An in-situ versatile screening method for identifying SVOC sources in indoor environments.

Indoor semivolatile organic compounds (SVOCs) pose a substantial threat to human health. However, identifying the sources of these emissions has been challenging owing to the scarcity of convenient and practical on-site methodologies. Herein, a novel method for source screening was proposed using aluminum silicate sampling strips to adsorb SVOCs from the surface air of indoor materials. The adsorbed SVOC levels indicate the emission intensity of these materials into indoor environments. Additionally, compact sampling strips can be readily fixed to any vertical surface using a static sticker, facilitating the characterization of various materials in practical settings. Laboratory-simulated experiments demonstrated the capability of the proposed method to differentiate between source and non-source materials within a 10-cm distance in the same space. In practical scenarios, the primary emission sources identified via this method exhibited a consistent correlation with the contents of the corresponding materials obtained from the traditional solvent-extraction method. As the adsorbed SVOCs were directly transferred to a GC-MS through thermal desorption instead of the solvent-extraction procedure, the proposed method demonstrated several-fold improvements in analytical sensitivity and efficiency. Using this versatile screening technique, some emerging and important SVOC species were identified within specific indoor materials. Eliminating these sources has been demonstrated as an effective approach to mitigate SVOC pollution. Overall, the proposed method offers a powerful tool for managing indoor pollutants and safeguarding human health.

Rocaglamide promotes infiltration and differentiation of T cells and coordinates with PD-1 inhibitor to overcome checkpoint resistance in multiple tumor models.

Tumor-infiltrating lymphocyte (TIL) deficiency is the most conspicuous obstacle to limit the cancer immunotherapy. Immune checkpoint inhibitors (ICIs), such as anti-PD-1 antibody, have achieved great success in clinical practice. However, due to the limitation of response rates of ICIs, some patients fail to benefit from monotherapy. Thus, novel combination therapy that could improve the response rates emerges as new strategies for cancer treatment. Here, we reported that the natural product rocaglamide (RocA) increased tumor-infiltrating T cells and promoted Th17 differentiation of CD4+ TILs. Despite RocA monotherapy upregulated PD-1 expression of TILs, which was considered as the consequence of T cell activation, combining RocA with anti-PD-1 antibody significantly downregulated the expression of PD-1 and promoted proliferation of TILs. Taken together, these findings demonstrated that RocA could fuel the T cell anti-tumor immunity and revealed the remarkable potential of RocA as a therapeutic candidate when combining with the ICIs.

Gully regulates snowmelt runoff, sediment and nutrient loss processes in Mollisols region of Northeast China.

Gully is a prominent indicator of land degradation in agroecosystems, functioning as a crucial pathway connecting upslopes to downstream channels. However, little is known about how gully regulates runoff, sediment, and nutrient loss processes in the catchment during snowmelt. In this study, we monitored these processes in situ at both the gully head (the upslope accumulated catchment of the gully head, CGH) and outlet of two representative and typical gully-dominated catchments (F1 and F2) during snowmelt in Mollisols region of Northeast China. Our results showed that runoff discharge of CGH and outlet exhibited a multi-peak trend during snowmelt, driven by the transition from snow melting to soil thawing. This transition resulted in distinct runoff patterns in both CGH and outlet, with significant differences in their response to air temperature. The total runoff yield of CGH accounted for 57.8 % in F1 and 40.6 % in F2 of the total runoff yield of the outlet. Notably, the peak sediment concentration displayed a marked lag compared to the peak runoff discharge, primarily dominated by the increased sensitivity of gully erosion after the thawing of gully slopes. Gully erosion was the main source of sediment yield in the catchment, contributing 98.2 % in F1 and 96.6 % in F2. Furthermore, nutrient concentrations exhibited a decreasing trend during snowmelt. The comparison of high nutrient concentrations in CGH and relatively low nutrient concentrations in outlet highlighted the gully's role in intercepting and diluting runoff nutrients. Hysteresis analysis confirmed the differential contribution of CGH and gully to nutrient sources. CGH accounting for 50.9 % and 93.3 % of runoff TN and runoff TP loss, while contributing only 8.3 % and 5.8 % to sediment TN and sediment TP loss, respectively. These findings offer valuable insights for effective erosion control and nonpoint source pollution management in gully-dominated agroecosystems during snowmelt.

