Sensitization with Fungal Protease Allergen Establishes Long-Lived, Allergenic Th Cell Memory in the Lung.

Allergic asthma is a chronic inflammatory disease that affects millions of individuals worldwide. Exposure to allergens produced by a variety of otherwise harmless microbes, including fungi, predisposes individuals to immunopathologic disease upon subsequent encounters with allergen. We developed a mouse model that employs a purified protease produced by Aspergillus (Asp f 13) to investigate the contributions of CD4+ Th cells to recurrent lung inflammation. Notably, memory CD4+ T cells enhanced the eosinophil response of sensitized/rechallenged animals. In addition, memory CD4+ T cells maintained allergenic features, including expression of GATA-binding protein 3 and IL-5. Th2 memory T cells persisted in the peribronchiolar interstitium of the lung and expressed markers of tissue residence, such as CD69, CCR8, and IL-33R. Lastly, we identified a peptide epitope contained within Asp f 13 and generated a peptide-MHC class II tetramer. Using these tools, we further demonstrated the durability and exquisite sensitivity of memory T cells in promoting lung eosinophilia. Our data highlight important features of memory T cells that strengthen the notion that memory T cells are principal drivers of eosinophilic disease in murine models of allergic sensitization and episodic airway inflammation.

FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.

MicroRNA-mediated gene silencing is a fundamental mechanism in the regulation of gene expression. It remains unclear how the efficiency of RNA silencing could be influenced by RNA-binding proteins associated with the microRNA-induced silencing complex (miRISC). Here we report that fused in sarcoma (FUS), an RNA-binding protein linked to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), interacts with the core miRISC component AGO2 and is required for optimal microRNA-mediated gene silencing. FUS promotes gene silencing by binding to microRNA and mRNA targets, as illustrated by its action on miR-200c and its target ZEB1. A truncated mutant form of FUS that leads its carriers to an aggressive form of ALS, R495X, impairs microRNA-mediated gene silencing. The C. elegans homolog fust-1 also shares a conserved role in regulating the microRNA pathway. Collectively, our results suggest a role for FUS in regulating the activity of microRNA-mediated silencing.

Dexterous manipulation: differential sensitivity of manipulation and grasp forces to task requirements.

How humans coordinate digit forces to perform dexterous manipulation is not well understood. This gap is due to the use of tasks devoid of dexterity requirements and/or the use of analytical techniques that cannot isolate the roles that digit forces play in preventing object slip and controlling object position and orientation (pose). In our recent work, we used a dexterous manipulation task and decomposed digit forces into FG, the internal force that prevents object slip, and FM, the force responsible for object pose control. Unlike FG, FM was modulated from object lift onset to hold, suggesting their different sensitivity to sensory feedback acquired during object lift. However, the extent to which FG and FM can be controlled independently remains to be determined. Importantly, how FG and FM change as a function of object property is mathematically indeterminate and therefore requires active modulation. To address this gap, we systematically changed either object mass or external torque. The FM normal component responsible for object orientation control was modulated to changes in object torque but not mass. In contrast, FG was distinctly modulated to changes in object mass and torque. These findings point to a differential sensitivity of FG and FM to task requirements and provide novel insights into the neural control of dexterous manipulation. Importantly, our results indicate that the proposed digit force decomposition has the potential to capture important differences in how sensory inputs are processed and integrated to simultaneously ensure grasp stability and dexterous object pose control.NEW & NOTEWORTHY Successful dexterous object manipulation requires simultaneous prevention of object slip and object pose control. How these two task goals are attained can be investigated by decomposing digit forces into grasp and manipulation forces, respectively. We found that these forces were characterized by differential sensitivity to changes in object properties (mass and torque). This finding suggests the involvement of distinct sensorimotor mechanisms that, combined, simultaneously ensure grasp stability and dexterous control of object pose.

Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT.

OBJECTIVE: Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. METHODS: We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. RESULTS: The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. CONCLUSION: Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.

Six novel species of the genus Methanoculleus isolated from various environments in Taiwan.

