End-expiratory lung volumes as a potential indicator for COVID-19 associated acute respiratory distress syndrome: a retrospective study.

BACKGROUND: End-expiratory lung volume (EELV) has been observed to decrease in acute respiratory distress syndrome (ARDS). Yet, research investigating EELV in patients with COVID-19 associated ARDS (CARDS) remains limited. It is unclear whether EELV could serve as a potential metric for monitoring disease progression and identifying patients with ARDS at increased risk of adverse outcomes. STUDY DESIGN AND METHODS: This retrospective study included mechanically ventilated patients diagnosed with CARDS during the initial phase of epidemic control in Shanghai. EELV was measured using the nitrogen washout-washin technique within 48 h post-intubation, followed by regular assessments every 3-4 days. Chest CT scans, performed within a 24-hour window around each EELV measurement, were analyzed using AI software. Differences in patient demographics, clinical data, respiratory mechanics, EELV, and chest CT findings were assessed using linear mixed models (LMM). RESULTS: Out of the 38 patients enrolled, 26.3% survived until discharge from the ICU. In the survivor group, EELV, EELV/predicted body weight (EELV/PBW) and EELV/predicted functional residual capacity (EELV/preFRC) were significantly higher than those in the non-survivor group (survivor group vs. non-survivor group: EELV: 1455 vs. 1162 ml, P = 0.049; EELV/PBW: 24.1 vs. 18.5 ml/kg, P = 0.011; EELV/preFRC: 0.45 vs. 0.34, P = 0.005). Follow-up assessments showed a sustained elevation of EELV/PBW and EELV/preFRC among the survivors. Additionally, EELV exhibited a positive correlation with total lung volume and residual lung volume, while demonstrating a negative correlation with lesion volume determined through chest CT scans analyzed using AI software. CONCLUSION: EELV is a useful indicator for assessing disease severity and monitoring the prognosis of patients with CARDS.

Transcriptome-wide analysis of RNA m6A methylation regulation of muscle development in Queshan Black pigs.

BACKGROUND: N6-methyladenosine (m6A) refers to the methylation modification of N6 position of RNA adenine, a dynamic reversible RNA epigenetic modification that plays an important regulatory role in a variety of life processes. In this study, we used MeRIP-Seq and RNA-Seq of the longissimus dorsi (LD) muscle of adult (QA) and newborn (QN) Queshan Black pigs to screen key genes with m6A modification involved in muscle growth by bioinformatics analysis. RESULTS: A total of 23,445 and 25,465 m6A peaks were found in the whole genomes of QA and QN, respectively. Among them, 613 methylation peaks were significantly different (DMPs) and 579 genes were defined as differentially methylated genes (DMGs). Compared with the QN group, there were 1,874 significantly differentially expressed genes (DEGs) in QA group, including 620 up-regulated and 1,254 down-regulated genes. In order to investigate the relationship between m6A and mRNA expression in the muscle of Queshan Black pigs at different periods, a combined analysis of MeRIP-Seq and RNA-Seq showed that 88 genes were significantly different at both levels. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes results showed that DEGs and DMGs were mainly involved in skeletal muscle tissue development, FoxO signaling pathway, MAPK signaling pathway, insulin signaling pathway, PI3K-Akt signaling pathway, and Wnt signaling pathway. Four DEGs (IGF1R, CCND2, MYOD1 and FOS) and four DMGs (CCND2, PHKB, BIN1 and FUT2), which are closely related to skeletal muscle development, were selected as candidate genes for verification, and the results were consistent with the sequencing results, which indicated the reliability of the sequencing results. CONCLUSIONS: These results lay the foundation for understanding the specific regulatory mechanisms of growth in Queshan Black pigs, and provide theoretical references for further research on the role of m6A in muscle development and breed optimization selection.

Effect of miR-149-5p on intramuscular fat deposition in pigs based on metabolomics and transcriptomics.

