Temperature-adaptive dual-modal photonic textiles for thermal management.

Maintaining a thermally comfortable living and working environment with renewable energy sources is crucial for human health. However, achieving temperature self-regulation in individual textiles without external interventions remains a challenge. Here, we present a dual-modal photonic textile capable of autonomously achieving both low-temperature solar heating and high-temperature radiative cooling under sunlight. This innovative textile is primarily composed of textile fibers that are functionalized with thermochromic microcapsules encapsulated in graphene and barium sulfate coatings, which exhibit approximately 80% visible light optical modulation when integrated into the fabric. We demonstrate that garment and tent (3.5 m × 2.9 m × 1.3 m) fabricated from these textiles can achieve temperature-adaptive, all-weather thermal management, expanding the thermal comfort range by 8.5°C. This research showcases notable potential for applications in fabric-related heat management and highlights the importance of exploring temperature-adaptive solutions for a sustainable and healthy lifestyle.

The serum uric acid to serum creatinine ratio is an independent risk factor for type 2 diabetes in community-dwelling elderly: A longitudinal analysis.

BACKGROUND AND AIM: Elevated serum uric acid (SUA) levels are an important marker of metabolic disorders. However, SUA levels largely depend on renal clearance function. This study aims to investigate the relationship between renal function-normalized SUA [SUA to serum creatinine (SCr) ratio] and the risk of developing type 2 diabetes in a community-dwelling elderly population. METHODS AND RESULTS: A retrospective cohort study was conducted on elderly, non-diabetic individuals from the Kunshan community in China, who participated in annual health check-ups between January 2018 and December 2023. The relationship between the baseline SUA/SCr ratio and the risk of type 2 diabetes was examined using Cox regression models, restricted cubic splines (RCS), and subgroup analyses. After a median follow-up of 3.88 years, 778 cases of type 2 diabetes were identified among 7671 elderly non-diabetic individuals. Adjusting for confounding variables, the baseline SUA/SCr ratio was significantly linked to type 2 diabetes risk (P < 0.001). Individuals in the highest SUA/SCr ratio quartile had a 1.323 times higher risk of developing type 2 diabetes compared to those in the lowest quartile (HR = 1.323, 95% CI 1.053-1.661, P = 0.016). RCS analysis further confirmed this positive association. Additionally, subgroup analyses suggested that this relationship was particularly pronounced in female individuals. CONCLUSIONS: In Chinese elderly community residents, the baseline SUA/SCr ratio is linked to the risk of type 2 diabetes. Monitoring this ratio could aid in predicting and assessing the risk of type 2 diabetes.

FYCO1 regulates autophagy and senescence via PAK1/p21 in cataract.

BACKGROUND: ARC (Age-related cataract) is one of the leading causes of vision impairment and blindness; however, its pathogenesis remains unclear. FYCO1 (FYVE and coiled-coil domain containing 1) serves as an autophagy adaptor. The present study investigated the role of FYCO1 in cataract. METHODS: Ultraviolet-B (UVB) irradiation was used to establish a cataract mice model. Hematoxylin and eosin (H&E) assay were used to observe lens morphology. Cell models were constructed by cultivating SRA 01/04 cells with H2O2 and UVB. Cell counting kit-8 (CCK8) and Senescence-associated ß-galactosidase (SA-ß-Gal) assay were performed to explore proliferation and senescence. The gene and protein expression were assessed by quantitative real-time PCR (qRT-PCR), western blot and immunofluorescence staining. RESULTS: We demonstrated lens structural damage and downregulation of FYCO1 in mice with UVB-induced cataracts. In vitro results revealed a deletion in autophagy levels along with the decrease of FYCO1 expression in human lens epithelial cells (HLECs) after H2O2 treatment, which was confirmed in vivo. The knockout of FYCO1 in the HLECs did not change basal autophagy and senescence but suppressed HLECs response in the induction of both. Further investigation indicated that FYCO1 knockout inhibited senescence and p21 levels by suppressing the expression of p21 activated kinase 1 (PAK1) in cataract cell models. CONCLUSIONS: This study has newly characterized the role of FYCO1 in UVB-induced cataracts and in oxidative stress, both of which are associated with ARCs. A novel association between FYCO1 and PAK1/p21 in lens epithelial cell autophagy, senescence, and cataractogenesis also appears to have been established.

