Genome oligopaint via local denaturation fluorescence in situ hybridization.

Cas9 in complex with a programmable guide RNA targets specific double-stranded DNA for cleavage. By harnessing Cas9 as a programmable loader of superhelicase to genomic DNA, we report a physiological-temperature DNA fluorescence in situ hybridization (FISH) method termed genome oligopaint via local denaturation (GOLD) FISH. Instead of global denaturation as in conventional DNA FISH, loading a superhelicase at a Cas9-generated nick allows for local DNA denaturation, reducing nonspecific binding of probes and avoiding harsh treatments such as heat denaturation. GOLD FISH relies on Cas9 cleaving target DNA sequences and avoids the high nuclear background associated with other genome labeling methods that rely on Cas9 binding. The excellent signal brightness and specificity enable us to image nonrepetitive genomic DNA loci and analyze the conformational differences between active and inactive X chromosomes. Finally, GOLD FISH could be used for rapid identification of HER2 gene amplification in patient tissue.

Mining genic resources regulating nitrogen-use efficiency based on integrative biological analyses and their breeding applications in maize and other crops.

Nitrogen (N) is an essential factor for limiting crop yields, and cultivation of crops with low nitrogen-use efficiency (NUE) exhibits increasing environmental and ecological risks. Hence, it is crucial to mine valuable NUE improvement genes, which is very important to develop and breed new crop varieties with high NUE in sustainable agriculture system. Quantitative trait locus (QTL) and genome-wide association study (GWAS) analysis are the most common methods for dissecting genetic variations underlying complex traits. In addition, with the advancement of biotechnology, multi-omics technologies can be used to accelerate the process of exploring genetic variations. In this study, we integrate the substantial data of QTLs, quantitative trait nucleotides (QTNs) from GWAS, and multi-omics data including transcriptome, proteome, and metabolome and further analyze their interactions to predict some NUE-related candidate genes. We also provide the genic resources for NUE improvement among maize, rice, wheat, and sorghum by homologous alignment and collinearity analysis. Furthermore, we propose to utilize the knowledge gained from classical cases to provide the frameworks for improving NUE and breeding N-efficient varieties through integrated genomics, systems biology, and modern breeding technologies.

Bile acid-induced IRF3 phosphorylation mediates cell death, inflammatory responses, and fibrosis in cholestasis-induced liver and kidney injury via regulation of ZBP1.

BACKGROUND AND AIMS: Cell death and inflammation play critical roles in chronic tissue damage caused by cholestatic liver injury leading to fibrosis and cirrhosis. Liver cirrhosis is often associated with kidney damage, which is a severe complication with poor prognosis. Interferon regulatory factor 3 (IRF3) is known to regulate apoptosis and inflammation, but its role in cholestasis remains obscure. In this study. APPROACH AND RESULTS: We discovered increased IRF3 phosphorylation in the liver of patients with primary biliary cholangitis and primary sclerosing cholangitis. In the bile duct ligation model of obstructive cholestasis in mice, we found that tissue damage was associated with increased phosphorylated IRF3 (p-IRF3) in the liver and kidney. IRF3 knockout ( Irf3-/- ) mice showed significantly attenuated liver and kidney damage and fibrosis compared to wide-type mice after bile duct ligation. Cell-death pathways, including apoptosis, necroptosis, and pyroptosis, inflammasome activation, and inflammatory responses were significantly attenuated in Irf3-/- mice. Mechanistically, we show that bile acids induced p-IRF3 in vitro in hepatocytes. In vivo , activated IRF3 positively correlated with increased expression of its target gene, Z-DNA-Binding Protein-1 (ZBP1), in the liver and kidney. Importantly, we also found increased ZBP1 in the liver of patients with primary biliary cholangitis and primary sclerosing cholangitis. We discovered that ZBP1 interacted with receptor interacting protein 1 (RIP1), RIP3, and NLRP3, thereby revealing its potential role in the regulation of cell-death and inflammation pathways. In conclusion. CONCLUSIONS: Our data indicate that bile acid-induced p-IRF3 and the IRF3-ZBP1 axis play a central role in the pathogenesis of cholestatic liver and kidney injury.

Natural polymorphisms in ZMET2 encoding a DNA methyltransferase modulate the number of husk layers in maize.

