Bioaccessibility and health risk assessment of hydrophobic organic pollutants in soils from four typical industrial contaminated sites in China.

There have been reports of potential health risks for people from hydrophobic organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), and organophosphate flame retardants (OPFRs). When a contaminated site is used for residential housing or public utility and recreation areas, the soil-bound organic pollutants might pose a threat to human health. In this study, we investigated the contamination profiles and potential risks to human health of 15 PAHs, 6 PCHs, and 12 OPFRs in soils from four contaminated sites in China. We used an in vitro method to determine the oral bioaccessibility of soil pollutants. Total PAHs were found at concentrations ranging from 26.4 ng/g to 987 ng/g. PCHs (0.27‒14.3 ng/g) and OPFRs (6.30‒310 ng/g) were detected, but at low levels compared to earlier reports. The levels of PAHs, PCHs, and OPFRs released from contaminated soils into simulated gastrointestinal fluids ranged from 1.74% to 91.0%, 2.51% to 39.6%, and 1.37% to 96.9%, respectively. Based on both spiked and unspiked samples, we found that the oral bioaccessibility of pollutants was correlated with their logKow and molecular weight, and the total organic carbon content and pH of soils. PAHs in 13 out of 38 contaminated soil samples posed potential high risks to children. When considering oral bioaccessibility, nine soils still posed potential risks, while the risks in the remaining soils became negligible. The contribution of this paper is that it corrects the health risk of soil-bound organic pollutants by detecting bioaccessibility in actual soils from different contaminated sites.

Clinical efficacy of laparoscopic cholecystectomy plus cholangioscopy for the treatment of cholecystolithiasis combined with choledocholithiasis.

BACKGROUND: Currently, endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy (LC) is the main treatment for cholecystolithiasis combined with choledocholithiasis. However, the treatment is unsatisfactory, and the development of better therapies is needed. AIM: To determine the clinical efficacy of LC plus cholangioscopy for cholecystolithiasis combined with choledocholithiasis. METHODS: Patients (n = 243) with cholecystolithiasis and choledocholithiasis admitted to The Affiliated Haixia Hospital of Huaqiao University (910th Hospital of Joint Logistic Support Force) between January 2019 and December 2023 were included in the study; 111 patients (control group) underwent ERCP + LC and 132 patients (observation group) underwent LC + laparoscopic common bile duct exploration (LCBDE). Surgical success rates, residual stone rates, complications (pancreatitis, hyperamylasemia, biliary tract infection, and bile leakage), surgical indicators [intraoperative blood loss (IBL) and operation time (OT)], recovery indices (postoperative exhaust/defecation time and hospital stay), and serum inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were compared. RESULTS: No significant differences in surgical success rates and residual stone rates were detected between the observation and control groups. However, the complication rate, IBL, OT, postoperative exhaust/defecation time, and hospital stays were significantly reduced in the observation group compared with the control group. Furthermore, CRP, TNF-α, and IL-6 Levels after treatment were reduced in the observation group compared with the levels in the control group. CONCLUSION: These results indicate that LC + LCBDE is safer than ERCP + LC for the treatment of cholecystolithiasis combined with choledocholithiasis. The surgical risks and postoperative complications were lower in the observation group compared with the control group. Thus, patients may recover quickly with less inflammation after LCBDE.

Association between serum cotinine and muscle mass: results from NHANES 2011-2018.

PURPOSE: Recently, the detrimental effect of cigarette smoking on muscle metabolism has attracted much attention, but the relationship between cigarette smoking and muscle mass is poorly understood. Thus, this study investigated the association between exposure to cigarette smoke, defined based on serum cotinine, and muscle mass in the US population. METHODS: We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2018 for analysis. Data on serum cotinine, muscle mass (quantified by appendicular skeletal muscle mass index, ASMI), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum cotinine and ASMI. Subgroup analyses were stratified by gender, race and smoking status. When nonlinearity was detected, the threshold effects were analyzed using a two-piecewise linear regression model. RESULTS: In total, 8004 participants were included for analysis. The serum level of cotinine was negatively associated with ASMI in the fully adjusted model. Furthermore, comparing participants in the highest vs. the lowest tertile of serum cotinine, we found that ASMI decreased by 0.135 Kg/m2. In subgroup analysis stratified by gender and race, the association between serum cotinine and ASMI remained significant in all genders and races. In addition, the association remained significant among current and former smokers, but not among those who never smoked. Smooth curve fittings showed nonlinear relationships between serum cotinine and ASMI, with the inflection points identified at 356 ng/mL. CONCLUSIONS: Our study revealed that serum cotinine was negatively related to muscle mass. This finding improves our understanding of the deleterious effects of cigarette smoking on muscle mass and highlights the importance of smoking cessation for muscle health.