Pharmacology and therapeutic potential of agarwood and agarwood tree leaves in periodontitis.

The main bioactive components of agarwood, derived from Aquilaria sinensis, include sesquiterpenes, 2-(2-phenethyl) chromone derivatives, aromatic compounds, and fatty acids, which typically exert anti-inflammatory, antioxidant, immune-modulating, hypoglycemic, and antitumor pharmacological effects in the form of essential oils. Agarwood tree leaves, rich in flavonoids, 2-(2-phenethyl) chromone compounds, and flavonoid compounds, also exhibit significant anti-inflammatory, antioxidant, and immune-modulating effects. These properties are particularly relevant to the treatment of periodontitis, given that inflammatory responses, oxidative stress, and immune dysregulation are key pathological mechanisms of the disease, highlighting the substantial potential of agarwood and agarwood tree leaves in this therapeutic area. However, the low solubility and poor bioavailability of essential oils present challenges that necessitate the development of improved active formulations. In this review, we will introduce the bioactive components, extraction methods, pharmacological actions, and clinical applications of agarwood and agarwood tree leaves, analyzing its prospects for the treatment of periodontitis.

Glycemic Variability in Pancreatogenic Diabetes Mellitus: characteristics, Risks, Potential Mechanisms, and Treatment Possibilities.

In recent years, pancreatogenic diabetes mellitus has garnered significant attention due to its high incidence, complications, and mortality rates. Glycemic variability (GV) can increase the risk of pancreatogenic diabetes mellitus and its associated complications; however, the precise mechanism remains unclear. The effective control of GV is crucial for preventing the onset of pancreatic diabetes mellitus and improving prognosis. Both diet and antidiabetic medications have substantial effects on GV. However, many patients are prescribed suboptimal or even harmful drugs. Therefore, to provide a comprehensive treatment basis for clinicians to prevent and treat pancreatogenic diabetes mellitus, this study aimed to elucidate the relationship between GV and pancreatogenic diabetes mellitus; investigate the potential mechanisms (such as oxidative stress, inflammatory response, insulin resistance, and lipid metabolism disorders); provide lifestyle guidance; and recommend drug selections to reduce the GV in patients with pancreatogenic diabetes mellitus.

LRRC45 promotes lung cancer proliferation and progression by enhancing c-MYC, slug, MMP2, and MMP9 expression.

BACKGROUND: The leucine-rich repeat-containing (LRRC) superfamily members are known for their significant roles in tumorigenesis and cellular proliferation. However, the specific regulatory role of LRRC45 in lung cancer remains unexplored. This study investigated the impact and underlying mechanisms of LRRC45 on the proliferative, migratory, and invasive capacities of lung adenocarcinoma (LUAD) cells, potentially identifying new targets for therapeutic intervention. MATERIAL AND METHODS: The importance of LRRC45 in lung cancer was analyzed using the online databases of UCSC Xena, TCGA, TISIDB, and UALCAN, whereas to detect target gene expression, we used the qRT-PCR, Western blot, and immunofluorescence confocal. The cell growth was monitored by colony formation assay and migration was examined by cell migration assay. Finally, a xenograft mouse tumor model using A549 â€‹cells was used to explore the in vivo effect of LRRC45 in lung cancer. RESULTS: Inhibition of LRRC45 expression led to a notable decrease in proliferation, migration, and invasion of A549 and H1299 â€‹cells. LRRC45 silencing significantly reduced the tumor volume and improved the mice's survival. Additionally, inhibition of LRRC45 expression dramatically suppressed c-MYC, Slug, MMP2, and MMP9 expression. Overexpression of c-MYC and/or Slug in the LRRC45-deficient cells can partially or totally restore the LRRC45 deficiency-suppressed growth. Moreover, the overexpression of MMP2 and/or MMP9 could partially or totally restore LRRC45 deficiency-reduced cell metastasis. CONCLUSIONS: LRRC45 could promote the proliferative, migrative, and invasive capacities of lung cancer cells by increasing c-MYC, Slug, MMP2, and MMP9 expression, indicating the therapeutic implications and potential significance of these pathways in lung cancer.

Effect of primary tumor volume on survival of concurrent chemoradiotherapy in stage IV non-small cell lung cancer.