As one of the important traits in pig production, meat quality has important research significance and value. Intramuscular fat (IMF) content is one of the most important factors affecting pork quality. Many experimental studies have shown that IMF content is closely related to the flavor, tenderness, and juiciness of pork. Therefore, it is of great significance to study the mechanism of porcine IMF deposition. Previous research indicated that miR-149-5p promoted the proliferation of porcine intramuscular (IM) preadipocytes and decreased their ability to differentiate, albeit the exact mechanism of action is unknown. In vitro, foreign pigs showed increased miR-149-5p expression and reduced fat deposition when compared to Queshan Black pigs. This study conducted metabolomics and transcriptomics analyses of porcine IM preadipocytes overexpressing miR-149-5p to verify their effects on lipid formation. According to metabolomics analysis, the overexpression of miR-149-5p has significantly altered the lipid, organic acid, and organic oxygen metabolites of porcine IM preadipocytes. Specially speaking, it has changed 115 metabolites, including 105 up-regulated and 10 down-regulated ones, as well as the composition of lipid, organic acid, and organic oxygen metabolism-related metabolites. RNA-seq analysis showed that overexpression of miR-149-5p significantly altered 857 genes, of which 442 were up-regulated, and 415 were down-regulated, with enrichment to MAPK, IL-17, PI3K-Akt, and ErbB signaling pathways. We found that overexpression of miR-149-5p inhibited adipogenic differentiation by changing cAMP signaling pathway in porcine IM preadipocytes. In addition, the overexpression of miR-149-5p may affect the transport of Cu2+ by targeting ATP7A and inhibiting adipogenic differentiation. These findings elucidate the regulatory function of miR-149-5p in porcine IM preadipocytes, which may be a key target for controlling pork quality.

Effects of diet and gender on the pharmacokinetics of oral lenvatinib: A clinical trial in healthy Chinese participants.

OBJECTIVE: Lenvatinib is a tyrosine kinase inhibitor that helps prevent angiogenesis. In this study, we investigated the potential influencing factors on lenvatinib pharmacokinetics to provide a reference for clinical application. MATERIALS AND METHODS: All healthy participants received a single dose of 4 mg lenvatinib mesylate capsules with a high-fat meal or fasted conditions. Lenvatinib plasma concentrations were determined via high-performance liquid chromatography-mass spectrometry/mass spectrometry, and the pharmacokinetic parameters were calculated using WinNonlin 8.1 software. A mixed effect model analysis was adopted to explore the influence factor for the pharmacokinetic parameters of lenvatinib. RESULTS: After a single oral dose of 4 mg lenvatinib mesylate, the pharmacokinetic parameters for the fasted and fed groups were as follows: tmax was 2.0 hours and 4.5 hours, Cmax was 53.60 ng/mL and 45.54 ng/mL, AUC0-t was 597.44 h×ng/mL and 561.51 h×ng/mL, CL was 6.82 L/h and 7.26 L/h, and Vd was 82.82 L and 94.04 L, respectively. Compared with those in the fasted group, decreased Cmax and increased tmax were observed in the fed group. The geometric mean ratios of fed/fasted for Cmax, AUC0-t, and AUC0-∞ were 86.9%, 94.0%, and 93.9%, respectively, and the pharmacokinetics of lenvatinib were significantly influenced by food intake. Gender influenced the pharmacokinetics of lenvatinib; females had higher Cmax and AUC0-t levels after 4 mg lenvatinib. Lenvatinib was well tolerated in healthy Chinese subjects. CONCLUSION: High-fat diet altered the pharmacokinetic profile of lenvatinib, but not sufficient to significantly impact its clinical efficacy. Therefore, lenvatinib is suitable for administration under fasted or fed conditions.

Pharmacokinetic comparison of nalbuphine with single injection and patient-controlled analgesia mimic method in healthy Chinese volunteers.