Effect of Bedside Ultrasound-Guided Versus Fluoroscopy-Guided Transvenous Cardiac Temporary Pacing in Children with Bradyarrhythmia.

To compare the efficacy and safety of bedside ultrasound-guided and fluoroscopy-guided transvenous cardiac temporary pacing in the treatment of bradyarrhythmia in children. Children treated by temporary intravenous cardiac pacing from January 2016 to June 2023 in Hunan Provincial Children's Hospital were enrolled, and the characteristics and data of the cases were summarized. Patients were divided into bedside ultrasound-guided group (ultrasound group) and fluoroscopy-guided group (fluoroscopy group) according to the implantation guidance methods. The efficacy, safety, and incidence of complications in children were compared, and follow-up analysis was carried out. A total of 30 children were enrolled, including 18 males and 12 females, with a median age of 5.5 (2.9, 10.0) years and a median weight of 18.7 (12.7, 32.7) kg. The most common primary diseases were fulminant myocarditis (13/30 cases) and congenital high-grade AVB (10/30 cases). Among them, the proportion of congenital high AVB in the fluoroscopy group was significantly higher than that in the ultrasound group, and the difference was statistically significant (p = 0.007). The implantation process was successful in all 30 children. From the time of pacing decision to implantation, the median time of ultrasound group was 56 (30, 60) min and that of fluoroscopy group was 154 (78,180) min, with a statistically significant difference (P < 0.001). A total of 5 cases developed complications. There was no statistically significant difference between the two groups (P > 0.05). Compared with traditional fluoroscopic temporary pacing, bedside ultrasound-guided temporary pacing technology can effectively shorten the operation time and reduce the occurrence of complications and has become a better choice for children's emergency and critical care treatment. The right internal jugular vein is preferred for intravenous implantation.

Predictive value of ultrasound diagnosis of aberrant right subclavian artery with non-recurrent laryngeal nerve.

Introduction: This study aims to evaluate the predictive value of color Doppler ultrasound for the diagnosis of aberrant right subclavian artery (ARSA) with a co-occurring non-recurrent right laryngeal nerve (NRLN). Material and methods: In the present study, 58 patients with ARSA (ARSA group) and 1,280 patients without ARSA (controls) were diagnosed by ultrasonography. In addition, 32 patients with ARSA (ARSA operation group) and controls underwent thyroidectomy with surgical exploration with or without NRLN. Then, the incidence of NRLN was analyzed. The right common carotid artery (RCCA) and right subclavian artery (RSA) trends were observed by ultrasound, and classified into two types: RCCA and RSA originating from the innominate artery (IA) (type I), and IA could not be detected (type II). Results: A total of 32 cases of NRLN were found in the ARSA operation group, but no case was found in controls, and the difference was statistically significant (p = 0.0006). The difference in the constituent ratio of type I and type II was statistically significant between the ARSA group and controls (p = 0.0002). That is, the IA could not be detected in the ARSA group, which was accompanied by the RCCA that originated from the aortic arch, while the IA was detected in most patients in the control group at the level of the sternoclavicular joints. Conclusions: Aberrant right subclavian artery can be rapidly detected by ultrasonography. Aberrant right subclavian artery occurs when the RCCA originates from the aortic arch during detection. Patients with ARSA sometimes have co-occurring NRLN. Hence, vigilance in protecting the NRLN is needed during an operation.

Zero-Dimensional Copper(I) Halide Microcrystals as Highly Efficient Scintillators for Flexible X-ray Imaging.

