Stable Oxyhalide-Nitride Fast Ionic Conductors for All-Solid-State Li Metal Batteries.

Rechargeable all-solid-state lithium metal batteries (ASSLMBs) utilizing inorganic solid-state electrolytes (SSEs) are promising for electric vehicles and large-scale grid energy storage. However, the Li dendrite growth in SSEs still constrains the practical utility of ASSLMBs. To achieve a high dendrite-suppression capability, SSEs must be chemically stable with Li, possess fast Li transfer kinetics, and exhibit high interface energy. Herein, a class of low-cost, eco-friendly, and sustainable oxyhalide-nitride solid electrolytes (ONSEs), denoted as LixNyIz-qLiOH (where x = 3y + z, 0 ≤ q ≤ 0.75), is designed to fulfill all the requirements. As-prepared ONSEs demonstrate chemically stable against Li and high interface energy (>43.08 meV Å-2), effectively restraining Li dendrite growth and the self-degradation at electrode interfaces. Furthermore, improved thermodynamic oxidation stability of ONSEs (>3 V vs Li+/Li, 0.45 V for pure Li3N), arising from the increased ionicity of Li─N bonds, contributes to the stability in ASSLMBs. As a proof-of-concept, the optimized ONSEs possess high ionic conductivity of 0.52 mS cm-1 and achieve long-term cycling of Li||Li symmetric cell for over 500 h. When coupled with the Li3InCl6 SSE for high-voltage cathodes, the bilayer oxyhalide-nitride/Li3InCl6 electrolyte imparts 90% capacity retention over 500 cycles for Li||1 mAh cm-2 LiCoO2 cells.

Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity.

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

Pd(II)-Catalyzed Desymmetrizing gem-Dimethyl C(sp3)-H Alkenylation/Aza-Wacker Cyclization Directed by PIP Auxiliary.

Desymmetrization of gem-dimethyl groups has been developed as an efficient pathway to achieve asymmetric C(sp3)-H functionalization. Herein, we described a Pd(II)-catalyzed desymmetrizing gem-dimethyl C(sp3)-H alkenylation/aza-Wacker cyclization directed by a bidentate 2-pyridinylisopropyl auxiliary. Chiral α-methyl γ-lactams were obtained in good yields (up to 82%) and high enantioselectivities (up to 91.5% ee).

Current status and breakthroughs in treating advanced non-small cell lung cancer with EGFR exon 20 insertion mutations.

Recently, targeted therapy and immunotherapy have emerged as effective treatment options for non-small cell lung cancer (NSCLC). This progress has been facilitated by the rapid development of diagnostic and therapeutic technologies and the continuous research and development of new drugs, leading to a new era in precision medicine for NSCLC. This is a breakthrough for patients with common mutations in the human epidermal growth factor receptor (EGFR) gene in NSCLC. Consequently, the use of targeted drugs has significantly improved survival. Nevertheless, certain rare genetic mutations are referred to as EGFR exon 20 insertion (ex20ins) mutations, which differ in structure from conventional EGFR gene mutations, namely, exon 19 deletion mutations (19-Del) and exon 21 point mutations. Owing to their distinct structural characteristics, patients harboring these EGFR ex20ins mutations are unresponsive to traditional tyrosine kinase inhibitor (TKI) therapy. This particular group of patients did not fall within the scope of their applicability. However, the activating A763_Y764insFQEA mutation elicits a more pronounced response than mutations in the near and far regions of the C-helix immediately following it and should, therefore, be treated differently. Currently, there is a lack of effective treatments for EGFR ex20ins mutations NSCLC. The efficacy of chemotherapy has been relatively favorable, whereas the effectiveness of immunotherapy remains ambiguous owing to inadequate clinical data. In addition, the efficacy of the first- and second-generation targeted drugs remains limited. However, third-generation and novel targeted drugs have proven to be effective. Although novel EGFR-TKIs are expected to treat EGFR ex20ins mutations in patients with NSCLC, they face many challenges. The main focus of this review is on emerging therapies that target NSCLC with EGFR ex20ins and highlight major ongoing clinical trials while also providing an overview of the associated challenges and research advancements in this area.

