Grassland productivity in arid Central Asia depends on the greening rate rather than the growing season length.

Climate change has induced substantial impact on the gross primary productivity (GPP) of terrestrial ecosystems by affecting vegetation phenology. Nevertheless, it remains unclear which among the mean rates of grass greening (RG), yellowing (RY), and the length of growing season (LOS) exhibit stronger explanatory power for GPP variations, and how RG and RY affect GPP variations under warming scenarios. Here, we explored the relationship between RG, RY, LOS, and GPP in arid Central Asia (ACA) from 1982 to 2019, elucidating the response mechanisms of RG, RY, and GPP to the mean temperature (TMP), vapor pressure deficit (VPD), precipitation (PRE), and soil moisture (SM). The results showed that the multi-year average length of greening (LG) in ACA was 22.7 days shorter than that of yellowing (LY) and the multi-year average GPP during LG (GPPlg) was 38.28 g C m-2 d -1 more than that of during LY (GPPly). RG and RY were positively correlated with GPPlg and GPPly, although the degree of correlation between RG and GPPlg was higher than that between RY and GPPly. Increases in RG and RY contributed to an increase in GPPlg (55.44 % of annual GPP) and GPPly (35.44 % of annual GPP). The correlation between RG and GPPlg was the strongest (0.49), followed by RY and GPPly (0.33), and LOS and GPP was the weakest (0.21). TMP, VPD, PRE, and SM primarily affected GPP by influencing RG and RY, rather than direct effects. The positive effects of TMP during LG (TMPlg), PRE during LG (PRElg), and SM during LG (SMlg) facilitated increases in RG and GPPlg, and higher VPD during LY (VPDly) and lower PRE during LY (PREly) accelerated increases in RY. Our study elucidated the impact of vegetation growth rate on GPP, thus providing an alternate method of quantifying the relationship between vegetation phenology and GPP.

Integrative analysis of proteomics and lipidomic profiles reveal the fat deposition and meat quality in Duroc × Guangdong small spotted pig.

Introduction: This study aims to explore the important factors affecting the characteristics of different parts of pork. Methods: Lipidomics and proteomics methods were used to analyze DAL (differential lipids) and DAPs (differential proteins) in five different parts (longissimus dorsi, belly meat, loin, forelegs and buttocks) of Duhua pig (Duroc × Guangdong small spotted pig), to identify potential pathways affecting meat quality, investigating fat deposition in pork and its lipid-protein interactions. Results: The results show that TG (triglyceride) is the lipid subclass with the highest proportion in muscle, and the pathway with the most significantly enriched lipids is GP. DAP clustered on several GO terms closely related to lipid metabolism and lipogenesis (lipid binding, lipid metabolism, lipid transport, and lipid regulation). In KEGG analysis, there are two main DAP aggregation pathways related to lipid metabolism, namely Fatty acid degradation and oxidative phosphorylation. In PPI analysis, we screened out 31 core proteins, among which NDUFA6, NDUFA9 and ACO2 are the most critical. Discussion: PC (phosphatidylcholine) is regulated by SNX5, THBS1, ANXA7, TPP1, CAVIN2, and VDAC2 in the phospholipid binding pathway. TG is regulated by AUH/HADH/ACADM/ACADL/HADHA in the lipid oxidation and lipid modification pathways. Potential biomarkers are rich in SFA, MUFA and PUFA respectively, the amounts of SFA, MUFA and PUFA in the lipid measurement results are consistent with the up- and down-regulation of potential biomarker lipids. This study clarified the differences in protein and lipid compositions in different parts of Duhua pigs and provided data support for revealing the interactions between pork lipids and proteins. These findings provide contributions to the study of intramuscular fat deposition in pork from a genetic and nutritional perspective.

YBX1 Promotes Esophageal Squamous Cell Carcinoma Progression via m5C­Dependent SMOX mRNA Stabilization.