WHAT IS KNOWN AND OBJECTIVE: Nalbuphine is a mu (µ) receptor partial antagonist/kappa (κ) receptor agonist analgesic and can be administered as a single injection or using patient-controlled analgesia (PCA) in the clinical setting. However, differences in the pharmacokinetics of the two administration methods are unclear. Here, a clinical trial was performed to compare the pharmacokinetic characteristics and superiority of nalbuphine with a single-injection or PCA-mimic method to provide a reference for the selection of an appropriate administration method. METHODS: Twenty healthy individuals were divided into two groups and injected with 10 mg nalbuphine intravenously using a single-injection or a PCA-mimic method (2 mg once for five times with a 30-min interval). Blood samples were collected, and safety was investigated. The liquid chromatography-tandem mass spectrometry was adopted to determine the concentration of nalbuphine in plasma. RESULTS AND DISCUSSION: The maximum concentration (Cmax ) and area under concentration-time curve (AUC0-t ) values of nalbuphine in the single-injection and PCA groups were as follows: Cmax , 81.3 ± 24.7 and 39.8 ± 6.4 ng/ml, respectively; moreover, AUC0-t , 110.3 ± 19.5 and 128.3 ± 23.0 h ng/ml, respectively. The effective analgesic concentration durations (EACDs) for the two administration methods were 1.39 ± 0.64 and 1.96 ± 0.91 h, respectively. Nalbuphine was well tolerated, and improvements were observed in the PCA group. WHAT IS NEW AND CONCLUSION: Compared with those in the single-injection group, the AUC0-t and EACDs in the PCA group were similar, whereas Cmax was decreased significantly. Therefore, the PCA method was more suitable for the clinical application of nalbuphine injection owing to the superiority of lower concentration fluctuation and the improved safety profile.

Risk sources quantitative appointment of ecological environment and human health in farmland soils: a case study on Jiuyuan District in China.

Heavy metals (HMs) in farmland soils lead to adverse influences on ecosystem and human health. Despite that, data on quantitative risk from different sources are still scarce. In this study, 100 farmland soil samples in Jiuyuan District were collected and analyzed for selected HMs (As, Cd, Co, Cr, Cu, Mn, Ni, Pb, V and Zn) content characteristics and pollution statuses. The positive matrix factorization (PMF) model combined with the Nemerow integrated risk index (NIRI) and human health risk assessment (HHRA) was used to quantitatively identify the primary risk sources. The results indicated that the mean contents or median values (mg/kg) of 10 HMs were all higher than the background values. The contamination factor (CF) and pollution load index (PLI) revealed that the soil was severely polluted. Based on PMF, the main source of HM pollution was anthropogenic activities, accounting for 78.91%. Sewage irrigation represented the biggest input but was not associated with the highest risk. The results of PMF-based NIRI and PMF-based HHRA showed that the chemical fertilizers and pesticides were the largest and priority risk sources with contribution rates of 38.10% to ecological risk and 34.61 and 32.82% to non-carcinogenic and carcinogenic risk, respectively. In addition, non-carcinogenic risk of children was higher than that of adults, while the carcinogenic risk was the opposite. The integrated approaches were beneficial for priority risk quantification from different sources and can provide direct risk information and effective policy recommendations for management and control of key risk sources.

Pharmacokinetic profile of ivabradine hemisulfate sustained-release tablets administered in Chinese healthy volunteers: An open-label, randomized, single-dose, three-period crossover study.

We aimed to determine the pharmacokinetics and safety of three single oral doses (5, 10 and 15 mg) of ivabradine hemisulfate sustained-release tablets in healthy Chinese volunteers. A total of 12 volunteers (six males and six females) were randomized to receive a single oral dose of ivabradine hemisulfate sustained-release tablets 5, 10 or 15 mg, with a 1-week washout between periods. Blood samples were collected at regular intervals from 0 to 48 h after drug administration, and the concentrations of ivabradine and N-desmethyl ivabradine were determined by HPLC-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis. After administering single doses of 5, 10 and 15 mg, the mean maximum concentration (Cmax ) levels of ivabradine were 4.36, 7.29 and 12.62 ng/mL, and the mean area under the curve from time 0 to 48 h (AUC0-48 ) values were 55.66, 101.16 and 182.09 h·ng/mL, respectively. The mean Cmax levels of N-desmethyl ivabradine were 1.05, 2.03 and 3.16 ng/mL, and the mean AUC0-48 values were 20.61, 39.44 and 65.72 h·ng/mL, respectively. The median time of maximum concentration (Tmax ) levels of ivabradine and N-desmethyl ivabradine were 5 h for all three doses tested. The pharmacokinetic properties of ivabradine hemisulfate sustained-release tablets were linear at doses from 5 to 15 mg. Ivabradine hemisulfate sustained-release tablet appears to be well tolerated in these healthy volunteers.

Proteomic analysis of boar sperm with differential ability of liquid preservation at 17 °C.

