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Abstract Background Metabolic reprogramming plays a pivotal role in tumorigenesis and development of lung adenocarcinoma (LUAD). However, the precise mechanisms and potential targets for metabolic reprogramming in LUAD remain elusive. Our prior investigations revealed that the mitochondrial ribosomal protein MRPL12, identified as a novel mitochondrial transcriptional regulatory gene, exerts a critical influence on mitochondrial metabolism. Despite this, the role and regulatory mechanisms underlying MRPL12’s transcriptional activity in cancers remain unexplored. Methods Human LUAD tissues, Tp53 fl/fl ;Kras G12D -driven LUAD mouse models, LUAD patient-derived organoids (PDO), and LUAD cell lines were used to explored the expression and function of MRPL12. The posttranslational modification of MRPL12 was analyzed by mass spectrometry, and the oncogenic role of key phosphorylation sites of MRPL12 in LUAD development was verified in vivo and in vitro. Results MRPL12 was upregulated in human LUAD tissues, Tp53 fl/fl ;Kras G12D -driven LUAD tissues in mice, LUAD PDO, and LUAD cell lines, correlating with poor patient survival. Overexpression of MRPL12 significantly promoted LUAD tumorigenesis, metastasis, and PDO formation, while MRPL12 knockdown elicited the opposite phenotype. Additionally, MRPL12 deletion in a Tp53 fl/fl ;Kras G12D -driven mouse LUAD model conferred a notable survival advantage, delaying tumor onset and reducing malignant progression. Mechanistically, we discovered that MRPL12 promotes tumor progression by upregulating mitochondrial oxidative phosphorylation. Furthermore, we identified UBASH3B as a specific binder of MRPL12, dephosphorylating tyrosine 60 in MRPL12 (MRPL12 Y60) and inhibiting its oncogenic functions. The decrease in MRPL12 Y60 phosphorylation impeded the binding of MRPL12 to POLRMT, downregulating mitochondrial metabolism in LUAD cells. In-depth in vivo, in vitro, and organoid models validated the inhibitory effect of MRPL12 Y60 mutation on LUAD. Conclusion This study establishes MRPL12 as a novel oncogene in LUAD, contributing to LUAD pathogenesis by orchestrating mitochondrial metabolism reprogramming towards oxidative phosphorylation (OXPHOS). Furthermore, it confirms Y60 as a specific phosphorylation modification site regulating MRPL12’s oncogenic functions, offering insights for the development of LUAD-specific targeted drugs and clinical interventions. Graphical Abstract

Abstract Background Lung cancer is the second most common cancer with the highest mortality in the world. Calumenin as a molecular chaperone that not only binds various proteins within the endoplasmic reticulum but also plays crucial roles in diverse processes associated with tumor development. However, the regulatory mechanism of calumenin in lung adenocarcinoma remains elusive. Here, we studied the impact of calumenin on lung adenocarcinoma and explored possible mechanisms. Methods 5-ethynyl-2’-deoxyuridine assay, colony formation, transwell and wound healing assays were performed to explore the effects of calumenin on the proliferation and migration of lung adenocarcinoma cells. To gain insights into the underlying mechanisms through which calumenin knockdown inhibits the migration and proliferation of lung adenocarcinoma, we performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis based on transcriptomics by comparing calumenin knockdown with normal A549 cells. Results The mRNA and protein levels of calumenin in lung adenocarcinoma are highly expressed and they are related to an unfavorable prognosis in this disease. Calumenin enhances the proliferation and migration of A549 and H1299 cells. Gene Set Enrichment Analysis revealed that knockdown of calumenin in A549 cells significantly inhibited MYC and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling pathways while activating interferon signals, inflammatory signals, and p53 pathways. Ingenuity pathway analysis provided additional insights, indicating that the interferon and inflammatory pathways were prominently activated upon calumenin knockdown in A549 cells. Conclusions The anti-cancer mechanism of calumenin knockdown might be related to the inhibition of MYC and KRAS signals but the activation of interferon signals, inflammatory signals and p53 pathways.

Objectives: Converging evidence indicates that Horticultural Therapy (HT) contributes to significant reductions in stress, loneliness, and depression, notable risk factors for suicidality. This pilot study aimed to assess the initial feasibility and acceptability of HT when virtually administered. Intervention: Telehealth-delivered horticultural therapy (TeleHT) was administered to groups of Veterans, including those with elevated suicide risk over the course of four weeks. Participants were each sent a package through the mail of at-home gardening supplies that were used to facilitate multisensory, nature experiences during weekly HT sessions administered via Zoom. Outcome measures: Participants completed thermometer-based scales for the suicide risk factors of stress, loneliness, depression, and pain before and after each TeleHT session. Post-intervention qualitative assessments were completed upon the conclusion of the four-week intervention. Results: Significant reductions in stress, depression, and loneliness risk were observed from weekly pre- to post-session measures (p

This work aimed to investigate how two different types of forage (saline and alkaline) impact the meat quality and muscle metabolism of Tibetan sheep. An integrative multi-omics analysis of meat quality and different metabolites was performed using untargeted and targeted metabolomics approaches. The research results indicated that GG grass (saline and alkaline forage) possessed superior characteristics in terms of apparent quality and secondary metabolite content compared with HG grass (Non saline alkali forage), regardless of the targeted metabolites or non-targeted ones. Simultaneously, under stress conditions, the carbohydrates-rich salt-alkali grass play a significant role in slowing down the decline in pH, increasing the unsaturated fatty acid content and reducing the thawing loss in Tibetan sheep. This study provides an understanding of the impact of different salt-alkali grass on the quality of Tibetan sheep meat, while providing a scientific basis for the future development of salt-alkali livestock industry.

Abstract Background The autophagy adapter SQSTM1/p62 is crucial for maintaining homeostasis in various organs and cells due to its protein–protein interaction domains and involvement in diverse physiological and pathological processes. Vascular endothelium cells play a unique role in vascular biology and contribute to vascular health. Methods Using the Cre-loxP system, we generated mice with endothelium cell-specific knockout of p62 mediated by Tek (Tek receptor tyrosine kinase)-cre to investigate the essential role of p62 in the endothelium. In vitro, we employed protein mass spectrometry and IPA to identify differentially expressed proteins upon knockdown of p62. Immunoprecipitation assays were conducted to demonstrate the interaction between p62 and FN1 or LAMC2 in human umbilical vein endothelium cells (HUVECs). Additionally, we identified the degradation pathway of FN1 and LAMC2 using the autophagy inhibitor 3-methyladenine (3-MA) or proteasome inhibitor MG132. Finally, the results of immunoprecipitation demonstrated that the interaction between p62 and LAMC2 was abolished in the PB1 truncation group of p62, while the interaction between p62 and FN1 was abolished in the UBA truncation group of p62. Results Our findings revealed that p62 Endo mice exhibited heart, lung, and kidney fibrosis compared to littermate controls, accompanied by severe cardiac dysfunction. Immunoprecipitation assays provided evidence of p62 acting as an autophagy adapter in the autophagy-lysosome pathway for FN1 and LAMC2 degradation respectively through PB1 and UBA domain with these proteins rather than proteasome system. Conclusions Our study demonstrates that defects in p62 within endothelium cells induce multi-organ fibrosis and cardiac dysfunction in mice. Our findings indicate that FN1 and LAMC2, as markers of (EndoMT), have detrimental effects on HUVECs and elucidate the autophagy-lysosome degradation mechanism of FN1 and LAMC2.

