Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

A medical big data access control model based on smart contracts and risk in the blockchain environment.

The rapid development of the Hospital Information System has significantly enhanced the convenience of medical research and the management of medical information. However, the internal misuse and privacy leakage of medical big data are critical issues that need to be addressed in the process of medical research and information management. Access control serves as a method to prevent data misuse and privacy leakage. Nevertheless, traditional access control methods, limited by their single usage scenario and susceptibility to single point failures, fail to adapt to the polymorphic, real-time, and sensitive characteristics of medical big data scenarios. This paper proposes a smart contracts and risk-based access control model (SCR-BAC). This model integrates smart contracts with traditional risk-based access control and deploys risk-based access control policies in the form of smart contracts into the blockchain, thereby ensuring the protection of medical data. The model categorizes risk into historical and current risk, quantifies the historical risk based on the time decay factor and the doctor's historical behavior, and updates the doctor's composite risk value in real time. The access control policy, based on the comprehensive risk, is deployed into the blockchain in the form of a smart contract. The distributed nature of the blockchain is utilized to automatically enforce access control, thereby resolving the issue of single point failures. Simulation experiments demonstrate that the access control model proposed in this paper effectively curbs the access behavior of malicious doctors to a certain extent and imposes a limiting effect on the internal abuse and privacy leakage of medical big data.

Efficacy and safety of music therapy for the treatment of anxiety and delirium in ICU patients: a meta-analysis and systematic review of randomized controlled trials.

INTRODUCTION: The medical application of music therapy (MT) has received widespread attention in recent years, some researchers have attempted to apply MT to the treatment of patients with anxiety and delirium in ICU. EVIDENCE ACQUISITION: Relevant randomized controlled trials (randomized controlled trials s) were searched in databases, such as Web of Science, PubMed, Embase, Cochrane Library, Medline, Scopus, and CINAHL. Researchers performed literature screening, data extraction, literature quality assessment, and heterogeneity analysis among RCTs. EVIDENCE SYNTHESIS: Fourteen studies met the inclusion criteria. In general, we included RCTs with low risk of bias, and the primary outcome indicators, including the Chinese version of the State-Trait Anxiety Inventory (C-STAI), Visual Analogue Scale for Anxiety Measurement (VAS-A), and Facial Anxiety Scale (FAS), have a recommended level of evidence of "strong". The pooled results indicated that MT was effective in alleviating the anxiety state of ICU patients (95% CI, SMD=-1.09 [-1.52, -0.67], P<0.05) and could reduce mental and physical fatigue in patients with anxious delirium in ICU (95% CI, WMD=-2.35 [-3.37, -1.33], P <0.05). There were significant differences in the therapeutic effects of MT with different intervention durations. Both 15-minute and 30-minute MT were effective in reducing anxiety levels in patients with anxiety disorders in the ICU (15min: 95%CI, SMD=-1.70[-2.15, -1.24], P<0.05; 30min: 95%CI, SMD=-0.73[-1.16, - 0.29], P<0.05). However, when the duration of MT exceeded 45 min, the overtreatment of MT instead interfered with patient rest and failed to produce a positive therapeutic effect (95% CI, SMD=-1.04 [-3.06, 0.97], P=0.31). In addition, a meta-analysis of physiological outcomes found that MT was effective in maintaining the stabilization of heart rate (HR), respiratory rate (RR), and systolic blood pressure (SBP) in ICU patients with anxiety (P<0.05), but did not affect patients' oxygen saturation, mean arterial pressure and diastolic blood pressure (P>0.05). No adverse events occurred during MT treatment in the reports of included 14 studies. CONCLUSIONS: MT can safely and effectively reduce the anxiety level of patients with anxiety and delirium in ICU and relieve their psychological and physical fatigue. And MT was able to maintain the stability of HR, RR, and SBP in ICU patients.

Improving Health Literacy of Elective Procedures in Pediatric Otolaryngology.