LncRNA Gm15834 Aggravates Cardiac Hypertrophy by Interacting with Sam68 and Activating NF-κB Mediated Inflammation.

BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

Traditional Chinese Medicine for Cancer Treatment.

In recent years, due to advancements in medical conditions and the development of scientific research, the fundamental research of TCM antitumor treatments has progressed from the cellular level to the molecular and genetic levels. Previous studies have demonstrated the significant role of traditional Chinese medicine (TCM) in antitumor therapy through various mechanisms and pathways. Its mechanism of action is closely associated with cancer biology across different stages. This includes inhibiting tumor cell proliferation, blocking invasion and metastasis to surrounding tissues, inducing tumor cell apoptosis, inhibiting tumor angiogenesis, regulating immune function, maintaining genome stability, preventing mutation, and regulating cell energy metabolism. The use of TCM for eliciting antitumor effects not only has a good therapeutic effect and low side effects, it also provides a solid theoretical basis for clinical treatment and medication. This paper reviews the mechanism of the antitumor effects of TCM based on tumor characteristics. Through our review, we found that TCM not only directly inhibits tumors, but also enhances the body's immunity, thereby indirectly inducing an antitumor effect. This function aligns with the TCM theory of "strengthening the body's resistance to eliminate pathogenic factors". Furthermore, TCM will play a significant role in tumor treatment in clinical settings.

A lost piece of the puzzle of the alkane cracking mechanism: a carbanion pathway on a solid base catalyst.

The alkane cracking mechanism has been a subject of intense scrutiny, with carbonium and free radical mechanisms being two well-established pathways which correlate to solid acid catalysis and thermal cracking, respectively. However, despite an understanding of these two mechanisms, certain intricacies remain unexplored, especially when it comes to alternative reaction routes over solid base materials. This gap in the knowledge hinders optimization of the desired product selectivity of alkane cracking processes. In this work, solid superbases were first prepared by impregnation of NaNO3 on MgO. The Na/MgO catalysts were characterized by XRD, BET, XPS and CO2-TPD techniques. To investigate the role of solid base materials, propane cracking was conducted over MgO and Na/MgO. SiO2 was chosen as a representative of thermal cracking. Na/MgO showed better selectivity for light olefins than MgO or SiO2. Ethylene and light olefin selectivity could reach about 65.8% and 91.7%, respectively. Meanwhile, in terms of Na/MgO, the ratio of ethylene selectivity and propylene selectivity is greater than 2, exhibiting the advantage of selectivity for ethylene, which is obviously different from MgO and SiO2. Propane cracking over Na/MgO with different loading amounts of NaNO3 was investigated further. The conversion rates of the samples presented a "volcano curve" with increasing Na content. Furthermore, DFT calculation showed that the base-catalyzed process of the propane cracking reaction follows a carbanion mechanism. The better product distribution and stronger surface base sites can be ascribed to charge transfer arising from the loading of NaNO3.

Dry environment on the expression of lacrimal gland S100A9, Anxa1, and Clu in rats via proteomics.

AIM: To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (n=10), and the rats fed in dry environment as the dryness group (n=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins. RESULTS: In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group. CONCLUSION: The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.

Integrated anatomical structure, physiological, and transcriptomic analyses to identify differential cold tolerance responses of Ziziphus jujuba mill. 'Yueguang' and its autotetraploid 'Hongguang'.