Understanding the liquid preservation ability of boar sperm is pivotal for efficient management and breeding of livestock. Although sperm proteins play an important role in semen quality and freezability, how the levels of protein change in boar sperm with different liquid preservation abilities at 17 °C remains unclear. In this study, two groups of boar sperm with extreme difference in liquid preservation ability, namely the good preservation ability (GPA) and the poor preservation ability (PPA) groups, were selected by evaluating sperm motility parameters on the 7th day of liquid preservation at 17 °C. Quantitative proteomics based on tandem mass tag (TMT) labeling was used, sperm proteomic characteristics from two groups were analyzed, and potentially key proteins related to the fluid preservation ability of sperm were identified. A total of 187 differentially expressed proteins (DEPs) were identified among 2791 quantified proteins, including 85 upregulated, and 102 downregulated proteins. Further, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the DEPs revealed that they were enriched in GO terms associated with response to oxidative stress, enzyme activity related to oxidative stress or redox reactions, and several metabolic activities. The significant KEGG pathways included peroxisome, metabolic pathways, selenocompound metabolism, and collection duct acid secretion. In addition, analysis of protein-protein interactions further identified 8 proteins that could be used as biomarker candidates, including GPX5, GLRX, ENO4, QPCT, BBS7, OXSR1, DHRS4 and AP2S1, which may play an essential role in indicating the liquid preservation ability of boar sperm. These findings in this study provide new insights into the underlying molecular mechanisms of the liquid preservation ability of boar sperm. Moreover, the selected candidate proteins can serve as a reference for evaluating sperm quality or preservation ability in boars and their application in related biotechnologies.

Nutritional status and nutritional intervention of older inpatients in China.

BACKGROUND: Malnutrition is a critical issue among older inpatients, yet limited large-scale research related to this issue has been conducted in China. This study aimed to examine the nutritional status and support of older inpatients in China, assess the associations between disease categories and malnutrition on admission, and explore effective nutritional intervention. METHODS: A total of 24,139 older participants from the China Nutrition Fundamental Data 2020 Project were included. Malnutrition was measured by the Global Leadership Initiative on Malnutrition criteria. Adjusted odds ratios (aORs) were calculated using logistic analysis. RESULTS: The overall frequency of malnutrition on admission was 18.9%. Participants with infections were more likely to have malnutrition (aOR = 1.929, 95% CI 1.486-2.504). Risks that were also noted for malnutrition included neoplasms (aOR = 1.822, 95% CI 1.697-1.957), hemic and lymphatic diseases (aOR = 1.671, 95% CI 1.361-2.051), nervous system diseases (aOR = 1.222, 95% CI 1.126-1.326), respiratory diseases (aOR = 1.613, 95% CI 1.490-1.746), and digestive system diseases (aOR = 1.462, 95% CI 1.357-1.577). Further, 32.26% inpatients with malnutrition during hospitalization didn't receive nutritional support. Oral nutrition supplements, enteral tube feeding, and parenteral nutrition were associated with stable or improved nutritional status. CONCLUSIONS: Older inpatients were at a high risk for malnutrition but did not receive adequate nutritional intervention. More resources and attention need to be devoted to the nutritional status of older inpatients and targeted nutritional support.

Expression Profile and Regulatory Properties of m6A-Modified circRNAs in the Longissimus Dorsi of Queshan Black and Large White Pigs.

It is well known that N6-methyladenosine (m6A) is the most abundant modification in linear RNA molecules, but many circRNA molecules have now been found to have a wide range of m6A modification sites as well. However, there are few relevant studies and information on the expression profile and functional regulatory properties of m6A-modified circRNAs (m6A-circRNAs) in longissimus dorsi. In this study, a total of 12 putative m6A-circRNAs were identified and characterized in the longissimus dorsi of Queshan Black and Large White pigs-8 of them were significantly more expressed in the longissimus dorsi of Queshan Black than in Large White pigs, while the other 4 were the opposite. These 12 putative m6A-circRNAs were also found to act as miRNA sponge molecules to regulate fat deposition by constructing the ceRNA regulatory network. Enrichment analysis also revealed that the 12 m6A-circRNAs parent genes and their adsorbed miRNA target genes were widely involved in fat deposition and cell proliferation and differentiation-related pathways, such as the HIF-1 signaling pathway, the pentose phosphate pathway, the MAPK signaling pathway, the glycosphingolipid biosynthesis-lacto and neolacto series, and the TNF signaling pathway, suggesting that the analyzed m6A-circRNAs may be largely involved in the formation of pork quality. These results provide new information to study the regulatory properties of m6A-circRNAs in the formation of pork quality.