Abstract The electrochemical conversion of nitrate to ammonia is a way to eliminate nitrate pollutant in water. Cu-Co synergistic effect was found to produce excellent performance in ammonia generation. However, few studies have focused on this effect in high-entropy oxides. Here, we report the spin-related Cu-Co synergistic effect on electrochemical nitrate-to-ammonia conversion using high-entropy oxide Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O. In contrast, the Li-incorporated MgCoNiCuZnO exhibits inferior performance. By correlating the electronic structure, we found that the Co spin states are crucial for the Cu-Co synergistic effect for ammonia generation. The Cu-Co pair with a high spin Co in Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O can facilitate ammonia generation, while a low spin Co in Li-incorporated MgCoNiCuZnO decreases the Cu-Co synergistic effect on ammonia generation. These findings offer important insights in employing the synergistic effect and spin states inside for selective catalysis. It also indicates the generality of the magnetic effect in ammonia synthesis between electrocatalysis and thermal catalysis.

Selenium (Se) is an essential trace element in living systems. In this study, we applied a spray of 50 mg/kg sodium selenite to alfalfa (Medicago sativa L.) at different stages of development (bud, initial bloom, and full bloom stages). After 0, 1, 3, 7, and 45 days of ensiling, we assessed the fermentation quality, chemical composition, and bacterial community of the alfalfa. Our findings indicated that the addition of Se led to an increase in the Se content and a decrease in the pH, acid detergent fiber (ADF), and neutral detergent fiber (NDF) contents. As ensiling fermentation progressed, the Se treatments increased the relative abundance of Lactobacillus, which was significantly greater than that in the control group (42.44% vs. 3.76%). In conclusion, the addition of sodium selenate to silage additive ensures the quality of the silage and reduces bacterial community diversity. This study provides valuable insights for the investigation of Se enrichment in alfalfa haylage silage.

Ageratina adenophora can enhance its invasive ability by using beneficial rhizosphere bacteria. Bacillus cereus is able to promote plant growth and provide a positive feedback effect to A. adenophora. However, the interaction between A. adenophora and B. cereus under the influence of native polyphagous insect feeding is still unclear. In this study, Eupatorium lindleyanum, a local species closely related to A. adenophora, was used as a control, aimed to compare the content of B. cereus in the roots of A. adenophora and rhizosphere soil after different densities of Aphis gossypii feeding, and then investigated the variations in the population of A. gossypii and soil characteristics after the addition of B. cereus. The result showed that B. cereus content in the rhizosphere soil and root of A. adenophora increased significantly under A. gossypii feeding compared with local plants, which also led to the change of α-diversity and β-diversity of the bacterial community, as well as the increase in nitrate nitrogen (NO3–N) content. The addition of B.cereus in the soil could also inhibit the population growth of A. gossypii on A. adenophora and increase the content of ammonium nitrogen (NH4+-N) in the soil. Our research demonstrated that B. cereus enhances the ability of A. adenophora to resist natural enemy by increasing soil ammonium nitrogen (NH4+-N) and accumulating other beneficial bacteria, which means that rhizosphere microorganisms help invasive plants defend themselves against local natural enemies by regulating the soil environment.

Abstract Objective We aimed to investigate whether serum cortisol associate with diabetic microvascular compliments in patients with type 2 diabetes mellitus (T2DM). Materials and methods The subjects were recruited from hospitalized patients with T2DM from 2019 to 2021. The odds ratios (OR) and corresponding 95% confidence intervals (CI) in relation to cortisol quartiles were obtained by multiple logistic regression analysis. Results (1) Cortisol level was positively correlated with the severity of microalbuminuria. The OR (95% CI) of microalbuminuria and macroalbuminuria in the last quartile were 3.396 (2.030, 5.682) and 8.407 (3.726, 18.971) compared with the first quartile (p

Substituting traditional protein feed with palm kernel meal (PKM) in the diet of Tibetan sheep can be a cost-effective feeding strategy. To determine the impact of PKM on flavor development in different adipose tissues of Tibetan sheep, subjects were fed with 15% and 18% of PKM, while the control group received no PKM. The fatty acids and volatile compounds in the samples were then analyzed by GC-MS and HS-GC-IMS. Adding PKM to the diet significantly increased the C12:0, C14:0, C16:0 and C18:1N9 content in adipose tissues compared with the control, and most of these were associated with flavor formation (p < 0.05). The flavor compounds in the adipose tissues predominantly consisted of alcohols, ketones, acids and aldehydes. In particular, including PKM in the diet increased the proportion of ketones but decreased the proportion of alcohols, acids and aldehydes in subcutaneous and tail fat. Specifically, the proportion of acetone, acetoin monomer, 2,3-butanedione, 2-butanone monomer, 2-methyl-2-propanol, 2-methyl-2-propanol and methyl acetate increased significantly in the subcutaneous and tail fat (p < 0.05), while that of ethanol, 1-propanol monomer, butanol monomer, acetic acid monomer and acetic acid monomer decreased. Intermuscular fat exhibited variable results, mainly because the addition of PKM resulted in higher proportions of alcohols, including ethanol, 1-propanol and butanol monomer, especially at 15% PKM. In summary, the addition of PKM improved the flavor of Tibetan sheep fat and increased the amount of favorable volatile flavor compounds. This study can serve as reference for understanding the effects of dietary PKM on the adipose tissue flavor profile of Tibetan sheep.

Functionalized imidazo[1,2-α]pyridines are important scaffolds in pharmaceuticals. Herein, we present an efficient 3-sulfonylmethylation protocol for imidazo[1,2-α]pyridines by sodium sulfinates in DMA and H2O (2:1) via an FeCl3-catalyzed three-component coupling reaction. Various sulfonylmethyl imidazo[1,2-α]pyridines were thus afforded in high yields with excellent functional group tolerance. A plausible oxidation-addition mechanism was proposed.

Abstract Jasmonic acid (JA) is an important and widely distributed plant hormone. However, the molecular and physiological mechanism of JA in improving drought tolerance in response to sodium selenite is limited. This work was performed to investigate the effects of exogenous sodium selenite application in promoting drought tolerance of cucumber. The drought tolerance of cucumber seedlings is enhanced under the application of selenite, positively influencing shoot fresh weight and chlorophyll relative content and altering the chloroplast ultrastructure. The contents of JA and JA-isoleucine (JA-ILE) increased significantly in response to selenite application under drought conditions. Furthermore, the expression of JA biosynthesis and regulatory genes, namely, LOX (Lipoxygenase), AOC (allene oxide cyclase), AOS (allene oxide synthase), and MYC2 (the basic helix-loop-helix (bHLH) protein) was upregulated to greater levels when selenite was added in combination with drought treatment. This study provides methods to mitigate drought stress and valuable theoretical support for further understanding the plant response to drought signals.