DNA methylation affects agronomic traits and the environmental adaptability of crops, but the natural polymorphisms in DNA methylation-related genes and their contributions to phenotypic variation in maize (Zea mays) remain elusive. Here, we show that a polymorphic 10-bp insertion/deletion variant in the 3'UTR of Zea methyltransferase2 (ZMET2) alters its transcript level and accounts for variation in the number of maize husk layers. ZMET2 encodes a chromomethylase and is required for maintaining genome-wide DNA methylation in the CHG sequence context. Disruption of ZMET2 increased the number of husk layers and resulted in thousands of differentially methylated regions, a proportion of which were also distinguishable in natural ZMET2 alleles. Population genetic analyses indicated that ZMET2 was a target of selection and might play a role in the spread of maize from tropical to temperate regions. Our results provide important insights into the natural variation of ZMET2 that confers both global and locus-specific effects on DNA methylation, which contribute to phenotypic diversity in maize.

Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis.

OBJECTIVE: Alcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury in a high fat-cholesterol-sugar diet (MASH diet)-induced model of MASH. DESIGN: C57BL/6 mice received either chow or the MASH diet for 3 months with or without weekly alcohol binges. Neutrophil infiltration, neutrophil extracellular traps (NETs) and fibrosis were evaluated. RESULTS: We found that alcohol binges in MASH increase liver injury and fibrosis. Liver transcriptomic profiling revealed differential expression of genes involved in extracellular matrix reorganisation, neutrophil activation and inflammation compared with alcohol or the MASH diet alone. Alcohol binges specifically increased NET formation in MASH livers in mice, and NETs were also increased in human livers with MASH plus alcohol use. We discovered that cell-free NETs are sensed via Nod-like receptor protein 3 (NLRP3). Furthermore, we show that cell-free NETs in vitro induce a profibrotic phenotype in hepatic stellate cells (HSCs) and proinflammatory monocytes. In vivo, neutrophil depletion using anti-Ly6G antibody or NET disruption with deoxyribonuclease treatment abrogated monocyte and HSC activation and ameliorated liver damage and fibrosis. In vivo, inhibition of NLRP3 using MCC950 or NLRP3 deficiency attenuated NET formation, liver injury and fibrosis in MASH plus alcohol diet-fed mice (graphical abstract). CONCLUSION: Alcohol binges promote liver fibrosis via NET-induced activation of HSCs and monocytes in MASH. Our study highlights the potential of inhibition of NETs and/or NLRP3, as novel therapeutic strategies to combat the profibrotic effects of alcohol in MASH.

Identification of key genes controlling monoterpene biosynthesis of Citral-type Cinnamomum bodinieri Levl. Based on transcriptome and metabolite profiling.

The citral-type is the most common chemotype in Cinnamomum bodinieri Levl (C. bodinieri), which has been widely used in the daily necessities, cosmetics, biomedicine, and aromatic areas due to their high citral content. Despite of this economic prospect, the possible gene-regulatory roles of citral biosynthesis in the same geographic environment remains unknown. In this study, the essential oils (EOs) of three citral type (B1, B2, B3) and one non-citral type (B0) varieties of C. bodinieri were identified by GC-MS after hydrodistillation extraction in July. 43 components more than 0.10% were identified in the EOs, mainly composed of monoterpenes (75.8-91.84%), and high content citral (80.63-86.33%) were identified in citral-type. Combined transcriptome and metabolite profiling analysis, plant-pathogen interaction(ko04626), MAPK signaling pathway-plant(ko04016), starch and sucrose metabolism(ko00500), plant hormone signal transduction(ko04075), terpenoid backbone biosynthesis (ko00900) and monoterpenoid biosynthesis (ko00902) pathways were enriched significantly. The gene expression of differential genes were linked to the monoterpene content, and the geraniol synthase (CbGES), alcohol dehydrogenase (CbADH), geraniol 8-hydroxylase-like (CbCYP76B6-like) and 8-hydroxygeraniol dehydrogenase (Cb10HGO) were upregulated in the citral-type, indicating that they were associated with high content of geraniol and citral. The activities of CbGES and CbADH in citral type were higher than in non-citral type, which was corroborated by enzyme-linked immunosorbent assay (ELISA). This study on the accumulation mechanism of citral provides a theoretical basis for the development of essential oil of C. bodinieri.

Regulating Protons to Tailor the Enol Conversion of Quinone for High-Performance Aqueous Zinc Batteries.