Unrecoverable lattice rotation governs structural degradation of single-crystalline cathodes.

Transitioning from polycrystalline to single-crystalline nickel-rich cathodes has garnered considerable attention in both academia and industry, driven by advantages of high tap density and enhanced mechanical properties. However, cathodes with high nickel content (>70%) suffer from substantial capacity degradation, which poses a challenge to their commercial viability. Leveraging multiscale spatial resolution diffraction and imaging techniques, we observe that lattice rotations occur universally in single-crystalline cathodes and play a pivotal role in the structure degradation. These lattice rotations prove unrecoverable and govern the accumulation of adverse lattice distortions over repeated cycles, contributing to structural and mechanical degradation and fast capacity fade. These findings bridge the previous knowledge gap that exists in the mechanistic link between fast performance failure and atomic-scale structure degradation.

Comprehensive prognostic and immunological analysis of Cullin2 in pan-cancer and its identification in hepatocellular carcinoma.

BACKGROUND: As a member of the Cullin family, Cullin2 (CUL2) is involved in the development and spread of different types of cancers. However, the precise role of CUL2 in human cancer remains largely elusive. METHODS: In this study, various databases were applied to observe the CUL2 expression. Kaplan-Meier and Spearman correlation analyses were employed to investigate the potential links between CUL2 level, patient prognosis, and the infiltration of immune cells. In addition, the association between CUL2 and the efficacy of immunotherapy in an immunotherapy cohort was investigated. Moreover, the expression and distribution of CUL2 in cells were observed using the Human Protein Atlas (THPA) database. Finally, clinical tissue specimens and in vitro function assays were conducted to validate the expressions and effects of CUL2 on the biological functions in hepatocellular carcinoma (HCC) cells. RESULTS: While there are variations in CUL2 expression across different organs and cell types, it is notably upregulated in a majority of tumor tissues. In addition, CUL2 gene mutations are common in multiple cancers with low mutation rates and CUL2 is closely related to the prognosis of some cancer's patients, some immune regulatory factors, TMB, MSI, MMR genes, and DNA methylation. Further, our results found that downregulating CUL2 inhibits the proliferation, and migration abilities. CONCLUSIONS: The expression of CUL2 has an impact on the prognosis of various tumors, and this correlation is particularly noteworthy due to its significant association with the infiltration of immune cells within tumors. CUL2 was an oncogene contributing to the progression of HCC.

Quercetin, a natural flavonoid, protects against hepatic ischemia-reperfusion injury via inhibiting Caspase-8/ASC dependent macrophage pyroptosis.

INTRODUCTION: Hepatic ischemia-reperfusion injury (IRI) is an inevitable adverse event following liver surgery, leading to liver damage and potential organ failure. Despite advancements, effective interventions for hepatic IRI remain elusive, posing a significant clinical challenge. The innate immune response significantly contributes to the pathogenesis of hepatic IRI by promoting an inflammatory cytotoxic cycle. We have reported that blocking GSDMD-induced pyroptosis in innate immunity cells protected hepatic IRI from inflammatory injury. However, the search for effective pyroptosis inhibitors continues. OBJECTIVES: This study aims to evaluate whether quercetin, a natural flavonoid, can inhibit GSDMD-induced pyroptosis and mitigate hepatic IRI. METHODS: We established the hepatic IRI murine model and cellular pyroptosis model to evaluate the efficacy of quercetin. RESULTS: Quercetin effectively alleviated hepatic IRI-induced tissue necrosis and inflammation. We found that during hepatic IRI, the cleavage of GSDMD occurred in hepatic macrophages, but not in other non-parenchymal cells. Quercetin inhibited the cleavage of GSDMD in macrophages. Moreover, we found that quercetin blocked the ASC assembly to inhibit the formation of NLRP3 inflammasomes and AIM2 inflammasomes, suppressing macrophage pyroptosis. Co-immunoprecipitation experiments confirmed that quercetin inhibited the interaction between ASC and Caspase-8, which is the mechanism of ASC complex and inflammasome formation. Overexpression of Caspase-8 abolished the anti-pyroptosis effect of quercetin in NLRP3 and AIM2 inflammasome signaling. Furthermore, we found that the hepatoprotective activity of quercetin was reduced in myelocytic GSDMD-deficient mice. CONCLUSION: Our findings suggest that quercetin has beneficial effects on hepatic IRI. Quercetin could attenuate hepatic IRI and target inhibition of macrophage pyroptosis via blocking Caspase-8/ASC interaction. We recommend that quercetin might serve as a targeted approach for the prevention and personalized treatment of hepatic IRI in perioperative patients.