Cold stress is a limiting stress factor that limits plant distribution and development; however, polyploid plants have specific characteristics such as higher resistance to abiotic stress, especially cold stress, that allow them to overcome this challenge. The cultivated cultivar Ziziphus jujuba Mill. 'Yueguang' (YG) and its autotetraploid counterpart 'Hongguang' (HG) exhibit differential cold tolerance. However, the underlying molecular mechanism and methods to enhance their cold tolerance remain unknown. Anatomical structure and physiological analysis indicated YG had a higher wood bark ratio, and xylem ratio under cold treatment compared to HG. However, the half-lethal temperature (LT50), cortex ratio, and malondialdehyde (MDA) content were significantly decreased in YG than HG, which indicated YG was cold tolerant than HG. Transcriptome analysis showed that 2084, 1725, 2888, and 2934 differentially expressed genes (DEGs) were identified in HC vs YC, H20 vs Y20, Y20 vs YC, and H20 vs HC treatment, respectively. Meanwhile, KEGG enrichment analysis of DEGs showed that several metabolic pathways, primarily plant hormone signal transduction and the MAPK signaling pathway, were involved in the differential regulation of cold tolerance between YG and HG. Furthermore, exogenous abscisic acid (ABA) and brassinolide (BR) treatments could improve their cold tolerance through increased SOD and POD activities, decreased relative electrical conductivity, and MDA content. All of these findings suggested that plant hormone signal transduction, particularly ABA and BR, might have an important role in the regulation of differential cold tolerance between YG and HG, laying the foundation for further improving cold tolerance in jujube and examining the molecular mechanisms underlying differences in cold tolerance among different ploidy cultivars.

Toward a Comprehensive Understanding of the Anomalously Small Contact Angle of Surface Nanobubbles.

Experimental studies have demonstrated that the gas phase contact angle (CA) of a surface nanobubble (SNB) is much smaller than that of a macroscopic gas bubble. This reduced CA plays a crucial role in prolonging the lifetime of SNBs by lowering the bubble pressure and preventing gas molecules from dissolving in the surrounding liquids. Despite extensive efforts to explain the anomalously small CA, a consensus about the underlying reasons is yet to be reached. In this study, we conducted experimental investigations to explore the influence of gas molecules adsorbed at the solid-liquid interface on the CA of SNBs created through the solvent exchange (SE) method and temperature difference (TD). Interestingly, no significant change is observed in the CA of SNBs on highly oriented pyrolytic graphite (HOPG) surfaces. Even for nanobubbles on micro/nano pancakes, the CA only exhibited a slight reduction compared to SNBs on bare HOPG surfaces. These findings suggest that gas adsorption at the immersed solid surface may not be the primary factor contributing to the small CA of the SNBs. Furthermore, the CA of SNBs formed on polystyrene (PS) and octadecyltrichlorosilane (OTS) substrates was also investigated, and a considerable increase in CA was observed. In addition, the effects of other factors including impurity, electric double layer (EDL) line tension, and pinning force upon the CA of SNBs were discussed, and a comprehensive model about multiple factors affecting the CA of SNBs was proposed, which is helpful for understanding the abnormally small CA and the stability of SNBs.

Long-term outcomes of endovascular therapy for right subclavian artery occlusive lesions: A multi-center experience.

OBJECTIVE: To review our multi-institutional experience with endovascular therapy for right subclavian artery occlusive disease and to evaluate the long-term outcomes. METHODS: We retrospectively evaluated all patients with right subclavian artery stenosis and occlusive disease who underwent endovascular therapy between March 2014 and September 2022 at two institutions. Patient baseline demographics, lesion characteristics, treatment strategies, and in-hospital and follow-up outcomes were prospectively collected and retrospectively analyzed. RESULTS: Between March 2014 and September 2022, 73 patients underwent endovascular treatment at the two institutions. The dominant cause of lesions in this cohort was atherosclerosis. Three different types of lesions were summarized, and the corresponding endovascular strategies were performed. 66 patients (90.4%) underwent successful endovascular treatment, and 62 patients (84.9%) underwent balloon-expandable stent deployment. The mean perioperative in-hospital stay was 4.0 days (range, 3-6 days). Two patients died due to myocardial infarction, and one died of cerebral hemorrhage resulting from a traffic accident within 30 days of the intervention. The median follow-up time was 31.6 months (range, 12-96 months). No complications, including death, stroke, stent fractures, or migration, were noted in any patient during the follow-up period. The overall complication rate was 7/73 (9.6%), and 5/7 (6.9%) of the complications required reintervention. CONCLUSIONS: Endovascular treatment of right subclavian artery lesions is safe, effective, and technically achievable. The reasonable use of balloon-expandable stents can achieve satisfactory outcomes with accurate orientation and promising patency.