Quinone-based electrodes using carbonyl redox reactions are promising candidates for aqueous energy storage due to their high theoretical specific capacity and high-rate performance. However, the proton storage manners and their influences on the electrochemical performance of quinone are still not clear. Herein, we reveal that proton storage could determine the products of the enol conversion and the electrochemical stability of the organic electrode. Specifically, the protons preferentially coordinated with the prototypical pyrene-4,5,9,10-tetraone (PTO) cathode, and increasing the proton concentration in the electrolyte can improve its working potentials and cycling stability by tailoring the enol conversion reaction. We also found that exploiting Al2(SO4)3 as a pH buffer can increase the energy density of the Zn||PTO batteries from 242.8 to 284.6 Wh kg-1. Our research has a guiding significance for emphasizing proton storage of organic electrodes based on enol conversion reactions and improving their electrochemical performance.

ZmWAK02 encoding an RD-WAK protein confers maize resistance against gray leaf spot.

Gray leaf spot (GLS) caused by Cercospora zeina or C. zeae-maydis is a major maize disease throughout the world. Although more than 100 QTLs resistant against GLS have been identified, very few of them have been cloned. Here, we identified a major resistance QTL against GLS, qRglsSB, explaining 58.42% phenotypic variation in SB12×SA101 BC1 F1 population. By fine-mapping, it was narrowed down into a 928 kb region. By using transgenic lines, mutants and complementation lines, it was confirmed that the ZmWAK02 gene, encoding an RD wall-associated kinase, is the responsible gene in qRglsSB resistant against GLS. The introgression of the ZmWAK02 gene into hybrid lines significantly improves their grain yield in the presence of GLS pressure and does not reduce their grain yield in the absence of GLS. In summary, we cloned a gene, ZmWAK02, conferring large effect of GLS resistance and confirmed its great value in maize breeding.

Construction and validation of a novel tumor morphology immune inflammatory nutritional score (TIIN score) for intrahepatic cholangiocarcinoma: a multicenter study.

BACKGROUND: Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. METHODS: A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). RESULTS: The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin-globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child-pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients. CONCLUSION: The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.

Ag(I)-Mediated Annulation of 2-(2-Enynyl)pyridines and Propargyl Amines to Access 1-(2H-Pyrrol-3-yl)indolizines.

An effective Ag(I)-mediated annulation of 2-(2-enynyl)pyridines and propargyl amines was developed, unexpectedly affording a broad range of functionalized 1-(2H-pyrrol-3-yl)indolizines in moderate to excellent yields. The developed method is characterized by operational simplicity, ready availability of starting materials, high regioselectivity, and broad substrate scope under mild reaction conditions. The Ag(I)-promoted cyclization of 2-(2-enynyl)pyridines and propargyl amines possibly results in the formation of the spiroindolizine, the ring-opening rearrangement of which may give the 1-(2H-pyrrol-3-yl)indolizine. Furthermore, a gram-scale reaction and synthetic transformations are also studied.

The prognostic value of age-adjusted Charlson comorbidity index in laparoscopic resection for hilar cholangiocarcinoma.

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37-3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma (p < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11-17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01-2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24-2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21-2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning.

Real-time observation of Cas9 postcatalytic domain motions.

CRISPR-Cas9 from Streptococcus pyogenes is an RNA-guided DNA endonuclease, which has become the most popular genome editing tool. Coordinated domain motions of Cas9 prior to DNA cleavage have been extensively characterized but our understanding of Cas9 conformations postcatalysis is limited. Because Cas9 can remain stably bound to the cleaved DNA for hours, its postcatalytic conformation may influence genome editing mechanisms. Here, we use single-molecule fluorescence resonance energy transfer to characterize the HNH domain motions of Cas9 that are coupled with cleavage activity of the target strand (TS) or nontarget strand (NTS) of DNA substrate. We reveal an NTS-cleavage-competent conformation following the HNH domain conformational activation. The 3' flap generated by NTS cleavage can be rapidly digested by a 3' to 5' single-stranded DNA-specific exonuclease, indicating Cas9 exposes the 3' flap for potential interaction with the DNA repair machinery. We find evidence that the HNH domain is highly flexible post-TS cleavage, explaining a recent observation that the HNH domain was not visible in a postcatalytic cryo-EM structure. Our results illuminate previously unappreciated regulatory roles of DNA cleavage activity on Cas9's conformation and suggest possible biotechnological applications.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

How outdoor horticultural activities affect elderly adults' thermal, physiological and psychological responses: a field study.

