Identifying factors influencing local governments' adoption of comprehensive smoke-free policies: an event history analysis based on panel data from 36 key cities in China (2013-2021).

Introduction: The issue of tobacco control remains a significant concern for public health worldwide. In recent years, remarkable progress has been made toward adopting smoke-free measures in indoor public places. Although China has yet to introduce a national regulation, specifically for smoke-free public places, more than a dozen cities have successively approved and implemented comprehensive smoke-free regulations. Different cities in China have diverse attitudes and behaviors toward smoke-free policies; however, the reasons for these policy differences and the influencing factors have not received sufficient attention and research. Methods: On the basis of the multiple streams framework, this study selects 36 key Chinese cities as research samples and uses a directed dyad-year event history analysis method to analyze the factors influencing the implementation of comprehensive smoke-free policies in cities. Results: Results show that the adoption of such policies is positively influenced by scientific evidence, focal events, media coverage, institutional foundations, economic comparisons, and the influence of health departments and of tobacco control groups. By contrast, policy adoption is negatively affected by the differences in administrative levels, central policy signals, and the influence of the tobacco industry. Discussion: This study contributes to understanding the internal logic behind local governments' adoption of comprehensive smoke-free policies, offering insights for further advocacy at the city and national levels in China and providing experiences that can promote the global tobacco control movement.

Tanshinone IIA improves Alzheimer's disease via RNA nuclear-enriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition characterized by oxidative stress and neuroinflammation. Tanshinone IIA (Tan-IIA), a bioactive compound isolated from Salvia miltiorrhiza plants, has shown potential neuroprotective effects; however, the mechanisms underlying such a function remain unclear. AIM: To investigate potential Tan-IIA neuroprotective effects in AD and to elucidate their underlying mechanisms. METHODS: Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology. To assess changes in oxidative stress and neuroinflammation, we performed enzyme-linked immunosorbent assay and western blotting. Additionally, the effect of Tan-IIA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Genetic changes related to the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1)/microRNA (miRNA, miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction. RESULTS: In vivo, Tan-IIA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice. In vitro experiments showed that Tan-IIA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability, apoptosis, oxidative stress, and neuroinflammation. In this process, the lncRNA NEAT1 - a potential therapeutic target - is highly expressed in AD mice and downregulated via Tan-IIA treatment. Mechanistically, NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p, which activates nuclear factor kappa-B (NF-κB) signaling, leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein, which exacerbates AD. Tan-IIA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling. CONCLUSION: This study demonstrates that Tan-IIA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway, serving as a foundation for the development of innovative approaches for AD therapy.

Enhancing the inhibition of cell proliferation and induction of apoptosis in H22 hepatoma cells through biotransformation of notoginsenoside R1 by Lactiplantibacillus plantarum S165 into 20(S/R)-notoginsenoside R2.

Notoginsenoside R2 is a crucial active saponin in Panax notoginseng (Burk.) F. H. Chen, but its natural content is relatively low. In this study, we investigated the biotransformation of notoginsenoside R1 to 20(S/R)-notoginsenoside R2 using Lactiplantibacillus plantarum S165, compared the inhibitory effects on cancer cell proliferation and conducted a mechanistic study. Notoginsenoside R1 was transformed using Lactiplantibacillus plantarum S165 at 37 °C for 21 days. The fermentation products were identified using a combination of HPLC, UPLC-MS/MS, and 13C-NMR methods. The inhibition effects of 20(S/R)-notoginsenoside R2 on H22 hepatoma cells were assessed by CCK-8 and TUNEL assays, and the underlying mechanism was investigated by Western blotting. Lactiplantibacillus plantarum S165 could effectively transform notoginsenoside R1 to 20(S/R)-notoginsenoside R2 with a conversion yield of 82.85%. Our results showed that 20(S/R)-notoginsenoside R2 inhibited H22 hepatoma cells proliferation and promoted apoptosis. The apoptosis of H22 hepatoma cells was promoted by 20(S/R)-notoginsenoside R2 through the blockade of the PI3K/AKT/mTOR signaling pathway. The biotransformation method used in this study resulted in the production of 20(S)-notoginsenoside R2 and 20(R)-notoginsenoside R2 from notoginsenoside R1, and the anti-tumor activity of the transformed substance markedly improved.

Lacticaseibacillus rhamnosus TF318 prevents depressive behavior in rats by inhibiting HPA-axis hyperactivity and upregulating BDNF expression.