Taiwan is situated in the subtropical region and its geographical location and topographical features contribute to a rich ecological diversity and scenic landscapes. We investigated the diversity of methanogens in different environments of Taiwan using a culture-dependent method. This report presents the characterization and taxonomy of six hydrogenotrophic methanogens obtained from cold seep sediments (strain FWC-SCC1T and FWC-SCC3T), marine sediments (strain CWC-02T and YWC-01T), estuarine sediments (strain Afa-1T), and a hot spring well (strain Wushi-C6T) in Taiwan. The proposed names of the six novel species are Methanoculleus frigidifontis (type strain FWC-SCC1T=BCRC AR10056T=NBRC 113993T), Methanoculleus oceani (CWC-02T=BCRC AR10055T=NBRC 113992T), Methanoculleus methanifontis (FWC-SCC3T=BCRC AR10057T=NBRC 113994T), Methanoculleus nereidis (YWC-01T=BCRC AR10060T=NBRC 114597T), Methanoculleus formosensis (Afa-1T=BCRC AR10054T=NBRC 113995T), and Methanoculleus caldifontis (Wushi-06T=BCRC AR10059T= NBRC 114596T).

Adsorption-driven reverse osmosis separation of ethanol/water using zeolite nanosheets.

Developing more energy-efficient and cost-effective membrane processes for the separation of ethanol and water represents a strategically important direction to facilitate the production of renewable biofuels. In this study, by employing state-of-the-art molecular simulations, the potential of zeolite nanosheets as reverse osmosis (RO) membranes in ethanol/water separation is investigated. These materials are predicted to offer unprecedentedly high fluxes and more importantly, the ethanol-to-water separation factor can be as large as approximately 800 if the structure is meticulously selected. The separation achieved herein can in fact be considered counter-intuitive as the membrane allows the larger ethanol molecules to permeate through while blocking smaller water molecules. Further investigations reveal that the observed selectivity is strongly correlated with the adsorption selectivity of the bulk materials, suggesting an adsorption-driven mechanism. Promising candidates also appear to have the largest cavity diameter of approximately 6 Å, a size that can be commensurate with the dimensions of ethanol to facilitate its adsorption. The hydrophilicity on the membrane surfaces is as well found to play a non-negligible role. Overall, this study demonstrates the great promise of zeolite nanosheets as RO membranes for extracting anhydrous ethanol from its aqueous mixture and provides guidance toward the selection of promising membrane candidates.

Developing an innovative national ACP-OSCE program in Taiwan: a mixed method study.

OBJECTIVES: To evaluate the process and the comprehensiveness of advance care planning (ACP), we designed a national ACP-OSCE (Objective Structured Clinical Examination) program. METHODS: The program was designed as a 40-minute OSCE test. Participants were categorized as different ACP team members to illustrate realistic scenarios. Preceptors were asked to observe ACP professionals' actions, responses, and communication skills during ACP with standardized patients (SP) through a one-way mirror. Participants' communication skills, medical expertise, legal knowledge, empathetic response and problem-solving skills of ACP were also self-evaluated before and after OSCE. Thematic analysis was used for qualitative analysis. RESULTS: In Nov 2019, a total of 18 ACP teams with 38 ACP professionals completed the ACP-OSCE program, including 15 physicians, 15 nurses, 5 social workers, and 3 psychologists. After the ACP-OSCE program, the average score of communication skills, medical expertise, legal knowledge, empathetic response, ACP problem-solving all increased. Nurses felt improved in medical expertise, legal knowledge, and problem-solving skills, psychologists and social workers felt improved in legal knowledge, while physicians felt no improved in all domain, statistically. Thematic analysis showed professional skills, doctoral-patient communication, benefit and difficulties of ACP were the topics which participants care about. Meanwhile, most participants agreed that ACP-OSCE program is an appropriate educational tool. CONCLUSION: This is the first national ACP-OSCE program in Asia. We believe that this ACP-OSCE program could be applied in other countries to improve the ACP process and quality.

Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Test-Retest Reliability, Criterion-Related Validity, and Ecological Validity of the Test of Visual-Motor Skills, Third Edition, in Kindergarten Children With Developmental Coordination Disorder.

