Effect of alterations in phospholipids and free fatty acids on aroma-active compounds in instant-boiled chuck tender, sirloin and silverside beef.

Beef flavor profiles are strongly influenced by cooking methods and lipid composition. However, the effect of instant-boiling on the aroma of different beef slices was unclear. This study investigated the lipid profiles and instant-boiling volatile profiles of chuck tender (M. Supraspinatus), sirloin (M. Longissimus dorsi) and silverside (M. Biceps femoris). Quantitative lipidomics identified 336 lipid molecular species, of which 84-112 were quantitatively different among the three beef slices. Sirloin had lower phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol and free fatty acids than chuck tender and silverside. The unsaturated fatty acid acyl chains in phosphatidylethanolamine differed significantly. Solid phase microextraction-gas chromatography-olfactometry-mass spectrometry (SPME-GC-O-MS) identified hexanal, octanal, nonanal, decanal, (E)-2-octenal, (E)-2-nonenal, (E)-2-undecenal, (E,E)-2,4-nonadienal, (E,E)-2,4-decadienal, 1-octen-3-ol, 2-pentylfuran and acetoin as the aroma-active compounds of instant-boiled beef. Unsaturated free fatty acids and phosphatidylglycerols with unsaturated fatty acid residues positively correlated with the aroma-active compounds and might be crucial in flavor differences among the three beef slices. These findings provide greater understanding of the lipid and instant-boiling aroma-active compound profiles in chuck tender, sirloin and silverside, and reflect the suitability of different beef slices for instant-boiling from the aroma perspective.

Umbilical cord mesenchymal stem cells in ulcerative colitis treatment: efficacy and possible mechanisms.

BACKGROUND: Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms. METHODS: This prospective, self-controlled clinical study was conducted at Henan Provincial People's Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation. RESULTS: Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1ß, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy. CONCLUSION: UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines. TRIAL REGISTRATION: The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

Impact of staged goal-directed fluid therapy on postoperative pulmonary complications in patients undergoing McKeown esophagectomy: a randomized controlled trial.

BACKGROUND: Our aim was to evaluate the influence of staged goal directed therapy (GDT) on postoperative pulmonary complications (PPCs), intraoperative hemodynamics and oxygenation in patients undergoing Mckeown esophagectomy. METHODS: Patients were randomly divided into three groups, staged GDT group (group A, n = 56): stroke volume variation (SVV) was set at 8-10% during the one lung ventilation (OLV) stage and 8-12% during the two lung ventilation (TLV) stage, GDT group (group B, n = 56): received GDT with a target SVV of 8-12% During the entire surgical procedure, and control group (group C, n = 56): conventional fluid therapy was administered by mean arterial pressure (MAP), central venous pressure (CVP), and urine volume. The primary outcome was the incidence of postoperative pulmonary complications within Postoperative days (POD) 7. The secondary outcomes were postoperative lung ultrasound (LUS) B-lines artefacts (BLA) scoring, incidence of other complications, the length of hospital stay, intraoperative hemodynamic and oxygenation indicators included mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), cardiac output (CO), oxygenation index (OI), respiratory indices (RI), alveolar-arterial oxygen difference (Aa-DO2). RESULTS: Patients in group A and group B had a lower incidence of PPCs (7/56 vs. 17/56 and 9/56 vs. 17/56, p < 0.05), and a fewer B-lines score on postoperative ultrasound (4.61 ± 0.51 vs. 6.15 ± 0.74 and 4.75 ± 0.62 vs. 6.15 ± 0.74, p < 0.05) compared to group C. The CI, CO, MAP, and OI were higher in group A compared to group B and group C in the stage of thoracic operation. During the abdominal operation stage, patients in group A and group B had a better hemodynamic and oxygenation indicators than group C. CONCLUSIONS: In comparison to conventional fluid therapy, intraoperative staged GDT can significantly reduce the incidence of postoperative pulmonary complications in patients undergoing McKeown esophagectomy, facilitating patient recovery. Compared to GDT, it can improve intraoperative oxygenation and stabilize intraoperative hemodynamics in patients. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry on 24/11/2021 (ChiCTR2100053598).

Bronchoalveolar lavage fluid analysis in patients with checkpoint inhibitor pneumonitis.

BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a relatively uncommon but potentially life-threatening immune-related adverse event (irAE). Lung biopsies have not been commonly performed for CIP patients. Bronchoalveolar lavage fluid (BALF) analysis is a useful diagnostic approach for interstitial lung disease. However, BALF features were inconsistent across different studies. METHODS: We retrospectively reviewed the medical records of 154 patients with pathologically confirmed malignancies and suffering from CIPs between July 2018 and December 2022. Patients who had bronchoalveolar lavage (BAL) data available were enrolled in our study. Patient clinical, laboratory, radiological and follow-up data were reviewed and analyzed. RESULTS: The BALF differential cell count and lymphocyte subset analysis were performed for 42 CIP patients. There were 32 males (76.2%). The mean age at diagnosis of CIP was 62.0 ± 10.4 (range: 31-78) years. The median time to onset of CIP was 98.5 days after the start of immunotherapy. There were 18 patients (42.9%) with low-grade CIPs and 24 patients (57.1%) with high-grade CIPs. The mean lymphocyte percentage was 36.7 ± 22.5%. There were 34 (81%) CIP patients with a lymphocytic cellular pattern. The median ratio of CD3+CD4+/CD3+CD8+ lymphocytes was 0.5 (0.3, 1.0). The ratio was less than 1.0 for 31 CIP patients (73.8%). However, there was no significant difference in the BALF features between patients with low-grade CIPs and those with high-grade CIPs. CONCLUSIONS: The CD3+CD8+ lymphocytosis pattern was the main inflammatory profile in the BALF of CIP patients in this cohort. Targeting CD3+CD8+ lymphocytes might be a treatment option for CIPs.

The assembly and comparative analysis of the first complete mitogenome of Lindera aggregata.

Lindera aggregata, a member belongs to the genus Lindera of Lauraceae family. Its roots and leaves have been used as traditional Chinese medicine or functional food for thousands of years. However, its mitochondrial genome has not been explored. Our aim is to sequence and assemble the mitogenome of L. aggregata to elucidate the genetic mechanism and evolutionary pathway. The results had shown that the mitogenome was extremely complex and had a unique multi-branched conformation with total size of 912,473 bp. Comprehensive analysis of protein coding genes of 7 related species showed that there were 40 common genes in their mitogenome. Interestingly, positive selection had become an important factor in the evolution of ccmB, ccmFC, rps10, rps11 and rps7 genes. Furthermore, our data highlighted the repeated trend of homologous fragment migrations between chloroplast and mitochondrial organelles, and 38 homologous fragments were identified. Phylogenetic analysis identified a tree that was basically consistent with the phylogeny of Laurales species described in the APG IV system. To sum up, this study will be helpful to the study of population genetics and evolution of Lindera species.

Comprehensive foodomics analysis reveals key lipids affect aroma generation in beef.

Lipids are vital precursors to beef aroma compounds, but the exact lipid molecules influencing aroma generation remain unconfirmed. This study employs gas chromatography-olfactometry-mass spectrometry and absolute quantitative lipidomics to identify beef's aroma and lipid profiles and to examine lipid alterations post-thermal processing. The aim is to understand the role of lipids in aroma generation during beef's raw-to-cooked transition. Eighteen key aroma compounds were identified as significant contributors to the aroma of beef. 265 lipid molecules were quantified accurately, and we found that triglycerides containing C18:1 or C18:2 chains, such as TG(16:0_18:1_18:1), TG(16:0_18:1_18:2), TG(16:0_16:1_18:1), as well as phosphatidylcholine and phosphatidylethanolamine containing PC(16:1e_20:4), PC(16:0e_20:4), PC(18:2e_18:2), and PE(16:1e_20:4), played important roles in the generation of key aroma compounds in beef. C18:1, C18:2, C18:3, and C20:4 were key substrates for the formation of aroma compounds. In addition, lysophosphatidylcholine and lysophosphatidylethanolamine containing unsaturated fatty acid chains may serve as important aroma retainers.

Prognostic analysis of concurrent Pneumocystis jirovecii pneumonia in patients with systemic lupus erythematosus: a retrospective study.

