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Ching-Hui Huang,1–3,* Ya-Yun Lai,4,* Yu-Jui Kuo,4,5 Su-Ching Yang,6 Yu-Jun Chang,7 Kuo-Kuan Chang,8 Wen-Kang Chen4 1Division of Cardiology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 2Department of Beauty Science, Graduate Institute of Beauty Science Technology, Chienkuo Technology University, Changhua, Taiwan; 3School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Applied Cosmetology, National Tainan Junior College of Nursing, Tainan, Taiwan; 5Department of Traditional Chinese Medicine, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan; 6Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan; 7Epidemiology and Biostatistics Center, Changhua Christian Hospital, Changhua, Taiwan; 8Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan *These authors contributed equally to this work Background: Liver cirrhosis is an uncommon but not rare side effect of amiodarone-induced hepatotoxicity. Patients with hepatitis B virus and hepatitis C virus infections are at a high risk for developing liver cirrhosis. However, the relationship between this treatment and risk of liver cirrhosis in high-risk chronic hepatitis B and chronic hepatitis C patients is unknown.Patients and methods: The present study identified amiodarone users (N=8,081) from the Taiwan National Health Insurance Research Database from 1997 through 2013. A total of 32,324 subjects with age, comorbidities, gender, and index date-matched non-amiodarone users were selected as controls (non-amiodarone cohort). The incidences of cumulative liver cirrhosis were compared between cohorts. Stratified Cox’s regression hazard models were used to assess possible comorbidity-attributable risks for liver cirrhosis.Results: The amiodarone cohort had a nonsignificant risk of liver cirrhosis compared with the non-amiodarone cohort, with a HR of 1.17 (95% CI: 0.93–1.47; P=0.1723). Patients with specific comorbid diseases, including type 2 diabetes mellitus, chronic hepatitis B, chronic hepatitis C, and heart failure, were probably at a high risk of developing liver cirrhosis. The use of statins was associated with a significant 42% reduction in the risk of liver cirrhosis.Conclusion: Patients in the amiodarone cohort had no excess risk of liver cirrhosis compared with patients in the non-amiodarone cohort. Long-term surveillance for liver toxicity in high-risk patients with amiodarone treatment is suggested. Keywords: amiodarone, liver cirrhosis, Taiwan, hepatitis

Shu-Wei Chen,1–3,* Quan Zhang,1–3,* Zhu-Ming Guo,1–3 Wen-Kuan Chen,1–3 Wei-Wei Liu,1–3 Yan-Feng Chen,1–3 Qiu-Li Li,1–3 Xue-Kui Liu,1–3 Hao Li,1–3 Dian Ou-Yang,1–3 Wei-Chao Chen,1–3 Xiao-Yan Fu,1–3 Xi-Di Wang,1–3 An-Kui Yang,1–3 Jin-Xin Bei,2–4 Ming Song1–3 1Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 2State Key Laboratory of Oncology in South China, 3Collaborative Innovation Center of Cancer Medicine, 4Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China *These authors contributed equally to this work Background: Global data demonstrate minimal improvement in the survival rate for oral cavity cancer (OCC) patients. We wished to know whether or not clinical features and survival rate have changed over time for OCC patients receiving initial treatment and follow-up at a large cancer center in China. Methods: Clinical features and survival data were collected on patients diagnosed during the successive decades of 1960–1969 (n=253), 1970–1979 (n=497), 1980–1989 (n= 659), 1990–1999 (n=793), and 2000–2009 (n=1,160) at the Sun Yat-sen University Cancer Center. Results: Over time, the overall 5-year survival rate for OCC patients was 52.0%. According to tumor localization, this rate was 71.4% for lip cancer, 56.3% for oral tongue cancer, and 42.7% for other parts of the oral cavity. From the 1960s to the 2000s, the 5-year survival rate steadily improved from 47.8% to 55.6% (P

A chiral W-shaped fully π-extended double [7]helicene ( ED7H ) has been synthesized and fully characterized. It displays fluorescence emission (λ em = 636 nm) with a quantum yield (Φ f ) of 0.10. In comparison to its X-shaped and monomict π-extended [7]helicene analogues, enantiopure W-shaped ED7H exhibited superior chiral optical characteristics, including distinct circular dichroism signals from 400 to 650 nm, a good dissymmetric emission factor | g lum | of 4 × 10 -3 , and a circularly polarized luminescence brightness value B CPL of 42 M -1 cm -1 .

The testis, as one of the important reproductive organs in men, has two major functions of secreting androgens and producing sperm. Androgen and spermatogenesis are the key factors for the evaluation of the testicular function. The lack of androgen or the decline of spermatogenic function is both a symbolic manifestation and a "product" of testis aging. In order to gain a deeper insight into the relationship between testis aging and overall health, this article reviews the relevant literature based on the correlation of androgen deficiency with various systemic diseases and the belief in the impacts of testis aging on the health of the cardiovascular and nervous systems through different channels, the development and progression of metabolic diseases, orthopedic diseases, PCa, kidney disease, peptic ulcer and other diseases. All these suggest that adequate attention should be paid to the studies of male reproductive health and its impact on overall health, so as to provide some new ideas and evidence for clinical diagnosis and treatment of relevant conditions.

Background and Purpose: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism., Experimental Approach: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway., Key Results: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice., Conclusion and Implications: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder., (© 2024 British Pharmacological Society.)