Colon-targeted oral nanoliposomes loaded with psoralen alleviate DSS-induced ulcerative colitis.

Oral administration, while convenient, but complex often faces challenges due to the complexity of the digestive environment. In this study, we developed a nanoliposome (NLP) encapsulating psoralen (P) and coated it with chitosan (CH) and pectin (PT) to formulate PT/CH-P-NLPs. PT/CH-P-NLPs exhibit good biocompatibility, superior to liposomes loaded with psoralen and free psoralen alone. After oral administration, PT/CH-P-NLPs remain stable in the stomach and small intestine, followed by a burst release of psoralen after reaching the slightly alkaline and gut microbiota-rich colon segment. In the DSS-induced ulcerative colitis of mice, PT/CH-P-NLPs showed significant effects on reducing inflammation, mitigating oxidative stress, protecting the integrity of the colon mucosal barrier, and modulating the gut microbiota. In conclusion, the designed nanoliposomes demonstrated the effective application of psoralen in treating ulcerative colitis.

Priming of hippocampal microglia by IFN-γ/STAT1 pathway impairs social memory in mice.

Social behavior is inextricably linked to the immune system. Although IFN-γ is known to be involved in social behavior, yet whether and how it encodes social memory remains unclear. In the current study, we injected with IFN-γ into the lateral ventricle of male C57BL/6J mice, and three-chamber social test was used to examine the effects of IFN-γ on their social preference and social memory. The morphology of microglia in the hippocampus, prelimbic cortex and amygdala was examined using immunohistochemistry, and the phenotype of microglia were examined using immunohistochemistry and enzyme-linked immunosorbent assays. The IFN-γ-injected mice were treated with lipopolysaccharide, and effects of IFN-γ on behavior and microglial responses were evaluated. STAT1 pathway and microglia-neuron interactions were examined in vivo or in vitro using western blotting and immunohistochemistry. Finally, we use STAT1 inhibitor or minocycline to evaluated the role of STAT1 in mediating the microglial priming and effects of primed microglia in IFN-γ-induced social dysfunction. We demonstrated that 500 ng of IFN-γ injection results in significant decrease in social index and social novelty recognition index, and induces microglial priming in hippocampus, characterized by enlarged cell bodies, shortened branches, increased expression of CD68, CD86, CD74, CD11b, CD11c, CD47, IL-33, IL-1ß, IL-6 and iNOS, and decreased expression of MCR1, Arg-1, IGF-1 and BDNF. This microglia subpopulation is more sensitive to LPS challenge, which characterized by more significant morphological changes and inflammatory responses, as well as induced increased sickness behaviors in mice. IFN-γ upregulated pSTAT1 and STAT1 and promoted the nuclear translocation of STAT1 in the hippocampal microglia and in the primary microglia. Giving minocycline or STAT1 inhibitor fludarabin blocked the priming of hippocampal microglia induced by IFN-γ, ameliorated the dysfunction in hippocampal microglia-neuron interactions and synapse pruning by microglia, thereby improving social memory deficits in IFN-γ injected mice. IFN-γ initiates STAT1 pathway to induce priming of hippocampal microglia, thereby disrupts hippocampal microglia-neuron interactions and neural circuit link to social memory. Blocking STAT1 pathway or inhibiting microglial priming may be strategies to reduce the effects of IFN-γ on social behavior.