The modification and recognition of 5-methylcytosine (m5C) are involved in the initiation and progression of various tumor types. However, the precise role and potential mechanism of Y-box-binding protein 1 (YBX1) in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, it is found that YBX1 is frequently upregulated in ESCC compared with matched nontumor tissues. Gain- and loss-of-function assays show that YBX1 promoted the proliferation and metastasis of ESCC cells both in vitro and in vivo. Functional studies revealed that NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is a critical RNA methyltransferase that facilitates YBX1-mediated ESCC progression. Mechanistically, integrated analysis based on RNA immunoprecipitation sequencing (RIP-seq) and m5C methylated RNA immunoprecipitation and sequencing (MeRIP-seq) assays identified spermine oxidase (SMOX) as a target gene containing an m5C site in its coding sequence (CDS) region, which coincided well with the binding site of YBX1. Overexpression of SMOX-WT but not SMOX-Mut partially restored the proliferation and invasion ability of ESCC cells curbed by YBX1 knockdown. Moreover, YBX1 activated the mTORC1 signaling pathway by stabilizing SMOX mRNA. The study reveals that YBX1 promotes ESCC development by stabilizing SMOX mRNA in an m5C-dependent manner, thus providing a valuable therapeutic target for ESCC.

Predictive Value of Magnetic Resonance Imaging Radiomics Combined with Serum PSA for the Extracapsular Extension of Prostate Cancer Prediction.

OBJECTIVE: We aimed to investigate the value of magnetic resonance imaging (MRI) radiomics combined with serum prostate-specific antigen (PSA) in predicting the extracapsular extension (ECE) of prostate cancer. METHODS: In total, 213 patients with prostate cancer admitted to our hospital from May 2021 to April 2023 were retrospectively enrolled as observation subjects. Based on the presence or absence of extracapsular extension, the patients were divided into occurrence (n = 70) and non-occurrence (n = 143) groups. The clinical data, PSA levels, Prostate Imaging Reporting and Data System (PI-RADS®), and MRI-ECE scores of the two groups were compared. RESULTS: In total, 80 patients were included in the occurrence (n = 40) and non-occurrence groups (n = 40), and no statistical significance was observed in the baseline data of the two groups. Preoperative PSA levels were significantly higher in the occurrence group than in the non-occurrence group, and the PI-RADS and MRI-ECE scores of each group differed significantly (p < 0.05). The area under the curve (AUC) for the combined determination of PSA levels and PI-RADS and MRI-ECE scores was 0.900, which was significantly higher than the AUC for the individual determination of the mentioned indicators (p < 0.05). CONCLUSIONS: The combination of MRI radiomics and PSA can accurately predict the extracapsular extension of prostate cancer; Thus, it is a favorable reference for subsequent precise diagnosis and treatment.

A deep learning-based approach for fully automated segmentation and quantitative analysis of muscle fibers in pig skeletal muscle.

Muscle fiber properties exert a significant influence on pork quality, with cross-sectional area (CSA) being a crucial parameter closely associated with various meat quality indicators, such as shear force. Effectively identifying and segmenting muscle fibers in a robust manner constitutes a vital initial step in determining CSA. This step is highly intricate and time-consuming, necessitating an accurate and automated analytical approach. One limitation of existing methods is their tendency to perform well on high signal-to-noise ratio images of intact, healthy muscle fibers but their lack of validation on more complex image datasets featuring significant morphological changes, such as the presence of ice crystals. In this study, we undertake the fully automatic segmentation of muscle fiber microscopic images stained with myosin adenosine triphosphate (mATPase) activity using a deep learning architecture known as SOLOv2. Our objective is to efficiently derive accurate measurements of muscle fiber size and distribution. Tests conducted on actual images demonstrate that our method adeptly handles the intricate task of muscle fiber segmentation, yielding quantitative results amenable to statistical analysis and displaying reliability comparable to manual analysis.

Exploring Tunable Properties, Solvent-Modulated Dynamics, and Novel C(sp3)-H Activation Mechanisms in Electron Donor-Acceptor Complexes.

Electron donor-acceptor (EDA) complex photochemistry has emerged as a vibrant area in visible-light-mediated synthetic radical chemistry. However, theoretical insights into the reaction mechanisms remain limited. Our study investigates the influence of solvent polarity and halogen atom types on radical reaction pathways in EDA complexes. We demonstrate that solvent polarity modulates the charge transfer and spatial arrangement within EDA complexes, thereby influencing their stability and reaction kinetics. Iodide ions play a crucial role in facilitating free radical generation and stabilizing reaction intermediates. Different halogen atom types exhibit distinct effects on radical reactions. Variations in radical concentration and solvent environment further affect the pathway selectivity. Additionally, light conditions influence the free radical generation and pathway selectivity. Our findings enhance the understanding of EDA complex photochemistry and radical reactions, offering insights for organic synthesis and photochemistry applications.