Growing evidence suggests that probiotics can ameliorate depression by regulating the microbiota-gut-brain axis. However, the mechanism of action of probiotics in depressive disorders remains incompletely understood. This study aimed to investigate the effect of Lacticaseibacillus rhamnosus TF318 in a corticosterone (CORT)-induced rat model of depression. The sucrose preference test (SPT) and Morris water maze (MWM) test showed that oral administration of L. rhamnosus TF318 for 21 d significantly prevented depressive behaviors. Administration of L. rhamnosus TF318 resulted in lower hippocampal levels of adrenocorticotropic hormone and corticotropin-releasing factor and serum levels of CORT and restoration of hippocampal levels of 5-hydroxytryptamine, dopamine, and norepinephrine. A marked increase was observed in the hippocampal concentration of brain-derived neurotrophic factor (BDNF), a change that may have involved the cyclic adenosine monophosphate (cAMP)/cAMP response element-binding (CREB)/BDNF signaling pathway. Treatment with L. rhamnosus TF318 corrected CORT-induced abnormalities in the gut microbiota, significantly increasing the relative abundance of Firmicutes. In conclusion, supplementation with L. rhamnosus TF318 prevented CORT-induced depressive behaviors by upregulating BDNF expression and modulating gut microbiota, suggesting that this strain has the potential as a novel probiotic with antidepressant effects.

Lactiplantibacillus plantarum ELF051 Alleviates Antibiotic-Associated Diarrhea by Regulating Intestinal Inflammation and Gut Microbiota.

Probiotics are widely recognized for their ability to prevent and therapy antibiotic-associated diarrhea (AAD). This study was designed to evaluate Lactiplantibacillus plantarum ELF051 ability to prevent colon inflammation and its effect on gut microbial composition in a mouse model of AAD. The mice were intragastrically administered triple antibiotics for 7 days and then subjected to L. plantarum ELF051 for 14 days. The administration of L. plantarum ELF051 ameliorated the pathological changes in the colon tissue, downregulated interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, and upregulated IL-10, and increased the intestinal short-chain fatty acids (SCFAs) level. Lactiplantibacillus plantarum ELF051 also regulated the Toll-like receptor/myeloid differentiation primary response 88/nuclear factor kappa light chain enhancer of activated B cells (TLR4/MyD88/NF-κB) and the phosphatidylinositol 3-kinase/protein kinase B/ NF-κB (PI3K/AKT/ NF-κB) inflammatory signaling pathways. 16S rRNA analyses showed that L. plantarum ELF051 increased the abundance and diversity of gut bacteria, restoring gut microbiota imbalance. A Spearman's rank correlation analysis showed that lactobacilli are closely associated with inflammatory markers and SCFAs. This work demonstrated that L. plantarum ELF051 can attenuate antibiotic-induced intestinal inflammation in a mouse AAD model by suppressing the pro-inflammatory response and modulating the gut microbiota.

An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation.

GSDME-dependent pyroptosis signaling pathway in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the serious chronic microvascular complications of diabetes, and leads to the increased morbidity and mortality in diabetic patients. Gasdermin E (GSDME)-dependent pyroptosis signaling pathway plays important roles in a variety of physiological and pathological processes. However, its role and mechanism in DN are still unclear. In this study, we established a rat DN model by intraperitoneal injection of streptozotocin (STZ) successfully. Structural and functional disorders in the kidney were exhibited on the 12th week after STZ injection; the expressions of caspase-3 and GSDME at protein level in renal cortex were significantly up-regulated. At the 20th week, GSDME-N increased significantly, accompanied by the upregulation of caspase-1 in renal cortex and the release of mature IL-1ß (mIL-1ß) in serum. Furthermore, we found the protein levels of GSDME, caspase-3, caspase-1 and IL-1ß were all increased in HK2 and HBZY-1 cells under high-glucose conditions. We also found that the expression of GSDME-N significantly decreased when caspase-3 was knockdown. In contrast, knockdown of GSDME has no effect on caspase-3. Interestingly, either caspase-3, caspase-1 or GSDME knockdown reduced the release of mIL-1ß. Finally, injection of adeno-associated virus (AAV) 9-shGSDME into the rat kidney reduced kidney damage and renal cell pyroptosis in comparison with wild-type diabetic rats. These results indicated that the activation of caspase-1 induced IL-1ß maturation, and the activation of caspase-3 mediated cleavage of GSDME responsible for the formation of plasma membrane pore, followed by cytoplasmic release of mIL-1ß. Overall, we identified a pro-pyroptosis role for GSDME in DN, which does provide an important basis for clinical therapeutic studies.