Abstract The access to P-stereogenic motifs has always been considered a very challenging and high attractive mission in modern organic synthesis. While several chiral auxiliaries employed by the practical Jugé-Stephan-like methodology have been developed, new type of readily accessible bifunctional ligands toward P-stereogenic building still remain much desirable. Herein, we present a powerful chiral template, camphor-derived 2,3-diols named CAMDOL, which were designed and synthesized from the commercially cheap camphorquinone in high yields at 50 grams scale with a column-free purification. Diverse P(III)-chiral compounds and their borane forms including phosphinous acids, phosphinites, and phosphines, as well as the corresponding P(V)-chiral compounds including phosphinates, phosphine oxides, phosphinothioates, phosphine sulfides, and secondary phosphine oxides were afforded in high yields and ee values through the optimal 2,3-diphenyl CAMDOL platform. An unusual C3-OP bond cleavage following the first P-OC2 bond breaking was observed during the ring-opening process when quenching by NH4Cl solution, which generates a unique but valuable camphor-epoxide scaffold as by-product.

IntroductionThis study investigated the effects of rumen-protected sulfur-containing amino acids (RPSAA) on the rumen and jejunal microbiota as well as on the metabolites and meat quality of the longissimus lumborum (LL) in Tibetan sheep.MethodsBy combining 16S rDNA sequencing with UHPLC-Q-TOF MS and Pearson correlation analysis, the relationship between gastrointestinal microbiota, muscle metabolites and meat quality was identified.ResultsThe results showed that feeding RPSAA can increase the carcass weight, abdominal fat thickness (AP-2 group), and back fat thickness (AP-2 and AP-3 group) of Tibetan sheep. The water holding capacity (WHC), texture, and shear force (SF) of LL in the two groups also increased although the fatty acids content and brightness (L*) value significantly decreased in the AP-2 group. Metabolomics and correlation analysis further showed that RPSAA could significantly influence the metabolites in purine metabolism, thereby affecting L* and SF. In addition, RPSAA was beneficial for the fermentation of the rumen and jejunum. In both groups, the abundance of Prevotella 1, Lachnospiraceae NK3A20 group, Prevotella UCG-003, Lachnospiraceae ND3007 group in the rumen as well as the abundance of Eubacterium nodatum group and Mogibacterium group in the jejunum increased. In contrast, that of Turicibacter pathogens in the jejunum was reduced. The above microorganisms could regulate meat quality by regulating the metabolites (inosine, hypoxanthine, linoleic acid, palmitic acid, etc.) in purine and fatty acids metabolism.DiscussionOverall, reducing the levels of crude proteins in the diet and feeding RPSAA is likely to improve the carcass quality of Tibetan sheep, with the addition of RPMET (AP-2) yielding the best edible quality, possibly due to its ability to influence the gastrointestinal microbiota to subsequently regulate muscle metabolites.

Abstract Understanding and mastering the structural evolution of water oxidation electrocatalysts lays the foundation to finetune their catalytic activity. Herein, we demonstrate that surface reconstruction of spinel oxides originates from the metal-oxygen covalency polarity in the MT–O–MO backbone. A stronger MO–O covalency relative to MT–O covalency is found beneficial for a more thorough reconstruction towards oxyhydroxides. The structure-reconstruction relationship allows precise prediction of the reconstruction ability of spinel pre-catalysts, based on which the reconstruction degree towards the in situ generated oxyhydroxides can be controlled. The investigations of oxyhydroxides generated from spinel pre-catalysts with the same reconstruction ability provide guidelines to navigate the cation selection in spinel pre-catalysts design. This work reveals the fundamentals for manipulating the surface reconstruction of spinel pre-catalysts for water oxidation.

Abstract Background The lateral anatomical and morphological characteristics of knees with varus knee osteoarthritis (OA) have not received sufficient attention. This study used several radiological parameters to describe the morphological characteristics of the lateral knee with OA to determine whether there are relationships between varus knee OA and parameters such as lateral plateau widening (LPW), proximal fibula curvature (PFC), and fibula height (FH). Methods The study retrospectively analyzed 1072 subjects who underwent standard radiography for diagnosing or evaluating symptomatic knee joint disease. The 163 Kellgren and Lawrence (K–L) grades 0 and I knees were categorized into the no-knee-OA group, and the 909 K–L grades II–IV knees were classified into the knee-OA group. Medial proximal tibial angle, joint line convergence angle, hip–knee–ankle angle, LPW, PFC, and FH were measured. T tests and chi-square tests were used to compare each index between the two groups. Binary logistic regression was performed to examine the correlation between indexes and knee OA occurrence. Ordinal logistic analysis, principal component analysis, and multivariable linear regression analysis were performed to examine the correlations between the three lateral parameters and K–L grades and the degree of varus deformity. Results LPW and PFC were significantly greater and FH was significantly smaller in the knee-OA group than in the no-knee-OA group. LPW, PFC, and FH were correlated with knee OA occurrence. One principal component, named the comprehensive principal component score of varus deformity, was extracted from the three indexes, and the total variance of the principal component interpretation was 76.60%. Ordinal logistics and multivariable linear regression analysis showed that, after adjusting for age and BMI, LPW and PFC were positively correlated with K–L grading and varus deformity. FH was significantly and negatively correlated with K–L grading and varus deformity (all P

Soybean (Glycine max (Linn.) Merr.) is highly suitable as animal feed. The silage quality and microbial characteristics of soybean silage are still unclear. Forage soybean (HN389), at six different growth stages (R2-R7), were used as experimental materials to investigate the changes in fermentation, nutritional quality, and microbial characteristics of semidry silage after 0, 7, 14, 30, and 45 d. As the growth period extended, the content of crude protein (CP) and crude fat (EE) gradually increased, while the neutral detergent fiber (NDF) and the acid detergent fiber (ADF) content decreased. The pH value also decreased gradually with fermentation time, accompanied by increases in the proportion of ammonia-N and the content of lactic acid (LA) and acetic acid (AA). In addition, competitive inhibition was observed in the microbial fermentation. With the process of ensiling, Lactobacillus became the dominant bacterial species. The results indicate that the most active stage of fermentation during ensiling occurred within the first 7 days, the fermentation and nutritional quality of the soybean forage were improved, and the optimal mowing stage was the grain stage. Comparison of the microbial abundance showed that all microorganisms entered a stable stage at 30 days of silage. After storage, the dominant bacteria were Lactobacillus, Enterobacter, and Pantoea.

The purpose of this study was to investigate the differences in meat quality between two local breeds of Tibetan sheep, the White Tibetan sheep and the Black Tibetan sheep in Qinghai, and to search for metabolic mechanisms that produce meat quality differences by analyzing differential metabolites and key rumen microorganisms. The meat quality results showed that one breed, SG73, was superior to the other (WG). Further investigation identified differences in the composition of muscle metabolites and rumen microorganisms between the two Tibetan sheep breeds. It also regulates muscle tenderness, water retention, fat content and the composition and content of AA and FA through two major metabolic pathways, AA metabolism and carbohydrate metabolism. These findings could be beneficial for the development of breeding strategies for Tibetan sheep in Qinghai in the future.