OBJECTIVE: To identify if the addition of supplementary material, such as video or written resources, to the consent process, can improve a patient's or guardian's health literacy in pediatric otolaryngology. STUDY DESIGN: Prospective randomized crossover design. SETTING: Tertiary Academic Center. METHODS: From April 18, 2022 to August 29, 2023, 151 children scheduled to undergo 1 of 6 procedures by the same provider were queried and completed a 6-question baseline test based on the information. They each watched a 2-minute video and read a written summary about the procedure; the order of resources was randomized. They answered the same 6-questions after viewing each resource. All tests were scored based on accuracy using an ordinal scale of 1 to 6. Resource preference was collected. Wilcoxon signed-rank tests were run to analyze differences in scores after the addition of supplementary resources and logistic regression modeling was run to analyze demographic effects on postresource score differences. RESULTS: Of 151 participants, 74.2% were guardians, with 78.8% having completed a high school or greater education. The Wilcoxon signed-rank test indicated that postresource scores were statistically significantly higher (P < .001) than pretest scores. Logistic regression modeling showed that participants were less likely to show score improved if they were younger than 18 and were of white race. A majority (87.4%) preferred the addition of a video to the consent process. CONCLUSION: The addition of video or written resources significantly improves understanding of elective procedures. The development of procedure-specific resources can supplement the consent process and ensure decision-makers have adequate health literacy for informed decision-making.

Global impact of enhanced-efficiency fertilizers on vegetable productivity and reactive nitrogen losses.

Vegetables are the most consumed non-staple food globally, and their production is crucial for dietary diversity and public health. Use of enhanced-efficiency fertilizers (EEFs) in vegetable production could improve vegetable yield and quality while reducing reactive nitrogen (Nr) losses. However, different management and environmental factors has significantly distinctive impacts on the effectiveness of EEFs. In this study, a worldwide meta-analysis based on the data collected from 144 studies was performed to assess the impacts of EEF (nitrification inhibitor [NI] and polymer-coated urea [PCU]) application on vegetable yield, nitrogen (N) uptake, nitrogen use efficiency (NUE), vegetable quality and Nr losses (nitrous oxide [N2O] emissions, ammonia [NH3] volatilization, and nitrate [NO3-] leaching). The effects of the applied EEFs on vegetable yields and N2O emissions were assessed with different management practices (cultivation system, vegetable type and N application rate) and environmental conditions (climatic conditions and soil properties). Compared to conventional fertilizers, EEFs significantly improved vegetable yield (7.5-8.1 %) and quality (vitamin C increased by 10.7-13.6 %, soluble sugar increased by 9.3-10.9 %, and nitrate content reduced by 17.2-25.1 %). Meanwhile, the application of EEFs demonstrated a great potential for Nr loss reduction (N2O emissions reduced by 40.5 %, NO3- leaching reduced by 45.8 %) without compromising vegetable yield. The NI was most effective in reducing N2O emissions (40.5 %), but it significantly increased NH3 volatilization (32.4 %). While PCU not only significantly reduced N2O emissions (24.4 %) and NO3- leaching (28.7 %), but also significantly reduced NH3 volatilization (74.5 %). And N application rate, soil pH, and soil organic carbon (SOC) were the main factors affecting the yield and environmental effects of EEFs. Moreover, the yield-enhancing effect of NI and PCU were better at low soil N availability and SOC, respectively. Thus, it is important to adopt the appropriate EEF application strategy targeting specific environmental conditions and implement it at the optimal N application rate.

Space-specific flux estimation of atmospheric chemicals from point sources to soil.

Predicting chemical flux to soil from industrial point sources accurately at a regional scale has been a significant challenge due to high uncertainty in spatial heterogeneity and quantification. To address this challenge, we developed an innovative approach by combining California Air Resources Board Puff (CALPUFF) and mass balance models, leveraging their complementary strengths in quantitative accuracy and spatial precision. Specifically, CALPUFF was used to predict the polycyclic aromatic hydrocarbons (PAHs) flux to soil due to industrial sources. Additionally, the spatial distribution coefficient of PAHs flux (e.g., si for spatial unit i) was calculated by neural network and combined with the mass balance model to obtain the results of total PAHs fluxes, which were then combined with the results predicted by CALPUFF to effectively estimate the contribution of industrial sources to soil PAHs flux. Taking a petrochemical industry region located in Zhejiang province, China as a case study, results showed the input Phenanthrene (Phe) and Benzo(a)pyrene (BaP) fluxes predicted by CALPUFF were generally lower than those by the mass balance model, with slightly different distribution patterns. CALPUFF results, based on 36 industrial sources, partially represent those of the mass balance model, which includes all sources and pathways. It was suggested that industrial sources contributed 49%-89% and 65%-100% of soil Phe and BaP, respectively across the study area. The average Phe flux from point sources by deposition averaged 2.68 mg m-2∙a-1 in 2021, accounting for approximately 60% of the total Phe flux to soil. The average BaP flux from point sources by deposition averaged 0.0755 mg m-2∙a-1, accounting for only 0.1%-3.65% of the total BaP flux to soil. Thereby, our approach fills up a gap between the relevance to point sources and the accuracy of deposition quantification in estimating chemical flux from specific point sources to soil at a regional scale.

Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease.

BACKGROUND: Despite the benefits of exercise, many individuals are unable or unwilling to adopt an exercise intervention. PURPOSE: The purpose of this analysis was to identify putative genetic variants associated with dropout from exercise training interventions among individuals in the STRRIDE trials. METHODS: We used a genome-wide association study approach to identify genetic variants in 603 participants initiating a supervised exercise intervention. Exercise intervention dropout occurred when a subject withdrew from further participation in the study or was otherwise lost to follow-up. RESULTS: Exercise intervention dropout was associated with a cluster of single-nucleotide polymorphisms with the top candidate being rs722069 (T/C, risk allele = C) (unadjusted p = 2.2 × 10-7, odds ratio = 2.23) contained within a linkage disequilibrium block on chromosome 16. In Genotype-Tissue Expression, rs722069 is an expression quantitative trait locus of the EARS2, COG7, and DCTN5 genes in skeletal muscle tissue. In subsets of the STRRIDE genetic cohort with available muscle gene expression (n = 37) and metabolic data (n = 82), at baseline the C allele was associated with lesser muscle expression of EARS2 (p < .002) and COG7 (p = .074) as well as lesser muscle concentrations of C2- and C3-acylcarnitines (p = .026). CONCLUSIONS: Our observations imply that exercise intervention dropout is genetically moderated through alterations in gene expression and metabolic pathways in skeletal muscle. Individual genetic traits may allow the development of a biomarker-based approach for identifying individuals who may benefit from more intensive counseling and other interventions to optimize exercise intervention adoption. CLINICAL TRIAL INFORMATION: STRRIDE I = NCT00200993; STRRIDE AT/RT = NCT00275145; STRRIDE-PD = NCT00962962.

Regular participation in exercise can provide a myriad of health benefits. Although individuals recognize these benefits, many are unable or unwilling to adopt an exercise intervention once initiated. The purpose of this analysis was to identify genetic variants associated with dropout from an exercise training intervention. We found exercise intervention dropout to be genetically moderated through changes in gene expression and metabolic pathways in muscle. Thus, individual genetic traits may allow for the development of a biomarker-based targeted approach for identifying individuals who may benefit from more intensive counseling and interventions to optimize the adoption of an exercise intervention program.

CircALMS1 Alleviates Pulmonary Microvascular Endothelial Cell Dysfunction in Pulmonary Hypertension.

BACKGROUND: Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. METHODS AND RESULTS: Deep RNA sequencing and quantitative real-time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P<0.0001). Molecular biology and histopathology experiments were used to elucidate the roles of circALMS1 in regulating PMEC dysfunction among patients with PH. The circALMS1 expression was decreased in the plasma of patients with PH (P=0.0315). Patients with lower circALMS1 levels had higher risk of death (P=0.0006). Moreover, the circALMS1 overexpression of adeno-associated viruses improved right ventricular function and reduced pulmonary vascular remodeling in monocrotaline-PH and sugen/hypoxia-PH rats (P<0.05). Furthermore, circALMS1 overexpression promoted apoptosis and inhibited PMEC proliferation and migration under hypoxia by directly downregulating miR-17-3p (P<0.05). Dual luciferase assay confirmed the direct binding of circALMS1 to miR-17-3p and miR-17-3p binding to its target gene YT521-B homology domain-containing family protein 2 (YTHDF2) (P<0.05). The YTHDF2 levels were also downregulated in hypoxic PMECs (P<0.01). The small interfering RNA YTHDF2 reversed the effects of miR-17-3p inhibitors on PMEC proliferation, migration, and apoptosis. Finally, the results indicated that, although YTHDF2, as an N(6)-methyladenosine reader protein, contributes to the degradation of many circular RNAs, it could not regulate the circALMS1 levels in PMECs (P=0.9721). CONCLUSIONS: Our study sheds new light on circALMS1-regulated dysfunction of PMECs by the miR-17-3p/YTHDF2 pathway under hypoxia and provides insights into the underlying pathogenesis of PH.