BACKGROUND: Systemic lupus erythematosus (SLE) has been less deadly since the advent of corticosteroid-sparing medications. SLE patients still have a higher mortality rate than the general population. Infectious disease is reported as one of the major causes of death in patients with SLE. Although bacteria are the most often isolated pathogens from patients with SLE, Pneumocystis jirovecii pneumonia (PJP) is more deadly than bacterial infection. METHODS: We retrospectively enrolled consecutive patients with SLE concurrent with PJP (SLE-PJP) in our center between January 2014 and December 2022. The participants were classified into two groups: survivors and non-survivors. Cox regression models and Kaplan‒Meier survival analyses were conducted to explore prognostic factors for survival. RESULTS: There were 57 patients with SLE (42.0 ± 15.8 years old, 78.9% female) complicated with PJP, 22 (38.6%) of whom died. Compared with the survival group, the non-survival group had more patients with hyperglycemia or diabetes mellitus, invasive ventilation (p < 0.01), respiratory failure, intensive care unit admission, non-invasive ventilation, and hospital-acquired pneumonia (p < 0.05). The non-survival group showed a higher neutrophil percentage, lactate dehydrogenase, D-dimer (p < 0.001), urea, high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), and ferritin (p < 0.05). It also had lower minimal albumin, hemoglobin (p < 0.001), immunoglobulin G, complement 3, peripheral lymphocyte count, platelet, NK cell count, and CD4+ T-cell count (p < 0.05). Multivariate analysis indicated that hyperglycemia or diabetes mellitus (HR = 4.25, p < 0.01, 95% CI: 1.51-11.97), thrombocytopenia (HR = 4.22, p < 0.01, 95% CI: 1.63-10.91) and lower complement 3 (C3) (HR = 4.06, p < 0.01, 95% CI: 1.60-10.33) were independent risk factors for the survival of SLE-PJP patients. CONCLUSIONS: The mortality rate of patients with SLE-PJP is still high. Hyperglycemia, decreased C3, and thrombocytopenia are independent survival risk factors.

An ultra-efficient pretreatment method adopted LPUV/CoFe2O4/PMS-based photolysis for accurate detection of Cd(II) and Pb(II) in water via SWASV.

Dissolved organic matter (DOM) is a widely occurring substance in rivers that can strongly complex with heavy metal ions (HMIs), severely interfering with the electrochemical signal of anodic stripping voltammetry (ASV) and reducing the detection accuracy of HMIs in water. In this study, we investigated a novel advanced oxidation process (AOP) that involves the activation of peroxymonosulfate (PMS) using low-pressure ultraviolet (LPUV) radiation and CoFe2O4 photocatalysis. This novel AOP was used for the first time as an effective pretreatment method to break or weaken the complexation between HMIs and DOM, thereby restoring the electrochemical signals of HMIs. The key parameters, including the PMS concentration, CoFe2O4 concentration, and photolysis time, were optimized to be 6 mg/L, 12 mg/L, and 30 s for eliminating DOM interference during the electrochemical analysis of HMIs via LPUV/CoFe2O4-based photolysis. Investigations of the microstructure, surface morphology, specific surface area, and pore volume of CoFe2O4 were conducted to reveal the exceptional signal recovery capability of LPUV/CoFe2O4/PMS-based photolysis in mitigating interference from DOM during HMIs analysis. The PMS activation mechanism, which is critical to the signal recovery process, was elucidated by analyzing the reactive oxygen species (ROS) and the surface elemental composition of CoFe2O4. Additionally, the degradation and transformation behavior of humus-HMIs complexes were analyzed to study the mechanism of ASV signal recovery further. Notably, the detection results of HMIs in actual water samples obtained using the proposed pretreatment method were compared with those obtained from ICP-MS, yielding an RMSE less than 0.04 µg/L, which indicated the satisfactory performance of the proposed pretreatment method for the ASV detection of HMIs in complex actual samples.

Polystyrene microplastics facilitate renal fibrosis through accelerating tubular epithelial cell senescence.

Microplastics (MPs), emerging contaminants, are easily transported and enriched in the kidney, suggesting the kidney is susceptible to the toxicity of MPs. In this study, we explored the toxicity of MPs, including unmodified polystyrene (PS), negative-charged PS-SO3H, and positive-charged PS-NH2 MPs, in mice models for 28 days at a human equivalent concentration. The results showed MPs significantly increased levels of UREA, urea nitrogen (BUN), creatinine (CREA), and uric acid (UA) levels in serum and white blood cells, protein, and microalbumin in urine. In the kidney, MPs triggered persistent inflammation and renal fibrosis, which was caused by the increased senescence of tubular epithelial cells. Moreover, we identified the critical role of the Klotho/Wnt/ß-catenin signaling pathway in the process of MPs induced senescence of tubular epithelial cells, promoting the epithelial-mesenchymal transformation of epithelial cells. MPs supported the secretion of TGF-ß1 by senescent epithelial cells and induced the activation of renal fibroblasts. On the contrary, restoring the function of Klotho can alleviate the senescence of epithelial cells and reverse the activation of fibroblasts. Thus, our study revealed new evidence between MPs and renal fibrosis, and adds an important piece to the whole picture of the plastic pollution on people's health.