IntroductionStudies showing associations between inflammation in suicide are typically cross-sectional. Present study investigated how cytokine levels track with suicidal ideation and severity longitudinally.MethodsVeterans with a diagnosis of major depressive disorder (MDD) with or without suicide attempt history (MDD/SA n = 38, MDD/NS n = 41) and non-psychiatric non-attempter controls (HC n = 33) were recruited, MDD/SA and HC groups were followed longitudinally at 3 months and 6 months. Blood plasma was collected and processed using Luminex Immunology Multiplex technology.ResultsSignificant differences in depression severity (BDI) and suicidal ideation severity (SSI) were observed across all groups at study entry, wherein MDD/SA group had the highest scores followed by MDD/NS and HC, respectively. Cytokines IL-1β, IL-4, TNF-α, IFN-γ, and IL-6 were examined at study entry and longitudinally, with IL6 levels differing significantly across the groups (p = 0.0123) at study entry. Significant differences in changes in cytokine levels between depressed attempters and the control group were detected for IL-6 (interaction F1,91.77 = 5.58, p = 0.0203) and TNF-α (F1,101.73 = 4.69, p = 0.0327). However, only depressed attempters showed a significant change, in IL-6 and TNF-α levels, decreasing over time [IL-6: b = −0.04, 95% CI = (−0.08, −0.01), p = 0.0245 and TNF-α: b = −0.02, 95% CI = (−0.04, −0.01), p = 0.0196]. Although IL-6 levels were not predictive of suicidal ideation presence [OR = 1.34, 95% CI = (0.77, 2.33), p = 0.3067], IL-6 levels were significantly associated with suicidal ideation severity (b = 0.19, p = 0.0422).DiscussionIL-6 was not associated with presence of suicidal ideation. IL-6 however, was associated with severity of ideation, suggesting that IL-6 may be useful in clinical practice, as an objective marker of heightened suicide risk.

Grazing by local livestock is the traditional human practice in Qinghai-Tibetan Plateau grassland, and moderate intensity grazing can maintain high productivity and diversity of alpine grassland. Grazing ecosystems are often nitrogen-limited, but N2-fixing communities in response to yak grazing and Tibetan sheep grazing in Qinghai-Tibetan Plateau grassland have remained underexplored. In this study, we applied quantitative PCR quantitation and MiSeq sequencing of nifH under yak grazing and Tibetan grazing through a manipulated grazing experiment on an alpine grassland. The results showed that the grazing treatments significantly increased the soil ammonium nitrogen (AN) and total phosphorus (TP), but reduced the diazotrophs abundance. Compared with no grazing treatment, the composition of diazotrophs could be maximally maintained when the ratio of yak and Tibetan sheep were 1:2. The foraging strategies of grazing livestock reduced the legumes biomass, and thus reduced the diazotrophs abundance. Data analysis suggested that the direct key factors in regulating diazotrophs are AN and TP, and the changes of these two soil chemical properties were affected by the dung and urine of herbivore assemblages. Overall, these results indicated that the mixed grazing with a ratio of yak to Tibetan sheep as 1:2 can stabilize the soil diazotrophsic community, suggesting that MG12 are more reasonable grazing regimes in this region.

Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide but current drug therapeutics show important limitations. Here, the authors exploit a selfpropelling nano-penetrator with high fuel loading and controllable motion which is molecularly co-assembled using a photothermal photosensitizer and a photothermal-activable NO donor.

Abstract Background Mitochondrial dysfunction is an important pathogenic event in acute kidney injury (AKI). GCN5L1 is a specific acetyltransferase in mitochondria, which regulates glucose and fatty acid metabolism. However, the role of GCN5L1 in mitochondrial dysfunction and the pathogenesis of ischemic AKI are not fully understood. Methods The protein level of GCN5L1 was detected by western blot assay. Acetylated proteomics was used to explore the level of acetylated TFAM. Duolink proximity ligation assay and co-immunoprecipitation were used to detect the interaction of TFAM and translocase of outer membrane 70 (TOM70). mtDNA copy number, the expression of mitochondrial electron transport chain complexes, the number and morphology of mitochondria were measured. The renal injury of AKI mice was reflected by the levels of creatinine and urea nitrogen and the pathological changes of renal tissue. Results We showed that GCN5L1 was highly expressed in vivo and in vitro and renal tubules specific knockdown of GCN5L1 could effectively attenuate AKI-induced mitochondrial impairment. Besides, acetylated proteomics revealed that acetylated TFAM was significantly upregulated in AKI mice kidney, which reminded us that TFAM might be an acetylating substrate of GCN5L1. Mechanistically, we evidenced that GCN5L1 could acetylate TFAM at its K76 site and subsequently inhibited its binding to TOM70, thereby reducing TFAM import into mitochondria and mitochondrial biogenesis. Clinically, GCN5L1 and acetylated TFAM were positively correlated with disease severity (all p

In this paper we present a detailed single-pulse and polarization study of PSR J0614+2229 based on the archived data observed on 2019 August 15 (MJD 58710) and 2019 September 12 (MJD 58738) using the ultra−wide-bandwidth low-frequency receiver on the Parkes radio telescope. The single-pulse sequences show that this pulsar switches between two emission states, in which the emission of state A occurs earlier than that of state B in pulse longitude. We found that the variation in relative brightness between the two states varies temporally and both states follow a simple power law very well. Based on the phase-aligned multifrequency profiles, we found that there is a significant difference in the distributions of spectral index across the emission regions of the two states. Furthermore, we obtained the emission height evolution for the two emission states and found that, at a fixed frequency, the emission height of state A is higher than that of state B. What is even more interesting is that the emission heights of both states A and B do not change with frequency. Our results suggest that the mode switching of this pulsar is possibly caused by changes in the emission heights that alter the distributions of spectral index across the emission regions of states A and B, resulting in frequency-dependent behaviors, i.e., intensity and pulse width.

Summary: Acute kidney injury (AKI) is a serious disease with no effective treatment. Abnormal opening of mitochondrial permeability transition pore (MPTP) is an important pathological process in ischemia reperfusion injury (IRI), the key factor of AKI. It is essential to elucidate MPTP regulation mechanism. Here, we identified mitochondrial ribosomal protein L7/L12 (MRPL12) specifically binds to adenosine nucleotide translocase 3 (ANT3) under normal physiological conditions, stabilizes MPTP and maintains mitochondrial membrane homeostasis in renal tubular epithelial cells (TECs). During AKI, MRPL12 expression was significantly decreased in TECs, and MRPL12-ANT3 interaction was reduced, leading to ANT3 conformation change, MPTP abnormal opening, and cell apoptosis. Importantly, MRPL12 overexpression protected TECs from MPTP abnormal opening and apoptosis during hypoxia/reoxygenation (H/R). Our results suggest MRPL12-ANT3 axis involves in AKI by regulating MPTP, and MRPL12 could be potential intervention target for treatment of AKI.