Objectives: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD)., Methods: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo., Results: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF + ECMO-neutrophil counts and ACKR3 + effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors., Conclusions: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To establish a medically valuable normal reference interval of follicle-stimulating hormone (FSH) levels in males with normal semen and to assess the predictive value of FSH in males exhibiting semen abnormalities., Methods: The study involved male patients who underwent their initial serum sex hormone test and semen test between October 2013 and June 2023. The reference interval was identified as the 95% confidence interval (CI) of FSH values in the patients with normal semen parameters. Then, in the total study population, receiver operating characteristic (ROC) curves were performed to evaluate the discriminatory ability of FSH for oligozoospermia and non-obstructive azoospermia (NOA). Besides, multivariable logistic regression was performed to investigate the association of FSH with oligozoospermia and NOA adjusted by age., Results: A total of 11,929 patients were finally enrolled in the study. The normal reference interval of FSH ranged from 1.70 IU/L to 7.60 IU/L (median: 3.98 IU/L) based on 4595 patients with normal semen routine parameters. In the total patients, ROC curves showed FSH to have a "fair" discriminatory ability for oligozoospermia (area under receiver operating characteristic curve (AUC) 0.747, threshold 7.32 IU/L, accuracy 0.734, positive predictive value (PPV) 0.754, negative predictive value (NPV) 0.726), while ROC curves showed FSH to have a "excellent" discriminatory ability for NOA (AUC: 0.921, threshold 10.18 IU/L, accuracy 0.903, PPV 0.593, NPV 0.972). Besides, multivariable logistic regression showed that FSH ≥ 7.32 IU/L was associated with a 8.51-fold increase in the risk of oligozoospermia adjusted by age, while FSH ≥ 10.18 IU/L was associated with a 38.93-fold increase in the risk of NOA., Conclusions: Our findings indicated that the reference interval for FSH in males with normal semen was 1.70-7.60 IU/L and found that FSH was capable of effectively discerning oligospermia and NOA., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes., Methods: The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes., Results: The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528)., Conclusions: Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Photocatalytic CO 2 reduction is one of the best solutions to solve the global energy crisis and to realize carbon neutralization. The tetradentate phosphine-bipyridine (bpy)-phosphine (PNNP)-type Ir(III) photocatalyst, Mes-IrPCY2, was reported with a high HCOOH selectivity but the photocatalytic mechanism remains elusive. Herein, we employ electronic structure methods in combination with radiative, nonradiative, and electron transfer rate calculations, to explore the entire photocatalytic cycle to either HCOOH or CO, based on which a new mechanistic scenario is proposed. The catalytic reduction reaction starts from the generation of the precursor metal-to-ligand charge transfer ( 3 MLCT) state. Subsequently, the divergence happens from the 3 MLCT state, the single electron transfer (SET) and deprotonation process lead to the formation of one-electron-reduced species and Ir(I) species, which initiate the reduction reaction to HCOOH and CO, respectively. Interestingly, the efficient occurrence of proton or electron transfer reduces barriers of critical steps. In addition, nonadiabatic transitions play a nonnegligible role in the cycle. We suggest a lower free-energy barrier in the reaction-limiting step and the very efficient SET in 3 MLCT are cooperatively responsible for a high HCOOH selectivity. The gained mechanistic insights could help chemists to understand, regulate, and design photocatalytic CO 2 reduction reaction of similar function-integrated molecular photocatalyst., (© 2023 Wiley-VCH GmbH.)

Background: Synovial chondromatosis (SC) primarily affects the major joints and is characterized by the formation of benign cartilaginous nodules. In the present study, we evaluated the differences in the histology and gene expression of SC and normal cartilages and further elucidated the function of hub genes in SC., Methods: Histological staining and biochemical analysis were performed to measure collagen and glycosaminoglycan (GAG) contents in SC and normal cartilage samples. Then, microarray analysis was performed using knee joint samples (three normal and three SC samples) to identify the differentially expressed genes (DEGs). Subsequently, bioinformatics analysis was performed to identify the hub genes and explore the mechanisms underlying SC. The intersection of the top 10 upregulated DEGs, top 10 downregulated DEGs, and hub genes was validated in SC tissues. Lastly, in vitro experiments and our clinical cohort were used to determine the potential biological functions and diagnostic value, respectively, of the most significant gene., Results: The GAG and collagen contents were comparable to or higher in SC tissues than in normal tissues. Microarray analysis revealed 143 upregulated and 107 downregulated DEGs in SC. Furthermore, functional enrichment analysis revealed an association between immunity and metabolism-related pathways and SC development. Among 20 hub genes, two intersection genes, namely, collagen type III alpha 1 chain (COL3A1) and HSPA8, were notably expressed in SC tissues, with COL3A1 exhibiting a more significant difference in mRNA expression. Furthermore, COL3A1 can promote chondrocyte migration and cell cycle progression. Additionally, clinical data revealed COL3A1 can be a diagnostic marker for primary SC (AUC = 0.82) and be a positive correlation with neutrophil-to-lymphocyte ratio., Conclusions: These results suggest that SC tissues contained the abundant GAG and collagen. COL3A1 can affect the function of chondrocytes and be a diagnostic marker of primary SC patients. These findings provide a novel approach and a fundamental contribution for diagnosis and treatment in SC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Telemedicine can facilitate social distancing during an infectious disease pandemic and reduce the burden on health-care resources. Moreover, telemedicine can be utilized for medical care in remote island regions, in home health care, and during isolated major disasters such as regional earthquakes. However, the effectiveness of telemedicine for emergency consultation remains unclear. This study introduced and analyzed the national emergency medical teleconsultation (NEMTC) established in Taiwan in 2022 during the COVID-19 pandemic., Methods: In response to the COVID-19 pandemic, Taiwan's Centers for Disease Control established a temporary 24-h NEMTC contingency system. Patient information was collected from consultations through the NEMTC from April 28 to June 28, 2022. After successful consultation, physicians made recommendations for home observation, emergency department (ED) visit, or outpatient follow-up. ED visits were divided into two categories, namely self-transport and transport, by the emergency medical service system (EMSS)., Results: During the aforementioned period, 20,902 consultation requests were made through the NEMTC, and 11,804 consultations (56.5% of 20,902) were successful. Consultation success rates were significantly higher for those who had a consultation between 08:00 and 16:00, had a waiting time of less than 10 min, and were not aged between 18 and 45 years. Moreover, 8.2% of the analyzed patients were advised to visit the ED, and only 0.4% required ambulance transportation. Children and older individuals and patients with cardiovascular symptoms, shortness of breath, or neurological or abdominal symptoms had a significantly higher chance of being referred to the ED than did other individuals., Conclusions: The NEMTC response system can enhance the efficiency of the EMSS and can reduce the burden of patients with mild conditions overloading the EMSS and EDs. The NEMTC could serve as an effective rapid response system during future pandemics., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Recently, chalcogen bond catalysts with telluronium cations have garnered considerable attention in organic reactions. In this work, chalcogen bond catalysis on the bromination reaction of anisole with N-bromosuccinimide (NBS) with the telluronium cationic catalysts has been explored with density functional theory (DFT). The catalytic reaction is divided into two stages: the bromine transfer step and the proton transfer step. Based on the computational results, one can find the rate-determining step is the bromine transfer step. Moreover, the present study elucidates that a stronger chalcogen bond between catalysts and NBS will give better catalytic performance. Additionally, this work also clarified the importance of the electrostatic and polarization effects in the chalcogen bond between the oxygen atom of NBS and the Te atom of the catalyst in this bromination reaction. The electrostatic and polarization effects are significantly influenced by the electron-withdrawing ability of the substitution groups on the catalysts. Moreover, the structure-property relationship between the strength of chalcogen bond, electrostatic effect, polarization effect and catalytic performance are established for the design of more efficient chalcogen bond catalysts., (© 2023 Wiley-VCH GmbH.)