Metformin reduces basal subpopulation and attenuates mammary epithelial cell stemness in FVB/N mice.

Metformin shows promise in breast cancer prevention, but its underlying mechanisms remain unclear. This study investigated the impact of metformin on the repopulation dynamics of mammary epithelial cells (MECs) and the signaling pathways in non-tumorigenic FVB/N mice. This study aimed to enhance our understanding of the role of metformin in reducing the susceptibility of MECs in premalignant tissues to oncogenic factors. In this study, female mice were administered 200 mg/kg/day of metformin via intraperitoneal (i.p.) injection from 8 to 18 weeks of age. After this treatment period, morphogenesis, flow cytometry, analyses of MEC stemness, and RNA sequencing were performed. The study findings indicated that metformin treatment in adult mice reduced mammary gland proliferation, as demonstrated by decreased Ki67+ cells and lateral bud formation. Additionally, metformin significantly reduced both basal and mammary repopulating unit subpopulations, indicating an impact on mammary epithelial cell repopulation. Mammosphere, colony-forming cell, and 3D culture assays revealed that metformin adversely affected mammary epithelial cell stemness. Furthermore, metformin downregulated signaling in key pathways including AMPK/mTOR, MAPK/Erk, PI3K/Akt, and ER, which contribute to its inhibitory effects on mammary proliferation and stemness. Transcriptome analysis with RNA sequencing indicated that metformin induced significant downregulation of genes involved in multiple critical pathways. KEGG-based pathway analysis indicated that genes in PI3K/Akt, focal adhesion, ECM-receptor, small cell lung cancer and immune-modulation pathways were among the top groups of differentially regulated genes. In summary, our research demonstrates that metformin inhibits MEC proliferation and stemness, accompanied by the downregulation of intrinsic signaling. These insights suggest that the regulatory effects of metformin on premalignant mammary tissues could potentially delay or prevent the onset of breast cancer, offering a promising avenue for developing new preventive strategies.

Engineering of Erythrocytes as Drug Carriers for Therapeutic Applications.

Erythrocytes, also known as red blood cells (RBCs), have garnered considerable attention as potential carriers for drug delivery, owing to their inherent properties such as biocompatibility, biodegradability, and prolonged circulation half-life. This paper presents a comprehensive overview of the role of erythrocytes in drug delivery, elucidating recent advancements in delivering a diverse array of therapeutic agents, including small molecules, nucleic acids, antibodies, protein enzymes, and nanoparticles. Two primary strategies for encapsulating drugs within erythrocytes are systematically discussed: internal loading and surface loading. Each strategy offers distinct advantages in terms of drug stability and release kinetics. Notably, the utilization of erythrocyte membrane camouflaged nanocarriers holds promise for enhancing the biocompatibility of conventional nanoparticles and facilitating targeted drug delivery. Furthermore, the broad spectrum of biomedical applications of erythrocyte-based drug delivery systems are examined, ranging from cancer treatment to diabetes management, thrombosis prevention, and immunotherapy. This review provides a comprehensive evaluation of current technologies in erythrocyte-loaded drug delivery, highlighting the strengths, weaknesses, and future directions for advancing therapeutic interventions in various disease contexts.

Pemphigus oral lesions area index (POLAI): A new scoring scale for assessing oral pemphigus vulgaris.

OBJECTIVES: Current scales for Pemphigus vulgaris (PV) do not adequately represent the clinical variability of oral lesions. This study aimed to develop an independent scale, the Pemphigus Oral Lesions Area Index (POLAI), for assessment of oral PV exclusively, and compare POLAI, Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Oral Disease Severity Score (ODSS) regarding inter- and intra-observer reliability and validity. MATERIALS AND METHODS: Retrospective cohort included 209 sets of digital-photographs. Additional clinical cohort included 32 PV patients. All visits were assessed by four clinicians using the PDAI, ABSIS, ODSS and POLAI, and were rated by three specialists using the Physician's Global Assessment (PGA). RESULTS: The intraclass correlation coefficient showed the inter-observer reliability with 0.89 and 0.86 for PDAI, 0.87 for ABSIS, 0.93 for ODSS, 0.96 for POLAI, and 0.97 and 0.96 for PGA. Intra-observer agreements showed excellent reliability for all 4 scores. Highest correlation was observed between PGA and POLAI (correlation coefficients were 0.96). The mean time taken to complete each scale was within 1.5 min. CONCLUSION: POLAI is valid for the assessment of oral PV with superior inter- and intra-observer reliability to PDAI, ABSIS and ODSS, and is feasible in clinic.