TNIK regulation of interferon signaling and endothelial cell response to virus infection.

Background: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored. Methods: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs. Results: Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log (p-value) >11], downregulation of IFN-related genes, and inhibition of Hypercytokinemia/Hyperchemokinemia [-log (p-value) >8]. The validation process encompassed qRT-PCR to evaluate mRNA expression of crucial IFN-related genes, immunoblotting to gauge STAT1 and STAT2 protein levels, and ELISA for the quantification of IFN and cytokine secretion in siTNIK-depleted ECs. These assessments consistently revealed substantial reductions upon TNIK depletion. When transducing HUVECs with replication incompetent E1-E4 deleted adenovirus expressing green fluorescent protein (Ad-GFP), it was demonstrated that TNIK depletion did not affect the uptake of Ad-GFP. Nonetheless, TNIK depletion induced cytopathic effects (CPE) in ECs transduced with wild-type human adenovirus serotype 5 (Ad-WT). Summary: Our findings suggest that TNIK plays a crucial role in regulating the EC response to virus infections through modulation of the IFN pathway.

Transformation of Ginsenosides by Lactiplantibacillus plantarum MB11 Fermentation: Minor Ginsenosides Conversion and Enhancement of Anti-Colorectal Cancer Activity.

The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared with the model group. Immunofluorescence and TdT-mediated dUTP nick end labeling (TUNEL) analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/mTOR autophagy pathway and regulate JAK2/STAT3 and Bax/Bcl-2/caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.

Comprehensive bioinformatics analysis reveals biomarkers of DNA methylation-related genes in varicose veins.

Background: Patients with Varicose veins (VV) show no obvious symptoms in the early stages, and it is a common and frequent clinical condition. DNA methylation plays a key role in VV by regulating gene expression. However, the molecular mechanism underlying methylation regulation in VV remains unclear. Methods: The mRNA and methylation data of VV and normal samples were obtained from the Gene Expression Omnibus (GEO) database. Methylation-Regulated Genes (MRGs) between VV and normal samples were crossed with VV-associated genes (VVGs) obtained by weighted gene co-expression network analysis (WGCNA) to obtain VV-associated MRGs (VV-MRGs). Their ability to predict disease was assessed using receiver operating characteristic (ROC) curves. Biomarkers were then screened using a random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM). Next, gene set enrichment analysis (GSEA) was performed to explore the functions of biomarkers. Furthermore, we also predicted their drug targets, and constructed a competing endogenous RNAs (ceRNA) network and a drug target network. Finally, we verified their mRNA expression using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Total three VV-MRGs, namely Wnt1-inducible signaling pathway protein 2 (WISP2), Cysteine-rich intestinal protein 1 (CRIP1), and Odd-skipped related 1 (OSR1) were identified by VVGs and MRGs overlapping. The area under the curves (AUCs) of the ROC curves for these three VV-MRGs were greater than 0.8. RF was confirmed as the optimal diagnostic model, and WISP2, CRIP1, and OSR1 were regarded as biomarkers. GSEA showed that WISP2, CRIP1, and OSR1 were associated with oxidative phosphorylation, extracellular matrix (ECM), and respiratory system functions. Furthermore, we found that lncRNA MIR17HG can regulate OSR1 by binding to hsa-miR-21-5p and that PAX2 might treat VV by targeting OSR1. Finally, qRT-PCR results showed that the mRNA expression of the three genes was consistent with the results of the datasets. Conclusion: This study identified WISP2, CRIP1, and OSR1 as biomarkers of VV through comprehensive bioinformatics analysis, and preliminary explored the DNA methylation-related molecular mechanism in VV, which might be important for VV diagnosis and exploration of potential molecular mechanisms.

Weft-Knitted Spacer Fabric for Highly Stretchable-Compressible Strain Sensor, Supercapacitor, and Joule Heater.