Nonadiabatic dynamics (NAMD) simulations have become powerful tools for elucidating complicated photoinduced processes in various systems from molecules to semiconductor materials. In this review, we present an overview of our recent research on photophysics of molecular systems and periodic semiconductor materials with the aid of ab initio NAMD simulation methods implemented in the generalized trajectory surface-hopping (GTSH) package. Both theoretical backgrounds and applications of the developed NAMD methods are presented in detail. For molecular systems, the linear-response time-dependent density functional theory (LR-TDDFT) method is primarily used to model electronic structures in NAMD simulations owing to its balanced efficiency and accuracy. Moreover, the efficient algorithms for calculating nonadiabatic coupling terms (NACTs) and spin-orbit couplings (SOCs) have been coded into the package to increase the simulation efficiency. In combination with various analysis techniques, we can explore the mechanistic details of the photoinduced dynamics of a range of molecular systems, including charge separation and energy transfer processes in organic donor-acceptor structures, ultrafast intersystem crossing (ISC) processes in transition metal complexes (TMCs), and exciton dynamics in molecular aggregates. For semiconductor materials, we developed the NAMD methods for simulating the photoinduced carrier dynamics within the framework of the Kohn-Sham density functional theory (KS-DFT), in which SOC effects are explicitly accounted for using the two-component, noncollinear DFT method. Using this method, we have investigated the photoinduced carrier dynamics at the interface of a variety of van der Waals (vdW) heterojunctions, such as two-dimensional transition metal dichalcogenides (TMDs), carbon nanotubes (CNTs), and perovskites-related systems. Recently, we extended the LR-TDDFT-based NAMD method for semiconductor materials, allowing us to study the excitonic effects in the photoinduced energy transfer process. These results demonstrate that the NAMD simulations are powerful tools for exploring the photodynamics of molecular systems and semiconductor materials. In future studies, the NAMD simulation methods can be employed to elucidate experimental phenomena and reveal microscopic details as well as rationally design novel photofunctional materials with desired properties.

Both DFT and TD-DFT methods are used to elaborate on the excited-state properties and dual-emission mechanism of a thiolate-protected Au42 nanocluster. A three-state model (S 0 , S 1 , and T 1 ) is proposed with respect to the results. The intersystem crossing (ISC) process from S 1 to T 1 benefits from a small reorganization energy due to the similar geometric structures of S 1 and T 1 . However, the ISC process is suppressed by relatively small spin-orbit coupling resulting from the similarity of the electronic structures of S 1 and T 1 . As a result of the counterbalance, the ISC rate is comparable with the fluorescence emission rate. In the T 1 state, the phosphorescence emission prevails the reverse ISC process back to the S 1 state. Taken together, fluorescence and phosphorescence are achieved simultaneously. The present work provides deep mechanistic insights to aid the rational design of NIR dual-emissive metal nanoclusters.

"Carbene-metal(I)-amide" (CMA) complexes have garnered significant attention due to their remarkable properties and potential TADF applications in organic electronics. However, the atomistic working mechanism is still elusive. Herein, we chose two CMA complexes, i.e. , cyclic (alkyl)(amino) carbene-copper[gold](I)-carbazole (CAAC-Cu[Au]-Cz), and employed both DFT and TD-DFT methods, in combination with radiative and nonradiative rate calculations, to investigate geometric and electronic structures of these two complexes in the ground and excited states, including orbital compositions, electronic transitions, absorption and emission spectra, and the luminescence mechanism. It is found that the coplanar or perpendicular conformations are coexistent in the ground state (S 0 ), the lowest excited singlet state (S 1 ), and the triplet state (T 1 ). Both the coplanar and perpendicular S 1 and T 1 states have similar ligand-to-ligand charge transfer (LLCT) character between CAAC and Cz, and some charge-transfer character between metal atoms and ligands, which is beneficial to minimize the singlet-triplet energy gaps (Δ E ST ) and increase the spin-orbit coupling (SOC). An interesting three-state (S 0 , S 1 , T 1 ) model involving two regions (coplanar and perpendicular) is proposed to rationalize the experimental TADF phenomena in the CMA complexes. In addition to the coplanar ones, the perpendicular S 1 and T 1 states also play a role in promoting the repopulation of the coplanar S 1 exciton, which is a primary source for the delayed fluorescence.

Based on the analysis of the total concentrations of 10 metals in the sediment core and total concentrations and chemical fractions of seven metals in the surface sediments of Qionghai Lake in Xichang City, Sichuan Province, the spatial-temporal characteristics of metal accumulation and pollution over the past century and the potential ecological risk of metals in surface sediments were studied. Before the 1970s, metal concentrations in the sediment core were stable. The total concentrations of Al, Fe, K, and Cr in the sediment core exhibited visible peaks in the 1970s, which were related to the enhanced input of fine-grained topsoil caused by increasing precipitation, lake reclamation, and deforestation. Since the 1990s, the total concentrations of Al, Fe, K, and Cr decreased with the reduced topsoil erosion, whereas the total concentrations of As, Cd, Cu, Pb, and Zn gradually increased or remained stable. The enrichment factor results showed that Cd, Pb, and Zn were the main contaminants, with Cd as the typical contaminant in the sediment core. The Cd contamination started in the 1960s and has remained at a moderate level since the 1990s. In the surface sediments, the total concentrations of Cd were higher in the northwest lake area, and no visible spatial concentration trends of the other metals were displayed. The bioavailable fractions of Cd, Pb, and Zn accounted for 95%, 63%, and 48% of the total metal concentrations on average. Among the bioavailable fractions, Cd was mainly in the acid-soluble fraction, and Pb and Zn were mainly in the reducible and oxidized fractions. The bioavailable fractions of the other metals were less than 27%. The results of total concentrations and bioavailable fractions of metals revealed that Pb and Zn in the surface sediments were slightly or moderately contaminated, and Cd was moderately contaminated on average. Cd contamination was at a severe level in the northwest lake area. The concentrations of anthropogenic Cd, Pb, and Zn in the surface sediments estimated from the total and bioavailable concentrations were comparable ( P >0.05), indicating that anthropogenic metals primarily existed in bioavailable fractions in the sediment. Integrating the assessment results from sediment quality guidelines, potential ecological risk index, and chemical forms of metals, Cd in surface sediments may pose a high ecological risk, whereas the other metals has a low ecological risk.