Characterization of the Effects of Low-Sodium Salt Substitution on Sensory Quality, Protein Oxidation, and Hydrolysis of Air-Dried Chicken Meat and Its Molecular Mechanisms Based on Tandem Mass Tagging-Labeled Quantitative Proteomics.

The effects of low-sodium salt mixture substitution on the sensory quality, protein oxidation, and hydrolysis of air-dried chicken and its molecular mechanisms were investigated based on tandem mass tagging (TMT) quantitative proteomics. The composite salt formulated with 1.6% KCl, 0.8% MgCl2, and 5.6% NaCl was found to improve the freshness and texture quality scores. Low-sodium salt mixture substitution significantly decreased the carbonyl content (1.52 nmol/mg), surface hydrophobicity (102.58 µg), and dimeric tyrosine content (2.69 A.U.), and significantly increased the sulfhydryl content (74.46 nmol/mg) and tryptophan fluorescence intensity, suggesting that protein oxidation was inhibited. Furthermore, low-sodium salt mixture substitution significantly increased the protein hydrolysis index (0.067), and cathepsin B and L activities (102.13 U/g and 349.25 U/g), suggesting that protein hydrolysis was facilitated. The correlation results showed that changes in the degree of protein hydrolysis and protein oxidation were closely related to sensory quality. TMT quantitative proteomics indicated that the degradation of myosin and titin as well as changes in the activities of the enzymes, CNDP2, DPP7, ABHD12B, FADH2A, and AASS, were responsible for the changes in the taste quality. In addition, CNDP2, ALDH1A1, and NMNAT1 are key enzymes that reduce protein oxidation. Overall, KCl and MgCl2 composite salt substitution is an effective method for producing low-sodium air-dried chicken.

Identification of CD8+ T-cell exhaustion signatures for prognosis in HBV-related hepatocellular carcinoma patients by integrated analysis of single-cell and bulk RNA-sequencing.

BACKGROUND: HBV infection is the leading risk factor for HCC. HBV infection has been confirmed to be associated with the exhaustion status of CD8+ T cells and immunotherapeutic efficacy in HCC. In this study, we aimed to investigate the prognostic value of the CD8+ T-cell exhaustion signature and immunotherapy response in patients with HBV-related HCC. METHODS: We identified different clusters of HBV-related HCC cells by single-cell RNA sequencing (scRNA-seq) and identified CD8+ T-cell exhaustion-related genes (TERGs) by pseudotime analysis. We conducted differential expression analysis and LASSO Cox regression to detect genes and construct a CD8+ T-cell exhaustion index (TEI). We next combined the TEI with other clinicopathological factors to design a prognostic nomogram for HCC patients. We also analysed the difference in the TEI between the non-responder and responder groups during anti-PD-L1 therapy. In addition, we investigated how HBV induces CD8+ T lymphocyte exhaustion through the inhibition of tyrosine metabolism in HCC using gene set enrichment analysis and RT‒qPCR. RESULTS: A CD8+ T-cell exhaustion index (TEI) was established with 5 TERGs (EEF1E1, GAGE1, CHORDC1, IKBIP and MAGOH). An AFP level > 500 ng, vascular invasion, histologic grade (G3-G4), advanced TNM stage and poor five-year prognosis were related to a higher TEI score, while HBV infection was related to a lower TEI score. Among those receiving anti-PD-L1 therapy, responders had lower TEIs than non-responders did. The TEI also serves as an independent prognostic factor for HCC, and the nomogram incorporating the TEI, TNM stage, and vascular invasion exhibited excellent predictive value for the prognosis in HCC patients. RT‒qPCR revealed that among the tyrosine metabolism-associated genes, TAT (tyrosine aminotransferase) and HGD (homogentisate 1,2 dioxygenase) were expressed at lower levels in HBV-HCC than in non-HBV HCC. CONCLUSION: Generally, we established a novel TEI model by comprehensively analysing the progression of CD8+ T-cell exhaustion, which shows promise for predicting the clinical prognosis and potential immunotherapeutic efficacy in HBV-related HCC patients.

High-Fidelity, Low-Hysteresis Bionic Flexible Strain Sensors for Soft Machines.