Identification and Functional Prediction of Long Non-Coding RNA in Longissimus Dorsi Muscle of Queshan Black and Large White Pigs.

Long non-coding RNA (lncRNA) participates in the regulation of various biological processes, but its function and characteristics in intramuscular fat (IMF) deposition in different breeds of pigs have not been fully understood. IMF content is one of the important factors affecting pork quality. In the present study, the differentially expressed lncRNAs (DE lncRNAs) and their target genes were screened by comparing Queshan Black (QS) and Large White (LW) pigs based on RNA-seq. The results displayed 55 DE lncRNAs between QS and LW, 29 upregulated and 26 downregulated, with 172 co-located target genes, and 6203 co-expressed target genes. The results of GO and KEGG analysis showed that the target genes of DE lncRNAs were involved in multiple pathways related to lipogenesis and lipid metabolism, such as the lipid biosynthetic process, protein phosphorylation, activation of MAPK activity, and the Jak-STAT signaling pathway. By constructing regulatory networks, lincRNA-ZFP42-ACTC1, lincRNA-AMY2-STAT1, and/or lincRNA-AMY2/miR-204/STAT1 were sieved, and the results indicate that lncRNA could participate in IMF deposition through direct regulation or ceRNA. These findings provide a basis for analyzing the molecular mechanism of IMF deposition in pigs and lay a foundation for developing and utilizing high-quality resources of local pig breeds.

Genome-Wide Analysis of MAMSTR Transcription Factor-Binding Sites via ChIP-Seq in Porcine Skeletal Muscle Fibroblasts.

Myocyte enhancer factor-2-activating motif and SAP domain-containing transcriptional regulator (MAMSTR) regulates its downstream through binding in its promoter regions. However, its molecular mechanism, particularly the DNA-binding sites, and coregulatory genes are quite unexplored. Therefore, to identify the genome-wide binding sites of the MAMSTR transcription factors and their coregulatory genes, chromatin immunoprecipitation sequencing was carried out. The results showed that MAMSTR was associated with 1506 peaks, which were annotated as 962 different genes. Most of these genes were involved in transcriptional regulation, metabolic pathways, and cell development and differentiation, such as AMPK signaling pathway, TGF-beta signaling pathway, transcription coactivator activity, transcription coactivator binding, adipocytokine signaling pathway, fat digestion and absorption, skeletal muscle fiber development, and skeletal muscle cell differentiation. Lastly, the expression levels and transcriptional activities of PID1, VTI1B, PRKAG1, ACSS2, and SLC28A3 were screened and verified via functional markers and analysis. Overall, this study has increased our understanding of the regulatory mechanism of MAMSTR during skeletal muscle fibroblast development and provided a reference for analyzing muscle development mechanisms.

Seminal plasma metabolomics analysis of differences in liquid preservation ability of boar sperm.

The preservation of semen is pivotal in animal reproduction to ensure successful fertilization and genetic improvement of livestock and poultry. However, investigating the underlying causes of differences in sperm liquid preservation ability and identifying relevant biomarkers remains a challenge. This study utilized liquid chromatography-mass spectrometry (LC-MS) to analyze the metabolite composition of seminal plasma (SP) from two groups with extreme differences in sperm liquid preservation ability. The two groups namely the good liquid preservation ability (GPA) and the poor preservation ability (PPA). The aim was to explore the relationship between metabolite composition in SP and sperm liquid preservation ability, and to identify candidate biomarkers associated with this ability of sperm. The results revealed the identification of 756 metabolites and 70 differentially expressed metabolites (DEM) in the SP from two groups of boar semen with differing liquid preservation abilities at 17 °C. The majority of identified metabolites in the SP belonged to organic acids and derivatives as well as lipids and lipid-like molecules. The DEM in the SP primarily consisted of amino acids, peptides, and analogs. The Kyoto Encyclopedia of Genes and Genomes analysis also demonstrated that the DEM are mainly concentrated in amino acid synthesis and metabolism-related pathways (P < 0.05). Furthermore, eleven key metabolites were identified and six target amino acids were verified, and the results were consistent with the non-targeted metabolic analysis. These findings indicated that amino acids and their associated pathways play a potential role in determining boar sperm quality and liquid preservation ability. D-proline, arginine, L-citrulline, phenylalanine, leucine, DL-proline, DL-serine, and indole may serve as potential biomarkers for early assessment of boar sperm liquid preservation ability. The findings of this study are helpful in understanding the causes and mechanisms of differences in the liquid preservation ability of boar sperm, and provide valuable insights for improving semen quality assessment methods and developing novel extenders or protocols.