Background: Dual antiplatelet therapy (DAPT) is a standard treatment option for acute myocardial infarction (AMI). The difference between the efficacy of ticagrelor and clopidogrel in the emergency department (ED) before percutaneous coronary intervention (PCI) remains unknown. The present study compared the in-hospital major adverse cardiovascular event (MACE) rates between patients with AMI treated with clopidogrel and those treated with ticagrelor in the ED before PCI., Methods: We retrospectively collected the data of patients diagnosed as having AMI in the ED. Patients were only included if they had successfully received complete DAPT with aspirin and ticagrelor/clopidogrel in the ED and had undergone PCI. The patients were divided into two groups according to their DAPT regimen. The primary outcome was the rate of in-hospital MACEs. The secondary outcomes included an unexpected return to the ED within 72 h, readmission within 14 d, and revascularization., Results: A total of 1836 patients were enrolled. Patients in the ticagrelor group had a lower in-hospital MACE rate (3.01% versus 7.51%, p < 0.001) and in-hospital mortality rate (2.15% versus 5.70%, p < 0.001) than those in the clopidogrel group. Multivariate logistic regression analysis revealed ticagrelor was independently associated with a lower risk of in-hospital MACEs (odds ratio [OR]: 0.53, 95% CI: 0.32-0.88, p = 0.013). After propensity score matching, the risk of in-hospital MACEs remained significantly lower in the ticagrelor group (OR 0.42, 95% CI: 0.21-0.85, p = 0.016)., Conclusion: DAPT with ticagrelor and aspirin in the ED before PCI is associated with a lower in-hospital MACE rate among patients with AMI.

Palmitoyl acyltransferases (PATs) have been suggested to be involved in learning and memory. However, the underlying mechanisms have not yet been fully elucidated. Here, we found that the activity of DHHC2 was upregulated in the hippocampus after fear conditioning, and DHHC2 knockdown impaired fear induced memory and long-term potentiation (LTP). Additionally, the activity of DHHC2 and its synaptic expression were increased after high frequency stimulation (HFS) or glycine treatment. Importantly, fear learning selectively augmented the palmitoylation level of AKAP150, not PSD-95, and this effect was abolished by DHHC2 knockdown. Furthermore, 2-bromopalmitic acid (2-BP), a palmitoylation inhibitor, attenuated the increased palmitoylation level of AKAP150 and the interaction between AKAP150 and PSD-95 induced by HFS. Lastly, DHHC2 knockdown reduced the phosphorylation level of GluA1 at Ser845, and also induced an impairment of LTP in the hippocampus. Our results suggest that DHHC2 plays a critical role in regulating fear memory via AKAP150 signaling., Competing Interests: The authors report no biomedical financial interests or potential conflicts of interest., (© 2023 The Author(s).)

Background: Balance impairments are common in cerebellar ataxia. Exercises are beneficial in this population., Objective: Explore the benefits of therapeutic exercises on disease severity, balance and functional independence in cerebellar ataxia., Methods: Databases were searched from inception until July 2021. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale and the Newcastle-Ottawa Scale (NOS); and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool., Results: Twenty-six studies were included and eight studies of low to high PEDro methodological quality were meta-analyzed. 'Low' to 'moderate' GRADE quality evidence supports the use of therapeutic exercises to reduce disease severity, assessed using the Scale for the Assessment and Rating of Ataxia [weighted mean difference (WMD): -3.3; 95% confidence interval (95%CI): -3.7, -2.8; p < .01]; and improve balance, assessed using the Berg Balance Scale (WMD: 2.6; 95%CI: 1.1, 4.2; p < .01). The effect of therapeutic exercises on functional independence was insignificant (WMD: 1.6; 95%CI: -1.5, 4.6; p = .31)., Conclusion: Low to moderate evidence from studies of low to high methodological quality provides some support for therapeutic exercises for reducing disease severity among non-hereditary degenerative cerebellar ataxia and improving balance among acquired cerebellar ataxia. Exercises did not benefit functional independence. Additional studies of large sample size and high methodological quality are necessary to substantiate these findings.

Objectives: To analyze the treatment outcomes and prognostic factors of mucosal melanoma of the head and neck (MMHN) from a single institution., Methods: From December 1989 to November 2018, 190 patients diagnosed with MMHN were included. Survival analysis was performed using the Kaplan-Meier method for univariate analysis with a log-rank test for significance and Cox regression for multivariate analysis., Results: With a median follow-up time of 43.5 months, 126 (68.5%) patients died. The median DSS was 35 months. The 3- and 5-year disease-specific survival (DSS) rates were 48.1% and 33.7%, respectively. The median overall survival (OS) was 34 months. The 3- and 5-year OS rates were 47.0% and 32.9%, respectively. In univariate analysis, the T3 stage, received surgery, R0 resection, and combined therapy (surgery+biotherapy/biochemotherapy) were significantly associated with better survival. Multivariable Cox regression analysis revealed that the T4 stage (HR = 1.692; 95% CI, 1.175-2.438; p  = .005) and the N1 stage (HR = 1.600; 95% CI, 1.023-2.504; p  = .039) were strong prognostic factors for poor survival, and that combined therapy (surgery+biotherapy/biochemotherapy) was a strong prognostic factor for better survival outcome (HR = 0.563; 95% CI, 0.354-0.896; p  = .015)., Conclusion: The prognosis of MMHN remains poor. Systemic treatment is warranted to reduce MMHN progression. Surgery combined with biotherapy may improve survival., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