OBJECTIVE: To explore the survival effect of thoracic gross tumor volume (GTV) in three-dimensional (3D) radiotherapy for stage IV non-small cell lung cancer (NSCLC). METHODS: The data cases were obtained from a single-center retrospective analysis. From May. From 2008 to August 2018, 377 treatment criteria were enrolled. GTV was defined as the volume of the primary lesion and the hilus as well as the mediastinal metastatic lymph node. Chemotherapy was a platinum-based combined regimen of two drugs. The number of median chemotherapy cycles was 4 (2-6), and the cut-off value of the planning target volume (PTV) dose of the primary tumor was 63 Gy (30-76.5 Gy). The cut-off value of GTV volume was 150 cm3 (5.83-3535.20 cm3). RESULTS: The survival rate of patients with GTV <150 cm3 is better than patients with GTV ≥150 cm3. Multivariate Cox regression analyses suggested that peripheral lung cancer, radiation dose ≥63 Gy, GTV <150 cm3, 4-6 cycles of chemotherapy, and CR + PR are good prognostic factors for patients with stage IV non-small cell lung cancer. The survival rate of patients with GTV <150 cm3 was longer than patients with ≥150 cm3 when they underwent 2 to 3 cycles of chemotherapy concurrent 3D radiotherapy (p < 0.05). When performing 4 to 6 cycles of chemotherapy concurrent 3D radiotherapy, there was no significant difference between <150 cm3 and ≥150 cm3. CONCLUSIONS: The volume of stage IV NSCLC primary tumor can affect the survival of patients. Appropriate treatment methods can be opted by considering the volume of tumors to extend patients' lifetime to the utmost.

Optimal timing of invasive intervention for high-risk non-ST-segment-elevation myocardial infarction patients.

OBJECTIVE: To compare the immediate, early, and delayed percutaneous coronary intervention (PCI) strategies in non-ST-segment-elevation myocardial infarction (NSTEMI) patients with high-risk. METHODS: Medical records of patients treated at the Daping Hospital, Third Military Medical University, Chongqing, China between 2011 and 2021 were retrospectively reviewed. Only patients with complete available information were included. All patients assigned into three groups based on the timing of PCI including immediate (< 2 h), early (2-24 h) and delayed (≥ 24 h) intervention. Multivariable Cox hazards regression and simpler nonlinear models were performed. RESULTS: A total of 657 patients were included in the study. The median follow-up length was 3.29 (interquartile range: 1.45-4.85) years. Early PCI strategy improved the major adverse cardiac event (MACE) outcome compared to the immediate or delayed PCI strategy. Early PCI, diabetes mellitus, and left main or/and left anterior descending or/and left circumflex stenosis or/and right coronary artery ≥ 99% were predictors for MACE outcome. The optimal timing range for PCI to reduce MACE risk is 3-14 h post-admission. For high-risk NSTEMI patients, early PCI reduced primary clinical outcomes compared to immediate or delayed PCI, and the optimal timing range was 3-14 h post-admission. Delayed PCI was superior for NSTEMI with chronic kidney injury. CONCLUSIONS: Delayed invasive strategy was helpful to reduce the incidence of MACE for high-risk NSTEMI with chronic kidney injury. An immediate PCI strategy might increase the rate of MACE.

The Association Between Triglyceride Glucose-Body Mass Index and Kidney Impairment in Patients with Type 2 Diabetes Mellitus.

Purpose: Insulin resistance is associated with kidney impairment in patients with type 2 diabetes mellitus (T2DM). The triglyceride glucose-body mass index (TyG-BMI), which combines the TyG index with body mass index (BMI), has received significant attention as a tool for evaluating insulin resistance. Thus, the aim of this study was to explore the association between TyG-BMI and kidney impairment in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: The cross-sectional analysis included 1080 patients with T2DM, and data were collected retrospectively. TyG-BMI was calculated by fasting blood glucose, triglyceride, and body mass index. Results: TyG-BMI was significantly higher in T2DM patients with albuminuria than those without albuminuria (232.16 [206.52-268.02] vs 229.83 [206.11-255.64], p =0.023). T2DM patients with chronic kidney disease (CKD) showed a significantly higher value of TyG-BMI compared with those without CKD (232.23 [206.46-268.28] vs 229.73 [206.11-255.49], p=0.014). Correlation analysis showed a significantly positive association between TyG-BMI and metabolic parameters including BMI (r = 0.866, p < 0.001), TG (r = 0.630, p < 0.001), TC (r = 0.119, p < 0.001), HDL-C (r = -0.374, p < 0.001), FBG (r = 0.297, p < 0.001), and HbA1c (r = 0.116, p < 0.001) in patients with T2DM. The binary logistic regression analysis found that TyG-BMI was an independent factor for albuminuria (OR = 1.004, 95% CI: 1.001-1.008, p = 0.010) and CKD (OR = 1.005, 95% CI: 1.001-1.008, p = 0.005) in patients with T2DM respectively. Conclusion: The study suggests that TyG-BMI is associated with kidney impairment in patients with T2DM. Given that TyG-BMI is a novel parameter of insulin resistance, the study results indicates that clinicians should pay close attention to screening for kidney impairment in T2DM patients with insulin resistance.