The current main method for preserving boar semen used in artificial insemination is liquid preservation. However, the preservation ability of boar sperm has large individual differences, and understanding the factors that influence this ability of sperm and identifying relevant biomarkers present challenges. Given the crucial role of seminal plasma (SP) in sperm survival and functionality maintenance, this study utilized liquid chromatography-mass spectrometry to analyze the metabolite composition of the SP from two groups with extreme differences in sperm liquid preservation ability. The aim was to explore the relationship between metabolites in SP and sperm liquid preservation ability, and identify candidate biomarkers associated with this ability of sperm. The results revealed the important role of amino acids and related pathways in determining boar sperm quality and storage ability. Several potential biomarkers for early evaluation of boar sperm liquid preservation ability, including D-proline, arginine, L-citrulline, phenylalanine, leucine, DL-proline, DL-serine, and indole were identified. This study provides valuable insights into the reasons and mechanisms behind differences in sperm liquid preservation ability and offers possibilities for improving semen preservation techniques.

Effect of Food Intake on Pharmacokinetics of Oral Almonertinib: A Randomized Crossover Trial in Healthy Chinese Participants.

The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) almonertinib (HS-10296) targets both EGFR-sensitizing and T790M resistance mutations. This randomized, open-label, two-period crossover trial investigated the effect of food intake on the single-dose pharmacokinetic properties of almonertinib and its metabolite HAS-719. Twenty healthy adults received a single dose of almonertinib tablets (110 mg) on days 1 and 22 under overnight fasting or fed conditions, respectively. Plasma samples were collected 216 hours post-dosing and almonertinib and HAS-719 concentrations were determined using liquid chromatography-tandem mass spectrometry. For almonertinib, the geometric mean ratio (GMR, fed/fasting) and 90% confidence interval (CI) for the area under the curve (AUC) from time 0 to 216 hours and apparent oral clearance (CLz /F) were 119.9 (110.0-130.7) and 83.5 (76.6-90.9), respectively. Fasting and fed groups showed significant differences in these parameters, but not for maximum concentration (Cmax ) and time to Cmax (Tmax ). The Cmax GMR of HAS-719 was 81.7 (75.8-88.0), which decreased significantly in the fed group. The drug-related adverse reaction (AR) incidence was similar in the two groups, 50% in the fasting group and 52.6% in the fed group. ARs were mainly gastrointestinal diseases and abnormal laboratory test results, and all participants fully recovered. In conclusion, a high-fat diet slightly affected the pharmacokinetic profile of almonertinib in healthy participants, but not the safety tolerance. Therefore, almonertinib is suitable for administration under fasting or fed conditions.

Prediction of janagliflozin pharmacokinetics in type 2 diabetes mellitus patients with liver cirrhosis or renal impairment using a physiologically based pharmacokinetic model.

Janagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes mellitus (T2DM). The janagliflozin pharmacokinetics (PK) in T2DM patients with cirrhosis or renal impairment (RI) are unknown. To predict the janagliflozin PK in these patients, we constructed a physiologically based PK (PBPK) model that predicted the janagliflozin PK in normal animals. The model was extrapolated to healthy humans and optimized with the measured data. A PBPK model for T2DM patients was developed and optimized with the measured data. Based on the physiological alterations in cirrhosis or RI patients, the T2DM model was applied to predict the janagliflozin PK in these patients. Results were validated using fold error values. The predicted AUC values were 21,880, 24,881, 26,996, and 28,419 ng/ml·h in T2DM patients with no cirrhosis, Child-Pugh-A, B, and C, respectively, and those in T2DM patients with RI-mild, RI-moderate, and RI-severe were 21,810, 21,840, and 22,845 ng/ml·h, respectively. Janagliflozin exposure increased with increasing cirrhosis severity, whereas it remained stable regardless of the RI severity. The PBPK model predicted the janagliflozin PK in patients with T2DM and liver cirrhosis or RI. Dose adjustment is less critical for these patients. Risk benefit assessment in janagliflozin dosing for T2DM patients with liver disease is recommended.

