Isoprenoid flavonoids isolated from Sophora davidii and their activities induces apoptosis and autophagy in HT29 cells.

Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.

Neoadjuvant radiochemotherapy is safe and feasible for breast conserving surgery or immediate reconstruction.

This study aimed to evaluate the survival outcomes of neoadjuvant radiochemotherapy (NARCT) for early breast cancer. Female patients ≤ 80 years old with unilateral T1-T4 invasive ductal breast cancer treated with neoadjuvant chemotherapy (NAC) and radiation therapy (RT) between 2006 and 2015 were enrolled from SEER database. Baseline differences in clinical and pathological characteristics were evaluated using chi-square test. The survival outcomes were estimated by Kaplan-Meier analysis and compared using Cox hazards models. The effects of baseline differences on survival outcome in patients treated with neoadjuvant radiation therapy (NART) and post-operation radiation therapy (PORT) were circumvented by propensity score matching (PSM). Altogether 14,151 patients receiving NAC and RT were enrolled, among whom 386 underwent NART. Based on a 1:4 PSM cohort, NART was an independent unfavorable prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) for the whole cohort. However, among patients receiving breast conserving surgery (BCS) (HR 1.029, P = 0.915 for BCSS; HR 1.003, P = 0.990 for OS) or implant-based immediate breast reconstruction (IBR) (HR 1.039, P = 0.921 for BCSS; HR 1.153, P = 0.697 for OS), those treated with NART had similar survival outcomes compared with patients treated with PORT. In conclusion, NARCT was a safe and feasible approach for patients undergoing BCS and IBR.

Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

Predicting the immunity landscape and prognosis with an NCLs signature in liver hepatocellular carcinoma.

BACKGROUND: Activated neutrophils release depolymerized chromatin and protein particles into the extracellular space, forming reticular Neutrophil Extracellular Traps (NETs). This process is accompanied by programmed inflammatory cell death of neutrophils, known as NETosis. Previous reports have demonstrated that NETosis plays a significant role in immune resistance and microenvironmental regulation in cancer. This study sought to characterize the function and molecular mechanism of NETosis-correlated long non-coding RNAs (NCLs) in the prognostic treatment of liver hepatocellular carcinoma (LIHC). METHODS: We obtained the transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and evaluated the expression of NCLs in LIHC. A prognostic signature of NCLs was constructed using Cox and Last Absolute Shrinkage and Selection Operator (Lasso) regression, while the accuracy of model was validated by the ROC curves and nomogram, etc. In addition, we analyzed the associations between NCLs and oncogenic mutation, immune infiltration and evasion. Finally, LIHC patients were classified into four subgroups based on consensus cluster analysis, and drug sensitivity was predicted. RESULTS: After screening, we established a risk model combining 5 hub-NCLs and demonstrated its reliability. Independence checks suggest that the model may serve as an independent predictor of LIHC prognosis. Enrichment analysis revealed a concentration of immune-related pathways in the high-risk group. Immune infiltration indicates that immunotherapy could be more effective in the low-risk group. Upon consistent cluster analysis, cluster subgroup 4 presented a better prognosis. Sensitivity tests showed the distinctions in therapeutic effectiveness among various drugs in different subgroups. CONCLUSION: Overall, we have developed a prognostic signature that can discriminate different LIHC subgroups through the 5 selected NCLs, with the objective of providing LIHC patients a more precise, personalized treatment regimen.

Sudden Secondary Sensorineural Hearing Loss Following Hand, Foot, and Mouth Disease in an Adult Patient: A Case Report.

Introduction: Sudden sensorineural hearing loss (SSNHL) can present as sudden hearing loss within 72 hours. Studies have shown that viral infection, including direct invasion, indirect reactions, stress responses, and immune-mediated hearing loss, is the main cause of SSNHL. Viral infection may play an important role in SSNHL by causing injury to the inner ear through blood or cerebrospinal fluid. In this article, we describe an adult case of SSNHL following hand, foot, and mouth disease (HFMD). Case Report: A 34-year-old man presented with sudden hearing loss in the right ear 4 days after HFMD onset. Tinnitus, ear fullness, and a slightly heavy head appeared synchronously as accompanying symptoms. Before 6 days, he had a fever for 2 days (the highest temperature was 39.4°C), followed by vesicles in the oral mucosa and papules on the hands and feet after cohabitation with his child diagnosed with HFMD.