The Impact of Regulatory Reforms in China on Drug Lag: The Role of Clinical Development Strategies.

In recent years, there has been significant focus on China's new drug lag, but relevant research is limited. This study explores the reasons for drug lag by assessing the impact of reforms in China's drug review system, particularly focusing on the influence of clinical development strategies. This study selected drugs first launched in the United States between 2017 and 2022, examining absolute and relative lag between China and the first-launch country (including submission and review lag). These delays with drugs approved in the European Union and Japan during the same period were compared with uncover the roots of delays in China, further identifying potential factors that could reduce these delays. The results indicate that the National Medical Products Administration (NMPA) has a longer relative lag compared with the European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA). The submission lag time of the NMPA significantly surpasses that of the EMA and PMDA, whereas the review lag time of the NMPA exceeds that of the PMDA but falls short of the EMA. Focusing on clinical trial strategies, bridging trials and multiregional clinical trials (MRCTs) are typically required by the NMPA in East Asia, resulting in longer clinical delay time. Whereas the EMA and PMDA primarily require international MRCTs in Europe and America, with a clinical delay of < 5 months. It is evident that there is a significant gap in clinical trial durations between China and other countries. Further optimization of clinical trial management is necessary to address the lag for new drugs in China.

Enhanced SSD framework for detecting defects in cigarette appearance using variational Bayesian inference under limited sample conditions.

In high-speed cigarette manufacturing industries, occasional minor cosmetic cigarette defects and a scarcity of samples significantly hinder the rapid and accurate detection of defects. To tackle this challenge, we propose an enhanced single-shot multibox detector (SSD) model that uses variational Bayesian inference for improved detection of tiny defects given sporadic occurrences and limited samples. The enhanced SSD model incorporates a bounded intersection over union (BIoU) loss function to reduce sensitivity to minor deviations and uses exponential linear unit (ELU) and leaky rectified linear unit (ReLU) activation functions to mitigate vanishing gradients and neuron death in deep neural networks. Empirical results show that the enhanced SSD300 and SSD512 models increase the model's detection accuracy mean average precision (mAP) by up to 1.2% for small defects. Ablation studies further reveal that the model's mAP increases by 1.5%, which reduces the computational requirements by 5.92 GFLOPs. The model also shows improved inference in scenarios with limited samples, thus highlighting its effectiveness and applicability in high-speed, precision-oriented cigarette manufacturing industries.

Early Mortality After the First Dose of COVID-19 Vaccination: A Target Trial Emulation.

BACKGROUND: Vaccine hesitancy persists alongside concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines. We aimed to examine the effect of COVID-19 vaccination on risk of death among US veterans. METHODS: We conducted a target trial emulation to estimate and compare risk of death up to 60 days under two COVID-19 vaccination strategies: vaccination within 7 days of enrollment versus no vaccination through follow-up. The study cohort included individuals aged ≥18 years enrolled in the Veterans Health Administration system and eligible to receive a COVID-19 vaccination according to guideline recommendations from 1 March 2021 through 1 July 2021. The outcomes of interest included deaths from any cause and excluding a COVID-19 diagnosis. Observations were cloned to both treatment strategies, censored, and weighted to estimate per-protocol effects. RESULTS: We included 3 158 507 veterans. Under the vaccination strategy, 364 993 received vaccine within 7 days. At 60 days, there were 156 deaths per 100 000 veterans under the vaccination strategy versus 185 deaths under the no vaccination strategy, corresponding to an absolute risk difference of -25.9 (95% confidence limit [CL], -59.5 to 2.7) and relative risk of 0.86 (95% CL, .7 to 1.0). When those with a COVID-19 infection in the first 60 days were censored, the absolute risk difference was -20.6 (95% CL, -53.4 to 16.0) with a relative risk of 0.88 (95% CL, .7 to 1.1). CONCLUSIONS: Vaccination against COVID-19 was associated with a lower but not statistically significantly different risk of death in the first 60 days. These results agree with prior scientific knowledge suggesting vaccination is safe with the potential for substantial health benefits.

Associated factors of depression in primiparas with hypothyroidism during pregnancy.