In this work, we implemented an approximate algorithm for calculating nonadiabatic coupling matrix elements (NACMEs) of a polyatomic system with ab initio methods and machine learning (ML) models. Utilizing this algorithm, one can calculate NACMEs using only the information of potential energy surfaces (PESs), i.e., energies, and gradients as well as Hessian matrix elements. We used a realistic system, namely CH 2 NH, to compare NACMEs calculated by this approximate PES-based algorithm and the accurate wavefunction-based algorithm. Our results show that this approximate PES-based algorithm can give very accurate results comparable to the wavefunction-based algorithm except at energetically degenerate points, i.e., conical intersections. We also tested a machine learning (ML)-trained model with this approximate PES-based algorithm, which also supplied similarly accurate NACMEs but more efficiently. The advantage of this PES-based algorithm is its significant potential to combine with electronic structure methods that do not implement wavefunction-based algorithms, low-scaling energy-based fragment methods, etc., and in particular efficient ML models, to compute NACMEs. The present work could encourage further research on nonadiabatic processes of large systems simulated by ab initio nonadiabatic dynamics simulation methods in which NACMEs are always required.

The arginine dependency of cancer cells creates metabolic vulnerability. In this study, we examine the impact of arginine availability on DNA replication and genotoxicity resistance. Using DNA combing assays, we find that limiting extracellular arginine results in the arrest of cancer cells at S phase and a slowing or stalling of DNA replication. The translation of new histone H4 is arginine dependent and influences DNA replication. Increased proliferating cell nuclear antigen (PCNA) occupancy and helicase-like transcription factor (HLTF)-catalyzed PCNA K63-linked polyubiquitination protect arginine-starved cells from DNA damage. Arginine-deprived cancer cells display tolerance to genotoxicity in a PCNA K63-linked polyubiquitination-dependent manner. Our findings highlight the crucial role of extracellular arginine in nutrient-regulated DNA replication and provide potential avenues for the development of cancer treatments., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Acute cholecystitis is a gallbladder inflammation, and the Tokyo Guidelines 2018 (TG18) can be used to predict its presence and severity with high sensitivity and specificity. However, TG18 grading require the collection of excessive parameters. Monocyte distribution width (MDW) is a parameter used to detect sepsis early. Therefore, we investigated the correlation between MDW and cholecystitis severity., Methods: We conducted a retrospective study of patients with cholecystitis admitted to our hospital from November 1, 2020, to August 31, 2021. The primary outcome was severe cholecystitis analyzed as a composite of intensive care unit (ICU) admission and mortality. The secondary outcomes were length of hospital stay, ICU stay, and TG18 grade., Results: A total of 331 patients with cholecystitis were enrolled in this study. The average MDWs for TG18 grades 1, 2, and 3 were 20.21 ± 3.99, 20.34 ± 3.68, and 25.77 ± 6.61, respectively. For patients with severe cholecystitis, the average MDW was 25.42 ± 6.83. Using the Youden J statistic, we set a cutoff MDW of 21.6. Multivariate logistic regression revealed that patients with an MDW≥21.6 had a higher risk of severe cholecystitis (odds ratio=4.94; 95 % CI, 1.71-14.21; p=0.003). The Cox model revealed that patients with an MDW≥21.6 were more likely to have a prolonged hospital stay., Conclusions: MDW is a reliable indicator of severe cholecystitis and prolonged length of stay. Additional MDW testing and a complete blood count may provide simple information for predicting severe cholecystitis early., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background and Aims: There are currently no clear conclusions about whether major depression (MD) and bipolar disorder (BD) increase the risk of erectile dysfunction (ED). In our study, we used a Mendelian randomization (MR) analysis to discover the causal associations between MD, BD and ED., Methods: We got single-nucleotide polymorphisms (SNPs) related to MD, BD and ED from the MRC IEU Open genome-wide association study (GWAS) datasets. After a series of selection, SNPs left were selected as instrumental variables (IVs) of MD and BD for the following MR test to evaluate the relationship of genetically predicted MD or BD with the incidence of ED. Among them, we used the random-effects inverse-variance weighted (IVW) method as the main analysis. Finally, sensitivity analyses were further performed using Cochran's Q test, funnel plots, MR-Egger regression, Leave-one-out method and MR- pleiotropy residual sum and outlier (PRESSO)., Results: Genetically-predicted MD was causally related to the incidence of ED in the IVW methods (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.19-1.96; p = 0.001), while no causal impact of BD on the risk of ED (OR = 0.95, 95% CI 0.87-1.04; p = 0.306). The results of sensitivity analyses supported our conclusion, and no directional pleiotropy were found., Conclusion: The findings of this research found evidence of a causal relationship between MD and ED. However, we did not find a causal relationship between BD and ED in European populations., (© 2023. The Author(s).)

Objective: To examine the short-term curative effect with minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure. Methods: The clinical data of 60 patients who underwent video-assisted thoracoscopic transaortic modified Morrow procedure from August 2021 to August 2022 at Department of Cardiovascular Surgery, Zhejiang Provincial People's Hospital were retrospectively analyzed. There were 31 males and 29 females, with the age ( M (IQR)) of 54.0(22.3) years (range: 15 to 71 years). The echocardiography confirmed the diagnosis of moderate mitral regurgitation in 30 patients, and severe mitral regurgitation in 13 patients. Systolic anterior motion (SAM) was present preoperatively in 54 patients. All 60 patients underwent transaortic modified Morrow procedure through a right infra-axillary thoracotomy using femorofemoral cardiopulmonary bypass. Surgical procedures mainly included transverse aortic incision, exposure of left ventricular outflow tract (LVOT), septal myectomy, and correction of the abnormal mitral valve and subvalvular structures. Results: All 60 patients underwent the programmatic procedures successfully without conversion to full sternotomy. The cardiopulmonary bypass time was (142.0±32.1) minutes (range: 89 to 240 minutes), while the cross-clamp time was (95.0±23.5) minutes (range: 50 to 162 minutes). The patients had a postoperative peak LVOT gradient of 7.0 (5.0) mmHg (range: 0 to 38 mmHg) (1 mmHg=0.133 kPa). A total of 57 patients were extubated on the operating table. The drainage volume in the first 24 h was (175.9±57.0) ml (range: 60 to 327 ml). The length of intensive care unit stay was 21.0 (5.8)h (range: 8 to 120 h) and postoperative hospital stay was 8 (5) days (range: 5 to 19 days). The postoperative septal thickness was 11 (2) mm (range: 8 to 14 mm). All patients had no iatrogenic ventricular septal perforation or postoperative residual SAM. The patients were followed up for 4 (9) months (range: 1 to 15 months), and none of them needed cardiac surgery again due to valve dysfunction or increased peak LVOT gradient during follow-up. Conclusion: Using a video-assisted thoracoscopic transaortic modified Morrow procedure through a right infra-axillary minithoracotomy can provide good visualization of the LVOT and hypertrophic ventricular septum, ensure optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures, so that allows satisfactory short-term surgical results.