Association of systemic inflammatory response index with ST segment elevation myocardial infarction and degree of coronary stenosis: a cross-sectional study.

BACKGROUND: Systemic Inflammatory Response Index (SIRI), a composite inflammatory marker encompassing neutrophils, monocytes, and lymphocytes, has been recognized as a reliable marker of systemic inflammation. This article undertakes an analysis of clinical data from ST-segment Elevation Myocardial Infarction (STEMI) patients, aiming to comprehensively assess the relationship between SIRI, STEMI, and the degree of coronary stenosis. METHODS: The study involved 1809 patients diagnosed with STEMI between the years 2020 and 2023. Univariate and multivariate logistic regression analyses were conducted to evaluate the risk factors for STEMI. Receiver operating characteristic (ROC) curves were generated to determine the predictive power of SIRI and neutrophil-to-lymphocyte ratio (NLR). Spearman correlation analysis was performed to assess the correlation between SIRI, NLR, and the Gensini score (GS). RESULTS: Multivariate logistic regression analysis showed that the SIRI was the independent risk factor for STEMI (adjusted odds ratio (OR) in the highest quartile = 24.96, 95% confidence interval (CI) = 15.32-40.66, P < 0.001). In addition, there is a high correlation between SIRI and GS (ß:28.54, 95% CI: 24.63-32.46, P < 0.001). The ROC curve analysis was performed to evaluate the predictive ability of SIRI and NLR for STEMI patients. The area under the curve (AUC) for SIRI was 0.789. The AUC for NLR was 0.754. Regarding the prediction of STEMI in different gender groups, the AUC for SIRI in the male group was 0.771. The AUC for SIRI in the female group was 0.807. Spearman correlation analysis showed that SIRI exhibited a stronger correlation with GS, while NLR was lower (SIRI: r = 0.350, P < 0.001) (NLR: r = 0.313, P < 0.001). CONCLUSION: The study reveals a strong correlation between the SIRI and STEMI as well as the degree of coronary artery stenosis. In comparison to NLR, SIRI shows potential in predicting acute myocardial infarction and the severity of coronary artery stenosis. Additionally, SIRI exhibits a stronger predictive capability for female STEMI patients compared to males.

Effectiveness of perioperative low-dose esketamine infusion for postoperative pain management in pediatric urological surgery: a prospective clinical trial.

BACKGROUND: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. METHODS: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. RESULTS: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). CONCLUSIONS: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).

Unraveling the effect of combined heat and high-pressure homogenization treatment on the improvement of chickpea protein solubility from the perspectives of colloidal state change and structural characteristic modification.

Chickpea protein (CP) is a promising plant protein ingredient, but the poor solubility has limited its broad application. In this study, heating followed by high-pressure homogenization (HPH) was used to improve the solubility of CP. The results showed that combined heat (80℃, 30 min) and HPH (80 MPa, 2 cycles) treatment exhibited an additive effect in improving the solubility of CP. This improvement could be attributed to the dissociation and the rearrangement of large insoluble protein aggregates into small-sized soluble protein aggregates, the increased exposure of hydrophobic residues and reactive sulfhydryl groups, the transformation of α-helices to ß-sheets and ß-turns. Moreover, the 11S subunits of CP could form reinforced disulfide covalent cross-links under heating + HPH, which may provide steric hindrance preventing the reassembly of large protein bodies. This work proposes an interesting approach to enhance the physicochemical properties of CP for tailoring techno-functional plant protein ingredients in food formulations.

Chemotherapy is of prognostic significance to metaplastic breast cancer.

