The contribution of natural and anthropogenic causes to soil acidification rates under different fertilization practices and site conditions in southern China.

Excessive application of mineral fertilizers has accelerated soil acidification in China, affecting crop production when the pH drops below a critical value. However, the contributions of natural soil acidification, induced by leaching of bicarbonate, and anthropogenic causes of soil acidification, induced by nitrogen (N) transformations and removal of base cations over acid anions, are not well quantified. In this study, we quantified soil acidification rates, in equivalents (eq) of acidity, by assessing the inputs and outputs of all major cations and anions, including calcium, magnesium, potassium, sodium, ammonium, nitrate, bicarbonate, sulphate, phosphate and chloride, for 13 long-term experimental sites in southern China. The acidification rates strongly varied among fertilizer treatments and with the addition of animal manure. Bicarbonate leaching was the dominant acid production process in calcareous soils (23 keq ha-1 yr-1) and in non-calcareous paddy soils (9.6 keq ha-1 yr-1), accounting for 80 % and 68 % of the total acid production rate, respectively. The calcareous soils were strongly buffered, and acidification led no or a limited decline in pH. In contrast, N transformations were the most important driver for soil acidification at one site with upland crops on a non-calcareous soil, accounting for 72 % of total acid production rate of 8.4 keq ha-1 yr-1. In this soil, the soil pH considerably decreased being accompanied by a substantial decline in exchangeable base cation. Reducing the N surplus decreased the acidification rate with 10 to 54 eq per kg N surplus with the lowest value occurring in paddy soils and the highest in the upland soil. The use of manure, containing base cations, partly mitigated the acidifying impact of N fertilizer inputs and crop removal, but enhanced phosphorus (P) accumulation. Combining mineral fertilizer, manure and lime in integrative management strategies can mitigate soil acidification and minimize N and P losses.

Molecular characterization of m6A RNA methylation regulators with features of immune dysregulation in IgA nephropathy.

The role of RNA N6-methyladenosine (m6A) modification in immunity is being elucidated. This study aimed to explore the potential association between m6A regulators and the immune microenvironment in IgA nephropathy (IgAN). The expression profiles of 24 m6A regulators in 107 IgAN patients were obtained from the Gene Expression Omnibus (GEO) database. The least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis were utilized to construct a model for distinguishing IgAN from control samples. Based on the expression levels of m6A regulators, unsupervised clustering was used to identify m6A-induced molecular clusters in IgAN. Gene set enrichment analysis (GSEA) and immunocyte infiltration among different clusters were examined. The gene modules with the highest correlation for each of the three clusters were identified by weighted gene co-expression network analysis (WGCNA). A model containing 10 m6A regulators was developed using LASSO and logistic regression analyses. Three molecular clusters were determined using consensus clustering of 24 m6A regulators. A decrease in the expression level of YTHDF2 in IgAN samples was significantly negatively correlated with an increase in resting natural killer (NK) cell infiltration and was positively correlated with the abundance of M2 macrophage infiltration. The risk scores calculated by the nomogram were significantly higher for cluster-3, and the expression levels of m6A regulators in this cluster were generally low. Immunocyte infiltration and pathway enrichment results for cluster-3 differed significantly from those for the other two clusters. Finally, the expression of YTHDF2 was significantly decreased in IgAN based on immunohistochemical staining. This study demonstrated that m6A methylation regulators play a significant role in the regulation of the immune microenvironment in IgAN. Based on m6A regulator expression patterns, IgAN can be classified into multiple subtypes, which might provide additional insights into novel therapeutic methods for IgAN.

Effects of Connectivity Isomerization on Electron Transport Through Thiophene Heterocyclic Molecular Junction.

