparing the effects of oxy and the air environment, different reburning fuels, residence time, H 2 O concentration, CH 4 /NO ratio, and equivalence ratio on the NO reduction. The results show that de-NOx efficiency in an oxy environment is significantly enhanced compared to the air environment. Improvement in the de-NOx efficiency is considerably higher with a pressure increase of up to 10 atm, but the effect is less prominent above 10 atm. The formation of HCN is significantly reduced while the N 2 formation is enhanced as the pressure increases from 1 to 10 atm. The residence time required for the maximum NO reduction decreases as the pressure increases from 1 atm to 15 atm. At the higher pressure, the NO reduction rises prominently when the ratio of CH 4 /NO increases from 1 to 2; however, the effect fades after that. At higher pressure, the NO reduction by CH 4 reburning decreases as the H 2 O concentration increases from 0 to 35%. The optimum equivalence ratio and high pressure for maximum NO reduction are 1.5 and 10 atm, respectively. This study could provide guidance for designing and optimizing a pressurized reburning process for NOx reduction in POC systems., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Human hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) represent a promising cell source for the assessment of hepatotoxicity and pharmaceutical safety testing. However, the hepatic functionality of HLCs remains significantly inferior to primary human hepatocytes. The bioactive vitamin D (VD), calcitriol, promotes the differentiation of many types of cells, and its deficiency is correlated to the severity of liver diseases. Whether calcitriol contributes to the differentiation of HLCs needs to be explored. Here, we found that the supplementation of calcitriol improved the functionalities of hPSCs-derived HLCs in P450 activities, urea production, and albumin secretion. Moreover, calcitriol also enhanced mitochondrial respiratory function with increased protein expression levels of the subunit of respiratory enzyme complexes in HLCs. Further analyses showed that the mitochondrial biogenesis regulators and mitophagy were increased by calcitriol, thus improving the mitochondrial quality. These improvements in functionality and mitochondrial condition were dependent on vitamin D receptor (VDR) because the improvements were abolished under VDR-deficient conditions. Our finding provides a cost-effective chemical process for HLC maturation to meet the demand for basic research and potential clinic applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: This study aimed to reveal the effects of icaritin (ICT) on lipotoxicity induced by palmitate (PA) in hepatic cells and steatosis in high-fat diet (HFD)-fed mice as well as exploring the potential mechanisms., Main Methods: Primary mouse hepatocytes and human hepatoma Huh7 cells were used to evaluate ICT effect in vitro. HFD-fed mice were used to evaluate the ICT effect in vivo., Results: In vitro study indicated that ICT significantly rescued PA-induced steatosis, mainly through a combination of robust increased mitochondrial respiration, fatty acid oxidation and mildly decreased synthesis of fatty acid. An HFD-fed mouse model with 8 weeks HFD-fed showed metabolic disorders, while ICT application significantly reduced the weight, serum glucose levels, insulin resistance, hepatic steatosis level and adipose contents. In consistent with the observations in cell lines, ICT rescued the HFD-impaired functions and contents of key factors related to fatty acid β-oxidation through elevated expression of peroxisome proliferator-activated receptor α (PPARα). Meanwhile, it also reversed the decreased phosphoryl levels of AKT and glucogen synthase kinase 3 (GSK3β), leading to the improvement of insulin resistance., Significance: ICT administration had a therapeutic effect on PA- or HFD-induced hepatic steatosis and metabolic disorders. It may provide a novel strategy to construct preventive and therapeutic means for hepatic steatosis., (Copyright © 2020. Published by Elsevier Inc.)