This study aimed to evaluate the significance of chemotherapy (CT) among metaplastic breast cancer (MpBC), and to compare the survival outcomes between triple negative MpBC (MpBC-TNBC) and triple negative invasive ductal carcinoma (IDC-TNBC). SEER database was indexed to identify female unilateral primary MpBC diagnosed from 2010 to 2017. Patients were classified into neoadjuvant chemotherapy (NAC) with response (NAC-response), NAC-no response, adjuvant chemotherapy, and no CT. Breast cancer-specific survival (BCSS) and overall survival (OS) was estimated using the Kaplan-Meier method and compared by log-rank test. Cox regression was used to evaluate the independent prognostic factors. A 1:4 propensity score matching method was adopted to balance baseline differences. Altogether 1186 MpBC patients were enrolled, among them 181 received NAC, 647 received adjuvant CT and 358 did not receive any CT. Chemotherapy was an independent favorable prognostic factor. NAC-response and adjuvant CT had a significant or an obvious trend of survival improvement compared with NAC-no response or no CT. MpBC-TNBC was an independent unfavorable prognostic factor compared with IDC-TNBC. Among them, there was significant or trend of survival improvement among all TNBCs receiving NAC or adjuvant CT compared with no CT. Chemotherapy was of important significance to MpBC prognosis and should be integrated in comprehensive treatment for MpBC.

Free heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Red blood cells (RBCs) transfusion is related to perioperative neurocognitive disorders. The toxic effect of free heme has been identified in many pathologies. However, the underlying mechanisms of RBCs transfusion or free heme in cognitive impairment have not been clearly explored. Therefore, this research was conducted to determine the mechanism of free heme-induced neuroinflammation and cognitive impairment. METHODS: Rats were received intraperitoneal injection of hemin alone or combined with intracerebroventricular injection of Hemopexin (HPX), and MWM test was conducted to measure cognitive function. The amount of heme-HPX complexes was evaluated by flow cytometry for CD91 + cells. The microglial inflammatory response in rat brain was observed by immunofluorescence staining of Iba-1, and the inflammatory factors of TNF-α, IL-1ß and IL-6 in rat brain and BV2 cells were detected by ELISA analysis. Furthermore, neuronal apoptosis in HT22 cells alone and in HT22 + BV2 coculture system was detected by flow cytometry and immunofluorescence staining. Finally, western blot was conducted to detect TLR4/MyD88/NF-κB proteins in rat brain and BV2 cells treated with hemin or combined with pathway inhibitors. Additionally, the M1 surface marker CD86 was observed in BV2 cells to further confirm neuroinflammation. RESULTS: Intraperitoneal injection of hemin induced cognitive impairment, increase of CD91 + cells, up-regulation of TNF-α and IL-1ß, down-regulation of IL-6, activation of microglia, and activation of the TLR4/MyD88/NF-κB signaling pathway in rat brain. Significantly, intracerebroventricular injection of HPX reduced the above effects. Hemin induced boost of TNF-α, IL-1ß and IL-6 in BV2 cells, as well as apoptosis in HT22 cells. Notably, when HT22 cells were cocultured with BV2 cells, apoptosis was significantly increased. Hemin also induced activation of the TLR4/MyD88/NF-κB signaling pathway and increased the M1 surface marker CD86 in BV2 cells, and inhibiting this pathway reduced the inflammatory responses. CONCLUSIONS: Free heme induces cognitive impairment, and the underlying mechanism may involve neuronal apoptosis and microglial inflammation via the TLR4/MyD88/NF-κB signaling pathway. HPX may have potential therapeutic effects. Video Abstract.

Synthesis of Amphiphilic Block Copolymer and Its Application in Pigment-Based Ink.

Amphiphilic block copolymers-based aqueous color inks show great potential in the field of visual communication design. However, the conventional step-by-step chemistry employed to synthesize the amphiphilic block copolymers is intricate, with low yield and high economic and environmental costs. In this work, we present a novel method for preparing an amphiphilic AB di-block copolymer of PCL-b-PAA by employing a combined polymerization strategy that involves both cationic ring-opening polymerization (ROP) of the ε-caprolactone monomer and the reversible addition-fragmentation chain-transfer (RAFT) polymerization on the acrylic acid monomer simultaneously. The corresponding polycaprolactone (PCL) and polyacrylic acid (PAA) serve as the hydrophobic and hydrophilic units, respectively. The effectiveness of the amphiphilic AB di-block copolymer as the polymeric pigment dispersant for water-based color inks is evaluated. The amphiphilic AB di-block copolymer of PCL-b-PAA exhibits a molecular weight of 1400 g mol-1, which is consistent with the theoretical value and suitable for polymeric dispersant application. The high surface excess (Γmax) of the PCL-b-PAA in water indicates a densely packed molecular morphology at the water/air interface. Additionally, micelles can be stably formed in the aqueous PCL-b-PAA solution at very low concentrations by demonstrating a low CMC value of 10-4 wt% and a micelle dimension of approximately 30 nm. The model ink dispersion is prepared using organic dyes (Disperse Yellow 232) and the amphiphilic block copolymer of PCL-b-PAA. The dispersion demonstrates near-Newtonian behavior, which is highly favorable for the application as inkjet ink. Furthermore, the ink dispersion displays a low viscosity, making it particularly suitable for visual communication design and printing purposes. Moreover, the ink dispersion demonstrates an unimodal distribution of the particle size, with an average diameter of approximately 500 nm. It retains exceptional stability of dispersion and even conducts a thermal aging treatment at 60 °C for 5 days. This work presents a facile and efficient synthetic strategy and molecular design of AB di-block copolymer-based dispersants for dye dispersions.