Successful management of postpartum venous thrombosis following splenectomy for traumatic splenic rupture: a case report.

Traumatic splenic rupture is rare in pregnant women; and multiple venous thromboses of the portal vein system, inferior vena cava and ovarian vein after caesarean section and splenectomy for splenic rupture has not been previously reported. This case report describes a case of multiple venous thromboses after caesarean section and splenectomy for traumatic splenic rupture in late pregnancy. A 34-year-old G3P1 female presented with abdominal trauma at 33+1 weeks of gestation. After diagnosis of splenic rupture, she underwent an emergency caesarean section and splenectomy. Multiple venous thromboses developed during the recovery period. The patient eventually recovered after anticoagulation therapy with low-molecular-weight heparin and warfarin. These findings suggest that in patients that have had a caesarean section and a splenectomy, which together might further increase the risk of venous thrombosis, any abdominal pain should be thoroughly investigated and thrombosis should be ruled out, including the possibility of multiple venous thromboses. Anticoagulant therapy could be extended after the surgery.

A Real-Time Monitoring Method for Selective Laser Melting of TA1 Materials Based on Radiation Detection of a Molten Pool.

Selective laser melting (SLM) technology is a promising additive manufacturing technology. However, due to the numerous influencing factors in this complex process, a reliable real-time method is needed to monitor the forming process of SLM. The molten pool is the smallest forming unit in the SLM process, the consistency of which can effectively reflect the quality of the printing process. By using a coaxial optical path structure and a compound amplifier circuit, high-speed acquisition of molten pool radiation can be realized. Next, single factor analysis and orthogonal experimentation were used to investigate the influence levels of key process parameters on the radiation of molten pool. In addition, numerical simulation was carried out with the same parameter setting schemes, the results of which are consistent with those in radiation detection experiments. It is shown that the laser power has the greatest effect on the radiation of the molten pool, while the scanning speed and the hatch spacing have little effect on the radiation. Finally, the positioning experiment involving the small hole structure was carried out, and the experimental results showed that the device could accurately locate the position coordinates of the given hole structure.

Terf2ip deficiency accelerates non-alcoholic steatohepatitis through regulating lipophagy and fatty acid oxidation via Sirt1/AMPK pathway.

BACKGROUND & AIMS: Our previous study has demonstrated that Telomeric repeat-binding factor 2-interacting protein 1(Terf2ip), played an important role in hepatic ischemia reperfusion injury. This study is aimed to explore the function and mechanism of Terf2ip in non-alcoholic steatohepatitis (NASH). METHODS: The expression of Terf2ip was detected in liver tissue samples obtained from patients diagnosed with NASH. Mice NASH models were constructed by fed with high-fat diet (HFD) or methionine/choline deficient diet (MCD) in Terf2ip knockout and wild type (WT) mice. To further investigate the role of Terf2ip in NASH, adeno-associated viruses (AAV)-Terf2ip was administrated to mice. RESULTS: We observed a significant down-regulation of Terf2ip levels in the livers of NASH patients and mice NASH models. Terf2ip deficiency was associated with an exacerbation of hepatic steatosis in mice under HFD or MCD. Additionally, Terf2ip deficiency impaired lipophagy and fatty acid oxidation (FAO) in NASH models. Mechanically, we discovered that Terf2ip bound to the promoter region of Sirt1 to regulate Sirt1/AMPK pathway activation. As a result, Terf2ip deficiency was shown to inhibit lipophagy through the AMPK pathway, while the activation of Sirt1 alleviated steatohepatitis in the livers of mice. Finally, re-expression of Terf2ip in hepatocyes alleviated liver steatosis, inflammation, and restored lipophagy. CONCLUSIONS: These results revealed that Terf2ip played a protective role in the progression of NASH through regulating lipophagy and FAO by binding to Sirt1 promoter. Our findings provided a potential therapeutic target for the treatment of NASH.