Dickkopf1 (DKK1) is a secreted inhibitor for the Wnt signalling, which is involved in cell proliferation, tissue regeneration and embryonic development. Using CRISPR/Cas9 editing, we established a homozygous mutant DKK1 human embryonic stem cell line (WAe001-A-21). It has a 41 bp deletion in exon 2 of DKK1, leading to its coding frame shift. The WAe001-A-21 cell line maintains a normal karyotype, pluripotency markers, typical stem cell morphology and the ability to differentiate into three germ layers., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Chemically strategies to generate hepatic cells from human pluripotent stem cells (hPSCs) for the potential clinical application have been improved. However, producing high quality and large quantities of hepatic cells remain challenging, especially in terms of step-wise efficacy and cost-effective production requires more improvements., Methods: Here, we systematically evaluated chemical compounds for hepatoblast (HB) expansion and maturation to establish a robust, cost-effective, and reproducible methodology for self-renewal HBs and functional hepatocyte-like cell (HLC) production., Results: The established chemical cocktail could enable HBs to proliferate nearly 3000 folds within 3 weeks with preserved bipotency. Moreover, those expanded HBs could be further efficiently differentiated into homogenous HLCs which displayed typical morphologic features and functionality as mature hepatocytes including hepatocyte identity marker expression and key functional activities such as cytochrome P450 metabolism activities and urea secretion. Importantly, the transplanted HBs in the injured liver of immune-defect mice differentiated as hepatocytes, engraft, and repopulate in the injured loci of the recipient liver., Conclusion: Together, this chemical compound-based HLC generation method presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery application.

Excessive ethanol consumption causes cellular damage, leading to fetal alcohol syndrome and alcohol liver diseases, which are frequently seen with vitamin D (VD) deficiency. A great deal of progress has been achieved in the mechanisms of ethanol-induced hepatocyte damage. However, there are limited intervention means to reduce or rescue hepatocytes damage caused by ethanol. On the basis of our preliminary limited screen process, calcitriol showed a positive effect on protecting hepatocyte viability. Therefore, the molecular basis is worth elucidating. We found that calcitriol pretreatment markedly improved the cell viability, decreased cell apoptosis and oxidative stress and alleviated the abnormal mitochondrial morphology and membrane potential of hepatocytes induced by ethanol. Notably, autophagy was significantly enhanced by calcitriol, as evident by the increasing number of autophagosomes and autolysosomes, upregulated LC3B-Ⅱ and ATG5 levels, and promotion of p62 degradation. Furthermore, calcitriol pretreatment increased the colocalization of GFP-LC3-labeled autophagosomes with mitochondria, suggesting that calcitriol effectively promoted ethanol-induced mitophagy in hepatocytes. In addition, the inhibition of autophagy attenuated the protective and preventive effect of calcitriol. Furthermore, the effect of calcitriol on autophagy was regulated by AMPK/mTOR signaling, and signaling transduction was dependent on the Vitamin D receptor (VDR). In conclusion, calcitriol ameliorates ethanol-induced hepatocyte damage by enhancing autophagy. It may offer a convenient preventive and hepatoprotective mean for people on occasional social drink., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In 2 O 3 is a wide bandgap oxide semiconductor, which has the potential to be used as an active material for transparent flexible electronics and UV photodetectors. However, the high concentration of unintentional background electrons existing in In 2 O 3 makes it hard to be modulated by the electric field or form p-n heterojunctions with a sufficient band-bending width at the interface. In this work, we report the reduction of the background electrons in In 2 O 3 by Mg doping (Mg-In 2 O 3 ) and thereby improve the device performance of p-n diodes based on the NiO/Mg-In 2 O 3 heterojunction. In particular, Mg doping compensates the free electrons in In 2 O 3 and reduces the electron concentration from 1.7 × 10 19 cm -3 without doping to 1.8 × 10 17 cm -3 with 5% Mg doping. Transparent p-n heterojunction diodes were fabricated based on p-type NiO and n-type Mg-In 2 O 3 . The device performance was considerably enhanced by Mg doping with a high rectification ratio of 3 × 10 4 and a remarkable high breakdown voltage of >20 V. High-resolution X-ray photoelectron spectroscopy was used to investigate the interfacial electronic structure between NiO and Mg-In 2 O 3 , revealing a type II band alignment with a valence band offset of 1.35 eV and a conduction band offset of 2.15 eV. A large built-in potential of 0.98 eV was found for the undoped In 2 O 3 but decreased to 0.51 eV for 5% Mg doping of In 2 O 3 . The NiO/Mg-In 2 O 3 diodes with an improved rectification ratio and wider depletion region provide the possibility of achieving photodetectors with rapid photoresponse.