Targeted desialylation and cytolysis of tumour cells by fusing a sialidase to a bispecific T-cell engager.

Bispecific T-cell engagers (BiTEs) bring together tumour cells and cytotoxic T cells by binding to specific cell-surface tumour antigens and T-cell receptors, and have been clinically successful for the treatment of B-cell malignancies. Here we show that a BiTE-sialidase fusion protein enhances the susceptibility of solid tumours to BiTE-mediated cytolysis of tumour cells via targeted desialylation-that is, the removal of terminal sialic acid residues on glycans-at the BiTE-induced T-cell-tumour-cell interface. In xenograft and syngeneic mouse models of leukaemia and of melanoma and breast cancer, and compared with the parental BiTE molecules, targeted desialylation via the BiTE-sialidase fusion proteins enhanced the formation of immunological synapses, T-cell activation and T-cell-mediated tumour-cell cytolysis in the presence of the target antigen. The targeted desialylation of tumour cells may enhance the potency of therapies relying on T-cell engagers.

Deep learning in the diagnosis for cystic lesions of the jaws: a review of recent progress.

Cystic lesions of the gnathic bones present challenges in differential diagnosis. In recent years, artificial intelligence (AI) represented by deep learning (DL) has rapidly developed and emerged in the field of dental and maxillofacial radiology (DMFR). Dental radiography provides a rich resource for the study of diagnostic analysis methods for cystic lesions of the jaws and has attracted many researchers. The aim of the current study was to investigate the diagnostic performance of DL for cystic lesions of the jaws. Online searches were done on Google Scholar, PubMed, and IEEE Xplore databases, up to September 2023, with subsequent manual screening for confirmation. The initial search yielded 1862 titles, and 44 studies were ultimately included. All studies used DL methods or tools for the identification of a variable number of maxillofacial cysts. The performance of algorithms with different models varies. Although most of the reviewed studies demonstrated that DL methods have better discriminative performance than clinicians, further development is still needed before routine clinical implementation due to several challenges and limitations such as lack of model interpretability, multicentre data validation, etc. Considering the current limitations and challenges, future studies for the differential diagnosis of cystic lesions of the jaws should follow actual clinical diagnostic scenarios to coordinate study design and enhance the impact of AI in the diagnosis of oral and maxillofacial diseases.

E3 ubiquitin ligase BCA2 promotes breast cancer stemness by up-regulation of SOX9 by LPS.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Breast cancer stem cells (BCSCs) are believed to play a crucial role in the carcinogenesis, therapy resistance, and metastasis of TNBC. It is well known that inflammation promotes stemness. Several studies have identified breast cancer-associated gene 2 (BCA2) as a potential risk factor for breast cancer incidence and prognosis. However, whether and how BCA2 promotes BCSCs has not been elucidated. Here, we demonstrated that BCA2 specifically promotes lipopolysaccharide (LPS)-induced BCSCs through LPS induced SOX9 expression. BCA2 enhances the interaction between myeloid differentiation primary response protein 88 (MyD88) and Toll-like receptor 4 (TLR4) and inhibits the interaction of MyD88 with deubiquitinase OTUD4 in the LPS-mediated NF-κB signaling pathway. And SOX9, an NF-κB target gene, mediates BCA2's pro-stemness function in TNBC. Our findings provide new insights into the molecular mechanisms by which BCA2 promotes breast cancer and potential therapeutic targets for the treatment of breast cancer.

Identification and Functional Verification of the Glycosyltransferase Gene Family Involved in Flavonoid Synthesis in Rubus chingii Hu.