Engineering improved strategies for spinel cathodes in high-performing zinc-ion batteries.

The development of high-performing cathode materials for aqueous zinc-ion batteries (ZIBs) is highly important for the future large-scale energy storage. Owing to the distinctive framework structure, diversity of valences, and high electrochemical activity, spinel materials have been widely investigated and used for aqueous ZIBs. However, the stubborn issues of low electrical conductivity and sluggish kinetics plague their smooth applications in aqueous ZIBs, which stimulates the development of effective strategies to address these issues. This review highlights the recent advances of spinel-based cathode materials that include the configuration of aqueous ZIBs and corresponding reaction mechanisms. Subsequently, the classifications of spinel materials and their properties are also discussed. Then, the review mainly summarizes the effective strategies for elevating their electrochemical performance, including their morphology and structure design, defect engineering, heteroatom doping, and coupling with a conductive support. In the final section, several sound prospects in this fervent field are also proposed for future research and applications.

Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency.

5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency is a folate metabolism disorder known as a rare autosomal recessive neurodevelopmental disorder (MIM: #618367). With central nervous system involvements, it is mainly characterized by developmental delay, epilepsy, microcephaly, hypertonia, and cranial nerves involvement. Here, we report three new cases with MTHFS deficiency from two non-consanguineous Chinese families. All patients showed white matter dysplasia and global developmental delay, of which only patient 1 and 2 manifested tonic-clonic seizures. Moreover, patient 2 had severe eczema and patient 3 had recurrent diarrhea. Both phenotypic features are firstly found in MTHFS deficiency. Trio whole-exome sequencing and sanger sequencing were used to identify four novel variants, p.Y169Tfs*17, p.S53F, c.117+1delG, and p.E61G in the MTHFS gene. The identification of four novel pathogenic variants and varied clinical features in three affected patients expands the genotype and phenotype spectrum of MTHFS deficiency. We also reviewed all cases of MTHFS deficiency that had previously been reported. The experience of diagnosis and treatment from these cases provides us a more comprehensive understanding of this rare disease.

Recent progress in structural modification of polymer gel electrolytes for use in solid-state zinc-ion batteries.

Zinc-ion batteries are one of the promising energy storage devices, which have the advantages of environmental friendliness, high safety and low price and are expected to be used in large-scale battery application fields. However, four prominent water-induced adverse reactions, including zinc dendrite formation, zinc corrosion, passivation and the hydrogen evolution reaction in aqueous systems, seriously shorten the cycling life of zinc-ion batteries and greatly hinder their development. Based on this, polymer gel electrolytes have been developed to alleviate these issues due to their unique network structure, which can reduce water activity and suppress water-induced side reactions. Based on the challenges of polymer gel electrolytes, this review systematically summarizes the latest research progress in the use of additives in them and explores new perspectives in response to the existing problems with polymer electrolytes. In order to expand the performance of polymer gel electrolytes in zinc-ion batteries, a range of different types of additives are added via physical/chemical crosslinking, such as organic or inorganic substances, natural plants, etc. In addition, different types of additives and polymerization crosslinking from different angles essentially improve the ionic conductivity of the gel electrolyte, inhibit the growth of zinc dendrites, and reduce hydrogen evolution and oxygen-absorbed corrosion. After these modifications of polymer gel electrolytes, a more stable and superior electrochemical performance of zinc-ion batteries can be obtained, which provides some strategies for solid-state zinc-ion batteries.