Stretchable flexible strain sensors based on conductive elastomers are rapidly emerging as a highly promising candidate for popular wearable flexible electronic and soft-mechanical sensing devices. However, due to the intrinsic limitations of low fidelity and high hysteresis, existing flexible strain sensors are unable to exploit their full application potential. Herein, a design strategy for a successive three-dimensional crack conductive network is proposed to cope with the uncoordinated variation of the output resistance signal arising from the conductive elastomer. The electrical characteristics of the sensor are dominated by the successive crack conductive network through a greater resistance variation and a concise sensing mechanism. As a result, the developed elastomer bionic strain sensors exhibit excellent sensing performance in terms of a smaller overshoot response, a lower hysteresis (∼2.9%), and an ultralow detection limit (0.00179%). What's more, the proposed strategy is universal and applicable to many conductive elastomers with different conductive fillers (including 0-D, 1-D, and 2-D conductive fillers). This approach improves the sensing signal accuracy and reliability of conductive elastomer strain sensors and holds promising potential for various applications in the fields of e-skin and soft robotic systems.

Magnetically controlled nanorobots induced oriented and rapid clearance of the cytokine storm for acute lung injury therapy.

Cytokine storms characterized by excessive secretion of circulating cytokines and immune-cell hyperactivation are life-threatening systemic inflammatory syndromes. The new strategy is in great demand to inhibit the cytokine storm. Here, we designed a type of magnetically controlled nanorobots (MAGICIAN) by fusing neutrophil membranes onto Fe3O4 nanoparticles (Fe3O4NPs). In our study, the receptors of neutrophil membranes were successfully coated to the surface of Fe3O4NPs. The associated membrane functions of neutrophils were highly preserved. MAGICIAN could in vitro neutralize the inflammatory cytokines including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Interestingly, MAGICIAN could be navigated to the liver sites under magnetic control and accelerated the cytokine clearance by the liver. Administration of MAGICIAN could efficiently relieve the inflammation in the acute lung injury mouse model. In addition, MAGICIAN displayed good biosafety in systemic administration. The present study provides a safe and convenient approach for the clearance of cytokine storms, indicating the potential for clinical application in acute lung injury therapy.

BMP9-ID1 Pathway Attenuates N6-Methyladenosine Levels of CyclinD1 to Promote Cell Proliferation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignant neoplasm, and the involvement of bone morphogenetic protein 9 (BMP9) has been implicated in the pathogenesis of liver diseases and HCC. Our goal was to investigate the role of BMP9 signaling in regulating N6-methyladenosine (m6A) methylation and cell cycle progression, and evaluate the therapeutic potential of BMP receptor inhibitors for HCC treatment. We observed that elevated levels of BMP9 expression in tumor tissues or serum samples from HCC patients were associated with a poorer prognosis. Through in vitro experiments utilizing the m6A dot blotting assay, we ascertained that BMP9 reduced the global RNA m6A methylation level in Huh7 and Hep3B cells, thereby facilitating their cell cycle progression. This effect was mediated by an increase in the expression of the inhibitor of DNA-binding protein 1 (ID1). Additionally, using methylated RNA immunoprecipitation qPCR(MeRIP-qPCR), we showed that the BMP9-ID1 pathway promoted CyclinD1 expression by decreasing the m6A methylation level in the 5' UTR of mRNA. This occurred through the upregulation of the fat mass and obesity-associated protein (FTO) in Huh7 and Hep3B cells. In our in vivo mouse xenograft models, we demonstrated that blocking the BMP receptor with LDN-212854 effectively suppressed HCC growth and induced global RNA m6A methylation. Overall, our findings indicate that the BMP9-ID1 pathway promotes HCC cell proliferation by down-regulating the m6A methylation level in the 5' UTR of CyclinD1 mRNA. Targeting the BMP9-ID1 pathway holds promise as a potential therapeutic strategy for treating HCC.

Quantitative proteomic analysis and verification identify global protein profiling dynamics in pig during the estrous cycle.

The current estrus detection method is generally time-consuming and has low accuracy. As such, a deeper understanding of the physiological processes during the estrous cycle accelerates the development of estrus detection efficiency and accuracy. In this study, the label-free acquisition mass spectrometry was used to explore salivary proteome profiles during the estrous cycle (day -3, day 0, day 3, and day 8) in pigs, and the parallel reaction monitoring (PRM) was applied to verify the relative profiles of protein expression. A total of 1,155 proteins were identified in the label-free analysis, of which 115 were identified as differentially expressed proteins (DEPs) among different groups (p ≤ 0.05). Functional annotation revealed that the DEPs were clustered in calcium ion binding, actin cytoskeleton, and lyase activity. PRM verified the relative profiles of protein expression, in which PHB domain-containing protein, growth factor receptor-bound protein 2, elongation factor Tu, carboxypeptidase D, carbonic anhydrase, and trefoil factor 3 were confirmed to be consistent in both label-free and PRM approaches. Comparative proteomic assays on saliva would increase our knowledge of the estrous cycle in sows and provide potential methods for estrus detection.