Precipitation variation: a key factor regulating plant diversity in semi-arid livestock grazing lands.

Livestock presence impacts plant biodiversity (species richness) in grassland ecosystems, yet extent and direction of grazing impacts on biodiversity vary greatly across inter-annual periods. In this study, an 8-year (2014-2021) grazing gradient experiment with sheep was conducted in a semi-arid grassland to investigate the impact of grazing under different precipitation variability on biodiversity. The results suggest no direct impact of grazing on species richness in semi-arid Stipa grassland. However, increased grazing indirectly enhanced species richness by elevating community dominance (increasing the sheltering effect of Stipa grass). Importantly, intensified grazing also regulates excessive community biomass resulting from increased inter-annual wetness (SPEI), amplifying the positive influence of annual humidity index on species richness. Lastly, we emphasize that, in water-constrained grassland ecosystems, intra-annual precipitation variability (PCI) was the most crucial factor driving species richness. Therefore, the water-heat synchrony during the growing season may alleviate physiological constraints on plants, significantly enhancing species richness as a result of multifactorial interactions. Our study provides strong evidence for how to regulate grazing intensity to increase biodiversity under future variable climate patterns. We suggest adapting grazing intensity according to local climate variability to achieve grassland biodiversity conservation.

Pivotal Evaluation of Novel Dedicated Venous Stent for Iliofemoral Venous Obstruction: A Prospective Cohort Study.

PURPOSE: The purpose was to evaluate the clinical outcomes of a dedicated venous stent with the tripartite composite segments for the treatment of iliofemoral venous obstruction (IVO) in a mixed cohort of nonthrombotic iliac vein lesion (NIVL) and post-thrombotic syndrome (PTS) over a period of 12 months. METHODS: The Grency Trial is a prospective, multicenter, single-arm, open-label, pivotal study, which was conducted at 18 large tertiary hospitals in China from August 2019 to October 2020. A total of 133 hospitalized patients were screened and 110 patients with clinical, etiology, anatomical, and pathophysiology clinical class (CEAP) clinical grade C>3 and iliac vein stenosis >50% or occlusion, including 72 patients with NIVL and 38 patients with PTS, were implanted with Grency venous stents. Primary endpoint was stent patency at 12 months follow-up, and secondary outcomes were technical success; improvement in venous clinical severity score (VCSS) at 3, 6, and 12 month follow-up; and rates of clinical adverse events. RESULTS: Among 110 patients who were implanted with Grency venous stents, 107 patients completed the 12 month follow-up. All 129 stents were successfully implanted in 110 limbs. Twelve-month primary patency rate was 94.39% [95% confidence interval [CI]=88.19%-97.91%] overall, and 100% [94.94%-100%] and 83.33% [67.19%-93.63%] in the NIVL and PTS subgroups, respectively. Venous clinical severity score after iliac vein stenting improved significantly up to 12 months follow-up. There were 3 early major adverse events (1 intracerebral hemorrhage and 2 stent thrombosis events related to anticoagulation therapy), and 7 late major adverse events (1 cardiovascular death, 1 intracranial hemorrhage with uncontrolled hypertension, and 5 in-stent restenosis cases without stent fractures or migration). CONCLUSIONS: The Grency venous stent system appeared excellent preliminary safe and effective for IVO treatment. Further large-scale studies with longer-term follow-up are needed to evaluate long-term patency and durability of stent. CLINICAL IMPACT: The design of venous stents for iliofemoral venous obstruction (IVO) must address engineering challenges distinct from those encountered in arterial stenting. The Grency venous stent, a nitinol self-expanding stent specifically tailored for IVO, features a composite structure designed to meet the stent requirements of various iliac vein segments. The Grency Trial is a prospective, multicenter, single-arm, open-label pivotal study aimed at evaluating the efficacy and safety of the Grency stent system. Following a 12-month follow-up period, the Grency venous stent system has demonstrated both safety and efficacy in treating iliofemoral venous outflow obstruction.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney, and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways.