Enhancing mechanical performance of hydroxyapatite-based bone implants via citric acid post-processing in binder jetting additive manufacturing.

Binder jetting is a promising technology in the additive manufacturing of bone implants, particularly for printing brittle bioceramics that are susceptible to thermal residual stresses. However, challenges in this field include low strength and undesirable size changes due to post-sintering treatments, as well as the absence of necessary organic matter like Glycosaminoglycans, citric acid, etc. To address these issues, a novel approach was introduced using citric acid (CA) as a post-processing agent to enhance the mechanical performance of green samples and add organic matter, with boric acid (BA) as a control. A hydroxyapatite (HA) based powder mixed with 25 wt.% high-viscosity polyvinyl alcohol (PVA) was prepared and printed using a self-made printer with deionized water as the binder. The post-processing effects were analyzed in terms of mechanical properties and microstructure. The application of 5 wt.% CA solution increased the thickness of the PVA film between HA particles by 320.0%, leading to an increase in compressive strength (7.37 ± 0.28 MPa) and modulus (102.81 ± 6.74 MPa) by 840.7% and 1571.3%, respectively, achieving the mechanical standards for human trabecular bone. This work presents a simple and rapid room-temperature post-processing strategy for enhancing the mechanical properties of bone implants produced by binder jetting additive manufacturing.

CircRNA ATF6 suppresses bladder cancer cell proliferation and migration via miR-146a-5p/FLNA axis.

BACKGROUND: Bladder cancer (BCa) is the most common malignancy with increasing morbidity and mortality. Circular RNA (circRNA) ATF6 level was downregulated in BCa after GSE92675 CircRNA microarray dataset was analyzed using GEO2R. However, its function and mechanism in BCa remain largely unknown. METHODS: GEO2R and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to measure levels of circRNA ATF6, microRNA-146a-5p (miR-146a-5p), and filamin A (FLNA). CircRNA ATF6 stability was assessed by actinomycin D and RNase R assays, while circRNA ATF6 cellular localization was examined by FISH experiments in T24 cells. Cell counting kit-8 (CCK-8), colony formation, wound-healing, and transwell assays were used to study circRNA ATF6's function in growth, motility, and invasion. By examining luciferase, starBase, RNA pull-down, and RNA immunoprecipitation (RIP) experiments, we anticipated and confirmed miR-146a-5p interactions with circRNA ATF6, as well as miR-146a-5p interactions with FLNA. On tumor-bearing mice, in vivo experiments were conducted. RESULTS: MiR-146a-5p expression in Bca was elevated, while circRNA ATF6 and FLNA were downregulated. CircRNA ATF6 showed better stability in BCa cells, with its expression primarily in the cytoplasm. Upregulating circRNA ATF6 lowered BCa cell viability, colony numbers, and invasion numbers, but broadened their migratory pattern. MiR-146a-5p was directly sponged up by circRNA ATF6, which also detrimentally affected miR-146a-5p levels in BCa. MiR-146a-5p reduced BCa FLNA expression by targeting FLNA. FLNA silencing abolished circRNA ATF6's mitigating function in BCa cell proliferation, motility, and invasion. In vivo, overexpression of circRNA ATF6 significantly reduced tumor volume and weight. CONCLUSION: CircRNA ATF6 suppresses BCa cell growth, migration and invasion through the miR-146a-5p/FLNA axis.

Appropriate delay of primary tumour radiotherapy may lead to better long-term overall survival for non-small cell lung cancer treated with EGFR-TKIs.