Evaluation of semen DNA integrity and related parameters with COVID-19 infection: a prospective cohort study.

BACKGROUND: In the context of Corona Virus Disease 2019 (COVID-19) global pandemic, Its impact on male reproductive function should be concerned. METHODS: Our study is a prospective cohort study that recruited participants infected or uninfected with COVID-19 between December 2022 and March 2023. All laboratory tests and questionnaire data were completed at the First Affiliated Hospital of Nanchang University. A total of 132 participants were enrolled, with 78 COVID-19 positive patients as the positive group and 54 COVID-19 negative participants as the negative group. Semen quality was assessed by the fifth World Health Organization criteria. The general characteristics of semen samples were assessed using CASA (computer-assisted sperm analysis). DNA damage and the high density stainability was assessed by sperm chromatin structure analysis (SCSA) based on flowcytometry. RESULTS: The sperm concentration, progressive motility and motility in COVID-19 negative group were significantly higher than positive group. In the following DNA damage analysis, a remarkably lower sperm DNA fragmentation index (DFI) in the COVID-19 negative group. In the positive group, unhealthy lifestyles had no significant effect on semen parameters, DNA fragmentation and nuclear compaction. CONCLUSIONS: After excluding the interference of unhealthy lifestyle, the COVID-19 infection can have a significant impact on the quality of semen, especially the DFI,. Therefore, it shows that COVID-19 can adversely affects male fertility, and this result provides advisory guidance for clinicians.

Differential Diagnosis of Intracranial Malignant Tumors Using MRI Based on Morphological Features and Signal Intensity Ratio of Lesions.

Objective: To investigate the clinical value of conventional MRI morphological features and signal intensity ratio in the differential diagnosis of intracranial malignant tumors (high-grade glioma (HGG), primary central nervous system Lymphoma (PCNSL) and single brain metastasis (BM). Methods: Retrospective analysis of 92 cases of HGG, 27 cases of PCNSL, and 35 cases of BM. MRI data in The General Hospital of Western Theater Command from August 2014 to December 2021, comparative analysis of morphological characteristics of tumors and lesion/normal brain parenchyma signal ratio (lesiontonormal parenchymaratio, LNR), five indexes were included T1WI signal ratio (LNRT1), T2WI signal intensity ratio (LNRT2), T2WI/T1WI signal ratio (LNRT2/T1), T1WI enhanced signal ratio (LNRT1CE) and contrast enhancement ratio (CER). The differential diagnostic performance was also assessed by subject operating characteristic (ROC) curves. Results: HGG, PCNSL, and BM were all seen more frequently in the supratentorial region, More than 50% of HGG mainly showed irregular morphology, intratumoral necrosis, cystic degeneration, peritumoral severe edema, cyclic uneven enhancement after enhancement, PCNSL significantly enhanced the main uniformity, necrosis cyst became rare, BM group showed uneven enhancement, no obvious specificity, and the differences in tumor morphology, peritumor edema, intratumor hemorrhage, necrotic cystic lesions, and enhancement patterns were statistically significant among the three (P < .05). PCNSL LNRT1 and its LNRT1CE (LNRT1: 0.558 ± 0.050, LNRT1CE: 1.637 ± 0.125) were significantly higher than those of HGG (LNRT1: 0.480 ± 0.077, LNRT1CE: 1.425 ± 0.160) and BM (LNRT1: 0.514 ± 0.120, LNRT1CE: 1.375 ± 0.122), while LNRT2 and LNRT2/T1 (LNRT2: 1.389 ± 0.086, LNRT2/T1: 2.511 ± 0.295) were significantly lower than those of HGG (LNRT2: 1.527 ± 0.191, LNRT2/T1: 3.263 ± 0.657), and BM (LNRT2: 1.504 ± 0.089, LNRT2/T1: 3.103 ± 0.830). There was no significant difference in CER among the three groups (P > .05). ROC curve analysis of LNRT1, LNRT2, LNRT1CE, and LNRT2/T1 could be used to discriminate PCNSL from HGG and BM, with LNRT1CE having the largest area under the curve of 0.873, sensitivity of 0.963 and specificity of 0.669. Conclusion: MRI lesion morphological features and signal intensity ratio are important for discriminating HGG from PCNSL and BM. As a quantitative parameter, tumor signal intensity ratio can provide an important supplement for subjective judgment, to improve the accuracy of tumor qualitative diagnosis and differential diagnosis.