BACKGROUND: Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear. AIM: To evaluate the therapeutic effects and the possible mechanism of JPGS on DN. METHODS: We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3). RESULTS: The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors. CONCLUSION: JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.

Origin and dispersal history of Hepatitis B virus in Eastern Eurasia.

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.

Sex-based outcomes after thoracic endovascular aortic repair: a systematic review and meta-analysis.

OBJECTIVE: As it remains unclear whether there are sex-based differences in clinical outcomes after thoracic endovascular aortic repair (TEVAR), this meta-analysis aimed to evaluate differences in early outcomes and overall survival between female and male patients who underwent TEVAR. METHODS: The PubMed, Embase, Web of Science, and Cochrane Central databases were searched for eligible studies published through June 10, 2023, that reported sex-based differences in clinical outcomes after TEVAR. The primary outcome was operative mortality; second outcomes included stroke, spinal cord ischemia, acute kidney injury, hospital length of stay, and overall survival. Patient characteristics, operative data, and early outcomes were aggregated using the random-effects model, presenting pooled risk ratio (RR) or standardized mean difference along with their corresponding 95% confidence intervals (CIs). Overall survival was assessed by reconstructing individual patient data to generate sex-specific pooled Kaplan-Meier curves. This study was registered in PROSPERO (CRD42023426069). RESULTS: Of the 1785 studies retrieved, 14 studies met all eligibility criteria, encompassing a total of 17,374 patients, comprising 5026 female and 12,348 male patients. Female patients were older, had a smaller maximum aortic diameter, had lower rates of smoking and coronary artery disease, and had higher rates of anemia. Intraoperatively, female patients were more likely to use iliac conduits and require blood transfusions. There were no sex-based differences in operative mortality (RR: 1.12, 95% CI: 0.90-1.40; P = .309), stroke (RR: 1.14, 95% CI: 0.95-1.38; P = .165), spinal cord ischemia (RR: 1.33, 95% CI: 0.83-2.14; P = .234), acute kidney injury (RR: 0.78, 95% CI: 0.52-1.17; P = .228), and hospital length of stay (standardized mean difference: 0.09, 95% CI: -0.03 to 0.20; P = .141). Pooled Kaplan-Meier estimates showed a worse overall survival in female patients compared with male patients (87.2% vs 89.8% at 2 years, log-rank P = .001). CONCLUSIONS: Among patients treated by TEVAR, female sex was not associated with increased risk of operative mortality or major morbidity. However, female patients exhibited a lower overall survival after TEVAR compared with male patients.

Association between metabolic syndrome severity score and cardiovascular disease: results from a longitudinal cohort study on Chinese adults.

Objective: This study aimed to quantify the severity of metabolic syndrome(MetS) and investigate its association with cardiovascular disease(CVD) risk on Chinese adults. Methods: 13,500 participants from the Zhejiang Adult Chronic Disease Study were followed up between 2010 and 2021. A continuous MetS severity score derived from the five components of MetS was used to quantify MetS severity, and the association between MetS severity and the risk of incident CVD was assessed using Cox proportional hazard and restricted cubic spline regression. Results: Both the presence and severity of MetS were strongly associated with CVD risk. MetS was related to an increased risk of CVD (hazard ratio(HR):1.700, 95% confidence interval(CI): 1.380-2.094). Compared with the hazard ratio for CVD in the lowest quartile of the MetS severity score, that in the second, third, and highest quartiles were 1.812 (1.329-2.470), 1.746 (1.265-2.410), and 2.817 (2.015-3.938), respectively. A linear and positive dose-response relationship was observed between the MetS severity and CVD risk (P for non-linearity = 0.437). Similar results were found in various sensitivity analyses. Conclusion: The MetS severity score was significantly associated with CVD risk. Assessing MetS severity and further ensuring intervention measures according to the different severities of MetS may be more useful in preventing CVD.

Role of BP-ANN in simulating greenhouse gas emissions from global aquatic ecosystems via carbon component-environmental factor coupling.