Construction and Comprehensive Analysis of miRNAs and Target mRNAs in Longissimus dorsi Muscle of Queshan Black and Large White Pigs.

A miRNA-mRNA combination analysis was performed on the longissimus dorsi muscle of adult Queshan Black and Large White pigs by RNA-seq technology to reveal the molecular mechanism affecting pork quality traits. The sequencing results showed that 39 miRNAs were differentially expressed between Queshan Black and Large White pigs, which targeted 5234 mRNAs, and 15 differentially expressed miRNAs targeted 86 differentially expressed mRNAs. The qRT-PCR results showed that miRNAs showed similar expression patterns to RNA-seq. The GO analysis indicated that differentially expressed miRNAs with differential target mRNAs were primarily involved in biological processes such as phospholipase activity, MAP-kinase scaffold activity, lipase activity, and regulation of the extent of cell growth. The KEGG analysis also revealed that such mRNAs were significantly enriched in the ECM-receptor interaction, sphingolipid metabolism, apoptosis, PI3K-Akt signaling pathway, and AMPK signaling pathway. In addition, software predictions showed that 17 (13 of which were upregulated and four were downregulated) of 39 differentially expressed miRNAs targeted 118 negatively correlated expression mRNAs. The upregulated miRNAs contained 103 negatively correlated target mRNAs, whereas the downregulated miRNAs contained 15 negatively correlated target mRNAs. The GO analysis showed that such mRNAs were primarily involved in MAP-kinase scaffold activity, myoblast development, and peptidyl-lysine methylation, and the KEGG analysis showed significant enrichment in ECM-receptor interaction and focal adhesion. The functional enrichment analysis of miRNA target genes revealed that miR-328 was screened out as a key miRNA, and preliminary functional validation was performed. Moreover, the overexpressed miR-328 could affect the expression of proliferation-related genes, such as CDK2, CDK4, CCNB1, CCND1, CCNE1, and PCNA. These results indicated that miR-328 may regulate fat deposition and affect meat quality by influencing related pathways. This study revealed that the miRNA-mRNA regulatory axis affects fat deposition and skeletal muscle development, which provides a theoretical basis for further study on the molecular mechanism of meat quality.

Green and Scalable Fabrication of Sandwich-like NG/SiOx/NG Homogenous Hybrids for Superior Lithium-Ion Batteries.

SiOx is considered as a promising anode for next-generation Li-ions batteries (LIBs) due to its high theoretical capacity; however, mechanical damage originated from volumetric variation during cycles, low intrinsic conductivity, and the complicated or toxic fabrication approaches critically hampered its practical application. Herein, a green, inexpensive, and scalable strategy was employed to fabricate NG/SiOx/NG (N-doped reduced graphene oxide) homogenous hybrids via a freeze-drying combined thermal decomposition method. The stable sandwich structure provided open channels for ion diffusion and relieved the mechanical stress originated from volumetric variation. The homogenous hybrids guaranteed the uniform and agglomeration-free distribution of SiOx into conductive substrate, which efficiently improved the electric conductivity of the electrodes, favoring the fast electrochemical kinetics and further relieving the volumetric variation during lithiation/delithiation. N doping modulated the disproportionation reaction of SiOx into Si and created more defects for ion storage, resulting in a high specific capacity. Deservedly, the prepared electrode exhibited a high specific capacity of 545 mAh g-1 at 2 A g-1, a high areal capacity of 2.06 mAh cm-2 after 450 cycles at 1.5 mA cm-2 in half-cell and tolerable lithium storage performance in full-cell. The green, scalable synthesis strategy and prominent electrochemical performance made the NG/SiOx/NG electrode one of the most promising practicable anodes for LIBs.