Enhancement of anaerobic digestion of high salinity food waste by magnetite and potassium ions: Digestor performance, microbial and metabolomic analyses.

The study investigated the effectiveness of magnetite and potassium ions (K+) in enhancing anaerobic digestion of high salinity food waste. Results indicated that both magnetite and K+ improved anaerobic digestion in high-salt environments, and their combination yielded even better results. The combination of magnetite and K+ promoted microorganism activity, and resulted in increased abundance of DMER64, Halobacteria and Methanosaeta. Metabolomic analysis revealed that magnetite mainly influenced quorum sensing, while K+ mainly stimulated the synthesis of compatible solutes, aiding in maintaining osmotic balance. The combined additives regulated pathways such as ATP binding cassette transport, methane metabolism, and inhibitory substance metabolism, enabling cells to resist environmental stress and maintain normal metabolic activity. Overall, this study demonstrated the potential of magnetite and K+ to enhance food waste anaerobic digestion in high salt conditions and provided valuable insights into the molecular mechanism.

NSUN2 stimulates tumor progression via enhancing TIAM2 mRNA stability in pancreatic cancer.

NSUN2 is a nuclear RNA methyltransferase which catalyzes 5-methylcytosine (m5C), a posttranscriptional RNA modification. Aberrant m5C modification has been implicated in the development of multiple malignancies. However, its function in pancreatic cancer (PC) needs to be elucidated. Herein, we determined that NSUN2 was overexpressed in PC tissues and related to aggressive clinical features. Silence of NSUN2 by lentivirus weakened the capability of proliferation, migration and invasion of PC cells in vitro and inhibited the growth and metastasis of xenograft tumors in vivo. Contrarily, overexpression of NSUN2 stimulated PC growth and metastasis. Mechanistically, m5C-sequencing (m5C-seq) and RNA-sequencing (RNA-seq) were carried out to identify downstream targets of NSUN2 and results showed that loss of NSUN2 led to decreased m5C modification level concomitant with reduced TIAM2 mRNA expression. Further validation experiments proved that NSUN2 silence accelerated the decay of TIAM2 mRNA in a YBX1-dependent manner. Additionally, NSUN2 exerted its oncogenic function partially through enhancing TIAM2 transcription. More importantly, disruption of the NSUN2/TIAM2 axis repressed the malignant phenotype of PC cells through blocking epithelial-mesenchymal transition (EMT). Collectively, our study highlighted the critical function of NSUN2 in PC and provided novel mechanistic insights into NSUN2/TIAM2 axis as promising therapeutic targets against PC.

TLR4 Overexpression Aggravates Bacterial Lipopolysaccharide-Induced Apoptosis via Excessive Autophagy and NF-κB/MAPK Signaling in Transgenic Mammal Models.

Gram-negative bacterial infections pose a significant threat to public health. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and induces innate immune responses, autophagy, and cell death, which have major impacts on the body's physiological homeostasis. However, the role of TLR4 in bacterial LPS-induced autophagy and apoptosis in large mammals, which are closer to humans than rodents in many physiological characteristics, remains unknown. So far, few reports focus on the relationship between TLR, autophagy, and apoptosis in large mammal levels, and we urgently need more tools to further explore their crosstalk. Here, we generated a TLR4-enriched mammal model (sheep) and found that a high-dose LPS treatment blocked autophagic degradation and caused strong innate immune responses and severe apoptosis in monocytes/macrophages of transgenic offspring. Excessive accumulation of autophagosomes/autolysosomes might contribute to LPS-induced apoptosis in monocytes/macrophages of transgenic animals. Further study demonstrated that inhibiting TLR4 downstream NF-κB or p38 MAPK signaling pathways reversed the LPS-induced autophagy activity and apoptosis. These results indicate that the elevated TLR4 aggravates LPS-induced monocytes/macrophages apoptosis by leading to lysosomal dysfunction and impaired autophagic flux, which is associated with TLR4 downstream NF-κB and MAPK signaling pathways. This study provides a novel TLR4-enriched mammal model to study its potential effects on autophagy activity, inflammation, oxidative stress, and cell death. These findings also enrich the biological functions of TLR4 and provide powerful evidence for bacterial infection.