Inland waters (IW), estuarine areas (EA), and offshore areas (OA) function as aquatic systems in which the transport of carbon components results in the release of greenhouse gases (GHGs). Interconnected subsystems exhibit a greater greenhouse effect than individual systems. Despite this, there is a lack of research on how carbon loading and its components impact GHG emissions in various aquatic systems. In this study, we analyzed 430 aquatic sites to explore trade-off mechanisms among dissolved organic carbon (DOC), particulate organic carbon, dissolved inorganic carbon (DIC), and GHGs. The results revealed that IW emerged as the most significant GHG source, possessing a comprehensive global warming potential (GWP) of 0.78 ± 0.08 (10-2 Pg CO2-ep ha-1 year-1) for combined carbon dioxide, methane, and nitrous oxide. This surpassed the cumulative potentials of EA and OA (0.35 ± 0.05 (10-2 Pg CO2-ep ha-1 year-1)). Additionally, structural equation modeling indicated that GHG emissions resulted from a combination of carbon component loading and environmental factors. DOC exhibited a positive correlation with GWPs when influenced by biodegradable DOC. Total alkalinity and pH influenced DIC, leading to elevated pCO2 in aquatic systems, thereby enhancing GWPs. Predictive modeling using backpropagation artificial neural networks (BP-ANN) for GWPs, incorporating carbon components and environmental factors, demonstrated a good fit (R2 = 0.6078, RMSEaverage = 0.069, p > 0.05) between observed and predicted values. Enhancing the estimation of aquatic region feedback to GHG changes was achieved by incorporating corresponding water quality parameters. In summary, this study underscores the pivotal role of carbon components and environmental factors in aquatic regions for GHG emissions. The application of BP-ANN to estimate greenhouse effects from aquatic regions is highlighted, providing theoretical and experimental support for future advancements in monitoring and developing policies concerning the influence of water quality on GHG emissions.

Rocaglamide regulates iron homeostasis by suppressing hepcidin expression.

The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.

The role of HPV11 E7 in modulating STING-dependent interferon ß response in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a rare benign tumor caused mainly by the infection of the respiratory tract epithelial cells by the human papillomavirus (HPV) type 6/11. However, the specific mechanisms underlying the inhibition of the host's innate immune response by HPV remain unclear. For this purpose, we employed single-cell RNA sequencing to analyze the states of various immune cells in RRP samples post-HPV infection and utilized a cellular model of HPV infection to elucidate the mechanisms by which HPV evades the innate immune system in RRP. The results revealed distinct immune cell heterogeneity in RRP and demonstrated that HPV11 E7 can inhibit the phosphorylation of the stimulator of interferon genes protein, thereby circumventing the body's antiviral response. In vitro co-culture experiments demonstrated that stimulation of macrophages to produce interferon-beta induced the death of HPV-infected epithelial cells, also reducing HPV viral levels. In summary, our study preliminarily identifies the potential mechanisms by which HPV evades the host's antiviral immune response, as well as the latent antiviral functions exhibited by activated macrophages. This research serves as an initial exploration of antiviral immune evasion in RRP, laying a solid foundation for investigating immunotherapeutic approaches for the disease.IMPORTANCESurgical tumor reduction is the most common treatment for recurrent respiratory papillomatosis (RRP). One of the characteristics of RRP is its persistent recurrence, and multiple surgeries are usually required to control the symptoms. Recently, some adjuvant therapies have shown effectiveness, but none of them can completely clear human papillomavirus (HPV) infection, and thus, a localized antiviral immune response is significant for disease control; after all, HPV infection is limited to the epithelium. Inhibition of interferon-beta (IFN-ß) secretion by HPV11 E7 viral proteins in epithelial cells by affecting stimulator of interferon genes phosphorylation may account for the persistence of low-risk HPV replication in the RRP. Moreover, suppression of the IFN-I pathway in RRP cell types might provide clues regarding the hyporeactive function of local immune cells. However, activation of macrophage groups to produce IFN-ß can still destroy HPV-infected cells.