Background: The pandemic of coronavirus disease 2019 (COVID-19) resulted in grave morbidity and mortality worldwide. There is currently no effective drug to cure COVID-19. Based on analyses of available data, we deduced that excessive prostaglandin E 2 (PGE 2 ) produced by cyclooxygenase-2 was a key pathological event of COVID-19. Methods: A prospective clinical study was conducted in one hospital for COVID-19 treatment with Celebrex to suppress the excessive PGE 2 production. A total of 44 COVID-19 cases were enrolled, 37 cases in the experimental group received Celebrex as adjuvant (full dose: 0.2 g, bid ; half dose: 0.2 g, qd ) for 7-14 days, and the dosage and duration was adjusted for individuals, while seven cases in the control group received the standard therapy. The clinical outcomes were evaluated by measuring the urine PGE 2 levels, lab tests, CT scans, vital signs, and other clinical data. The urine PGE 2 levels were measured by mass spectrometry. The study was registered and can be accessed at http://www.chictr.org.cn/showproj.aspx?proj=50474. Results: The concentrations of PGE 2 in urine samples of COVID-19 patients were significantly higher than those of PGE 2 in urine samples of healthy individuals (mean value: 170 ng/ml vs 18.8 ng/ml, p < 0.01) and positively correlated with the progression of COVID-19. Among those 37 experimental cases, there were 10 cases with age over 60 years (27%, 10/37) and 13 cases (35%, 13/37) with preexisting conditions including cancer, atherosclerosis, and diabetes. Twenty-five cases had full dose, 11 cases with half dose of Celebrex, and one case with ibuprofen. The remission rates in midterm were 100%, 82%, and 57% of the full dose, half dose, and control group, respectively, and the discharged rate was 100% at the endpoint with Celebrex treatment. Celebrex significantly reduced the PGE 2 levels and promoted recovery of ordinary and severe COVID-19. Furthermore, more complications, severity, and death rate were widely observed and reported in the COVID-19 group of elders and with comorbidities; however, this phenomenon did not appear in this particular Celebrex adjunctive treatment study. Conclusion: This clinical study indicates that Celebrex adjuvant treatment promotes the recovery of all types of COVID-19 and further reduces the mortality rate of elderly and those with comorbidities., (Copyright © 2020 Hong, Chen, You, Tan, Wu, Tao, Chen, Zhang, Xiong, Yuan, Yang, Chen, Chen, Peng, Tai, Wang, Zhang and Li.)

Oxy-combustion is one of the most promising technologies for carbon capture and sequestration. When CO 2 -neutral biomass is burned under oxy-combustion conditions, named "oxy-biomass combustion" a negative CO 2 emission can be achieved. However, the high content of potassium and chlorine in biomass results in sever ash deposition and corrosion in air fired furnaces, which are further aggravated in oxy-combustion mode due to the enrichment of corrosive species by flue gas recycle. In this paper, the hot corrosion behaviors and mechanism of two representative materials (TP347H, HR3C) used for superheaters in furnaces are studied. The effects of oxy-combustion atmosphere, KCl deposition, effect of SO 2 , effect of water vapor, and temperature on the corrosion kinetics at the starting stage are investigated. The corrosion severity of the materials was determined using the weight gain method, and the microstructures and chemical compositions of corrosion layers were characterized by the scanning electron microscopy with energy dispersive spectroscopy, and X-ray diffraction. The results show that the hot corrosion rate is significantly sped up by KCl deposition, more than five times the gas corrosion rate under the same gas composition and temperature. HR3C with higher Cr and Ni contents is more likely to form Cr enrichment on the interface between the corrosion layer and the substrate than TP347H, resulting in stronger resistance to the hot corrosion than TP347H. When the corrosion atmosphere is changed from air-combustion to oxy-combustion, the hot corrosion rate is reduced with a denser Cr oxide film and less metal sulfides. The increase of temperature in the presence of KCl deposition significantly affects the hot corrosion rate, e.g. the corrosion rate at 650 °C is 16 times higher than that at 450 °C. Water vapor and SO 2 concentrations have opposite influences on the hot corrosion, respectively. Compared to the dry environment, a high-humidity environment decreases the hot corrosion rate; however, a higher SO 2 concentration facilitates the sulfation of KCl deposits, leading to stronger damage to the chromium oxide film and thereby an increased hot corrosion rate., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Clostridium perfringens (C. perfringens) has the ability to form metabolically-dormant spores that can survive food preservation processes and cause food spoilage and foodborne safety risks upon germination outgrowth. This study was conducted to investigate the effects of different AGFK concentrations (0, 50, 100, 200 mM/mL) on the spore germination of C. perfringens in four matrices, including Tris-HCl, FTG, milk, and chicken soup. C. perfringens spore germinability was investigated using near infrared spectroscopy (NIRS) combined with chemometrics. The spore germination rate (S), the OD 600 %, and the Ca 2+ -DPA% were measured using traditional spore germination methods. The results of spore germination assays showed that the optimum germination rate was obtained using 100 mM/L concentrations of AGFK in the FTG medium, and the S, OD 600 % and Ca 2+ -DPA% were 98.6%, 59.3% and 95%, respectively. The best prediction models for the S, OD 600 % and Ca 2+ -DPA% were obtained using SNV as the preprocessing method for the original spectra, with the competitive adaptive weighted resampling method (CARS) as the characteristic variables related to the selected spore germination methods from NIRS data. The results of the S showed that the optimum model was built by CARS-PLSR (RMSEV = 0.745, R c  = 0.897, RMSEP = 0.769, R p  = 0.883). For the OD 600 %, interval partial least squares regression (CARS-siPLS) was performed to optimize the models. The calibration yielded acceptable results (RMSEV = 0.218, R c  = 0.879, RMSEP = 0.257, R p  = 0.845). For the Ca 2+ -DPA%, the optimum model with CARS-siPLS yielded acceptable results (RMSEV = 44.7, R c  = 0.883, RMSEP = 50.2, R p  = 0.872). This indicated that quantitative determinations of the germinability of C. perfringens spores using NIR technology is feasible. A new method based on NIR was provided for rapid, automatic, and non-destructive determination of the germinability of C. perfringens spores., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Liver fibrosis biomarker, Type IV collagen, may function as hepatocarcinogenesis niche. However, among the six isoforms, the isoforms providing tumor microenvironment and their regulatory network are still unclarified. Based on bioinformatics analysis of hundreds of HCC transcriptome datasets from public databases, we found that COL4A1/2 expressions were significantly correlated with hepatocarcinogenesis, progression, and prognosis. The expressions of COL4A1/2 were significantly upregulated in the preneoplastic and HCC tissues compared with normal tissues. Moreover, the overexpression of COL4A2 was highly correlated with shorter progression-free survival in HCC patients. Bioinformatics analysis also generates an interactive regulatory network in which COL4A1/2 directly binding to integrin alpha-2/beta-1 initiates a sequentially and complicated signaling transduction, to accelerate cell cycle and promote tumorigenesis. Among those pathways, the PI3K-Akt pathway is significantly enriched in cooperative mutations and correlation analysis. This suggests that the key activated signaling is PI3K-Akt pathway which severing as the centerline linked with other pathways (Wnt and MAPK signaling) and cell behaviors signaling (cell cycle control and cytoskeleton change). Switching extracellular matrix collagen isoform may establish pro-tumorigenic and metastatic niches. The findings of COL4A1/2 and related signaling networks are valuable to be further investigated that may provide druggable targets for HCC intervention.

Transdifferentiation of other cell type into human neuronal cells (hNCs) provides a platform for neural disease modeling, drug screening and potential cell-based therapies. Among all of the cell donor sources, human urine cells (hUCs) are convenient to obtain without invasive harvest procedure. Here, we report a novel approach for the transdifferentiation of hUCs into hNCs. Our study demonstrated that a combination of seven small molecules (CAYTFVB) cocktail induced transdifferentiation of hUCs into hNCs. These chemical-induced neuronal cells (CiNCs) exhibited typical neuron-like morphology and expressed mature neuronal markers. The neuronal-like morphology revealed in day 1, and the Tuj1-positive CiNCs reached to about 58% in day 5 and 38.36% Tuj1+/MAP2+ double positive cells in day 12. Partial electrophysiological properties of CiNCs was obtained using patch clamp. Most of the CiNCs generated using our protocol were glutamatergic neuron populations, whereas motor neurons, GABAergic or dopaminergic neurons were merely detected. hUCs derived from different donors were converted into CiNCs in this work. This method may provide a feasible and noninvasive approach for reprogramming hNCs from hUCs for disease models and drug screening.