The development of wearable electronic devices has greatly stimulated the research interest of textile-based strain sensors, which can effectively combine functionality with wearability. In this work, the fabrication of highly stretchable and compressible strain sensors from weft-knitted spacer fabric was reported. Carbon nanotubes and polypyrrole were deposited on the surface of fabric via an in situ polymerization approach to reduce the electrical resistance. The as-fabricated WSP-CNT-PPy strain sensor exhibits high electrical conductivity and stable strain-sensing performance under different stretching deformations. The WSP-CNT-PPy strain sensor can be stretched up to 450% and compressed to 60% with a pressure of less than 50 KPa, which can be attributed to the unique loop and interval filament structures. The distinguishing response efficiency of WSP-CNT-PPy can effectively detect faint and strenuous body movements. In addition, the electrochemical behavior of WSP-CNT-PPy was also characterized to study the comprehensive properties. The electro-heating performance was also evaluated for feasible Joule heater applications. This work demonstrates the practicability of WSP-CNT-PPy strain sensor fabric for real-time monitoring in promising wearable garments.

Transcriptomic Analysis Provides Insights into the Differential Effects of Aluminum on Peanut (Arachis hypogaea L.).

In acidic soils, high concentrations of aluminum ions (Al3+) in dissolved form reduce root growth and development of most crops. In addition, Al3+ is also a beneficial element in some plant species in low concentrations. However, the regulatory mechanism of the growth and development of peanut (Arachis hypogaea L.) treated with different concentrations of Al3+ has been rarely studied. In this study, peanut seedlings were treated with AlCl3.18H2O in Hoagland nutrient solution at four different concentrations of Al3+, i.e., 0 (pH 6.85), 1.25 (pH 4.03), 2.5 (pH 3.85), and 5 (pH 3.69) mmol/L, which are regarded as Al0, Al1, Al2, and Al3. The results showed that low concentrations of Al treatment (Al1) promoted peanut growth, while high concentrations of Al treatments (Al2 and Al3) significantly inhibited peanut growth. Compared with the control (Al0), transcriptome analysis showed that the differentially expressed genes (DEGs) of starch and sucrose metabolic pathways were significantly enriched at low concentrations, i.e., Al1 treatment, whereas the expression of AhERD6 (sugar transporter) was significantly up-regulated, and the soluble sugar content was significantly increased. The DEGs of the plant hormone signaling transduction pathway were significantly enriched at high concentrations of Al2 and Al3 treatments, whereas the expression of AhNCED1 (9-cis-epoxycarotenoid dioxygenase) was significantly up-regulated, and the content of ABA was significantly increased. Moreover, the expression of transcription factors (TFs) in peanut was affected by different concentrations of Al. Overall, low concentrations of Al1 promoted peanut growth by increasing soluble sugar content, while high concentrations of Al2 and Al3 inhibited the growth of peanut, induced AhNCED1 gene expression, and increased endogenous ABA content. For peanut, the exposure of Al at low concentrations not only derived an adaptive mechanism to cope with Al stress, but also acted as a stimulator to promote its growth and development.

Lactobacillus plantarum S9 alleviates lipid profile, insulin resistance, and inflammation in high-fat diet-induced metabolic syndrome rats.

Probiotics are considered to play an crucial role in the treatment of high-fat diet (HFD)-induced lipid metabolic diseases, including metabolic syndrome (MS). This study aimed to investigate the effects of Lactobacillus plantarum S9 on MS in HFD-fed rats, and to explore the underlying role of probiotics in the treatment of MS. Sprague-Dawley rats were fed with HFD for 8 weeks, followed by the treatment of L. plantarum S9 for 6 weeks, and The body weight and blood glucose level of rats were detected on time. The results showed that L. plantarum S9 significantly decreased the body weight gain, Lee's index, and liver index. Additionally, L. plantarum S9 reduced the levels of serum lipids and insulin resistance. L. plantarum S9 also decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in liver. Moreover, the serum levels of MS-related inflammatory signaling molecules, including lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α), were significantly elevated. Western blot analysis showed that L. plantarum S9 inhibited the activation of nuclear factor-κB (NF-κB) pathway, decreased the expression level of Toll-like receptor 4 (TLR4), suppressed the activation of inflammatory signaling pathways, and reduced the expression levels of inflammatory factors in HFD-fed rats. Moreover, it further decreased the ratios of p-IκBα/IκBα, p-p65/NF-κB p65, and p-p38/p38. In summary, L. plantarum S9, as a potential functional strain, prevents or can prevent onset of MS.

Dynamic changes in soluble suppression of tumorigenicity 2 levels predict major adverse cardiovascular events in patients with ST­segment elevation myocardial infarction.