IntroductionAlthough vascular dementia (VaD) is the second most prevalent form of dementia, there is currently a lack of effective treatments. Tilianin, isolated from the traditional drug Dracocephalum moldavica L., may protect against ischemic injury by inhibiting oxidative stress and inflammation via the CaMKII-related pathways but with weak affinity with the CaMKII molecule. microRNAs (miRNAs), functioning in post-transcriptional regulation of gene expression, may play a role in the pathological process of VaD via cognitive impairment, neuroinflammatory response, and neuronal dysfunction. This study aimed to investigate the role of tilianin in VaD therapy and the underlying mechanism through which tilianin regulates CaMKII signaling pathways based on miRNA-associated transcriptional action.MethodsRats with 2-vessel occlusion (2VO), a standard model of VaD, were treated with tilianin, vehicle control, and target overexpression or downregulation. High-throughput sequencing, qRT-PCR, and western blot analyses were utilized to identify the downstream target genes and signaling pathways of tilianin involved in VaD.ResultsOur results showed that tilianin ameliorated cognitive deficits, neurodegeneration, and microglial and astrocytic activation in rats with 2VO. Subsequent high-throughput sequencing and qRT-PCR analyses revealed that tilianin increased the downregulated miR-193b-3p and miR-152-3p levels in the cortex and hippocampus of 2VO rats. Mechanistically, miR-193b-3p targeting CaM and miR-152-3p targeting CaMKIIα were identified to play a role in VaD-associated pathology, inhibiting the p38 MAPK/NF--κB p65 pathway and decreasing TNF-α and IL-6 levels. Further gain- and loss-of-function experiments for these key genes showed that tilianin-exerted cognitive improvement by activating the p38 MAPK/NF--κB p65 and Bcl-2/Bax/caspase-3/PARP pathways in the brain of 2VO rats was abolished by miR-193b-3p and miR-152-3p inhibition. Moreover, CaM and CaMKIIα overexpression eliminated the elevated effects of miR-193b-3p and miR-152-3p on tilianin’s protection against ischemic injury through increased inflammatory reactions and apoptotic signaling.DiscussionTogether, these findings indicate that tilianin improves cognition by regulating the miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways, suggesting a potential small-molecule regulator of miRNA associated with inflammatory signaling for VaD treatment.

Abstract A new direct sulfenylation method of indoles by sodium sulfinates and hydroiodic acid was developed giving variety of 3‐sulfenylindoles in high yields under mild conditions without using any catalysts or other additives. In situ‐generated RS‐I species are supposed to be mainly responsible for the key electrophilic alkyl‐ or aryl‐thiolation process.

Three different herbivore grazing assemblages, namely, yak grazing (YG), Tibetan sheep grazing (SG) and yak and Tibetan sheep co-grazing (MG), are practiced in alpine meadows on the Qinghai-Tibetan Plateau (QTP), but the effects of the different herbivore assemblages on soil microbes are relatively unknown. The microbial community plays an important role in the functional stability of alpine grassland ecosystems. Therefore, it is important to understand how the microbial community structure of grassland ecosystems changes under different herbivore grazing assemblages to ensure their sustainable development. To fill this gap, a field study was carried out to investigate the effects of YG, SG, and MG on plant communities, soil physico-chemical properties and microbial communities under moderate grazing intensity in alpine meadows. Grazing increased the β-diversity of the bacteria community and decreased the β-diversity of the fungal community. The herbivore assemblage affected the microbial community diversity, but not the plant community diversity. Total phosphorus, soil bulk density, root biomass, and plant α-diversity were correlated with both the bacterial and fungal community composition, available phosphorus and soil moisture were correlated only with the bacterial community composition, while available potassium and above-ground net primary production (ANPP) were correlated only with the fungal community composition. Soil available nitrogen, soil available phosphorus and soil bulk density were highest in SG, while ANPP was highest in MG. It was concluded that MG can improve ANPP and stabilize the soil microbial community, suggesting that MG is an effective method for sustainable use and conservation of alpine meadows on the QTP.

This study investigated the effects of ultra-filtered polysaccharides from Berberis dasystachya Maxim. (UBDP) on the gut microbiota and glucose metabolism in high-fat diet/streptozotocin -induced diabetic rats, and clarified the possible action mechanisms of UBDP in the treatment of type 2 diabetes mellitus (T2DM). The results showed that UBDP administration for 4 weeks significantly ameliorated glucose tolerance, improved organ function, reduced fasting blood glucose and HbA1c levels, decreased the glycosylated hemoglobin index, improved insulin sensitivity of the pancreas, and reduced colon morphogen and oxidative stress in the diabetic rats (P

The traditional method does not accurately select the ecological landscape pattern index of urban wetland, which leads to the problems of low accuracy and long planning time, in order to solve this problem, an urban wetland ecological landscape planning model based on MSPA analysis method is constructed. By analyzing the basic components of urban wetland ecological landscape, such as patch density, aggregation index, dispersion index, average fractal dimension, landscape segmentation, shape index, spread index and Shannon diversity index, MSPA analysis method is used to extract the core area, patch area and ring of urban wetland. According to the extraction results, the minimum function of cloud fusion transformation of three-dimensional wetland ecological landscape is calculated, and the function is used to calculate the three-dimensional translation transformation amount and rotation matrix of three-dimensional wetland ecological landscape model. The data in the three-dimensional model are used for wetland ecological landscape planning, so as to complete the construction of wetland ecological landscape planning model. The simulation results show that the urban wetland ecological landscape planning accuracy of the model is high and the planning time is short.

Twelve Liuyang black goats were selected and divided into three groups in a randomized design and they were provided one of the three treatment diets with different chop lengths of ramie silage [1 cm (RS1), 2 cm (RS2), and 3 cm (RS3)]. The length had no effect on pH or the content of acetic acid, butyric acid, and valeric acid. In contrast, NH3-N decreased (P = 0.024) and the ratio of acetate to propionate (P = 0.083) and total volatile fatty acid (TVFA) content (P = 0.087) tended to decrease, and the proportion of propionic acid tended to increase (P = 0.096) with an increase in the chop length of ramie. The increasing lengths of ramie silage decreased the content of total essential amino acids (AA) (P = 0.001), total non-essential AA (P = 0.003), and total AA (P = 0.001), and decreased the concentration of aspartic acid (P = 0.076) in the ruminal fluid. Ramie silage affected xylanase activity (P = 0.043), with greater activity in RS1 than in RS2 and RS3. The recommended chop length of ramie silage is 1 cm because of increasing TVFA, amino acid concentration, and xylanase activity in the ruminal fluid of goats.