This cross-sectional study aimed to explore the associated factors of depression in primiparas with hypothyroidism during pregnancy. The research subjects were 200 primiparas with hypothyroidism during pregnancy who were admitted to our hospital between December 2016 and December 2019. Self-rating depression scale scores were used to evaluate the depression, and the incidence of depression were examined. The data from all the subjects were collected to compare the differences between primiparas with hypothyroidism during pregnancy with and without depression. A logistic regression equation was used to analyze the influencing factors of depression in these patients. Of the 200 primiparas who took part in this study, 27 suffered from depression, accounting for 13.50%. There were differences in age, education level, economic income, sleep quality, and conjugal relations between the depressed and the nondepressed participants. When the above factors were included in the logistic regression equation, it was found that the odds ratio values for these factors were all >1, which indicated that they had an influence on maternal depression in primiparas with hypothyroidism during pregnancy. This study demonstrated that pregnancy-associated hypothyroidism in primiparas is affected by age, education level, economic income, sleep quality, and conjugal relations, all of which increase the incidence of depression. Relevant preventive measures should be provided in clinical practice to avoid the occurrence of depression.

Design of high performance nitrogen reduction electrocatalysts by doping defective polyoxometalate with a single atom promoter.

Single-atom catalysts (SACs) are emerging as promising candidates for electrochemical nitrogen reduction reaction (NRR). Previous studies have shown that the single-atom centers of SACs can not only serve as active sites, but also act as promoters to affect the catalytic properties. However, the use of single metal atoms as promoters in electrocatalysis has rarely been studied. In this work, the defective Keggin-type phosphomolybdic acid (PMA) is used as a substrate to support the single metal atoms. We aim to tune the electronic structures of the exposed molybdenum active sites on defective PMA by using these supported single atoms as promoters for efficient NRR. Firstly, the stability and N2 adsorption capacity were studied to screen for an effective catalyst capable of activating N2. Most of the SACs were found to have good stability and N2 adsorption capacity. Then, we compared the selectivity and NRR activity of the catalysts and found that catalysts with metal atom promoters have improved NRR selectivity and activity. Finally, electronic structure analysis was carried out to understand the promoting effect of the promoter on N2 activation and the activity of the NRR process. This work provides a new strategy for designing efficient catalysts for electrocatalytic reactions by introducing promoters.

Effect of tubeimoside I on the activity of cytochrome P450 enzymes in human liver microsomes.

This study assessed the effect of tubeimoside I on CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 to reveal the potential of tubeimoside I to induce drug-drug interaction.The evaluation of cytochromes P450 enzyme (CYP) activity was performed in pooled human liver microsomes with probing substrates of CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Typical inhibitors were employed as positive controls and the effect of 0, 2.5, 5, 10, 25, 50, and 100 µM tubeimoside I was investigated.The activity of CYP2D6, 2E1, and 3A4 was significantly inhibited by tubeimoside I with the IC50 values of 10.34, 11.58, and 9.74 µM, respectively. The inhibition of CYP2D6 and 2E1 was competitive with the Ki value of 5.66 and 5.29 µM, respectively. While the inhibition of CYP3A4 was non-competitive with the Ki value of 4.87 µM. Moreover, the inhibition of CYP3A4 was time-dependent with the KI and Kinact values of 0.635 µM-1 and 0.0373 min-1, respectively.Tubeimoside I served as a competitive inhibitor of CYP2D6 and 2E1 exerting weak inhibition and a non-competitive inhibitor of CYP3A4 exerting moderate inhibition.

Gut-joint axis: Oral Probiotic ameliorates Osteoarthritis.

Osteoarthritis (OA) etiology is multifactorial, and its prevalence is growing globally. The Gut microbiota shapes our immune system and impacts all aspects of health and disease. The idea of utilizing probiotics to treat different conditions prevails. Concerning musculoskeletal illness and health, current data lack the link to understand the interactions between the host and microbiome. We report that S. thermophilus, L. pentosus (as probiotics), and γ-aminobutyric acid (GABA) harbour against osteoarthritis in vivo and alleviate IL-1ß induced changes in chondrocytes in vitro. We examined the increased GABA concentration in mice's serum and small intestine content followed by bacterial treatment. The treatment inhibited the catabolism of cartilage and rescued mice joints from degradation. Furthermore, the anabolic markers upregulated and decreased inflammatory markers in mice knee joints and chondrocytes. This study is the first to represent GABA's chondrogenic and chondroprotective effects on joints and human chondrocytes. This data provides a foundation for future studies to elucidate the role of GABA in regulating chondrocyte cell proliferation. These findings opened future horizons to understanding the gut-joint axis and OA treatment. Thus, probiotic/GABA therapy shields OA joints in mice and could at least serve as adjuvant therapy to treat osteoarthritis.