Introduction：The predictive value of soluble suppression of tumorigenicity 2 (sST2) for the occurrence of major adverse cardiovascular events (MACEs) in patients with ST­segment elevation myocardial infarction (STEMI) remains unclear. OBJECTIVES: We aimed to investigate the role of sST2 in predicting MACEs in STEMI patients after primary percutaneous coronary intervention (pPCI). PATIENTS AND METHODS: A total of 350 patients were enrolled in this study. The levels of sST2, N­terminal pro-B­type natriuretic peptide (NT­proBNP), cardiac troponin I (TnI), and creatine kinase-MB (CK­MB) were measured on admission as well as 24 hours and 5 days after pPCI. The end point was the incidence of MACEs. RESULTS: Compared with the values on admission, sST2 levels increased 24 hours post pPCI and decreased significantly at day 5 after the procedure in the whole cohort. The pattern of sST2 level changes between the 3 time points was similar in the MACE and MACE­free groups. Notably, the change in the sST2 level from admission to 24 hours post pPCI (Δ1sST2) was significantly higher in the MACE group. After multivariable adjustment, Δ1sST2 was an independent risk factor for MACEs, with an area under the curve of 0.621 (95% CI, 0.547-0.695). Patients with a greater Δ1sST2 had a significantly higher incidence of composite MACEs, coronary revascularization, and cardiac rehospitalization. However, the change in sST2 levels from admission to 5 days post pPCI, as well as the dynamic changes in NT­proBNP, TnI, and CK­MB levels had no predictive value. CONCLUSIONS: The increase in plasma sST2 levels from admission to 24 hours post pPCI has a potential value for independently predicting the incidence of coronary revascularization and cardiac rehospitalization at 1 year in patients with STEMI.

Chondroitin sulfate stimulates the secretion of H2S by Desulfovibrio to improve insulin sensitivity in NAFLD mice.

Hydrogen sulfide (H2S) is a bioactive gas regulating insulin secretion and sensitivity, produced by sulfate-reducing bacteria in the gut. The present study investigated the effect of chondroitin sulfate (CS) treatment, which indirectly increased the H2S production on nonalcoholic fatty liver disease (NAFLD). A 7-week CS supplementation had beneficial effects on body weight gain, liver function, hepatic histology, and serum lipid levels. CS could ameliorate diet-induced insulin resistance and improve insulin sensitivity via the AKT pathway, and modulate gut microbiota composition, especially increased the abundance of Desulfovibrio and elevated levels of hydrogen sulfide (H2S). Collectively, these findings suggested that CS treatment was positively correlated with Desulfovibrio in the gut, and the metabolic H2S flowed into the liver via the gut-liver axis, thereby triggering the AKT signaling pathway and improving insulin resistance. Thus, CS-induced alterations in the gut microbiota seem a promising for ameliorating NAFLD.

MicroRNA-like snoRNA-Derived RNAs (sdRNAs) Promote Castration-Resistant Prostate Cancer.

We have identified 38 specifically excised, differentially expressed snoRNA fragments (sdRNAs) in TCGA prostate cancer (PCa) patient samples as compared to normal prostate controls. SnoRNA-derived fragments sdRNA-D19b and -A24 emerged among the most differentially expressed and were selected for further experimentation. We found that the overexpression of either sdRNA significantly increased PC3 (a well-established model of castration-resistant prostate cancer (CRPC)) cell proliferation, and that sdRNA-D19b overexpression also markedly increased the rate of PC3 cell migration. In addition, both sdRNAs provided drug-specific resistances with sdRNA-D19b levels correlating with paclitaxel resistance and sdRNA-24A conferring dasatinib resistance. In silico and in vitro analyses revealed that two established PCa tumor suppressor genes, CD44 and CDK12, represent targets for sdRNA-D19b and sdRNA-A24, respectively. This outlines a biologically coherent mechanism by which sdRNAs downregulate tumor suppressors in AR-PCa to enhance proliferative and metastatic capabilities and to encourage chemotherapeutic resistance. Aggressive proliferation, rampant metastasis, and recalcitrance to chemotherapy are core characteristics of CRPC that synergize to produce a pathology that ranks second in cancer-related deaths for men. This study defines sdRNA-D19b and -A24 as contributors to AR-PCa, potentially providing novel biomarkers and therapeutic targets of use in PCa clinical intervention.

The Index of Esophageal Cancer Related Ischemic Stroke: A Retrospective Patient Control Study.