PURPOSE: The most appropriate time of primary tumor radiotherapy in non-small cell lung cancer(NSCLC) with EGFR-TKIs remains unclear. The aim of this study was to investigate the effect of the time factor of primary tumor radiotherapy on long-term overall survival(OS)and provide a theoretical basis for further clinical research. PATIENTS AND METHODS: In total, 238 patients with EGFR-TKIs and OS ≥ 12 months were statistically analysed. Patients were grouped: the D group without primary tumor radiotherapy and the R group with it.The R group were divided into three groups according to the interval between the start of EGFR-TKIs and the start of primary tumor radiotherapy: R0 - 30(<30 days), R30 - PD(≥ 30 days and disease stable), and RPD(radiotherapy after disease progression). The Kaplan-Meier method and log-rank test were used for survival analyses. Exploratory landmark analyses were investigated. RESULTS: The OS rates at 1, 2, 3, 5 years for the R group and D group were 96.8%, 62.9%, 38.3%, 17.1%, and 95.6%, 37.7%, 21.8%, 2.9%, respectively; the corresponding MST was 29 months(95% CI: 24.3-33.7) for the R group and 22 months(95% CI: 20.4-23.6) for the D group (χ2 = 13.480, p<0.001). Multivariate analysis revealed that primary tumor radiotherapy was independent predictors of prolonged OS.Among the four groups, The R30 - PD appeared to have the best OS (D, χ2 = 19.307, p<0.001;R0 - 30, χ2 = 11.687, p = 0.01; RPD, χ2 = 4.086, p = 0.043). Landmark analyses(22 months) showed the R30 - PD group had a significant long-term OS.The incidence of radiation pneumonitis ≥ grade 2 was17.3%(n = 19)and radiation esophagitis ≥ grade 2 was observed in 32 patients(29.1%). CONCLUSIONS: Our results showed that primary tumour radiotherapy may prolong long-term OS with acceptable toxicities. Appropriate delay(R30 - PD)of primary tumour radiotherapy may be the best choice.Premature radiotherapy(R0 - 30) and radiotherapy after disease progression (RPD)may not be reasonable for long-term OS.

Association between the atherogenic index of plasma and kidney stones: a nationally representative study.

PURPOSE: The atherogenic index of plasma (AIP) is a novel comprehensive lipid index. We aimed to investigate a possible relationship between AIP index and kidney stones in US adults. METHODS: This cross-sectional study was conducted among adults with complete AIP index and questionnaire records on kidney stones from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. The AIP index served as the exposure variable, defined as the logarithm of the ratio between triglycerides (TG, mmol/L) and high-density lipoprotein cholesterol (HDL-c, mmol/L). Self-reported history of kidney stones was utilized as the outcome variable. The independent relationship between AIP index and the risk of kidney stones was fully assessed. RESULTS: A total of 14,833 participants were included in this study, with an average AIP index of -0.07 ± 0.01. The proportion of kidney stones progressively increased with higher AIP index tertile intervals (7.33% vs. 9.97% vs. 12.57%, P < 0.001). Furthermore, AIP index was found to be independently associated with the risk of kidney stones after adjusting for confounding factors (OR = 1.32, 95% CI 1.08-1.61, P = 0.006). Restricted cubic spline (RCS) analysis confirmed the robustness of our results. There was no significant interaction observed based on subgroup analysis stratified by age, gender, race, body mass index (BMI, kg/m2), smokers, diabetes, hypertension, and cardiovascular disease (P for interaction > 0.05). CONCLUSIONS: The AIP index may be a potential epidemiological tool to quantify the role of dyslipidemia in the risk of kidney stones in US adults.

Construction of Molecularly Dispersed Polyoxometalate-Alumina Hybrid Hollow Nanoflowers via Water-Induced Kirkendall Effect.