Quality evaluation and identification of Houttuynia cordata bleached with sodium metabisulfite based on whole spectrum metabolomics.

Houttuynia Cordata (HC) is a widely distributed plant in Asia and is used extensively for both food and medicinal purposes. A preliminary investigation found that HC is often bleached with sodium metabisulfite solution during its field processing, leading to health risks. In this study, the effects of sodium metabisulfite on the quality of HC were comprehensively evaluated using volatile and non-volatile targeted metabolomic methods. The results revealed a positive correlation between the extent of chemical composition changes and the bleaching time. These notable changes mainly occurred at the initial stage of bleaching. Subsequently, an untargeted UPLC/Q-TOF MS method was used to explore the potential chemical bleaching markers in bleached HC. The marker 1-hydroxy-3-oxodecane-1-sulfonic acid was subsequently prepared, isolated, and identified. Market sample verification further validated the accuracy and effectiveness of this marker.

Sub-Band Assisted Z-Scheme for Effective Non-Sacrificial H2O2 Photosynthesis.

Photosynthesis of H2O2 from earth-abundant O2 and H2O molecules offers an eco-friendly route for solar-to-chemical conversion. The persistent challenge is to tune the photo-/thermo- dynamics of a photocatalyst toward efficient electron-hole separation while maintaining an effective driving force for charge transfer. Such a case is achieved here by way of a synergetic strategy of sub-band-assisted Z-Scheme for effective H2O2 photosynthesis via direct O2 reduction and H2O oxidation without a sacrificial agent. The optimized SnS2/g-C3N4 heterojunction shows a high reactivity of 623.0 µmol g-1 h-1 for H2O2 production under visible-light irradiation (λ > 400 nm) in pure water, ≈6 times higher than pristine g-C3N4 (100.5 µmol g-1 h-1). Photodynamic characterizations and theoretical calculations reveal that the enhanced photoactivity is due to a markedly promoted lifetime of trapped active electrons (204.9 ps in the sub-band and >2.0 ns in a shallow band) and highly improved O2 activation, as a result of the formation of a suitable sub-band and catalytic sites along with a low Gibbs-free energy for charge transfer. Moreover, the Z-Scheme heterojunction creates and sustains a large driving force for O2 and H2O conversion to high value-added H2O2.

Investigation of epidemiological and clinical characteristics of people infected with SARS-CoV-2 during the second pandemic of COVID-19 in Chengdu, China.

Objective: This study investigated the epidemiological and clinical characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients during the second pandemic of COVID-19 (coronavirus disease of 2019) in Chengdu, China. Furthermore, the differences between first infection and re-infection cases were also compared and analyzed to provide evidence for better prevention and control of SARS-CoV-2 re-infection. Methods: An anonymous questionnaire survey was conducted using an online platform (wjx.cn) between May 20, 2023 to September 12, 2023. Results: This investigation included 62.94% females and 32.97% of them were 18-30 years old. Furthermore, 7.19-17.18% of the participants either did not receive vaccination at all or only received full vaccination, respectively. Moreover, 577 (57.64%) participants were exposed to cluster infection. The clinical manifestations of these patients were mainly mild to moderate; 78.18% of participants had a fever for 1-3 days, while 37.84% indicated a full course of disease for 4-6 days. In addition, 40.66% of the participants had re-infection and 72.97% indicated their first infection approximately five months before. The clinical symptoms of the first SARS-CoV-2 infection were moderate to severe, while re-infection indicated mild to moderate symptoms (the severity of symptoms other than diarrhea and conjunctival congestion had statistically significant differences) (p < 0.05). Moreover, 70.53 and 59.21% of first and re-infection cases had fever durations of 3-5 and 0-2 days, respectively. Whereas 47.91 and 46.40% of first and re-infection cases had a disease course of 7-9 and 4-6 days. Conclusion: The SARS-CoV-2 infected individuals in Chengdu, China, during the second pandemic of COVID-19 had mild clinical symptoms and a short course of disease. Furthermore, compared with the first infection, re-infection cases had mild symptoms, low incidences of complications, short fever duration, and course of disease.