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene (TP) aromatic ring substituted by two dihydrobenzo[b]thiophene (BT) groups with ethynyl spacers (m,n-TP-BT, (m,n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10-4.83 G0 (2,4-TP-BT) < 10-4.78 G0 (3,4-TP-BT) < 10-4.06 G0 (2,3-TP-BT) < 10-3.75 G0 (2,5-TP-BT). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = EF leads the smallest conductance value for 2,4-TP-BT. This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

Monolayer Vacancy-Induced MXene Memory for Write-Verify-Free Programming.

The fundamental logic states of 1 and 0 in Complementary Metal-Oxide-Semiconductor (CMOS) are essential for modern high-speed non-volatile solid-state memories. However, the accumulated storage signal in conventional physical components often leads to data distortion after multiple write operations. This necessitates a write-verify operation to ensure proper values within the 0/1 threshold ranges. In this work, a non-gradual switching memory with two distinct stable resistance levels is introduced, enabled by the asymmetric vertical structure of monolayer vacancy-induced oxidized Ti3C2Tx MXene for efficient carrier trapping and releasing. This non-cumulative resistance effect allows non-volatile memories to attain valid 0/1 logic levels through direct reprogramming, eliminating the need for a write-verify operation. The device exhibits superior performance characteristics, including short write/erase times (100 ns), a large switching ratio (≈3 × 104), long cyclic endurance (>104 cycles), extended retention (>4 × 106 s), and highly resistive stability (>104 continuous write operations). These findings present promising avenues for next-generation resistive memories, offering faster programming speed, exceptional write performance, and streamlined algorithms.

Reducing cherry rain-cracking: Enhanced wetting and barrier properties of chitosan hydrochloride-based coating with dual nanoparticles.

The synergistic effects of phosphorylated zein nanoparticles (PZNP) and cellulose nanocrystals (CNC) in enhancing the wetting and barrier properties of chitosan hydrochloride (CHC)-based coating are investigated characterized by Fourier Transform Infrared Spectra (FTIR), X-ray Diffraction (XRD), atomic force microscopy and by investigating the mechanical properties, etc., with the aim of reducing cherry rain cracking. FTIR and XRD showed dual nanoparticles successfully implanted into CHC, CHC-PZNP-CNC combined moderate ductility (elongation at break: 7.8 %), maximum tensile strength (37.5 MPa). The addition of PZNP alone significantly improved wetting performance (Surface Tension, CHC: 55.3 vs. CHC-PZNP: 48.9 mN/m), while the addition of CNC alone led to a notable improvement in the water barrier properties of CHC (water vapor permeability, CHC: 6.75 × 10-10 vs. CHC-CNC: 5.76 × 10-10 gm-1 Pa-1 s-1). The final CHC-PZNP-CNC coating exhibited enhanced wettability (51.2 mN/m) and the strongest water-barrier property (5.32 × 10-10 gm-1 Pa-1 s-1), coupled with heightened surface hydrophobicity (water contact angle: 106.4°). Field testing demonstrated the efficacy of the CHC-PZNP-CNC coating in reducing cherry rain-cracking (Cracking Index, Control, 42.3 % vs. CHC-PZNP-CNC, 19.7 %; Cracking Ratio, Control, 34.6 % vs. CHC-PZNP-CNC, 15.8 %). The CHC-PZNP-CNC coating is a reliable option for preventing rain-induced cherry cracking.

Establishing national reference materials for genetic testing of cytochrome P450.

OBJECTIVES: Reference materials for in-vitro diagnostic reagents play a critical role in determining the quality of reagents and ensuring the accuracy of clinical test results. This study aimed to establish a national reference material (NRM) for detecting cytochrome P450 (CYP) genes related to drug metabolism by screening databases on the Chinese population to identify CYP gene polymorphism characteristics. METHODS: To prepare the NRM, we used DNA extracted from healthy human immortalized B lymphoblastoid cell lines as the raw material. Samples of these cell lines were obtained from the Chinese Population PGx Gene Polymorphism Biobank. Further, we used Sanger sequencing, next-generation sequencing, and commercial assay kits to validate the polymorphic genotypes. RESULTS: Among the CYP superfamily genes, we confirmed 24 riboswitch loci related to drug metabolism, with evidence levels of 1A, 2A, 3, and 4. We confirmed the polymorphic loci and validated their genotypes using various sequencing techniques. Our results were consistent with the polymorphism information of samples obtained from the biobank, thus demonstrating high precision and stability of the established NRM. CONCLUSION: An NRM (360 056-202 201) for CYP genetic testing covering 24 loci related to drug metabolism was established and approved to assess in-vitro diagnostic reagents containing CYP family gene polymorphisms and perform clinical inter-room quality evaluations.