One recent experimental study reported a Ir(III) complex with thermally activated delayed fluorescence (TADF) phenomenon in solution, but its luminescent mechanism is elusive. In this work, we combined density functional theory (DFT), time-dependent DFT (TDDFT) and multi-state complete active space second-order perturbation theory (MS-CASPT2) methods to investigate excited-state properties, photophysics, and emission mechanism of this Ir(III) complex. Two main absorption bands observed in experiments can be attributed to the electronic transition from the S 0 state to the S 1 and S 2 states; while, the fluorescence and phosphorescence are generated from the S 1 and T 1 states, respectively. Both the S 1 and T 1 states have clear metal-to-ligand charge transfer (MLCT) character. The present computational results reveal a three-state model including the S 0 , S 1 and T 1 states to rationalize the TADF behavior. The small energy gap between the S 1 and T 1 states benefits the forward and reverse intersystem crossing (ISC and rISC) processes. At 300 K, the rISC rate is five orders of magnitude larger than the phosphorescence rate therefore enabling TADF. At 77 K, the rISC rate is sharply decreased but remains close to the phosphorescence rate; therefore, in addition to the phosphorescence, the delayed fluorescence could also contribute to the experimental emission. The estimated TADF lifetime agrees well with experiments, 9.80 vs. 6.67 μs, which further verifies this three-state model.

Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients' risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as a pivotal mechanism of glucolipotoxicity-mediated death of osteocytes and osteoblast, a novel form of programmed cell death resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), a fat-soluble vitamin, is clinically applied to prevent osteoporosis and improve coagulation. This study aimed to clarify the role and mechanism of VK2 in HG-mediated ferroptosis. We established the mouse T2DOP model by intraperitoneal injection of streptozotocin solution and a high-fat and high-sugar diet. We also cultured bone marrow mesenchymal stem cells (BMSCs) in HG to simulate the diabetic environment in vitro. Based on our data, VK2 inhibited HG-mediated bone loss and ferroptosis, the latter manifested by decreased levels of mitochondrial reactive oxygen species, lipid peroxidation, and malondialdehyde and increased glutathione in vitro. In addition, VK2 treatment was capable of restoring bone mass and strengthening the expression of SIRT1, GPX4, and osteogenic markers in the distal femurs. As for further mechanism exploration, we found that VK2 could activate AMPK/SIRT1 signaling, and knockdown of SIRT1 by siRNA prevented the VK2-mediated positive effect in HG-cultured BMSCs. Summarily, VK2 could ameliorate T2DOP through the activation of the AMPK/SIRT1 signaling pathway to inhibit ferroptosis.

Recently, we developed a low-scaling Multi-Layer Energy-Based Fragment (MLEBF) method for accurate excited-state calculations and nonadiabatic dynamics simulations of nonbonded fragment systems. In this work, we extend the MLEBF method to treat covalently bonded fragment ones. The main idea is cutting a target system into many fragments according to chemical properties. Fragments with dangling bonds are first saturated by chemical groups; then, saturated fragments, together with the original fragments without dangling bonds, are grouped into different layers. The accurate total energy expression is formulated with the many-body energy expansion theory, in combination with the inclusion-exclusion principle that is used to delete the contribution of chemical groups introduced to saturate dangling bonds. Specifically, in a two-layer MLEBF model, the photochemically active and inert layers are calculated with high-level and efficient electronic structure methods, respectively. Intralayer and interlayer energies can be truncated at the two- or three-body interaction level. Subsequently, through several systems, including neutral and charged covalently bonded fragment systems, we demonstrate that MLEBF can provide accurate ground- and excited-state energies and gradients. Finally, we realize the structure, conical intersection, and path optimizations by combining our MLEBF program with commercial and free packages, e.g., ASE and SciPy. These developments make MLEBF a practical and reliable tool for studying complex photochemical and photophysical processes of large nonbonded and bonded fragment systems.

Oxidative stress is preferentially treated as a risk factor for the development and progression of osteoporosis. Corynoline as a component of Corydalis bungeana Turcz presents antioxidative and anti-inflammatory properties. In the present study, the effects of Corynoline on osteoblasts following hydrogen peroxide (H 2 O 2 )-induced injury were evaluated accompanied by the investigation of the molecular mechanisms involved. It was found that Corynoline downregulated the intracellular reactive oxygen species (ROS) generation and restored the osteogenic potential of the disrupted osteoblasts by H 2 O 2 exposure. Furthermore, Corynoline was revealed to activate the Nrf2/HO-1 signaling pathway, while ML385 (an Nrf2 inhibitor) would prevent the Corynoline-mediated positive effects on the disrupted osteoblasts. In terms of the animal experiments, Corynoline treatment contributed to a significantly alleviated bone loss. These findings indicate that Corynoline may significantly attenuate the H 2 O 2 -induced oxidative damage of osteoblasts via the Nrf2/HO-1 signaling pathway, providing novel insights to the development of treatments for osteoporosis induced by oxidative injury., Competing Interests: There were no financial or other conflicts of interest in designing, performing, or drafting this work., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

A dinuclear Pt(II) compound was reported to exhibit thermally activated delayed fluorescence (TADF); however, the luminescence mechanism remains elusive. To reveal relevant excited-state properties and luminescence mechanism of this Pt(II) compound, both density function theory (DFT) and time-dependent DFT (TD-DFT) calculations were carried out in this work. In terms of the results, the S 1 and T 2 states show mixed intraligand charge transfer (ILCT)/metal-to-ligand CT (MLCT) characters while the T 1 state exhibits mixed ILCT/ligand-to-metal CT (LMCT) characters. Mechanistically, a four-state (S 0 , S 1 , T 1 , and T 2 ) model is proposed to rationalize the TADF behavior. The reverse intersystem crossing (rISC) process from the initial T 1 to final S 1 states involves two up-conversion channels (direct T 1 →S 1 and T 2 -mediated T 1 →T 2 →S 1 pathways) and both play crucial roles in TADF. At 300 K, these two channels are much faster than the T 1 phosphorescence emission enabling TADF. However, at 80 K, these rISC rates are reduced by several orders of magnitude and become very small, which blocks the TADF emission; instead, only the phosphorescence is observed. These findings rationalize the experimental observation and could provide useful guidance to rational design of organometallic materials with superior TADF performances., (© 2022 Wiley-VCH GmbH.)