Enantioselectivity regulation of antibody against chiral herbicide metolachlor based on interaction at chiral center.

Enantioselective antibodies have emerged as great potential biomaterials in the fields of immunoassays and chiral separation. However, cross-reactivity of antibodies to the distomer may severely restrict the application. Comprehending the interaction mechanism between antibodies and enantiomers could be beneficial to produce superior enantioselective antibodies. In this study, a pair of recombinant antibodies (RAbs) against metolachlor enantiomers at chiral carbon (αSS-MET and αSR-MET) were generated and characterized. The αSS-MET-RAb and αSR-MET-RAb showed comparable sensitivity and specificity to the parental monoclonal antibodies by icELISA, with IC50 values of 3.45 and 223.77 ng/mL, respectively. Moreover, the complex structures of RAbs and corresponding eutomer were constructed and analyzed, and site-specific mutagenesis was utilized to verify the reliability of the enantioselective mechanism elucidated. It demonstrated that the strength of the interaction between the chiral center region of eutomer and the antibody was the key factor for the enantioselectivity of antibody. Increasing this interaction could limit the conformational adjustment of the distomer in a specific chiral recognition cavity, thus decreasing the affinity of the antibody to the distomer. This work provided the in-depth analysis of enantioselective mechanism for two RAbs and paved the way to regulate antibody enantioselective performance for immunoassays of chiral compounds.

Exploring the therapeutic potential of porphyran extracted from Porphyra haitanensis in the attenuation of DSS-induced intestinal inflammation.

Ulcerative colitis is a chronic, spontaneous inflammatory bowel disease that primarily affects the colon. This study aimed to explore how Porphyra haitanensis porphyran (PHP) modulates the immune response and the associated mechanisms that alleviate dextran sulphate sodium-induced colitis in mice. Histological assessments via H&E staining and AB-PAS staining revealed that PHP intervention partially restored the number of goblet cells and improved intestinal mucosal function. Immunohistochemical and Western blot analyses of claudin-1, occludin, and MUC-2 demonstrated that PHP could repair the intestinal barrier and reduce colon damage by upregulating the expression of these proteins. PHP intervention was associated with a decrease in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokine expression. Moreover, the expression of proteins involved in intestinal immune homing, such as CCR-9, CCL-25, MAdCAM-1, and α4ß7, was significantly suppressed in response to PHP treatment. Conversely, PHP upregulates the expression of CD40 and TGF-ß1, both of these can promote healing and reduce inflammation in the gut lining. This study demonstrates that PHP can ameliorate ulcerative colitis by enhancing the intestinal barrier and modulating immune responses. These findings offer valuable insights into the potential utility of P. haitanensis as a promising natural product for managing ulcerative colitis.

Exploring trade-offs between residential and industrial functions in rural areas and their ecological impacts across transitioning agricultural systems: Evidence from the metropolitan suburbs of China.

The rapid transition of agricultural systems substantially affects residential and industrial land use systems in rural areas, often generating spatiotemporal trade-offs between residential and industrial functions and producing considerable ecological impacts, which has thus far not been well understood. We conduct an indicator-based assessment of transitioning agriculture systems, and then links the transitioning agricultural systems to trade-offs between residential and industrial functions from 2005 to 2020 by using a case study-the metropolitan suburbs of Beijing, China. Also, the associated ecological impacts of the trade-offs are characterized based on the calculation of the ecological quality index (EQI) and ecological contribution rate. The results show that trade-offs between residential and industrial functions in the metropolitan suburbs have gradually adapted to the different agricultural systems in transition, which can be characterized by increasing industrial function as well as declining residential function, together with the diversification of land use into a mixed pattern. Additionally, along with the transitioning process comes a U shape of the ecological quality curve, which indicates that relentless industrial sprawl into regions where the agricultural system has a low capacity for technology, as well as decay in rural areas attributed to a rural exodus and industrial decline in semi-subsistence agricultural areas, even cause ecological degradation. In general, trade-offs between residential and industrial functions (especially for the non-agricultural production function) in rural areas could partially and temporally generate unfavorable ecological impacts, but it seems to be a favorable phenomenon to promote ecological quality in the long term. Therefore, to achieve rural sustainable planning, it is necessary for land use management to observe the trade-offs between residential and industrial functions while avoiding negative impacts, such as low-density land use patterns, disordered land use functions, and eco-environmental deterioration. Such effective strategies can contribute to the feasible implementation of policies aiming to achieve the compatible development of liveable residences, highly efficient industrial production, and eco-friendly operations in rural areas.