Association of Serum AGR With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes.

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid.

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (ß = -0.18, 95%CI: -0.29 - -0.07, P = 0.002) and progressive motility (ß = -0.27, 95%CI: -0.43 - -0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: ß = 0.26, 95%CI: 0.01 - -0.51, Pinteraction = 0.047; progressive motility: ß = 0.64, 95%CI: 0.23 - 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

Nomogram model including LATS2 expression was constructed to predict the prognosis of advanced gastric cancer after surgery.

BACKGROUND: Gastric cancer is a leading cause of cancer-related deaths worldwide. Prognostic assessments are typically based on the tumor-node-metastasis (TNM) staging system, which does not account for the molecular heterogeneity of this disease. LATS2, a tumor suppressor gene involved in the Hippo signaling pathway, has been identified as a potential prognostic biomarker in gastric cancer. AIM: To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following radical surgery, and compare its predictive performance with traditional TNM staging. METHODS: A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted. The patients were divided into a training group (171 patients) and a validation group (74 patients) to develop and test our prognostic model. The performance of the model was determined using C-indices, receiver operating characteristic curves, calibration plots, and decision curves. RESULTS: The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set. Area under the curve values for three-year and five-year survival prediction were significantly robust, suggesting an excellent discrimination ability. Calibration plots confirmed the high concordance between the predictions and actual survival outcomes. CONCLUSION: We developed a nomogram model incorporating LATS2 expression, which significantly outperformed conventional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery. This model may serve as a valuable tool for individualized patient management, allowing for more accurate stratification and improved clinical outcomes. Further validation in larger patient cohorts will be necessary to establish its generalizability and clinical utility.

Repression of the SUMO-conjugating enzyme UBC9 is associated with lowered double minutes and reduced tumor progression.

Double minutes (DMs), extrachromosomal gene fragments found within certain tumors, have been noted to carry onco- and drug resistance genes contributing to tumor pathogenesis and progression. After screening for SUMO-related molecule expression within various tumor sample and cell line databases, we found that SUMO-conjugating enzyme UBC9 has been associated with genome instability and tumor cell DM counts, which was confirmed both in vitro and in vivo. Karyotyping determined DM counts post-UBC9 knockdown or SUMOylation inhibitor 2-D08, while RT-qPCR and Western blot were used to measure DM-carried gene expression in vitro. In vivo, fluorescence in situ hybridization (FISH) identified micronucleus (MN) expulsion. Western blot and immunofluorescence staining were then used to determine DNA damage extent, and a reporter plasmid system was constructed to detect changes in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Our research has shown that UBC9 inhibition is able to attenuate DM formation and lower DM-carried gene expression, in turn reducing tumor growth and malignant phenotype, via MN efflux of DMs and lowering NHEJ activity to increase DNA damage. These findings thus reveal a relationship between heightened UBC9 activity, increased DM counts, and tumor progression, providing a potential approach for targeted therapies, via UBC9 inhibition.

Establishment of a hydrodynamic delivery system in ducks.