Hybrid nanomaterials with controllable structures and diverting components have attracted significant interest in the functional materials field. Here, we develop a solvent evaporation-induced self-assembly (EISA) strategy to synthesize nanosheet-assembled phosphomolybdic acid (H3PMo)-alumina hybrid hollow spheres. The resulting nanoflowers display a high surface area (up to 697 m2 g-1), adjustable diameter, high chemical/thermal stability, and especially molecularly dispersed H3PMo species. By employing various microscopic and spectroscopic techniques, the formation mechanism is elucidated, revealing the simultaneous control of the morphology by heteropoly acids and water through the water-induced Kirkendall effect. The versatility of the synthesis method is demonstrated by varying surfactants, heteropoly acids, and metal oxide precursors for the facile synthesis of hybrid metal oxides. Spherical hybrid alumina serves as an attractive support material for constructing metal-acid bifunctional catalysts owing to its advantageous surface area, acidity, and mesoporous microenvironment. Pt-loaded hollow flowers exhibit excellent catalytic performance and exceptional stability in the hydrodeoxygenation of vanillin with recyclability for up to 10 cycles. This research presents an innovative strategy for the controllable synthesis of hybrid metal oxide nanospheres and hollow nanoflowers, providing a multifunctional platform for diverse applications.

Phase separation of phospho-HDAC6 drives aberrant chromatin architecture in triple-negative breast cancer.

How dysregulated liquid-liquid phase separation (LLPS) contributes to the oncogenesis of female triple-negative breast cancer (TNBC) remains unknown. Here we demonstrate that phosphorylated histone deacetylase 6 (phospho-HDAC6) forms LLPS condensates in the nuclei of TNBC cells that are essential for establishing aberrant chromatin architecture. The disordered N-terminal domain and phosphorylated residue of HDAC6 facilitate effective LLPS, whereas nuclear export regions exert a negative dominant effect. Through phase-separation-based screening, we identified Nexturastat A as a specific disruptor of phospho-HDAC6 condensates, which effectively suppresses tumor growth. Mechanistically, importin-ß interacts with phospho-HDAC6, promoting its translocation to the nucleus, where 14-3-3θ mediates the condensate formation. Disruption of phospho-HDAC6 LLPS re-established chromatin compartments and topologically associating domain boundaries, leading to disturbed chromatin loops. The phospho-HDAC6-induced aberrant chromatin architecture affects chromatin accessibility, histone acetylation, RNA polymerase II elongation and transcriptional profiles in TNBC. This study demonstrates phospho-HDAC6 LLPS as an emerging mechanism underlying the dysregulation of chromatin architecture in TNBC.

Infection Rates and Symptomatic Proportion of SARS-CoV-2 and Influenza in Pediatric Population, China, 2023.

We conducted a longitudinal cohort study of SARS-CoV-2 and influenza rates in childcare centers and schools in Wuxi, China, collecting 1,760 environmental samples and 9,214 throat swabs from 593 students (regardless of symptoms) in weekly collections during February-June 2023. We estimated a cumulative infection rate of 124.8 (74 episodes)/1,000 persons for SARS-CoV-2 and 128.2 (76 episodes)/1,000 persons for influenza. The highest SARS-CoV-2 infection rate was in persons 18 years of age, and for influenza, in children 4 years of age. The asymptomatic proportion of SARS-CoV-2 was 59.6% and 66.7% for influenza; SARS-CoV-2 symptomatic proportion was lower in 16-18-year-olds than in 4-6-year-olds. Only samples from frequently touched surface tested positive for SARS-CoV-2 (4/1,052) and influenza (1/1,052). We found asynchronous circulation patterns of SARS-CoV-2 and influenza, similar to trends in national sentinel surveillance. The results support vaccination among pediatric populations and other interventions, such as environmental disinfection in educational settings.

Measurement equipment and result analysis of B-H curve of current transformer core material under mixing frequency.

To examine the effect of mixed-frequency excitation conditions on the hysteresis and loss characteristics of ferromagnetic materials, this paper shows how to construct magnetic property test equipment for electrical steel using Epstein's square circle. Experiments were carried out to assess the hysteresis and loss properties of oriented silicon steel wafers under mixed-frequency sinusoidal operating conditions with different occupancy ratios. It used heterodyne extraction to investigate the effect of different occupancy ratios of industry and magnetization frequency on the hysteresis and loss characteristics of oriented silicon steel sheets.

Short-term exposure to ambient fine particulate matter constituents and myocardial infarction mortality.