Watching Excited State Dynamics with Optical and X-ray Probes: The Excited State Dynamics of Aquocobalamin and Hydroxocobalamin.

Femtosecond time-resolved X-ray absorption (XANES) at the Co K-edge, X-ray emission (XES) in the Co Kß and valence-to-core regions, and broadband UV-vis transient absorption are combined to probe the femtosecond to picosecond sequential atomic and electronic dynamics following photoexcitation of two vitamin B12 compounds, hydroxocobalamin and aquocobalamin. Polarized XANES difference spectra allow identification of sequential structural evolution involving first the equatorial and then the axial ligands, with the latter showing rapid coherent bond elongation to the outer turning point of the excited state potential followed by recoil to a relaxed excited state structure. Time-resolved XES, especially in the valence-to-core region, along with polarized optical transient absorption suggests that the recoil results in the formation of a metal-centered excited state with a lifetime of 2-5 ps. This combination of methods provides a uniquely powerful tool to probe the electronic and structural dynamics of photoactive transition-metal complexes and will be applicable to a wide variety of systems.

Pharmacokinetics, Bioequivalence, and Safety Evaluation of 2 Formulations of 10-mg Rivaroxaban Tablets: A 4-Period Crossover Trial.

This study compared the safety, bioequivalence, and pharmacokinetic properties of 2 formulations of 10-mg rivaroxaban tablets in healthy Chinese participants in fasting and fed arms. The trial was an open, randomized, 4-period, replicated crossover scheme, and 36 volunteers were recruited separately for the fasting and fed arms. Volunteers were randomly administered a single dose of the test or reference formulation (10 mg) orally, followed by a 5-day washout period. Rivaroxaban concentrations in the plasma were determined using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were obtained from the concentration-time profiles. The mean values of the test and the reference product for the area under the plasma concentration-time curve from time 0 to the last measurable concentration, area under the plasma concentration-time curve from time 0 to infinity, and maximum plasma concentration were 996 and 1014 ng • h/mL, 1024 and 1055 ng • h/mL, and 150 and 152 ng/mL in the fasting arm, respectively; the values were 1155 and 1167 ng • h/mL, 1160 and 1172 ng • h/mL, and 202 and 193 ng/mL in the fed arm, respectively. All the parameters were within acceptable limits in terms of bioequivalence. No serious adverse events were observed. This study demonstrated that the 2 rivaroxaban tablets were bioequivalent in healthy Chinese participants under fasting and fed conditions.

Probabilistic assessment of drought stress vulnerability in grasslands of Xinjiang, China.

In the process of climate warming, drought has increased the vulnerability of ecosystems. Due to the extreme sensitivity of grasslands to drought, grassland drought stress vulnerability assessment has become a current issue to be addressed. First, correlation analysis was used to determine the characteristics of the normalized precipitation evapotranspiration index (SPEI) response of the grassland normalized difference vegetation index (NDVI) to multiscale drought stress (SPEI-1 ~ SPEI-24) in the study area. Then, the response of grassland vegetation to drought stress at different growth periods was modeled using conjugate function analysis. Conditional probabilities were used to explore the probability of NDVI decline to the lower percentile in grasslands under different levels of drought stress (moderate, severe and extreme drought) and to further analyze the differences in drought vulnerability across climate zones and grassland types. Finally, the main influencing factors of drought stress in grassland at different periods were identified. The results of the study showed that the spatial pattern of drought response time of grassland in Xinjiang had obvious seasonality, with an increasing trend from January to March and November to December in the nongrowing season and a decreasing trend from June to October in the growing season. August was the most vulnerable period for grassland drought stress, with the highest probability of grassland loss. When the grasslands experience a certain degree of loss, they develop strategies to mitigate the effects of drought stress, thereby decreasing the probability of falling into the lower percentile. Among them, the highest probability of drought vulnerability was found in semiarid grasslands, as well as in plains grasslands and alpine subalpine grasslands. In addition, the primary drivers of April and August were temperature, whereas for September, the most significant influencing factor was evapotranspiration. The results of the study will not only deepen our understanding of the dynamics of drought stress in grasslands under climate change but also provide a scientific basis for the management of grassland ecosystems in response to drought and the allocation of water in the future.