Chronic hepatitis B virus (HBV) poses a significant global health challenge as it can lead to acute or chronic liver disease and hepatocellular carcinoma (HCC). To establish a safety experimental model, a homolog of HBV-duck HBV (DHBV) is often used for HBV research. Hydrodynamic-based gene delivery (HGD) is an efficient method to introduce exogenous genes into the liver, making it suitable for basic research. In this study, a duck HGD system was first constructed by injecting the reporter plasmid pLIVE-SEAP via the ankle vein. The highest expression of SEAP occurred when ducks were injected with 5 µg/mL plasmid pLIVE-SEAP in 10% bodyweight volume of physiological saline for 6 s. To verify the distribution and expression of exogenous genes in multiple tissues, the relative level of foreign gene DNA and ß-galactosidase staining of LacZ were evaluated, which showed the plasmids and their products were located mainly in the liver. Additionally, ß-galactosidase staining and fluorescence imaging indicated the delivered exogenous genes could be expressed in a short time. Further, the application of the duck HGD model on DHBV treatment was investigated by transferring representative anti-HBV genes IFNα and IFNγ into DHBV-infected ducks. Delivery of plasmids expressing IFNα and IFNγ inhibited DHBV infection and we established a novel efficient HGD method in ducks, which could be useful for drug screening of new genes, mRNAs and proteins for anti-HBV treatment.

Exogenous methyl jasmonate treatment induced the transcriptional responses and accumulation of volatile terpenoids in Oenanthe javanica (Blume) DC.

Water dropwort is favored by consumers for its unique flavor and medicinal value. Terpenoids were identified as the main volatile compounds related to its flavor. In this study, water dropwort was treated with different concentrations of exogenous methyl jasmonate (MeJA). The contents of volatile terpenoids were determined under various MeJA treatments. The results indicated that 0.1 mM of MeJA most effectively promoted the biosynthesis of flavor-related terpenoids in water dropwort. Terpinolene accounted the highest proportion among terpene compounds in water dropwort. The contents of jasmonates in water dropwort were also increased after exogenous MeJA treatments. Transcriptome analysis indicated that DEGs involved in the terpenoid biosynthesis pathway were upregulated. The TPS family was identified from water dropwort, and the expression levels of Oj0473630, Oj0287510 and Oj0240400 genes in TPS-b subfamily were consistent with the changes of terpene contents under MeJA treatments. Oj0473630 was cloned from the water dropwort and designated as OjTPS3, which is predicted to be related to the biosynthesis of terpinolene in water dropwort. Subcellular localization indicated that OjTPS3 protein was localized in chloroplast. Protein purification and enzyme activity of OjTPS3 protein were conducted. The results showed that the purified OjTPS3 protein catalyzed the biosynthesis of terpinolene by using geranyl diphosphate (GPP) as substrate in vitro. This study will facilitate to further understand the molecular mechanism of terpenoid biosynthesis and provide a strategy to improve the flavor of water dropwort.

Light Enables the Cathodic Interface Reaction Reversibility in Solid-State Lithium-Oxygen Batteries.

Limited triple-phase boundaries arising from the accumulation of solid discharge product(s) in solid-state cathodes (SSCs) pose a challenge to high-property solid-state lithium-oxygen batteries (SSLOBs). Light-assisted SSLOBs have been gradually explored as an ingenious system; however, the fundamental mechanisms of the SSCs interface behavior remain unclear. Here, we discovered that light assistance can enhance the fast inner-sphere charge transfer in SSCs and regulate the discharge products with spherical particles generated via the surface growth model. Moreover, the high photoelectron excitation and transportation capabilities of SSCs can retard cathodic catalytic decay by avoiding structural degradation of the cathode with a reduced charge voltage. The light-induced SSLOBs exhibited excellent stability (170 cycles) with a low discharge-charge polarization overpotential (0.27 V). Furthermore, transparent SSLOBs with exceptional flexibility, mechanical stability, and multiform shapes were fabricated for theory-to-practical applications in sunlight-induced batteries. Our study opens new opportunities for the introduction of solar energy into energy storage systems.

Multi-omics analysis reveals the biosynthesis of flavonoids during the browning process of Malus sieversii explants.