Background: Clinical data on the relationship between triglycerides (TG)/HDL ratio and insulin resistance (IR) suggest that TG/HDL ratio may be a risk factor for IR. However, there is evidence that different races have different ri sk of developing IR. The relationship on TG/HDL ratio and IR in various populations needs to be improved. Therefore, we investigated whether TG/HDL ratio was linked to I R in different groups in the United States after controlling for other covariates. Methods: The current research was conducted in a cross-sectional manner. From 2009 to 2018, the National Health and Nutrition Examination Survey (NHANES) had a total of 49,696 participants, all of whom were Americans. The target-independent variable was TG/HDL ratio measured at baseline, and the dependent variable was IR. Additionally, the BMI, waist circumference, education, race, smoking, alcohol use, alanine transaminase, aspartate transaminase, and other covariates were also included in this analysis. Results: The average age of the 10,132 participants was 48.6 ± 18.4 years, and approximately 4936 (48.7%) were males. After correcting for confounders, fully adjusted logistic regression revealed that TG/HDL ratio was correlated w ith IR (odds ratio = 1.51, 95% CI 1.42–1.59). A nonlinear interaction between TG/HDL ratio and IR was discovered, with a point of 1.06. The impact sizes and CIs on the left and right sides of the inflection point were 6.28 (4.66–8.45) and 1.69 (1.45–1.97), respectively. According to subgroup analysis, the correlation was strong in females, alcohol users, and diabetes patients. Meanwhile, the inverse pattern was observed in the aged, obese, high-income, and smoking populations. Conclusion: In the American population, the TG/HDL ratio is positively associated with IR in a nonlinear interaction pattern.

Abstract Background Posterior tibial slope (PTS) increases after medial open-wedge high tibial osteotomy (OWHTO) is challenging for patients. This study aims to determine whether use of a suspended and straightened knee joint position during the fixing of steel plates can prevent an increase in the PTS after OWHTO. Methods This study retrospectively analyzed 112 subjects (122 knees) [34 males, 78 females; mean age 59.1 ± 6.6 (range 48–76) years; mean body mass index 28.06 ± 3.61 kg/m2] who underwent OWHTO. A total of 78 knees that were suspended and extended by placing a sterile cloth ball under the ipsilateral ankle during the fixing of steel plates comprised the suspended and straightened knee joint position (SSP) group, and 44 knees that were kept naturally straightened without placing a sterile cloth ball under the ipsilateral ankle during the fixing of steel plates comprised the naturally straightened knee joint position (NSP) group. Patients were clinically assessed according to the visual analog pain scale (VAS), the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index, the Knee Society Scores (KSS) knee and function scores, the Hospital for Special Surgery (HSS) knee scores and the Lysholm knee scores. Radiological assessment was performed according to the changes in the PTS between preoperation, 1-day postoperation, and the final follow-up periods. Ultimately, the difference in postoperative PTS changes between the two groups was statistically analyzed. The median follow-up period was 2.2 years (range 1.6–3.7 years). Results In the final follow-up period, significant improvements were observed in the clinical VAS scores, WOMAC scores, KSS knee and function scores, HSS scores and the Lysholm knee scores in both groups (P 0.05). The increase in PTS in the NSP group was significantly greater than that in the SSP group at the 1-day postoperative (t = 2.243, P = 0.030) and final follow-up periods (t = 6.501, P

The evaluation of the intrinsic activity of catalysts is the most basic in searching energy- and cost-efficient catalyst materials for various applications. The accurate determination of the intrinsic activity is essential for identifying efficient catalysts. While a huge number of studies of electrocatalysis for various applications have been reported, the effects of electrode loading on the apparent intrinsic activity obtained experimentally have been rarely discussed. With a high mass loading on the electrode, not all the catalyst surfaces can be electrochemically active because not all the surfaces can be wetted by the electrolyte. The loading also affects the transport of electrons over the electrode as well as the transport of ions in the electrolyte, and thus affects the kinetics. These lead to the derivations of the apparent intrinsic activity from the real intrinsic activity. Herein, for better understanding the derivations, we evaluate and discuss the effects of electrode mass loading using oxygen evolution reaction as an example.

Abstract Aims/Introduction To investigate the associations between parathyroid hormone (PTH) and non‐proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes mellitus. Materials and Methods Data were collected from 2,322 patients with type 2 diabetes mellitus in hospital between 2017 and 2019. The odds ratio (OR) and the corresponding 95% confidence interval related to the quartiles of PTH were obtained by logistic regression analysis after adjusting the potential confounding variation. Results The patients were stratified into quartiles (Q1–Q4) based on the PTH levels, with the cut‐off limits of ≤23.74, 23.74–29.47, 29.47–37.30 and >37.30 pg/mL in men, and ≤24.47, 24.47–31.22, 31.22–39.49 and >39.49 pg/mL in women. The first quartile (Q1) represents the lowest quartile and the fourth quartile (Q4) is the highest. According to the quartiles (Q1–Q4), the prevalence rate of NPDR in patients showed a significantly decreasing trend (37.9%, 36.3%, 34.0% vs 24.0% in men; 43.2%, 40.5%, 31.1% vs 26.2% in women, both P

Abstract Aims/Introduction The aim of this study was to investigate the relationship between serum progesterone (P) and retinopathy in male patients with type 2 diabetes mellitus, and to investigate whether P is associated with its progression. Materials and methods A total of 1,376 male participants with type 2 diabetes mellitus were recruited from Affiliated Hospital of Medical College Qingdao University (Qingdao, China). Through logistic regression analysis after adjusting the potential confounding variation, the odds ratio (OR) and the corresponding 95% confidence interval related to the quartiles of progesterone were obtained. Results According to the quartiles of P levels, the prevalence rate of diabetic retinopathy (DR) in the last quartile is obviously greater to other quartiles (52.5–34.9%, 31.9%, 37.5%, P

Water oxidation to triplet oxygen requires a spin polarization process for faster kinetics. Here, the authors show an interface spin pinning effect between ferromagnetic oxides and reconstructed oxyhydroxide surface layer, where the spin ordering in paramagnetic oxyhydroxide catalyst layer can be tuned to improve the intrinsic activity.

This study aims to determine the impact of dietary energy levels on rumen microbial composition and its relationship to the quality of Black Tibetan sheep meat by applying metabolomics and Pearson's correlation analyses. For this purpose, UHPLC-QTOF-MS was used to identify the metabolome, whereas 16S rDNA sequencing was used to detect the rumen microbiota. Eventually, we observed that the high energy diet group (HS) improved the carcass quality of Black Tibetan sheep and fat deposition in the longissimus lumborum (LL) compared to the medium energy diet group (MS). However, HS considerably increased the texture, water holding capacity (WHC), and volatile flavor of the LL when compared to that of MS and the low energy diet group (LS). Metabolomics and correlation analyses revealed that dietary energy levels mainly affected the metabolism of carbohydrates and lipids of the LL, which consequently influenced the content of volatile flavor compounds (VOCs) and fats. Furthermore, HS increased the abundance of Quinella, Ruminococcus 2, (Eubacterium) coprostanoligenes, and Succinivibrionaceae UCG-001, all of which participate in the carbohydrate metabolism in rumen and thus influence the metabolite levels (stachyose, isomaltose, etc.) in the LL. Overall, a high-energy diet is desirable for the production of Black Tibetan sheep mutton because it improves the mouthfeel and flavor of meat by altering the composition of rumen microbiota, which influences the metabolism in the LL.