Short-term ambient fine particulate matter (PM2.5) exposure has been related to an increased risk of myocardial infarction (MI) death, but which PM2.5 constituents are associated with MI death and to what extent remain unclear. We aimed to explore the associations of short-term exposure to PM2.5 constituents with MI death and evaluate excess mortality. We conducted a time-stratified case-crossover study on 237,492 MI decedents in Jiangsu province, China during 2015-2021. Utilizing a validated PM2.5 constituents grid dataset at 1 km spatial resolution, we estimated black carbon (BC), organic carbon (OC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-) exposure by extracting daily concentrations grounding on the home address of each subject. We employed conditional logistic regression models to evaluate the exposure-response relationship between PM2.5 constituents and MI death. Overall, per interquartile range (IQR) increase of BC (lag 06-day; IQR: 1.75 µg/m3) and SO42- (lag 04-day; IQR: 5.06 µg/m3) exposures were significantly associated with a 3.91% and 2.94% increase in odds of MI death, respectively, and no significant departure from linearity was identified in the exposure-response curves for BC and SO42-. If BC and SO42- exposures were reduced to theoretical minimal risk exposure concentration (0.89 µg/m3 and 1.51 µg/m3), an estimate of 4.55% and 4.80% MI deaths would be avoided, respectively. We did not find robust associations of OC, NO3-, NH4+, and Cl- exposures with MI death. Individuals aged ≥80 years were more vulnerable to PM2.5 constituent exposures in MI death (p for difference <0.05). In conclusion, short-term exposure to PM2.5-bound BC and SO42- was significantly associated with increased odds of MI death and resulted in extensive excess mortality, notably in older adults. Our findings emphasized the necessity of reducing toxic PM2.5 constituent exposures to prevent deaths from MI and warranted further studies on the relative contribution of specific constituents.

Lenacapavir Exhibits Atropisomerism-Mechanistic Pharmacokinetics and Disposition Studies of Lenacapavir Reveal Intestinal Excretion as a Major Clearance Pathway.

Lenacapavir (LEN), a long-acting injectable, is the first approved human immunodeficiency virus type 1 capsid inhibitor and one of a few Food and Drug Administration-approved drugs that exhibit atropisomerism. LEN exists as a mixture of two class 2 atropisomers that interconvert at a fast rate (half-life < 2 hours) with a ratio that is stable over time and unaffected by enzymes or binding to proteins in plasma. LEN exhibits low systemic clearance (CL) in nonclinical species and humans; however, in all species, the observed CL was higher than the in vitro predicted CL. The volume of distribution was moderate in nonclinical species and consistent with the tissue distribution observed by whole-body autoradiography in rats. LEN does not distribute to brain, consistent with being a P-glycoprotein (P-gp) substrate. Mechanistic drug disposition studies with [14C]LEN in intravenously dosed bile duct-cannulated rats and dogs showed a substantial amount of unchanged LEN (31%-60% of dose) excreted in feces, indicating that intestinal excretion (IE) was a major clearance pathway for LEN in both species. Coadministration of oral elacridar, a P-gp inhibitor, in rats decreased CL and IE of LEN. Renal excretion was < 1% of dose in both species. In plasma, almost all radioactivity was unchanged LEN. Low levels of metabolites in excreta included LEN conjugates with glutathione, pentose, and glucuronic acid, which were consistent with metabolites formed in vitro in Hµrel hepatocyte cocultures and those observed in human. Our studies highlight the importance of IE for efflux substrates that are highly metabolically stable compounds with slow elimination rates. SIGNIFICANCE STATEMENT: LEN is a long-acting injectable that exists as conformationally stable atropisomers. Due to an atropisomeric interconversion rate that significantly exceeds the in vivo elimination rate, the atropisomer ratio of LEN remains constant in circulation. The disposition of LEN highlights that intestinal excretion has a substantial part in the elimination of compounds that are metabolically highly stable and efflux transporter substrates.

Status quo and factors of depression and anxiety in patients with non-muscle invasive bladder cancer after plasma electrocision.

BACKGROUND: Bladder cancer is a type of cancer with a high incidence in men. Plasma electrosurgery (PES) is often used in the treatment of bladder cancer. Postoperative complications often cause depression and anxiety in patients after surgery. AIM: To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them. METHODS: A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups. Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer. RESULTS: Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery, economic status, educational level, and marital status. A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer, and the results showed that whether the risk factors were whether or not it was the first surgery, monthly income between 3000 and 3000-6000, secondary or junior high school education level, single, divorced, and widowed statuses. CONCLUSION: The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries, economic status, level of education, and marital status. This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.