We recruited 162 healthy elderly adults to determine the thermal, physiological, and psychological effects of horticultural activities (flower arranging, transplanting, and rubble masonry) in outdoor open spaces. We linked these to local climate conditions, physiology, and comfort through a questionnaire survey. The results showed that: (1) the neutral physiological equivalent temperature (NPET) before the horticultural activities were 22.18 â„ƒ for flower arranging, 23.67 â„ƒ for transplanting, and 20.78 â„ƒ for rubble masonry, while the NPET decreased to 18.53 â„ƒ, 20.73 â„ƒ and 18.04 â„ƒ (respectively) after activities. (2) The heart rate and blood oxygen saturation changed significantly (p < 0.05) only after rubble masonry. (3) The average positive affect (PA) scores increased after flower arranging by 4.83, transplanting by 3.30, and rubble masonry by 4.00. (4) After activities, the thermal sensation vote was mainly influenced by globe temperature (41.36%), air temperature (33.47%), and wind speed (25.17%). Thermal comfort vote could be promoted because of 37.35% of an increasing positive and 21.20% of decreasing negative emotion.

The burden of knee osteoarthritis worldwide, regionally, and nationally from 1990 to 2019, along with an analysis of cross-national inequalities.

OBJECTIVE: To describe the disease burden of knee osteoarthritis (KOA) globally, regionally, and in 204 countries by age, sex, and sociodemographic index (SDI) from 1990 to 2019, and to explore cross-national inequalities across SDI. METHODS: The Global Burden of Disease (GBD) 2019 database collected data on KOA worldwide from 1990 to 2019, including prevalence, incidence, years lived with disability (YLDs). The average annual percentage change (AAPC) was used to measure temporal trends. In addition, the inequality slope index and the health concentration index were calculated to quantify the unequal distribution of the burden of KOA across 204 countries worldwide. RESULTS: In 2019, the global age-standardized prevalence rate increased by 7.5% compared with 1990, and the age-standardized incidence rate increased by about 6.2%; The age-standardized YLDs rate increased by about 7.8%. In addition to the Republic of Korea and the United States of America, the disease burden of KOA has increased year by year in other countries around the world. The incidence of KOA was highest at ages 50-59, while the prevalence and rates of YLDs were highest at ages 75-84. The burden of KOA was higher in women than in men. Cross-country inequality suggests that the inequality in the burden of KOA between high SDI and low SDI countries becomes greater, and that countries with high SDI bear a disproportionately high burden. CONCLUSION: The global KOA burden has risen steadily between 1990 and 2019, and cross-national inequality gaps remain large. Targeted measures must therefore be taken to address this inequality and the increasing global KOA disease burden.

Identification and functional analysis of a deduced geraniol synthase from Camphora officinarum.

The market demand for essential oil containing citral is increasing. Our research group identified a rare chemotype of Camphora officinarum whose leaves are high in citral content by examining over 1000 wild trees across the entire native distribution area of C. officinarum in China. Because C. officinarum is suitable for large-scale cultivation, it is therefore seen as a promising source of natural citral. However, the molecular mechanism of citral biosynthesis in C. officinarum is poorly understood. In this study, transcriptomic analyses of C. officinarum with different citral contents revealed a strong positive correlation between the expression of a putative geraniol synthase gene (CoGES) and citral content. The CoGES cDNA was cloned, and the CoGES protein shared high similarity with other monoterpene synthases. Enzymatic assays of CoGES with geranyl diphosphate (GPP) as substrate yielded geraniol as the single product, which is the precursor of citral. Further transient expression of CoGES in Nicotiana benthamiana resulted in a higher relative content of geranial and the appearance of a new substance, neral. These findings indicate that CoGES is a geraniol synthase-encoding gene, and the encoded protein can catalyze the transformation of GPP into geraniol, which is further converted into geranial and neral through an unknown mechanism in vivo. These findings expand our understanding of citral biosynthesis in Lauraceae plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01463-4.

Phase Engineering of High-Entropy Alloy for Enhanced Electrocatalytic Nitrate Reduction to Ammonia.

Directly electrochemical conversion of nitrate (NO3 -) is an efficient and environmentally friendly technology for ammonia (NH3) production but is challenged by highly selective electrocatalysts. High-entropy alloys (HEAs) with unique properties are attractive materials in catalysis, particularly for multi-step reactions. Herein, we first reported the application of HEA (FeCoNiAlTi) for electrocatalytic NO3 - reduction to NH3 (NRA). The bulk HEA is active for NRA but limited by the unsatisfied NH3 yield of 0.36 mg h-1 cm-2 and Faradaic efficiency (FE) of 82.66 %. Through an effective phase engineering strategy, uniform intermetallic nanoparticles are introduced on the bulk HEA to increase electrochemical active surface area and charge transfer efficiency. The resulting nanostructured HEA (n-HEA) delivers enhanced electrochemical NRA performance in terms of NH3 yield (0.52 mg h-1 cm-2) and FE (95.23 %). Further experimental and theoretical investigations reveal that the multi-active sites (Fe, Co, and Ni) dominated electrocatalysis for NRA over the n-HEA. Notably, the typical Co sites exhibit the lowest energy barrier for NRA with *NH2 to *NH3as the rate-determining step.