Sulfur trioxide (SO 3 ) is corrosive and environmentally harmful. Under oxy-combustion mode, the formation of SO 3 is aggravated due to flue gas recirculation, and should be more concerned than that under traditional air-combustion mode. In this paper, the catalytic formation of SO 3 by iron oxide (Fe 2 O 3 ) under oxy-combustion mode was experimentally studied in a fixed-bed reactor, and effects of temperature (300-900 °C), atmosphere, catalyst particle size, SO 2 , O 2 , and H 2 O concentrations were discussed. Results show that Fe 2 O 3 promotes SO 3 formation, and the yield of SO 3 reaches a maximum at 700 °C under both air- and oxy-combustion modes. Increasing O 2 concentration in a range of 5-20% promotes the catalytic formation of SO 3 , whose effect is restricted at a higher O 2 concentration. Both increases of SO 2 concentration in a range of 500-3000 ppm and steam concentration in a range of 0-20% decrease the SO 3 yield. A significant effect of Fe 2 O 3 particle size on SO 3 catalytic formation is observed. When the particle size decreases from 50-75 μm to 10-25 μm, the inflection temperature shifts from 700 °C to 600 °C, while the maximum SO 3 yield increases by 33%. Kinetics analysis results show that in this case, the catalytic conversion from SO 2 to SO 3 by Fe 2 O 3 has an apparent activation energy E a of 18.9 kJ/mol and a pre-exponential factor A of 5.2 × 10 -5 . At 700 °C and with Fe 2 O 3 particle size of 50-75 μm, the global reaction orders of SO 2 and O 2 for SO 3 formation are 0.71 and 0.13, respectively., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Biomass combustion under the oxy-fuel conditions (Oxy-biomass combustion) is one of the approaches achieving negative CO 2 emissions. KCl, K 2 CO 3 and K 2 SO 4 , as the major potassium species in biomass ash, can catalytically affect biomass combustion. In this paper, the catalysis of the representative potassium salts on oxy-biomass combustion was studied using a thermogravimetric analyzer (TGA). Effects of potassium salt types (KCl, K 2 CO 3 and K 2 SO 4 ), loading concentrations (0, 1, 3, 5, 8 wt%), replacing N 2 by CO 2 , and O 2 concentrations (5, 20, 30 vol%) on the catalysis degree were discussed. The comparison between TG-DTG curves of biomass combustion before and after water washing in both the 20%O 2 /80%N 2 and 20%O 2 /80%CO 2 atmospheres indicates that the water-soluble minerals in biomass play a role in promoting the devolatilization and accelerating the char-oxidation; and the replacement of N 2 by CO 2 inhibits the devolatilization and char-oxidation processes during oxy-biomass combustion. In the devolatilization stage, the catalysis degree of potassium monotonously increases with the increase of potassium salt loaded concentration. The catalysis degree order of the studied potassium salts is K 2 CO 3  > KCl > K 2 SO 4 . In the char-oxidation stage, with the increase of loading concentration the three kinds of potassium salts present inconsistent change tendencies of the catalysis degree. In the studied loading concentrations from 0 to 8 wt%, there is an optimal loading concentration for KCl and K 2 CO 3 , at 3 and 5 wt%, respectively; while for K 2 SO 4 , the catalysis degree on char-oxidation monotonically increases with the loading potassium concentration. For most studied conditions, regardless of the potassium salt types or the loading concentrations or the combustion stages, the catalysis degree in the O 2 /CO 2 atmosphere is stronger than that in the O 2 /N 2 atmosphere. The catalysis degree is also affected by the O 2 concentrations, and the lowest catalysis degree is generally around 20 vol% O 2 concentration. The kinetic parameters under the different studied conditions are finally obtained., (Copyright © 2018 Elsevier Ltd. All rights reserved.)