Colon adenocarcinoma (COAD) is one of the leading causes of cancer-associated deaths worldwide. Patients with microsatellite instability-high (MSI-H) tumors were shown to highly benefit from immune checkpoint inhibitors (ICIs) than patients with microsatellite stable (MSS) tumors. Furthermore, the infiltration of immune cells and the expression of cancer stem cells (CSCs) in COAD were associated with the anti-tumor immune response. However, the potential mechanisms showing the relationship between microsatellite instability and CSCs or tumor-infiltrating immune cells (TIICs) have not been elucidated. Accumulating evidence reveals that achaete-scute family bHLH transcription factor 2 (ASCL2) plays a crucial role in the initiation and progression of COAD and drug resistance. However, the specific biological functions of ASCL2 in COAD remain unknown. In this study, we performed weighted gene co-expression network analysis (WGCNA) between MSS and MSI-H subsets of COAD. The results revealed that ASCL2 was a potential key candidate in COAD. Subsequently, the single-cell RNA-seq revealed that ASCL2 was positively associated with CSCs. Further, ASCL2 was shown to indirectly affect tumor immune cell infiltration by negatively regulating the expression of DUSP4. Finally, we inferred that the immunotherapy-sensitive role of ASCL2/DUSP4 axis on COAD is partly attributed to the activation of WNT/β-catenin pathway. In conclusion, this study revealed that ASCL2 was positively correlated to CSCs and tumor immune infiltration in COAD. Therefore, ASCL2 is a promising predictor of clinical responsiveness to anti-PD-1/PD-L1 therapy in COAD.

Elymus sibiricus L. is a perennial allotetraploid belonging to Triticeae of Poaceae, Elymus L., as the type species of genus Elymus L. The existing geographical distribution pattern and genetic spatial structure of E. sibiricus on Qinghai–Tibetan Plateau (QTP) are not yet clear. In this study, population genetic structure and demography history of 216 individuals from 44 E. sibiricus populations on QTP were studied used specific-locus amplified fragment sequencing (SLAF-seq). The result of genetic diversity showed that there was no single genetic diversity center was observed across all E. sibiricus populations. The results of genetic variation showed that 44 populations were clearly divided into the following three groups: Qinghai Plateau (Group I), South Tibet (Group II), and Hengduan Mountains (Group III). From the three analyses of AMOVA, Mantel test and Treemix, strong genetic differentiation across all populations and low genetic differentiation among populations within three groups. Molecular dating indicated that E. sibiricus diverged at 16.08 Ma (during the early Miocene) can be linked to the Himalayan Motion stage of QTP uplift. It is speculated that the reasons affecting the current phylogeographical pattern are as follows: (1) The environmental changes due to the uplift of the QTP; (2) The geographic distance between the populations (Groups I and III are close in geographic distance, and gene flow are frequent); (3) Geographical barriers (the Tanggula and Bayangela Mountains between Groups I and II). This study provides new evidence and historical perspective to the future exploration of the evolution and geographic distribution pattern of Elymus L.

Weather risk causes uncertain crop yield and price and further influences the willingness of farmers to participate in contract farming and honour the contract. In this study, we investigate the optimal decisions for contract farming between a profit-maximizing manufacturer and multiple identical farmers under weather risk, using a game-theoretical approach. We discuss two different cases. In the first case, the manufacturer sets a contract price to ensure farmers to honour the contract under any weather condition. While in the second case, the manufacturer sets a lower contract price only to guarantee that farmers will not renege under certain weather condition but has a second chance to purchase products from the reneged farmers at a renegotiated price. We derive the optimal decisions of the manufacturer in both cases and show that the manufacturer gains much more profits in the second case, and therefore, the decisions in the second case are optimal. Moreover, we numerically investigate the sensitivity of the effectiveness of contract farming and the manufacturer’s optimal decisions to model parameters and get more managerial implications.

Bermudagrass (Cynodon dactylon Pers.) is a wild Poaceae turfgrass with various genotypes and phenotypes. In this study, 16 wild bermudagrass germplasms were collected from 16 different sites along latitudinal gradients, and different temperature treatments were compiled and used for physiological and transcriptome analysis. To explore the correlation between the key differentially expressed genes and physiological indicators, a total of 14,654 DEGs were integrated from the comparison of different temperature treatments and used for weighted gene co-expression network analysis. Through comparative transcriptome analysis and gene annotation, the results showed that differential gene expression profiles in networks are associated with the plant growth, photosystem, redox system, and transcriptional regulation to cold stress in bermudagrass. In particular, genes encoding HSP70/90 and HsfA3/A8 are not only regulated by temperature stress, but also directly or indirectly interplay with the processes of peroxide scavenging and chlorophyll synthesis under cold stress. Besides, through a weight evaluation analysis of various physiological indexes, we identified an accession of wild bermudagrass with relatively strong cold resistance. These results provide important clues and resources to further study the responses to low-temperature stress in bermudagrass.

In the present study, the complete chloroplast genome of Lonicera tangutica is presented and characterized for the first time. The complete chloroplast genome was 156,121 bp in length, including 23,899 bp inverted repeat (IR) regions, an 89,466 bp large single-copy (LSC) region, and an 18,851 bp small single-copy (SSC) region. A total of 129 genes, including 37 tRNA genes, eight rRNA genes, and 84 protein-coding genes, were annotated, and the overall GC content of the chloroplast genome was 38.35%. Two introns in the ycf3 gene and a single intron in another gene were detected. Maximum-likelihood phylogenetic analysis indicated that L. tangutica has a very close evolutionary relationship with Lonicera praeflorens, Lonicera hispida, Lonicera fragrantissima, and Lonicera stephanocarpa. These results are valuable for studying the evolution and genetic diversity of L. tangutica.

Objectives: Novel approaches to mental health and suicide prevention are lacking. Converging evidence has shown the effectiveness of horticultural therapy (HT) in improving mental health symptoms, but whether it would reduce suicide risk and contributing risk factors is unknown. Design: Using a cohort model, HT was delivered 3.5 h over four weekly, sessions administered by a registered horticultural therapist to veterans with history of suicide ideation or attempt who felt isolated and experienced ongoing environmental stressors with interest in learning new coping strategies. Setting: HT delivery occurred in an urban garden, through a community partnership between the VA (Veterans Administration) and the New York Botanical Garden. Guided by principles of biophilia, participating veterans took part in nature walks, self-reflection and journaling, and planting activities. Outcome measures: Stress, mood, pain, and social isolation levels were measured weekly pre-post HT sessions using thermometer scales, with concordant validity to validated clinical instruments. Results: Of the 20 men and women with a history of suicide attempts/ideation, HT demonstrated immediate improvements after each session across all symptom domains in magnitude of reduction in stress, pain, mood, and loneliness. The effect sizes were in medium to large range (Cohen’s d>.5). Additionally, a single HT session showed a sustained effect over subsequent 2-to-4 weeks as observed by the significantly decreased pre-session thermometer scores in subsequent weeks. Reductions in mood symptoms correlated with decline in suicidal ideation (rs = 0.63). Conclusion: HT intervention maybe a promising therapeutic modality for improving overall wellness in suicide prevention in at-risk veteran populations.