Hypoglycemic Effects of Gynura divaricata (L.) DC Polysaccharide and Action Mechanisms via Modulation of Gut Microbiota in Diabetic Mice.

Aiming to provide a basis for the application of Gynura divaricata (L.) DC polysaccharide (GDP) in functional foods, the hypoglycemic effects of GDP, and action mechanisms, were investigated. Results showed that GDP effectively inhibited α-glucosidase and remarkably increased the glucose absorption, glycogen content, and pyruvate kinase and hexokinase activities of insulin-resistant HepG2 cells, indicating its potent in vitro hypoglycemic effect. In streptozotocin-induced type 2 diabetes mice, GDP significantly improved various glycolipid metabolism-related indices in serum and liver, e.g., fasting blood glucose, oral glucose tolerance, glycosylated serum protein content, serum insulin level, antioxidant enzyme activities, TG, TC, LDL-C, and HDL-C levels, and hepatic glycogen content, and recovered the structure of gut microbiota to the normal level. It was also found that GDP significantly affected the expression of related genes in the PI3K/Akt, AMPK, and GS/GSK-3ß signaling pathways. Therefore, GDP regulates blood glucose possibly by directly inhibiting α-glucosidase, exerting antioxidant activity, and regulating intestinal microbiota.

Isotemporal Substitution Modeling on Sedentary Behaviors and Physical Activity With Mortality Among People With Different Diabetes Statuses: A Prospective Cohort Study From the National Health and Nutrition Examination Survey Analysis 2007-2018.

BACKGROUND: To assess the associations of replacing sedentary behavior with different types of physical activity with mortality among the US adults of varying diabetes statuses. METHODS: This prospective cohort study included 21,637 participants (mean age, 48.5 y) from the National Health and Nutrition Examination Survey 2007-2018. Physical activity including leisure-time moderate-vigorous-intensity activity (MVPA), walking/bicycling, worktime MVPA, and sedentary behavior. We conducted an isotemporal substitution analysis using Cox regression to estimate the associations between replacements and mortality risks. RESULTS: We found significant protective associations between replacing 30 minutes per day sedentary behavior with 3 types of physical activity and all-cause, cardiovascular disease (CVD) mortality risk (except worktime MVPA for CVD mortality) among total participants, with hazard ratio (HR; 95% confidence interval [CI]) ranging from 0.86 (0.77-0.95) to 0.96 (0.94-0.98). Among participants with diagnosed diabetes, replacing sedentary behavior with leisure-time MVPA was associated with a lower all-cause mortality risk (HR 0.81, 95% CI, 0.70-0.94), which was also observed in other subgroups, with HRs (95% CI) ranging from 0.87 (0.80-0.94) to 0.89 (0.81-0.99). Among those with prediabetes/undiagnosed diabetes, replacing sedentary behavior with walking/bicycling was associated with lower CVD mortality risk, and replacement to work-time MVPA was associated with lower all-cause and CVD mortality risk, with HRs (95% CI) ranging from 0.72 (0.63-0.83) to 0.96 (0.92-0.99). CONCLUSIONS: Replacing sedentary behaviors with 30 minutes per day leisure-time MVPA was associated with lower all-cause mortality, regardless of diabetes statuses. Among people with prediabetes/undiagnosed diabetes, walking/bicycling was additionally associated with lower CVD mortality, and worktime MVPA was associated with lower all-cause and CVD mortality.