Introduction: This study compared the casualties and types of rescues conducted on the main climbing route (MCR) and accessory climbing routes (ACRs) in Yushan National Park (YSNP) between 2008 and 2019., Methods: We collected the following information for all documented mountain rescue operations conducted on the MCRs and ACRs in YSNP between 2008 and 2019: accident location, casualty type, victim number, and type of rescue. The victims were categorized as to injury, illness, mortality, or no medical problem (NMP) groups according to their condition at the time of rescue., Results: Two-hundred forty-four rescue operations involving 329 victims were conducted during the 12-y study period. Among them, 105 (32%) did not require medical treatment, 102 (31%) were injured, 82 (25%) were ill, and 40 (12%) were deceased. Of the 82 individuals with illness, 69 (84%) had acute altitude sickness. The accident and mortality rates on the ACRs were significantly higher than those on the MCR (P<0.001; χ 2 ). The ACR incidents involved significantly higher percentages of helicopter-based rescues and victims in the NMP group (P<0.001)., Conclusions: Acute altitude sickness accounted for most of the rescues. ACRs had higher injury and mortality rates and required more helicopter-based rescues for patients who did not have medical problems. This study may serve as a reference to reduce casualties and overuse of helicopters by educating tourists on the appropriate use of maps and the evaluation of trails in relation to weather conditions., (Copyright © 2022 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Bone metabolism occurs in the entire life of an individual and is required for maintaining skeletal homeostasis. The imbalance between osteogenesis and osteoclastogenesis eventually leads to osteoporosis. Oxidative stress is considered a major cause of bone homeostasis disorder, and relieving excessive oxidative stress in bone mesenchymal stem cells (BMSCs) is a potential treatment strategy for osteoporosis. Carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide (CO), possesses antioxidation, antiapoptosis, and anti-inflammatory properties. In our study, we found that CORM-3 could reduce reactive oxygen species (ROS) accumulation and prevent mitochondrial dysfunction thereby restoring the osteogenic potential of the BMSCs disrupted by hydrogen peroxide (H 2 O 2 ) exposure. The action of CORM-3 was preliminarily considered the consequence of Nrf2/HO-1 axis activation. In addition, CORM-3 inhibited osteoclast formation in mouse primary bone marrow monocytes (BMMs) by inhibiting H 2 O 2 -induced polarization of M1 macrophages and endowing macrophages with M2 polarizating ability. Rat models further demonstrated that CORM-3 treatment could restore bone mass and enhance the expression of Nrf2 and osteogenic markers in the distal femurs. In summary, CORM-3 is a potential therapeutic agent for the treatment of osteoporosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Chen Jin et al.)

Background: As the survival rates of patients with renal cell carcinoma (RCC) continue to increase, noncancer causes of death cannot be ignored. The cause-specific mortality in patients with RCC is not well understood., Objective: Our study aimed to explore the mortality patterns of contemporary RCC survivors., Methods: We performed a retrospective cohort study involving patients with RCC from the Surveillance, Epidemiology, and End Results (SEER) database. We used standardized mortality ratios (SMRs) to compare the death rates in patients with RCC with those in the general population., Results: A total of 106,118 patients with RCC, including 39,630 who died (27%), were included in our study. Overall, compared with the general US population, noncancer SMRs were increased 1.25-fold (95% confidence intervals [CI], 1.22 to 1.27; observed, 11,235), 1.19-fold (95% CI, 1.14 to 1.24; observed, 2,014), and 2.24-fold (95% CI, 2.11 to 2.38; observed, 1,110) for stage I/II, III, and IV RCC, respectively. The proportion of noncancer causes of death increased with the extension of survival time. A total of 4,273 men with stage I/II disease (23.13%) died of RCC; however, patients who died from other causes were 3.2 times more likely to die from RCC ( n = 14,203 [76.87%]). Heart disease was the most common noncancer cause of death ( n = 3,718 [20.12%]; SMR, 1.23; 95% CI, 1.19-1.27). In patients with stage III disease, 3,912 (25.98%) died from RCC, and 2,014 (13.37%) died from noncancer causes. Most patients (94.99%) with stage IV RCC died within 5 years of initial diagnosis. Although RCC was the leading cause of death ( n = 12,310 [84.65%]), patients with stage IV RCC also had a higher risk of noncancer death than the general population (2.24; 95% CI, 2.11-2.38)., Conclusions: Non-RCC death causes account for more than 3/4 of RCC survivors among patients with stage I/II disease. Patients with stage IV are most likely to die of RCC; however, there is an increased risk of dying from septicemia, and suicide cannot be ignored. These data provide the latest and most comprehensive assessment of the causes of death in patients with RCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Chen, Wu, Wu, Xin, Jiang, Li and Zhang.)

Herein we investigated the luminescence mechanism of one "carbene-metal-amide" copper compound with thermally activated delayed fluorescence (TADF) using density functional theory (DFT)/multireference configuration interaction, DFT, and time-dependent DFT methods with the polarizable continuum model. The experimentally observed low-energy absorption and emission peaks are assigned to the S 1 state, which exhibits clear interligand and partial ligand-to-metal charge-transfer character. Moreover, it was found that a three-state (S 0 , S 1 , and T 1 ) model is sufficient to describe the TADF mechanism, and the T 2 state should play a negligible role. The calculated S 1 -T 1 energy gap of 0.10 eV and proper spin-orbit couplings facilitate the reverse intersystem crossing (rISC) from T 1 to S 1 . At 298 K, the rISC rate of T 1 → S 1 (∼10 6 s -1 ) is more than 3 orders of magnitude larger than the T 1 phosphorescence rate (∼10 3 s -1 ), thereby enabling TADF. However, it disappears at 77 K because of a very slow rISC rate (∼10 1 s -1 ). The calculated TADF rate, lifetime, and quantum yield agree very well with the experimental data. Methodologically, the present work shows that only considering excited-state information at the Franck-Condon point is insufficient for certain emitting systems and including excited-state structure relaxation is important.