Purpose: To investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke. Methods: We retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden's J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors. Results: A total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051-1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002-1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628-3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index. Conclusion: It was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.

Lactobacillus plantarum DP189 Reduces α-SYN Aggravation in MPTP-Induced Parkinson's Disease Mice via Regulating Oxidative Damage, Inflammation, and Gut Microbiota Disorder.

This study aimed to evaluate the attenuating effect of Lactobacillus plantarum DP189 on α-synuclein (α-SYN) aggregates in the substantia nigra (SN) of Parkinson's disease (PD) mice via 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced. Our results indicated that L. plantarum DP189 increased the levels of superoxide dismutase (SOD), glutathione peroxide (GSH-Px), and interleukin-10 (IL-10) and decreased the levels of malondialdehyde (MDA), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß). Moreover, L. plantarum DP189 reduced the α-SYN accumulation in SN. Mechanistically, L. plantarum DP189 activated the expression of nuclear factor erythroid 2-related factor (Nrf2)/ARE and PGC-1α pathways and suppressed the NLRP3 inflammasome. Furthermore, fecal analysis showed that L. plantarum DP189 reshaped the gut microbiota in PD mice by reducing the number of pathogenic bacteria (Proteobacteria and Actinobacteria) and increased the abundance of probiotics (Lactobacillus and Prevotella). Our results suggested that L. plantarum DP189 could delay the neurodegeneration caused by the accumulation of α-SYN in the SN of PD mice via suppressing oxidative stress, repressing proinflammatory response, and modulating gut microbiota.

Lactobacillus plantarum DP189 prevents cognitive dysfunction in D-galactose/AlCl3 induced mouse model of Alzheimer's disease via modulating gut microbiota and PI3K/Akt/GSK-3ß signaling pathway.

Probiotic intervention has beneficial effects on host brain function and behavior via regulating microbiota-gut-brain axis; however, the underlying mechanism is not yet understood. Herein, we investigated that the effects of Lactobacillus plantarum DP189 (DP189) administration in preventing cognitive dysfunction and pathology of Alzheimer's disease (AD) in D-galactose (D-gal) and AlCl3-induced AD model mice. After L. plantarum DP189 intervention for 10 weeks, we assessed cognitive behavior, neurotransmitter expression, histological changes, microbial communities, and the mechanisms underlying the disease in AD model mice. The results showed that L. plantarum DP189 intervention prevented cognitive dysfunction by behavioral test. Increased levels of serotonin, dopamine, and gamma-aminobutyric acid positively affected the pathological processes by ameliorating neuronal damage, beta-amyloid deposition, and tau pathology. L. plantarum DP189 intervention simultaneously modulated the gut microbial communities to alleviate gut dysbiosis. Moreover, L. plantarum DP189 inhibited tau hyperphosphorylation by regulating the PI3 K/Akt/GSK-3ß pathway. These findings indicated that L. plantarum DP189 intervention is a promising therapeutic strategy to prevent the onset and development of AD.

RNA-seq study reveals the signaling and carbohydrate metabolism regulators involved in dormancy release by warm stratification in Paris polyphylla var. yunnanensis.

Long-term seed dormancy of Paris polyphylla var. yunnanensis limits its large-scale artificial cultivation. It is crucial to understand the regulatory genes involving in dormancy release for artificial cultivation in this species. In this study, seed dormancy of Paris polyphylla var. yunnanensis was effectively released by warm stratification (20°C) for 90 days. The freshly harvested seeds (dormant) and stratified seeds (non-dormant) were used to sequence, and approximately 147 million clean reads and 28,083 annotated unigenes were detected. In which, a total of 10,937 differentially expressed genes (DEGs) were identified between dormant and non-dormant seeds. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) classification revealed that the majority unigenes involved in signaling transduction and carbohydrate metabolism. Of them, the signaling transduction-related DEGs were mainly hormones-, reactive oxygen species (ROS)-, and transcription factor (TF)-related genes. The largest number of signaling transduction-related DEGs were auxin-responsive genes (SAUR, AUX/IAA, and ARF) and AP2-like ethylene-responsive transcription factor (ERF/AP2). Moreover, at least 29 DEGs such as α-amylase (AMY), ß-glucosidase (Bglb/Bglu/Bglx), and endoglucanase (Glu) were identified involving in carbohydrate metabolism. These identified genes provide a valuable resource to investigate the molecular basis of dormancy release in Paris polyphylla var. yunnanensis.