Distinguish MnO2/Mn2+ Conversion/ Zn2+ Intercalation/ H+ Conversion Chemistries at Different Potentials in Aqueous Zn||MnO2 Batteries.

The rechargeable aqueous Zn||MnO2 chemistry has been extensively explored, but its electrochemical reaction mechanisms, especially in the context of MnO2/Mn2+ conversion and Zn2+/H+ intercalation chemistry, remain not fully understood. Here, we designed an amphiphilic hydrogel electrolyte, which distinguished the MnO2/Mn2+ conversion, Zn2+ intercalation, and H+ intercalation and conversion processes at three distinct discharge plateaus of an aqueous Zn||MnO2 battery. The amphiphilic hydrogel electrolyte is featured with an extended electrochemical stability window up to 3.0 V, high ionic conductivity, Zn2+-selective ion tunnels, and hydrophobic associations with cathode materials. This specifically designed electrolyte allows the MnO2/Mn2+ conversion reaction at a discharge plateau of 1.75 V. More interesting, the discharge plateaus of ~1.33 V, previously assigned as the co-intercalation of Zn2+ and H+ ions in the MnO2 cathode, are specified as the exclusive intercalation of Zn2+ ions, leading to an ultra-flat voltage plateau. Furthermore, with a distinct three-step electrochemical energy storage process, a high areal capacity of 1.8 mAh cm-2 and high specific energy of 0.858 Wh cm-2, even at a low MnO2 loading mass of 0.5 mg cm-2 are achieved. To our knowledge, this is the first report to fully distinguish different mechanisms at different potentials in aqueous Zn||MnO2 batteries.

Tellurium with Reversible Six-Electron Transfer Chemistry for High-Performance Zinc Batteries.

Chalcogens, especially tellurium (Te), as conversion-type cathodes possess promising prospects for zinc batteries (ZBs) with potential rich valence supply and high energy density. However, the conversion reaction of Te is normally restricted to the Te2-/Te0 redox with a low voltage plateau at ∼0.59 V (vs Zn2+/Zn) rather than the expected positive valence conversion of Te0 to Ten+, inhibiting the development of Te-based batteries toward high output voltage and energy density. Herein, the desired reversible Te2-/Te0/Te2+/Te4+ redox behavior with up to six-electron transfer was successfully activated by employing a highly concentrated Cl--containing electrolyte (Cl- as strong nucleophile) for the first time. Three flat discharge plateaus located at 1.24, 0.77, and 0.51 V, respectively, are attained with a total capacity of 802.7 mAh g-1. Furthermore, to improve the stability of Ten+ products and enhance the cycling stability, a modified ionic liquid (IL)-based electrolyte was fabricated, leading to a high-performance Zn∥Te battery with high areal capacity (7.13 mAh cm-2), high energy density (542 Wh kgTe-1 or 227 Wh Lcathdoe+anode-1), excellent cycling performance, and a low self-discharge rate based on 400 mAh-level pouch cell. The results enhance the understanding of tellurium chemistry in batteries, substantially promising a remarkable route for advanced ZBs.

High intestinal isoleucine is a potential risk factor for food allergy by regulating the mTOR/AKT pathway in dendritic cells.

Food allergy is a global food safety problem with a growing prevalence. People in industrial regions are more susceptible to allergy, but the mechanisms behind this are not fully understood. In this study, the probiotic Lactobacillus casei Zhang (LcZ) was administered to allergic individuals and the impact on allergy-related factors were determined. LcZ alleviated allergenic responses, and there was a significant correlation between the intestinal isoleucine content and IgE concentration. Metagenomics results suggest that the metabolism of the gut microbiota is a source of isoleucine. In a mouse model of food allergy, a high isoleucine diet exacerbated allergic responses and increased the activity of allergenic dendritic cell. In a dendritic cell model, a protein array revealed that the mTOR/AKT pathway mediated the function of isoleucine, and molecular docking suggested that Sestrin2 could be the potential receptor. Overall, this study revealed the role of isoleucine in promoting food allergy, elucidated the underlying mechanisms, and suggested that a high intake of isoleucine could be a potential risk factor for food allergy.