IMPORTANCE: Establishing empirical evidence on the psychometric properties of the Test of Visual-Motor Skills (3rd ed.; TVMS-3) is helpful for guiding its use as an assessment of visual-motor integration (VMI) skills in kindergarten children with developmental coordination disorder (DCD). OBJECTIVE: To investigate the test-retest reliability, criterion-related validity, and ecological validity of the TVMS-3 in Taiwanese kindergarten children with DCD. DESIGN: A nonexperimental, descriptive, correlational design. SETTING: A hospital in Central Taiwan. PARTICIPANTS: Fifty-seven kindergarten children with DCD were recruited in the study. OUTCOMES AND MEASURES: Intraclass correlation coefficient, percentage of minimal detectable change, and paired t test (Wilcoxon signed rank test) were used to investigate the test-retest reliability of the TVMS-3. The correlations (Pearson's r) between the TVMS-3 accuracy score and the scores of each of the four domains and the adaptive behavior composite score of the Vineland Adaptive Behavior Scales (3rd ed.; Vineland-3) were calculated, respectively, to examine criterion-related validity and ecological validity. RESULTS: The accuracy score of the TVMS-3 had excellent test-retest reliability and acceptable random measurement error. Moreover, it showed good criterion-related validity and sufficient ecological validity with the Vineland-3 in Taiwanese kindergarten children with DCD. CONCLUSIONS AND RELEVANCE: The accuracy score of the TVMS-3 is applicable to Taiwanese kindergarten children with DCD in clinical and research settings. Plain-Language Summary: The accuracy score of the Test of Visual-Motor Skills (3rd ed.; TVMS-3) is a useful assessment tool to detect deficits in visual-motor integration for Taiwanese kindergarten children with developmental coordination disorder. The TVMS-3 has excellent test-retest reliability, good criterion-related validity, and sufficient ecological validity.

Taiwan Society of Cardiology Heart Failure Registry 2020: Rationale and Design.

Background: Heart failure (HF) is a significant public health problem worldwide. Death and rehospitalization rates are similar across different HF phenotypes. However, the existing Taiwanese HF registries mainly enrolled inpatients with HF and reduced ejection fraction (HFrEF) before 2019, so their results may not apply to outpatients or patients with HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF) phenotypes. Methods: The Taiwan Society of Cardiology Heart Failure Registry 2020 is a prospective, multicenter, observational registry that will enroll patients with HF from 27 hospitals in Taiwan between 2020 and 2022 and will be followed for two years. Patients eligible for enrollment include those admitted due to acute decompensated heart failure or outpatients with a history of hospitalization for heart failure within the past six months. The registry will collect patient demographics, medical history, HF diagnosis, medication use, examination results, and comorbidities. The registry plans to enroll 3,370 patients, with the distribution of HFrEF/HFmrEF/HFpEF as 59%/13%/28%. Follow-up intervals will occur every six months for up to two years to monitor clinical outcomes and major cardiac interventions. The registry will conclude in December 2024. Conclusions: The Taiwan Society of Cardiology Heart Failure Registry 2020 is a comprehensive and meticulous effort to demonstrate the epidemiology, adherence to guidelines, clinical outcomes, and disease progression of Taiwanese patients with HF in contemporary clinical practice.

2024 Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

2024 TSOC/TSPS Joint Consensus: Strategies for Advanced Vascular Wound Management in Arterial and Venous Diseases.

The Taiwan Society of Cardiology (TSOC) and Taiwan Society of Plastic Surgery (TSPS) have collaborated to develop a joint consensus for the management of patients with advanced vascular wounds. The taskforce comprises experts including preventive cardiologists, interventionists, and cardiovascular and plastic surgeons. The consensus focuses on addressing the challenges in diagnosing, treating, and managing complex wounds; incorporates the perfusion evaluation and the advanced vascular wound care team; and highlights the importance of cross-disciplinary teamwork. The aim of this joint consensus is to manage patients with advanced vascular wounds and encourage the adoption of these guidelines by healthcare professionals to improve patient care and outcomes. The guidelines encompass a range of topics, including the definition of advanced vascular wounds, increased awareness, team structure, epidemiology, clinical presentation, medical treatment, endovascular intervention, vascular surgery, infection control, advanced wound management, and evaluation of treatment results. It also outlines a detailed protocol for assessing patients with lower leg wounds, provides guidance on consultation and referral processes, and offers recommendations for various wound care devices, dressings, and products. The 2024 TSOC/TSPS consensus for the management of patients with advanced vascular wounds serves as a catalyst for international collaboration, promoting knowledge exchange and facilitating advancements in the field of advanced vascular wound management. By providing a comprehensive and evidence-based approach, this consensus aims to contribute to improved patient care and outcomes globally.