A natural polymer-based hydrogel with shape controllability and high toughness and its application to efficient osteochondral regeneration.

Hydrogels prepared from sustainable natural polymers have broad prospects in the biological field. However, their poor mechanical properties and challenges in achieving shape control have limited their application. Herein, a novel preforming dual-effect post-enhancing method is proposed to address these issues. The method utilizes the hydrogen bonding of agar to obtain a shape-controllable preformed hydrogel at low polymer concentrations using casting, injection, or 3D printing techniques. Subsequently, the preformed hydrogel was subjected to a permeation process to form a post-enhanced multi-network (PEMN) hydrogel with hierarchical chain entanglements to ensure its high toughness, which exhibits tensile and compressive strengths of up to 0.51 MPa and 1.26 MPa with solely physically crosslinking networks. The excellent biocompatibility of the PEMN hydrogel prepared without the need for additional initiator agents under mild conditions was confirmed by both in vitro and in vivo experiments. Furthermore, the adaptability for irregular defects, suitable toughness, adhesive properties, and degradability of PEMN hydrogels are beneficial to provide mechanical support, induce endogenous cell mineralization, and accelerate the regeneration of cartilage and subchondral bone with more than 40% bone regeneration in 12 weeks. Our work has provided a novel solution to simultaneously achieve shape controllability and high toughness based on natural polymers among the already well-explored strategies for osteochondral regeneration.

Synergistically engineering of vacancy and doping in thiospinel to boost electrocatalytic oxygen evolution in alkaline water and seawater.

Electronic structure engineering lies at the heart of the catalyst design, however, utilizing one strategy to modify the electronic structure is still challenging to achieve optimal electronic states. Herein, an advanced approach that incorporating both Ru dopants and sulfur vacancies into thiospinel-type FeNi2S4 to synergistically modulate the electronic configuration, is proposed. Deep characterizations and theoretical study reveal that the in-situ formed Ni3+ species are real active centers. Ru doping and sulfur vacancies synergistically tune the electronic states of Ni2+ sites to a near-optimal value, leading to the formation of abundant oxygen evolution reaction (OER)-active Ni3+ species via electrochemical reconstruction. Consequently, the optimized Ru-FeNi2S4 catalyst can exhibit superb electrocatalytic performance towards OER, delivering the overpotentials of 253 mV and 340.8 mV at 10 mA·cm-2 in alkaline water and seawater, respectively. The proper combination of vacancy and heteroatom doping in this work may unlock the catalytic power of conventional catalysts toward electrochemical reactions.

Comprehensive effects of lifestyle reform, adherence, and related factors on hypertension control: A review.

Despite the effectiveness of currently available antihypertensive medications, there is still a need for new treatment strategies that are more effective in certain groups of hypertensive and for additional resources to combat hypertension. However, medication non-adherence was previously recognized as a major problem in the treatment of hypertension. The mechanisms behind the positive impacts of lifestyle changes might occur in different ways. In comparison with other studies, the efficacy and effectiveness of lifestyle modifications and antihypertensive pharmaceutical treatment for the prevention and control of hypertension and concomitant cardiovascular disease have been demonstrated in randomized controlled trials. However, in this review, the attitudinal lifestyle modifications and barriers to blood pressure control were elaborated on. An effective method for reducing blood pressure (BP) and preventing cardiovascular events with antihypertensive medications has been outlined. Maintaining healthy lifestyle factors (body mass index, diet, smoking, alcohol consumption, sodium excretion, and sedentary behavior) could lower systolic blood pressure BP by 3.5 mm Hg and reduce the risk of cardiovascular disease (CVD) by about 30%, regardless of genetic susceptibility to hypertension. Conducting a lifestyle intervention using health education could improve lifestyle factors, such as reducing salt, sodium, and fat intake, changing eating habits to include more fruits and vegetables, not smoking, consuming less alcohol, exercising regularly, maintaining healthy body weight, and minimizing stressful conditions. Each behavior could affect BP by modulating visceral fat accumulation, insulin resistance, the renin-angiotensin-aldosterone system, vascular endothelial function, oxidative stress, inflammation, and autonomic function. Evidence of the joint effect of antihypertensive medications and lifestyle reforms suggests a pathway to reduce hypertension.

Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells.

Background: Macrophages are known to play a crucial role in the chronic inflammation associated with Chronic Obstructive Pulmonary Disease (COPD). BML-111, acting as a lipoxin A4 (LXA4) receptor agonist, has shown to be effective in protecting against COPD. However, the precise mechanism by which BML-111 exerts its protective effect remains unclear. Methods: In order to establish a cell model of inflammation, cigarette smoke extract (CSE) was used on the RAW264.7 cell line. Afterwards, an Enzyme-linked immunosorbent assay (ELISA) kit was employed to measure concentrations of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1ß), interleukin-18 (IL-18), and interleukin-10 (IL-10) in the cell supernatants of the RAW264.7 cells.In this study, we examined the markers of macrophage polarization using two methods: quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Additionally, we detected the expression of Notch-1 and Hes-1 through Western blotting. Results: BML-111 effectively suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-18, as well as inflammasome factors NLRP3 and Caspase-1, while simultaneously up-regulating the expression of the anti-inflammatory cytokine IL-10 induced by CSE. Moreover, BML-111 reduced the expression of iNOS, which is associated with M1 macrophage polarization, and increased the expression of Arg-1, which is associated with M2 phenotype. Additionally, BML-111 downregulated the expression of Hes-1 and the ratio of activated Notch-1 to Notch-1 induced by CSE. The effect of BML-111 on inflammation and macrophage polarization was reversed upon administration of the Notch-1 signaling pathway agonist Jagged1. Conclusion: BML-111 has the potential to suppress inflammation and modulate M1/M2 macrophage polarization in RAW264.7 cells. The underlying mechanism may involve the Notch-1 signaling pathway.

Greenhouse gas emissions from extractive industries in a globalized era.

The extractive industry consumes vast amounts of energy and is a major contributor to greenhouse gas (GHG) emissions. However, its climatic impacts have not yet been fully accounted for. In this study, we estimated the GHG emissions from extractive activities globally with a focus on China, and assessed the main emission drivers. In addition, we predicted the Chinese extractive industry emissions in the context of global mineral demand and cycling. As of 2020, GHG emissions from the global extractive industry had reached 7.7 billion tons of CO2 equivalents (CO2e), accounting for approximately 15.0% of the global anthropogenic GHG emissions (excluding GHG emissions from land use, land-use change, and forestry activities (LULUCF), with China being the largest emitter, accounting for 3.5% of global emissions. Extractive industry GHG emissions are projected to peak by 2030 or even earlier to achieve low-carbon peak targets. The most critical pathway for reducing GHG emissions in the extractive industry is to control emissions from coal mining. Therefore, reducing methane emissions from mining and washing coal (MWC) should be prioritized.

Mercury Isotopes in Deep-Sea Epibenthic Biota Suggest Limited Hg Transfer from Photosynthetic to Chemosynthetic Food Webs.

Deep oceans receive mercury (Hg) from upper oceans, sediment diagenesis, and submarine volcanism; meanwhile, sinking particles shuttle Hg to marine sediments. Recent studies showed that Hg in the trench fauna mostly originated from monomethylmercury (MMHg) of the upper marine photosynthetic food webs. Yet, Hg sources in the deep-sea chemosynthetic food webs are still uncertain. Here, we report Hg concentrations and stable isotopic compositions of indigenous biota living at hydrothermal fields of the Indian Ocean Ridge and a cold seep of the South China Sea along with hydrothermal sulfide deposits. We find that Hg is highly enriched in hydrothermal sulfides, which correlated with varying Hg concentrations in inhabited biota. Both the hydrothermal and cold seep biota have small fractions (<10%) of Hg as MMHg and slightly positive Δ199Hg values. These Δ199Hg values are slightly higher than those in near-field sulfides but are 1 order of magnitude lower than the trench counterparts. We suggest that deep-sea chemosynthetic food webs mainly assimilate Hg from ambient seawater/sediments and hydrothermal fluids formed by percolated seawater through magmatic/mantle rocks. The MMHg transfer from photosynthetic to chemosynthetic food webs is likely limited. The contrasting Hg sources between chemosynthetic and trench food webs highlight Hg isotopes as promising tools to trace the deep-sea Hg biogeochemical cycle.