Commercially available rare-earth-doped inorganic oxide materials have been widely applied as X-ray scintillators, but the fragile characteristics, high detection limit, and harsh preparation condition seriously restrict their wide applications. Furthermore, it remains a huge challenge to realize X-ray flexible imaging technology for real-time monitoring of the curving interface of complex devices. To address these issues, we herein report two isostructural cuprous halides of zero-dimensional (0D) [AEPipz]CuX3·X·H2O (AEPipz = N-aminoethylpiperazine, X = Br and I) with controllable size to nanosize crystal as highly efficient scintillators toward flexible X-ray imaging. These cuprous halides exhibit highly efficient cyan photoluminescence and radioluminescence emissions with the highest quantum yield of 92.1% and light yield of 62,400 photons MeV-1, respectively, surpassing most of the commercially available inorganic scintillators. Meanwhile, the ultralow detection limit of 95.7 nGyair s-1 was far below the X-ray dose required for diagnosis (5.5 µGyair s-1). More significantly, the flexible film is facilely assembled with excellent foldability and high crack resistance, which further acts as a scintillation screen achieving a high spatial resolution of 17.4 lp mm-1 in X-ray imaging, demonstrating the potential application in wearable radiation radiography. The combined advantages of high light yield, low detection limit, and excellent flexibility promote these 0D cuprous halides as the most promising X-ray scintillators.

Esketamine mitigates mechanical ventilation-induced lung injury in chronic obstructive pulmonary disease rats via inhibition of the MAPK/NF-κB signaling pathway and reduction of oxidative stress.

PURPOSE: To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms. METHODS: Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays. RESULTS: Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue. CONCLUSION: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.

Adaptor protein CEMIP reduces the chemosensitivity of small cell lung cancer via activation of an SRC-YAP oncogenic module.

Small cell lung cancer (SCLC) is a recalcitrant malignancy with dismal prognosis due to rapid relapse after an initial treatment response. More effective treatments for SCLC are desperately needed. Our previous studies showed that cell migration-inducing hyaluronan binding protein (CEMIP) functionally promotes SCLC cell proliferation and metastasis. In this study, we investigated whether and how CEMIP regulates the chemosensitivity of SCLC. Through the GDSC database, we found that CEMIP expression levels were positively correlated with the IC50 values of several commonly used chemotherapeutic drugs in SCLC cells (cisplatin, gemcitabine, 5-fluorouracil and cyclophosphamide). We demonstrated that overexpression or knockdown of CEMIP in SCLC cells resulted in a notable increase or reduction in the IC50 value of cisplatin or etoposide, respectively. We further revealed that CEMIP functions as an adaptor protein in SCLC cells to interact with SRC and YAP through the 1-177 aa domain and 820-1361 aa domain, respectively, allowing the autophosphorylation of Y416 and activation of SRC, thus facilitating the interaction between YAP and activated SRC, and resulting in increased phosphorylation of Y357, protein stability, nuclear accumulation and transcriptional activation of YAP. Overexpressing SRC or YAP counteracted the CEMIP knockdown-mediated increase in the sensitivity of SCLC cells to cisplatin and etoposide. The combination of the SRC inhibitor dasatinib or the YAP inhibitor verteporfin and cisplatin/etoposide (EP regimen) displayed excellent synergistic antitumor effects on SCLC both in vitro and in vivo. This study demonstrated that targeted therapy against the CEMIP/SRC/YAP complex is a potential strategy for SCLC and provides a rationale for the development of future clinical trials with translational prospects.

Highly Efficient Photoelectrochemical Alkene Epoxidation on a Dye-Sensitized Photoanode.

In photoelectrochemical (PEC) cells, selective oxidation of organic substrates coupled with hydrogen evolution represents a promising approach for value-added chemical production and solar energy conversion. In this study, we report on PEC epoxidation of alkenes at a ruthenium dye-sensitized photoanode in a CH3CN/H2O mixed solvent with LiBr as a mediator and water as the oxygen source. The dye-sensitized photoanode was found to exhibit significant advantages in the simultaneous improvement of charge separation and suppression of charge recombination. First, LiBr as a redox mediator plays a critical role in charge separation, leading to an excellent excited electron injection efficiency of 95% and a high dye regeneration efficiency of 87%. Second, the predominant charge recombination pathway on the dye-sensitized photoanode is efficiently blocked by the reaction between alkene and the in situ generated bromine oxidant. As a result, the current system achieved a remarkable photocurrent density of over 4 mA cm-2 with a record-high incident photo-to-current efficiency (IPCE) of 51% and extraordinary selectivity of up to 99% for the epoxidation of a wide range of alkenes. Meanwhile, nearly 100% Faradaic efficiency for hydrogen evolution was obtained. The performance shown here exceeds that obtained by metal oxide-based semiconductor photoanodes under comparable conditions, demonstrating the great potential of dye-sensitized photoelectrodes for organic synthesis owing to their diversity and tunability.