MicroRNA-145-5p suppresses cell proliferation, migration, and invasion in upper tract urothelial carcinoma by targeting 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase.

Upper tract urothelial carcinoma (UTUC), including renal, pelvic, and ureteral carcinoma, has a high incidence rate in Taiwan, which is different from that in Western countries. Therefore, it is imperative to elucidate the mechanisms underlying UTUC growth and metastasis. To explore the function of miR-145-5p in UTUC, we transfected the BFTC909 cell line with miR-145-5p mimics and analyzed the differences in protein levels by performing two-dimensional polyacrylamide gel electrophoresis. Real-time polymerase chain reaction and Western blot analysis were used to analyze 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inositol monophosphate cyclohydrolase (ATIC) messenger RNA and protein levels. A dual-luciferase assay was performed to identify the target of miR-145-5p in ATIC. The effects of miR-145-5p and ATIC expression by cell transfection on cell proliferation, migration, and invasion were also assessed. miR-145-5p downregulated ATIC protein expression. High ATIC expression is associated with tumor stage, metastasis, recurrence, and a poor prognosis in patients with UTUC. Cell function assays revealed that ATIC knockdown inhibited the proliferation, migration, and invasive abilities of UTUC cells. In contrast, miR-145-5p affected the proliferation, migration, and invasive abilities of UTUC cells by directly targeting the 3'-untranslated regions of ATIC. Furthermore, we used RNA sequencing and Ingenuity Pathway Analysis to identify possible downstream genes regulated by ATIC and found that miR-145-5p regulated the protein levels of fibronectin 1, Slug, cyclin A2, cyclin B1, P57, and interferon-induced transmembrane 1 via ATIC. ATIC may be a valuable predictor of prognosis and a potential therapeutic target for UTUC.

A non-neutralizing antibody broadly protects against influenza virus infection by engaging effector cells.

Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HAmg) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HAfg) during lethal dose challenge. We employed a single B-cell screening platform to isolate the cross-protective monoclonal antibody (mAb) 651 from mice immunized with the HAmg of A/Brisbane/59/2007 (H1N1) influenza virus (Bris/07). The mAb 651 recognized the head domain of a broad spectrum of HAs from groups 1 and 2 influenza A viruses and offered prophylactic and therapeutic efficacy against A/California/07/2009 (H1N1) (Cal/09) and Bris/07 infections in mice. The antibody did not possess neutralizing activity; however, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis mediated by natural killer cells and alveolar macrophages were important in the protective efficacy of mAb 651. Together, this study highlighted the significance of effector functions for non-neutralizing antibodies to exhibit protection against influenza virus infection.

Polar map-free 3D deep learning algorithm to predict obstructive coronary artery disease with myocardial perfusion CZT-SPECT.

PURPOSE: Deep learning (DL) models have been shown to outperform total perfusion deficit (TPD) quantification in predicting obstructive coronary artery disease (CAD) from myocardial perfusion imaging (MPI). However, previously published methods have depended on polar maps, required manual correction, and normal database. In this study, we propose a polar map-free 3D DL algorithm to predict obstructive disease. METHODS: We included 1861 subjects who underwent MPI using cadmium-zinc-telluride camera and subsequent coronary angiography. The subjects were divided into parameterization and external validation groups. We implemented a fully automatic algorithm to segment myocardium, perform registration, and apply normalization. We further flattened the image based on spherical coordinate system transformation. The proposed model consisted of a component to predict patent arteries and a component to predict disease in each vessel. The model was cross-validated in the parameterization group, and then further tested using the external validation group. The performance was assessed by area under receiver operating characteristic curves (AUCs) and compared with TPD. RESULTS: Our algorithm preprocessed all images accurately as confirmed by visual inspection. In patient-based analysis, the AUC of the proposed model was significantly higher than that for stress-TPD (0.84 vs 0.76, p < 0.01). In vessel-based analysis, the proposed model also outperformed regional stress-TPD (AUC = 0.80 vs 0.72, p < 0.01). The addition of quantitative images did not improve the performance. CONCLUSIONS: Our proposed polar map-free 3D DL algorithm to predict obstructive CAD from MPI outperformed TPD and did not require manual correction or a normal database.