Malus sieversii is a precious apple germplasm resource. Browning of explants is one of the most important factors limiting the survival rate of plant tissue culture. In order to explore the molecular mechanism of the browning degree of different strains of Malus sieversii, we compared the dynamic changes of Malus sieversii and Malus robusta Rehd. during the whole browning process using a multi-group method. A total of 44 048 differentially expressed genes (DEGs) were identified by transcriptome analysis on the DNBSEQ-T7 sequencing platform. KEGG enrichment analysis showed that the DEGs were significantly enriched in the flavonoid biosynthesis pathway. In addition, metabonomic analysis showed that (-)-epicatechin, astragalin, chrysin, irigenin, isoquercitrin, naringenin, neobavaisoflavone and prunin exhibited different degrees of free radical scavenging ability in the tissue culture browning process, and their accumulation in different varieties led to differences in the browning degree among varieties. Comprehensive transcriptome and metabonomics analysis of the data related to flavonoid biosynthesis showed that PAL, 4CL, F3H, CYP73A, CHS, CHI, ANS, DFR and PGT1 were the key genes for flavonoid accumulation during browning. In addition, WGCNA analysis revealed a strong correlation between the known flavonoid structure genes and the selected transcriptional genes. Protein interaction predictions demonstrated that 19 transcription factors (7 MYBs and 12 bHLHs) and 8 flavonoid structural genes had targeted relationships. The results show that the interspecific differential expression of flavonoid genes is the key influencing factor of the difference in browning degree between Malus sieversii and Malus robusta Rehd., providing a theoretical basis for further study on the regulation of flavonoid biosynthesis.

Exploring the role of the LkABCG36 transporter in lignin accumulation.

Lignin is a complex biopolymer formed through the condensation of three monomeric precursors known as monolignols. However, the mechanism underlying lignin precursor transport remains elusive, with uncertainty over whether it occurs through passive diffusion or an active energized process. ATP-binding cassette 36 (ABCG36) plays important roles in abiotic stress resistance. In this study, we investigated the transport functions of LkABCG36 (Larix kaempferi) for lignin precursors and the potential effects of LkABCG36 overexpression in plants. LkABCG36 enhanced the ability of tobacco (Nicotiana tabacum) bright yellow-2 (BY-2) cells to resist monolignol alcohol stress. Furthermore, LkABCG36 overexpression promoted lignin deposition in tobacco plant stem tissue. To understand the underlying mechanism, we measured the BY-2 cell ability to export lignin monomers and the uptake of monolignol precursors in inside-out (inverted) plasma membrane vesicles. We found that the transport of coniferyl and sinapyl alcohols is an ATP-dependent process. Our data suggest that LkABCG36 contributes to lignin accumulation in tobacco stem tissues through a mechanism involving the active transport of lignin precursors to the cell wall. These findings shed light on the lignin biosynthesis process, with important implications for enhancing lignin deposition in plants, potentially leading to improved stress tolerance and biomass production.

A unique circulating microRNA pairs signature serves as a superior tool for early diagnosis of pan-cancer.

Cancer remains a major burden globally and the critical role of early diagnosis is self-evident. Although various miRNA-based signatures have been developed in past decades, clinical utilization is limited due to a lack of precise cutoff value. Here, we innovatively developed a signature based on pairwise expression of miRNAs (miRPs) for pan-cancer diagnosis using machine learning approach. We analyzed miRNA spectrum of 15832 patients, who were divided into training, validation, test, and external test sets, with 13 different cancers from 10 cohorts. Five different machine-learning (ML) algorithms (XGBoost, SVM, RandomForest, LASSO, and Logistic) were adopted for signature construction. The best ML algorithm and the optimal number of miRPs included were identified using area under the curve (AUC) and youden index in validation set. The AUC of the best model was compared to previously published 25 signatures. Overall, Random Forest approach including 31 miRPs (31-miRP) was developed, proving highly efficient in cancer diagnosis across different datasets and cancer types (AUC range: 0.980-1.000). Regarding diagnosis of cancers at early stage, 31-miRP also exhibited high capacities, with AUC ranging from 0.961 to 0.998. Moreover, 31-miRP exhibited advantages in differentiating cancers from normal tissues (AUC range: 0.976-0.998) as well as differentiating cancers from corresponding benign lesions. Encouragingly, comparing to previously published 25 different signatures, 31-miRP also demonstrated clear advantages. In conclusion, 31-miRP acts as a powerful model for cancer diagnosis, characterized by high specificity and sensitivity as well as a clear cutoff value, thereby holding potential as a reliable tool for cancer diagnosis at early stage.