Glycosylation is catalyzed by UDP-glycosyltransferase (UGT) and plays an important role in enriching the diversity of flavonoids. Rubus plants contain a lot of natural flavonoid glycosides, which are important plants with a homology of medicine and food. However, information about the Rubus UGT gene family is very limited. In this study, we carried out genome-wide analysis and identified the 172, 121, 130, 121 UGT genes in R. chingii, R. corchorifolius, R. idaeus, and R. occidentalis, respectively, and divided them into 18 groups. The analysis of the protein motif and gene structure showed that there were structural and functional conservations in the same group, but there were differences among different groups. Gene replication analysis showed that raspberry and dicotyledons had a higher homology. The expansion of the UGTs gene family was mainly driven by tandem replication events, and experienced purified selection during the long evolution of the raspberry. Cis-acting element analysis showed that they were related to plant growth and development, hormone regulation, and stress response. In addition, according to a comprehensive analysis of the co-expression network constructed by transcriptome data and phylogenetic homology, RchUGT169 was identified as a flavonoid glucosyltransferase. Through the transient expression in tobacco, it was verified that RchUGT169 could catalyze the conversion of kaempferol and quercetin to the corresponding flavonoid glycosides. In conclusion, this research enriched the understanding of the diversity of UGTs in Rubus and determined that RcUGT169 can catalyze flavonoids.

RNF31 alleviates liver steatosis by promoting p53/BNIP3-related mitophagy in hepatocytes.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the liver illnesses that may be affected by mitophagy, which is the selective removal of damaged mitochondria. RNF31, an E3 ubiquitin ligase, is carcinogenic in many malignancies. However, the influence of RNF31 on mitochondrial homeostasis and NAFLD development remains unknown. METHODS: Oleic-palmitic acid treated hepatocytes and high-fat diet (HFD)-fed mice were established to observe the effect of RNF31 on hepatocyte mitophagy and steatosis. Mitophagy processes were comprehensively assessed by mt-Keima fluorescence imaging, while global changes in hepatic gene expression were measured by RNA-seq. RESULTS: The present study discovered a reduction in RNF31 expression in lipotoxic hepatocytes with mitochondrial dysfunction. The observed decrease in RNF31 expression was associated with reduced mitochondrial membrane potential, disturbed mitophagy, and increased steatosis. Additionally, the findings indicated that RNF31 is a pivotal factor in the initiation of mitophagy and the facilitation of mitochondrial homeostasis, resulting in a decrease in steatosis in lipotoxic hepatocytes. Mechanistically, RNF31 enhanced p53 ubiquitination and subsequent proteasomal degradation. Down-regulation of p53 led to increased expression of the mitophagy receptor protein BCL2 and adenovirus E1B 19 kDa-interacting protein 3 (BNIP3), thereby promoting mitophagy in hepatocytes. Furthermore, it was demonstrated that the transportation of RNF31 via small extracellular vesicles derived from mesenchymal stem cells (referred to as sEV) had a substantial influence on reducing hepatic steatosis and restoring liver function in HFD-fed mice. CONCLUSIONS: The findings highlight RNF31's essential role in the regulation of mitochondrial homeostasis in hepatocytes, emphasizing its potential as a therapeutic target for NAFLD.

A new species of Populus and the extensive hybrid speciation arising from it on the Qinghai-Tibet Plateau.

While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides, species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata, naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata, resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys.

Tacrolimus alleviates pulmonary fibrosis progression through inhibiting the activation and interaction of ILC2 and monocytes.

Idiopathic pulmonary fibrosis (IPF) is a heterogeneous group of lung diseases with different etiologies and characterized by progressive fibrosis. This disease usually causes pulmonary structural remodeling and decreased pulmonary function. The median survival of IPF patients is 2-5 years. Predominantly accumulation of type II innate immune cells accelerates fibrosis progression by secreting multiple pro-fibrotic cytokines. Group 2 innate lymphoid cells (ILC2) and monocytes/macrophages play key roles in innate immunity and aggravate the formation of pro-fibrotic environment. As a potent immunosuppressant, tacrolimus has shown efficacy in alleviating the progression of pulmonary fibrosis. In this study, we found that tacrolimus is capable of suppressing ILC2 activation, monocyte differentiation and the interaction of these two cells. This effect further reduced activation of monocyte-derived macrophages (Mo-M), thus resulting in a decline of myofibroblast activation and collagen deposition. The combination of tacrolimus and nintedanib was more effective than either drug alone. This study will reveal the specific process of tacrolimus alleviating pulmonary fibrosis by regulating type II immunity, and explore the potential feasibility of tacrolimus combined with nintedanib in the treatment of pulmonary fibrosis. This project will provide new ideas for clinical optimization of anti-pulmonary fibrosis drug strategies.

Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.