Phocaeicola oris sp. nov., an anaerobic bacterium isolated from the saliva of a patient with oral squamous cell carcinoma.

A Gram-stain-negative or -positive, strictly anaerobic, non-spore-forming and pleomorphic bacterium (designated 14-104T) was isolated from the saliva sample of a patient with oral squamous cell carcinoma. It was an acid-tolerant neutralophilic mesophile, growing at between 20 and 40 °C (with optimum growth at 30 °C) and pH between pH 3.0 and 7.0 (with optimum growth at pH 6.0-7.0). It contained anteiso-C15 : 0 and C15 : 0 as the major fatty acids. The genome size of strain 14-104T was 2.98 Mbp, and the G+C content was 39.6 mol%. It shared <87 % 16S rRNA sequence similarity, <71 % orthologous average nucleotide identity, <76 % average amino acid identity and <68 %% of conserved proteins with its closest relative, Phocaeicola abscessus CCUG 55929T. Reconstruction of phylogenetic and phylogenomic trees revealed that strain 14-104T and P. abscessus CCUG 55929T were clustered as a distinct clade without any other terminal node. The phylogenetic and phylogenomic analyses along with physiological and chemotaxonomic data indicated that strain 14-104T represents a novel species in the genus Phocaeicola, for which the name Phocaeicola oris sp. nov. is proposed. The type strain is 14-104T (=BCRC 81305T= NBRC 115041T).

Photocatalytic Oxidative Cleavage of Alkenes by Molecular Oxygen: Reaction Scope, Mechanistic Insights, and Flow Application.

The oxidative cleavage of C═C bonds with molecular oxygen was promoted effectively by a catalytic amount of a decatungstate photocatalyst using black light irradiation (365 nm). Not only aromatic ketones but also aliphatic ketones were obtained by the photocatalytic protocol. The continuous flow reaction of α-methylstyrene using a high-power ultraviolet light-emitting diode (365 nm) dramatically decreased the reaction time.

Kinetics of the Simplest Criegee Intermediate Reaction with Water Vapor: Revisit and Isotope Effect.

The kinetics of the simplest Criegee intermediate (CH2OO) reaction with water vapor was revisited. By improving the signal-to-noise ratio and the precision of water concentration, we found that the kinetics of CH2OO involves not only two water molecules but also one and three water molecules. Our experimental results suggest that the decay of CH2OO can be described as d[CH2OO]/dt = -kobs[CH2OO]; kobs = k0 + k1[water] + k2[water]2 + k3[water]3; k1 = (4.22 ± 0.48) × 10-16 cm3 s-1, k2 = (10.66 ± 0.83) × 10-33 cm6 s-1, k3 = (1.48 ± 0.17) × 10-50 cm9 s-1 at 298 K and 300 Torr with the respective Arrhenius activation energies of Ea1 = 1.8 ± 1.1 kcal mol-1, Ea2 = -11.1 ± 2.1 kcal mol-1, Ea3 = -17.4 ± 3.9 kcal mol-1. The contribution of the k3[water]3 term becomes less significant at higher temperatures around 345 K, but it is not ignorable at 298 K and lower temperatures. By quantifying the concentrations of H2O and D2O with a Coriolis-type direct mass flow sensor, the kinetic isotope effect (KIE) was investigated at 298 K and 300 Torr and KIE(k1) = k1(H2O)/k1(D2O) = 1.30 ± 0.32; similarly, KIE(k2) = 2.25 ± 0.44 and KIE(k3) = 0.99 ± 0.13. These mild KIE values are consistent with theoretical calculations based on the variational transition state theory, confirming that the title reaction has a broad and low barrier, and the reaction coordinate involves not only the motion of a hydrogen atom but also that of an oxygen atom. Comparing the results recorded under 300 Torr (N2 buffer gas) with those under 600 Torr, a weak pressure effect of k3 was found. From quantum chemistry calculations, we found that the CH2OO + 3H2O reaction is dominated by the reaction pathways involving a ring structure consisting of two water molecules, which facilitate the hydrogen atom transfer, while the third water molecule is hydrogen-bonded outside the ring. Furthermore, analysis based on dipole capture rates showed that the CH2OO(H2O) + (H2O)2 and CH2OO(H2O)2 + H2O pathways will dominate in the three water reaction.