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Synthesis and Evaluation of Novel meso-Tetraphenyltetrabenzoporphyrins for Photodynamic Therapy.

To discover effective photosensitizers for photodynamic therapy (PDT), a series of new meso-tetraphenyltetrabenzoporphyrin (m-Ph4TBP) derivatives were designed, prepared, and characterized. All m-Ph4TBPs own two characteristic absorption bands in the range of 450-500 and 600-700 nm and have the ability to generate singlet oxygen upon photoexcitation. Most of the m-Ph4TBPs demonstrated high photoactivity, among which compounds I4, I6, I12, and I13 induced apoptosis and also exhibited excellent photodynamic activities in vivo. Nonetheless, the liver organs of the I4 and I6-PDT groups showed clear calcifications, whereas the liver tissues of the other PDT groups showed no calcification. It was indicated that compared to phenolic m-Ph4TBPs, glycol m-Ph4TBPs exhibited superior biological safety in mice. According to comprehensive evaluations, m-Ph4TBP I12 displayed excellent photodynamic antitumor efficacy and biological safety and can be regarded as a promising antitumor drug candidate.

Naoxintong capsule for treating cardiovascular and cerebrovascular diseases: from bench to bedside.

Naoxintong Capsule (NXT), a renowned traditional Chinese medicine (TCM) formulation, has been broadly applied in China for more than 30 years. Over decades, accumulating evidences have proven satisfactory efficacy and safety of NXT in treating cardiovascular and cerebrovascular diseases (CCVD). Studies have been conducted unceasingly, while this growing latest knowledge of NXT has not yet been interpreted properly and summarized comprehensively. Hence, we systematically review the advancements in NXT research, from its chemical constituents, quality control, pharmacokinetics, to its profound pharmacological activities as well as its clinical applications in CCVD. Moreover, we further propose specific challenges for its future perspectives: 1) to precisely clarify bioactivities of single compound in complicated mixtures; 2) to evaluate the pharmacokinetic behaviors of NXT feature components in clinical studies, especially drug-drug interactions in CCVD patients; 3) to explore and validate its multi-target mechanisms by integrating multi-omics technologies; 4) to re-evaluate the safety and efficacy of NXT by carrying out large-scale, multicenter randomized controlled trials. In brief, this review aims to straighten out a paradigm for TCM modernization, which help to contribute NXT as a piece of Chinese Wisdom into the advanced intervention strategy for CCVD therapy.

Automatic planning for functional lung avoidance radiotherapy based on function-guided beam angle selection and plan optimization.

Objective.This study aims to develop a fully automatic planning framework for functional lung avoidance radiotherapy (AP-FLART).Approach.The AP-FLART integrates a dosimetric score-based beam angle selection method and a meta-optimization-based plan optimization method, both of which incorporate lung function information to guide dose redirection from high functional lung (HFL) to low functional lung (LFL). It is applicable to both contour-based FLART (cFLART) and voxel-based FLART (vFLART) optimization options. A cohort of 18 lung cancer patient cases underwent planning-CT and SPECT perfusion scans were collected. AP-FLART was applied to generate conventional RT (ConvRT), cFLART, and vFLART plans for all cases. We compared automatic against manual ConvRT plans as well as automatic ConvRT against FLART plans, to evaluate the effectiveness of AP-FLART. Ablation studies were performed to evaluate the contribution of function-guided beam angle selection and plan optimization to dose redirection.Main results.Automatic ConvRT plans generated by AP-FLART exhibited similar quality compared to manual counterparts. Furthermore, compared to automatic ConvRT plans, HFL mean dose,V20, andV5were significantly reduced by 1.13 Gy (p< .001), 2.01% (p< .001), and 6.66% (p< .001) respectively for cFLART plans. Besides, vFLART plans showed a decrease in lung functionally weighted mean dose by 0.64 Gy (p< .01),fV20by 0.90% (p= 0.099), andfV5by 5.07% (p< .01) respectively. Though inferior conformity was observed, all dose constraints were well satisfied. The ablation study results indicated that both function-guided beam angle selection and plan optimization significantly contributed to dose redirection.Significance.AP-FLART can effectively redirect doses from HFL to LFL without severely degrading conventional dose metrics, producing high-quality FLART plans. It has the potential to advance the research and clinical application of FLART by providing labor-free, consistent, and high-quality plans.