Early and precise prediction is an important way to reduce the poor prognosis of lung adenocarcinoma (LUAD) patients. Nevertheless, the widely used tumor, node, and metastasis (TNM) staging system based on anatomical information only often could not achieve adequate performance on foreseeing the prognosis of LUAD patients. This study thus aimed to examine whether the long non-coding RNAs (lncRNAs), known highly involved in the tumorigenesis of LUAD through the competing endogenous RNAs (ceRNAs) mechanism, could provide additional information to improve prognosis prediction of LUAD patients. To prove the hypothesis, a dataset consisting of both RNA sequencing data and clinical pathological data, obtained from The Cancer Genome Atlas (TCGA) database, was analyzed. Then, differentially expressed RNAs (DElncRNAs, DEmiRNAs, and DEmRNAs) were identified and a lncRNA–miRNA–mRNA ceRNA network was constructed based on those differentially expressed RNAs. Functional enrichment analysis revealed that this ceRNA network was highly enriched in some cancer-associated signaling pathways. Next, lasso-Cox model was run 1,000 times to recognize the potential survival-related combinations of the candidate lncRNAs in the ceRNA network, followed by the “best subset selection” to further optimize these lncRNA-based combinations, and a seven-lncRNA prognostic signature with the best performance was determined. Based on the median risk score, LUAD patients could be well distinguished into high-/low-risk subgroups. The Kaplan–Meier survival curve showed that LUAD patients in the high-risk group had significantly shorter overall survival than those in the low-risk group (log-rank test P = 4.52 × 10–9). The ROC curve indicated that the clinical genomic model including both the TNM staging system and the signature had a superior performance in predicting the patients’ overall survival compared to the clinical model with the TNM staging system only. Further stratification analysis suggested that the signature could work well in the different strata of the stage, gender, or age, rendering it to be a wide application. Finally, a ceRNA subnetwork related to the signature was extracted, demonstrating its high involvement in the tumorigenesis mechanism of LUAD. In conclusion, the present study established a lncRNA-based molecular signature, which can significantly improve prognosis prediction for LUAD patients.

Nitrogen fertilization is a simple and effective field management strategy for increasing plant productivity, but the regulatory mechanisms of nitrogen forms and proportions on soil nutrients and plant growth remain unclear. Therefore, we investigated soil enzyme activities and nutrient contents of alfalfa under different forms and proportions of exogenous nitrogen addition. Results showed that nitrogen input significantly increased the activity of three oxidoreductases (hydroxylamine reductase, nitrate reductase, and nitrite reductase) while having no significant effects on urease. A high proportion of ammonium nitrogen significantly increased neutral protease activity. The amylase activity markedly increased under mixed-nitrogen addition but decreased under single-nitrogen addition. Additionally, the contents of soil nutrients (soil organic matter, total nitrogen, nitrate nitrogen, ammonium nitrogen, available phosphorus, and available potassium) were significantly increased under different exogenous nitrogen inputs, which drove the changes in enzyme activities. Further, nitrogen addition also improved the biomass and nitrogen content of alfalfa. These findings indicated that applying different forms and proportions of exogenous nitrogen may stimulate soil enzyme activities, which will accelerate the transformation of nutrients and then promote alfalfa growth.

In recent years, transmission Raman spectroscopy (TRS) has emerged as a potent new tool for rapid, nondestructive quantitation in pharmaceutical manufacturing. In order to expand the applicability of TRS and enhance its use in product quality monitoring during drug production, we aimed, in the present study, to apply partial least-squares (PLS) approaches to build a model consisting of 150 handmade tablets and covering 15 levels through the use of a multifactor orthogonal design of experiment (DOE), which was used to predict concentrations of validation tablets made by hand. The difference between results according to HPLC and TRS were negligible. The model was used to predict the active pharmaceutical ingredient (API) content in four random commercial paracetamol tablets, and corrected with the spectra of the commercial tablets to obtain four corresponding models. The results show that the content relative error in the model’s predictions after correction with commercially available tablets was significantly lower than that before correction. The corrected model was used to make predictions for 20 tablets from the brand Panadol. Compared with the HPLC results, the prediction relative error was basically less than 4.00%, and the relative standard deviation (RSD) of the content was 0.86%.

Abstract Substitutional doping of layered transition metal dichalcogenides (TMDs) has been proved to be an effective route to alter their intrinsic properties and achieve tunable bandgap, electrical conductivity and magnetism, thus greatly broadening their applications. However, achieving valid substitutional doping of TMDs remains a great challenge to date. Herein, a distinctive molten‐salt‐assisted chemical vapor deposition (MACVD) method is developed to match the volatilization of the dopants perfectly with the growth process of monolayer MoS2, realizing the substitutional doping of transition metal Fe, Co, and Mn. This doping strategy effectively alters the electronic structure and phononic properties of the pristine MoS2. In addition, a temperature‐dependent Raman spectrum is employed to explore the effect of dopants on the lattice dynamics and first‐order temperature coefficient of monolayer MoS2, and this doping effect is illustrated in depth combined with the theoretical calculation. This work provides an intriguing and powerful doping strategy for TMDs through employing molten salt in the CVD system, paving the way for exploring new properties of 2D TMDs and extending their applications into spintronics, catalytic chemistry and photoelectric devices.

In this study, activated carbons without any chemical residue were prepared from walnut shells. The preparation method in a tube furnace included a pyrolysis carbonization process and a CO 2 activation process. The influences of activation temperature and holding time on the specific surface area, yield, and pore structure were investigated. Adsorption performance of water vapor was also examined in details. Thermogravimetric analysis, N 2 adsorption–desorption isotherm, and scanning electron microscope were used to characterize samples. The result shows that the activation energy at different heating rates varies from 30.16 to 64.86 kJ/mol. The highest water vapor adsorption capacity of the sample is 0.3824 g/g and it takes only 30 min to realize regeneration. And the maximum Brunauer–Emmett–Teller specific surface area of 1228 m 2 /g also occurs in this optimal preparation condition. CO 2 physical activation method was found to have a positive effect on pore structure development of activated carbon for water vapor adsorption.

Postoperative cognitive dysfunction (POCD) is a severe complication of cardiopulmonary bypass (CPB) and has common characteristics such as acute cognitive dysfunction, impaired memory, and inattention. Mesenchymal stem cells (MSCs) are multipotent cells that have therapeutic potentials mainly through paracrine action via secreting growth factors and cytokines. Exosomes are one of the important paracrine factors and have been reported as potential cell-free therapy for the treatment of autoimmune and central nervous system disorders. In this study, we examined exosomes derived from antler MSCs (AMSCs) of POCD rats after CPB and evaluated their potential regulatory mechanisms. AMSC-derived exosomes reduced neurological damage and brain damage and prevent apoptosis in CPB rats. Furthermore, AMSC-derived exosomes were found to reduce hippocampal neuronal apoptosis and the expression of TLR2, TLR4, MyD88, and NF-κB in CPB rats. However, the above effects of AMSC-derived exosomes on CPB rats were abolished partially by toll-like receptor 2/4 (TLR2/TLR4) agonist (LPS-EB). In conclusion, AMSC-derived exosomes can improve cognitive function in CPB rats through inhibiting the TLR2/TLR4 signaling pathway.

Ubiquitin-specific protease 14 (USP14) is a proteasome-associated deubiquitinating enzyme with known roles in physiology and disease. Here the authors show that fatty acid synthase (FASN) is a substrate of USP14, and that by stabilizing FASN, it plays a role in hepatosteatosis.