Potential Effects of NO-Induced Hypoxia-Inducible Factor-1α on Yak Meat Tenderness during Post-Mortem Aging.

The objective of this study was to investigate the mechanism underlying nitric oxide (NO)-induced hypoxia-inducible factor-1α (HIF-1α) and its impact on yak muscle tenderness during post-mortem aging. The Longissimus thoracis et lumborum (LTL) muscle of yak were incubated at 4 °C for 0, 3, 6, 9, 12, 24, and 72 h after treatment with 0.9% saline, NO activator, or a combination of the NO activator and an HIF-1α inhibitor. Results indicated that elevated NO levels could increase HIF-1α transcription to achieve stable expression of HIF-1α protein (P < 0.05). Additionally, elevated NO triggered HIF-1α S-nitrosylation, which further upregulated the activity of key glycolytic enzymes, increased glycogen consumption, accelerated lactic acid accumulation, and decreased pH (P < 0.05). These processes eventually improved the tenderness of yak muscle during post-mortem aging (P < 0.05). The results demonstrated that NO-induced activation of HIF-1α S-nitrosylation enhanced glycolysis during post-mortem aging and provided a possible pathway for improving meat tenderness.

Blockade of aryl hydrocarbon receptor restricts omeprazole-induced chronic kidney disease.

Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME-induced tubular cell impairment in HK-2 cells. Taken together, these data indicate that OME induces CKD through the activation of the AHR-CYP axis in RTECs. Our findings suggest that blocking the AHR-CYP1A1 pathway acts as a potential strategy for the treatment of CKD caused by OME. KEY MESSAGES: We provide an omeprazole-induced chronic kidney disease (CKD) mice model. AHR activation and translocation process was involved in renal tubular damage and promoted the occurrence of CKD. The process of omeprazole nephrotoxicity can be ameliorated by blockade of the AHR-CYP1A1 axis.

Geometric analysis of SARS-CoV-2 variants.

SARS-CoV-2 as a severe respiratory disease has been prevalent around the world since its first discovery in 2019.As a single-stranded RNA virus, its high mutation rate makes its variants manifold and enables some of them to have high pathogenicity, such as Omicron variant, the most prevalent virus now. Research on the relationship of these SARS-CoV-2 variants, especially exploring their difference is a hot issue. In this study, we constructed a geometric space to represent all SARS-CoV-2 sequences of different variants. An alignment-free method: natural vector method was utilized to establish genome space. The genome space of SARS-CoV-2 was constructed based on the 24-dimensional natural vector and the appropriate metric was determined through performing phylogenetic analysises. Phylogenetic trees of different lineages constructed under the selected natural vector and metric coincided with the lineage naming standards, which means lineages with same alphabetical prefix cluster in phylogenetic trees. Furthermore, the relationships between the various GISAID clades as depicted by the natural graph primarily matched the description provided in the GISAID clade naming.The validity of our geometric space was demonstrated by these phylogenetic analysis results. So in this research, we constructed a geometry space for the genomes of the novel coronavirus SARS-CoV-2, which allows us to compare the different variants. Our geometric space is valuable for resolving the issues insides the virus.