Electron beam lithography of GeTe through polymorphic phase transformation.

We report two previously undiscovered phases of GeTe including the sphalerite (c-) phase and the hexagonal (h-) phase with interlayer van der Waals gaps. A polymorphic phase transformation from rhombohedral α-GeTe to c- and h-GeTe at near room temperature is first realized via electron beam irradiation. Their underlying thermodynamics and kinetics are illustrated using the in situ heating experiments and molecular dynamics simulations. Density-functional theory calculations indicate that c-GeTe exhibits typical metallic behavior and h-GeTe is a narrow-gap semiconductor with a strong spin-orbital coupling effect. Our findings shed light on a strategy for designing GeTe-based quantum devices compromising nanopillars and heterostructures via an atomic-scale electron beam lithography technique.

Supplementation of sodium acetate improves the growth performance and intestinal health of rabbits through Wnt/ß-catenin signaling pathway.

Acetic acid, which is one of the most abundant short-chain fatty acids (SCFA) in rabbits' cecum, has been reported to play an important function during various physiological metabolic processes. The present study was conducted to elucidate the effects of sodium acetate on growth performance and intestinal health by evaluating feed intake and efficiency, diarrhoea score, serum and cecum metabolites, cecal pH and SCFA, histological staining, nutritional composition of meat and gene expression profile of cecum in rabbits. As a result of sodium acetate supplement, the feed conversion ratio, diarrhoea score, and diameter of muscle fiber were significantly decreased (P < 0.05). Additionally, dietary sodium acetate significantly increased in total area of muscle fibers and content of crude ash (P < 0.05). Dietary sodium acetate significantly increased serum glucose, total bile acid, and total cholesterol levels and decreased amylase, lipase, and tCO2 content (P < 0.05). Further examination suggested that sodium acetate supplementation enhanced the micro-environment of cecum, evidenced by significantly increased levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase, and decreased pH and amylase levels (P < 0.05). According to transcriptome sequencing of cecal tissues, differentially expressed genes were predominantly enriched in cell cycle, ABC transporters, and chemokine signaling pathways. Sodium acetate was further suggested to stimulate the proliferation and migration of rabbits' cecum epithelial cells by activating Wnt/ß-catenin pathway both in vivo and in vitro. In conclusion, dietary sodium acetate supplementation improved growth performance and intestinal health in rabbits.

Life's essential 8, genetic susceptibility, and incident cardiac arrhythmias: a population-based prospective cohort study.

BACKGROUND: Ideal cardiovascular health (CVH) has been associated with reduced cardiovascular disease risk and mortality, but its association with cardiac arrhythmias were still unsettled. In this prospective cohort study, we investigated the relationship between CVH and subsequent arrhythmias risk, including atrial fibrillation/flutter (AF), ventricular arrhythmias, and bradyarrhythmias. METHODS: Data from 287,264 participants initially free of arrhythmias in the UK Biobank were included in the analysis. Cox regression models were used to examine the relationship between CVH levels calculated by the American Heart Association's Life's Essential 8 (LE8) metrics, with cardiac arrhythmias risk. RESULTS: During a median follow-up period of 12.8 years, 16,802 incident AF, 2186 incident ventricular arrhythmias, and 4128 incident bradyarrhythmias were identified. After adjustment for confounding factors, participants with high initial CVH levels had a significantly lower risk for AF (HR 0.63, 95% CI 0.59-0.68), ventricular arrhythmias (HR 0.48, 95% CI 0.40-0.59), and bradyarrhythmias (HR 0.64, 95% CI 0.55-0.74) compared to those with low CVH levels. Furthermore, each SD increase in LE8 scores was associated with a 15% lower risk of AF, 21% for ventricular arrhythmias, and 13% for bradyarrhythmias, respectively. Additionally, a significant interaction was observed between CVH levels and the genetic risk of AF (P for interaction, 0.021). The reverse correlation seemed to be more noticeable in individuals with a lower genetic susceptibility to AF. CONCLUSIONS: We concluded that higher levels of CVH, estimated by the LE8 metrics, were associated with significantly reduced risks of AF, ventricular arrhythmias, and bradyarrhythmias.