Inflammation and renal function decline in chronic coronary syndrome: a prospective multicenter cohort study.

BACKGROUND: Renal function decline is a frequently encountered complication in patients with chronic coronary syndrome. Aside from traditional cardiovascular risk factors, the inflammatory burden emerged as the novel phenotype that compromised renal prognosis in such population. METHODS: A cohort with chronic coronary syndrome was enrolled to investigate the association between inflammatory status and renal dysfunction. Levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α), adiponectin, matrix metalloproteinase-9, interleukin-6, lipoprotein-associated phospholipase A2, were assessed. Renal event was defined as > 25% decline in estimated glomerular filtration rate (eGFR). Inflammatory scores were calculated based on the aggregate of hs-CRP, TNF-α, and adiponectin levels. RESULTS: Among the 850 enrolled subjects, 145 patients sustained a renal event during an averaged 3.5 years follow-up. Multivariate analysis with Cox regression suggested elevations in hs-CRP, TNF-α, and adiponectin levels were independent risk factors for the occurrence of a renal event. Whereas, Kaplan-Meier curve illustrated significant correlation between high TNF-α (P = 0.005), adiponectin (P < 0.001), but not hs-CRP (P = 0.092), and eGFR decline. The aggregative effect of these biomarkers was also distinctly correlated with renal events (score 2: P = 0.042; score 3: P < 0.001). CONCLUSIONS: Inflammatory burden was associated with eGFR decline in patients with chronic coronary syndrome.

Qing Yan Li Ge Tang Induces Apoptosis in Human OEC-M1 Oral Cancer Cells.

Background: Since most patients with oral cancer do not benefit from current treatments, new therapeutic strategies or drugs must be developed to improve patient prognosis. Qing Yan Li Ge Tang (QYLGT), a Chinese herbal medicine, is known for its anticancer activity. This study aimed to investigate whether QYLGT has anticancer effects on human OEC-M1 oral cancer cells. Methods: To evaluate whether QYLGT affects viability, morphology, and colony formation ability of the OEC-M1 cells, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, morphology study, and colony formation assay were performed, respectively. Each assay was carried out in triplicate, and the whole set of experiments was performed three times independently. To investigate whether QYLGT induces apoptotic effects in OEC-M1 cells, the enzyme-linked immunosorbent (ELISA) was carried out to quantify cytokeratin 18 fragment (an apoptosis marker). Each assay was carried out in triplicate, and the whole set of experiments was performed three times independently. The immunoblotting assay was performed to detect the protein expression after QYLGT treatment. The whole set of experiments was performed two times independently. Results: The results from the MTT and colony formation assays indicate that QYLGT inhibited the cell viability and clonogenic growth capacity of OEC-M1 cells. The morphology study shows that QYLGT increased plasma membrane blebbing in OEC-M1 clles. The results of ELISA and an immunoblotting assay show that QYLGT increased cytokeratin 18 fragment release and poly ADP-ribose polymerase cleavage (another apoptosis marker) in OEC-M1 cells. In addition, the results from immunoblotting assay show that QYLGT also activated apoptotic executor proteins, including caspase-8, caspase-9, and caspase-3, and the results of ELISA indicate that treatment with the pan-caspase inhibitor, Z-VAD-FMK, inhibited QYLGT-induced cytokeratin 18 fragment release. These results indicate that QYLGT inhibited cell viability in OEC-M1 cells and induced OEC-M1 apoptosis through caspase activation. Additionally, QYLGT-activated c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-kappa B (NF-κB), and the related inhibitors, including SP600125, PD184352, SB202190, and Bay11-7082, were used to confirm which signaling was involved in QYLGT-induced apoptosis. Moreover, only Bay11-7082, the NF-κB inhibitor, could suppress QYLGT-induced the release of cytokeratin 18 fragments from OEC-M1 cells. Conclusions: QYLGT induced apoptosis in OEC-M1 cells via the NF-κB pathway.