Pulmonary Adenoid Cystic Carcinoma Mimicking Asthma-Like Symptoms: A Case Report and Literature Review.

Introduction: Pulmonary adenoid cystic carcinoma (PACC) is a rare, low-grade malignant salivary gland-type tumor characterized by a dormant onset and slow progression, often leading to misdiagnosis. Due to its rarity, limited cases have been reported in the literature. This report aimed to enhance clinicians' understanding of this infrequent disease. Case Presentation: We present the case of a 41-year-old female patient diagnosed with PACC. Our report provides a comprehensive analysis of the patient's imaging, pathology, and treatment, with a particular focus on immunohistochemical results. Importantly, we emphasize the significance of considering foreign bodies and tumors in the bronchus when encountering asthma-like symptoms unresponsive to conventional treatments. Due to the uncertain etiology and pathophysiology of PACC, there are currently no established guidelines for chemotherapy and radiotherapy. Conclusion: PACC predominantly manifests as bronchial lesions without significant clinical heterogeneity. Therefore, it is crucial to consider foreign bodies and tumors in the bronchus when dealing with asthma-like symptoms, especially in patients without chronic lung disease who do not respond to anti-infective, antispasmodic, and antiasthmatic treatments. Additionally, meticulous examination of lesions is essential for timely diagnosis and intervention, ultimately improving patient survival rates.

Dithiine-linked metalphthalocyanine framework with undulated layers for highly efficient and stable H2O2 electroproduction.

Realization of stable and industrial-level H2O2 electroproduction still faces great challenge due large partly to the easy decomposition of H2O2. Herein, a two-dimensional dithiine-linked phthalocyaninato cobalt (CoPc)-based covalent organic framework (COF), CoPc-S-COF, was afforded from the reaction of hexadecafluorophthalocyaninato cobalt (II) with 1,2,4,5-benzenetetrathiol. Introduction of the sulfur atoms with large atomic radius and two lone-pairs of electrons in the C-S-C linking unit leads to an undulated layered structure and an increased electron density of the Co center for CoPc-S-COF according to a series of experiments in combination with theoretical calculations. The former structural effect allows the exposition of more Co sites to enhance the COF catalytic performance, while the latter electronic effect activates the 2e- oxygen reduction reaction (2e- ORR) but deactivates the H2O2 decomposition capability of the same Co center, as a total result enabling CoPc-S-COF to display good electrocatalytic H2O2 production performance with a remarkable H2O2 selectivity of >95% and a stable H2O2 production with a concentration of 0.48 wt% under a high current density of 125 mA cm-2 at an applied potential of ca. 0.67 V versus RHE for 20 h in a flow cell, representing the thus far reported best H2O2 synthesis COFs electrocatalysts.

Comparative study on anthropogenic impacts on soil PAHs: Accumulation and source apportionment in tourist and industrial cities in Hebei Province, China.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic contaminants in urban soils. The accumulation and source identifications of PAHs within a city have been frequently studied. However, impacts of urbanization development modes on PAHs accumulation patterns by taking a city as a whole have been seldom reported. Four cities with two development modes in Hebei province, Chengde and Zhangjiakou (tourist cities) and Handan and Tangshan (industrial cities), were selected. The concentrations of 16 priority PAHs in soils in the study areas were investigated. The results showed that the average concentrations of Σ16PAHs in Handan (2517 µg/kg) and Tangshan (2256 µg/kg) were more than twice of those in Chengde (696 µg/kg) and Zhangjiakou (926 µg/kg) approximately. Lines of evidence, provided by a combination of diagnostic ratios, pairwise correlation, and PMF methods, revealed that the dominant sources of PAHs in either city were industrial emission, vehicle emission, and petrogenic/biogenic process but with different proportions. Linear fittings based on Bayesian kernel machine regression analysis (BKMR) were constructed to illustrate the impact of industrialization on PAHs accumulation. The probability of excessing the 10 % (376 µg/kg) and 50 % (1138 µg/kg) of current ∑16PAHs would be higher than 90 % given the gross industrial production per unit area >5.00 × 106 and 20.5 × 106 CNY/km2, respectively. The proposed threshold values of industrialization are of significance for determining industrial structure and proportion in urban management.