Enhanced biosafety, anticancer and antibacterial photodynamic activities using silver-pyropheophorbide-a nanoconjugates.

Aim: A study of the enhancement of photodynamic activities of pyropheophorbide-a using PG-Ag-PPa nanoconjugates. Materials & methods: The nanoconjugates were formulated from silver nanoparticles and PPa via amide linkage, then characterized, and their photodynamic activities were examined. Results: The nanoconjugates displayed a higher rate of reactive oxygen species generation, commendable cellular uptake by Eca-109 cancer cells, higher photocytotoxicity toward the cancer cells and better bio-safety. They revealed strong antibacterial activity against Escherichia coli following internal reactive oxygen species generation and membrane disintegration. The in vivo anticancer studies confirmed higher cytotoxicity of the nanoconjugates toward cancer cells and better safety than PPa. Conclusion: Therefore, PG-Ag-PPa nanoconjugates could be considered potential nano photosensitizers for photodynamic therapy of tumors and bacterial infection with good bio-safety.

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The Mechanism of Jinkui Wenjing Tang in the Treatment of Anovulatory Dysfunctional Uterine Bleeding was Explored Through Network Pharmacology and Molecular Docking Technology.

Objectives: Jinkui Wenjing Tang (JKWJT), a Traditional Chinese Medicine prescription for gynecological menstrual adjustment, is also used to treat continuous uterine bleeding and abdominal pain. However, the mechanism of action, potential targets, and active ingredients of JKWJT in the treatment of anovulatory dysfunctional uterine bleeding (ADUB) remain unknown. Therefore, it is imperative to explore the molecular mechanism of JKWJT. Methods: The chemical composition and target of JKWJT were obtained by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the SwissTargetPrediction website. ADUB-related targets were collected through the GeneCards database. The protein-protein interaction network was constructed from the target protein. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. The binding of the compounds in JKWJT and the potential therapeutic target molecules was verified by molecular docking. Finally, immunohistochemistry, Western Blotting, and qPCR were used for target expression validation within ADUB patient tissues. Results: The putative targets of JKWJT for the treatment of ADUB mainly involve ESR1, VEGFA, TNF, AR, OXTR, and PCNA. Functional enrichment analysis showed that the therapeutic effect of JKWJT on ADUB was correlated to response to estradiol, gland development, regulation of hormone levels as well as endocrine resistance, estrogen signaling pathway, HIF-1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, prolactin signaling pathway. Molecular docking showed that the target OXTR was expected to have a good binding affinity with 4 corresponding compounds (Girinimbin, icosa-11, 14, 17-trienoic acid methyl ester, Kanzonol F, and Obacunone). After treatment with JKWJT, OXTR relative protein expression and mRNA levels were significantly reduced in ADUB patients. Conclusion: In this study, the basic pharmacological effects, and mechanisms of JKWJT in the treatment of ADUB were elucidated, thus providing a clinical basis for the treatment of ADUB by JKWJT.

[Research progress in targeting DNA G-quadruplexes using natural products].

DNA G-quadruplex(G4) is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres. G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets. Natural products have long been important sources of anticancer drug development. In recent years, significant progress has been made in the discovery of natural drugs targeting DNA G4s, with many DNA G4s have been confirmed as promising targets of natural products, including MYC-G4, KRAS-G4, PDGFR-ß-G4, BCL-2-G4, VEGF-G4, and telomeric G4. This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms. It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s. This review will serve as a valuable reference for the research on natural products, particularly in the development of novel antitumor medications.