Objective: To evaluate the indications, safety, feasibility, and surgical technique for patients with head and neck cancers undergoing transoral robotic retropharyngeal lymph node (RPLN) dissection. Methods: The current study enrolled 12 consecutive head and neck cancer patients (seven males and four females) who underwent transoral robotic RPLN dissection with the da Vinci surgical robotic system at the Sun Yat-sen University Cancer Center from May 2019 to July 2020. Seven patients were diagnosed as nasopharyngeal carcinoma with RPLN metastasis after initial treatments, 4 patients were diagnosed as thyroid carcinoma with RPLN metastasis after initial treatments, and one patient was diagnosed as oropharyngeal carcinoma with RPLN metastasis before initial treatments. The operation procedure and duration time, intraoperative blood loss volume and complications, nasogastric feeding tube dependence, tracheostomy dependence, postoperative complications, and hospitalization time were recorded and analyzed. Results: All patients were successfully treated by transoral robotic dissection of the metastatic RPLNs, none of which was converted to open surgery. RPLNs were completely resected in 10 patients, and partly resected in 2 patients (both were nasopharyngeal carcinoma patients). The mean number of RPLN dissected was 1.7. The operation duration time and intraoperative blood loss volume were (191.3±101.1) min and (150.0±86.6) ml, respectively. There was no severe intraoperative complication such as massive haemorrhage or adjacent organ injury during surgery. Nasogastric tube use was required in all patients with (17.1±10.6) days of dependence, while tracheotomy was performed in 8 patients with (11.6±10.7) days of dependence. The postoperative hospitalization stay was (8.5±5.7) days. Postoperative complications occurred in 4 patients, including 2 of retropharyngeal incision and 2 of dysphagia. During a follow-up of (6.5±5.1) months, disease-free progression was observed in all patients, 10 patients were disease-free survival and other 2 patients were survival with tumor burden. Conclusions: The transoral robotic RPLN dissection is safety and feasible. Compared with the traditional open surgical approach, it is less traumatic and safer, has fewer complications and good clinical application potentiality. The indications for transoral robotic RPLN dissection include thyroid carcinoma, oropharyngeal carcinoma, and some selected nasopharyngeal carcinoma and other head and neck cancers. Metastatic RPLNs from some nasopharyngeal carcinoma with incomplete capsule, unclear border and adhesion to the surrounding vessels are not suitable for transoral robotic RPLN dissection.

Background: Overcrowding in emergency departments (ED) is a critical problem worldwide, and streaming can alleviate crowding to improve patient flows. Among triage scales, patients labeled as "triage level 3" or "urgent" generally comprise the majority, but there is no uniform criterion for classifying low-severity patients in this diverse population. Our aim is to establish a machine learning model for prediction of low-severity patients with short discharge length of stay (DLOS) in ED., Methods: This was a retrospective study in the ED of China Medical University Hospital (CMUH) and Asia University Hospital (AUH) in Taiwan. Adult patients (aged over 20 years) with Taiwan Triage Acuity Scale level 3 were enrolled between 2018 and 2019. We used available information during triage to establish a machine learning model that can predict low-severity patients with short DLOS. To achieve this goal, we trained five models-CatBoost, XGBoost, decision tree, random forest, and logistic regression-by using large ED visit data and examined their performance in internal and external validation., Results: For internal validation in CMUH, 33,986 patients (75.9%) had a short DLOS (shorter than 4 h), and for external validation in AUH, there were 13,269 (82.7%) patients with short DLOS. The best prediction model was CatBoost in internal validation, and area under the receiver operating cha racteristic curve (AUC) was 0.755 (95% confidence interval (CI): 0.743-0.767). Under the same threshold, XGBoost yielded the best performance, with an AUC value of 0.761 (95% CI: 0.742- 0.765) in external validation., Conclusions: This is the first study to establish a machine learning model by applying triage information alone for prediction of short DLOS in ED with both internal and external validation. In future work, the models could be developed as an assisting tool in real-time triage to identify low-severity patients as fast track candidates., (© 2022. The Author(s).)

Nonadiabatic dynamics simulation has become a powerful tool to describe nonadiabatic effects involved in photophysical processes and photochemical reactions. In the past decade, our group has developed generalized trajectory-based ab initio surface-hopping (GTSH) dynamics simulation methods, which can be used to describe a series of nonadiabatic processes, such as internal conversion, intersystem crossing, excitation energy transfer and charge transfer of molecular systems, and photoinduced nonadiabatic carrier dynamics of extended systems with and without spin-orbit couplings. In this contribution, we will first give a brief introduction to our recently developed methods and related numerical implementations at different computational levels. Later, we will present some of our latest applications in realistic systems, which cover organic molecules, biological proteins, organometallic compounds, periodic organic and inorganic materials, etc. Final discussion is given to challenges and outlooks of ab initio nonadiabatic dynamics simulations.

The Qinghai-Tibet Plateau Area (QTPA) has a complex natural ecosystem, causing a greatly increased risk of spreading various tick-borne diseases including rickettsial infections, which are regarded as one of the oldest known vector-borne zoonoses. However, the information of one of its pathogen, spotted fever group Rickettsia (SFG Rickettsia ), is limited in tick vectors and animals in this area. Therefore, this study focused on the investigation of SFG Rickettsia in tick vectors, yaks ( Bos grunniens ), and Tibetan sheep ( Ovis aries ) in the QTPA. A total of 1,000 samples were collected from nine sampling sites, including 425 of yaks, 309 of Tibetan sheep, 266 of ticks. By morphological examination, PCR, and sequencing, we confirmed the species of all collected ticks. All tick samples, all yak and Tibetan sheep blood samples were detected based on SFG Rickettsia ompA and sca4 gene. The results showed that all tick samples were identified to be Haemaphysalis qinghaiensis , and the positive rates of SFG Rickettsia were 5.9% (25/425), 0.3% (1/309), and 54.1% (144/266) in yaks, Tibetan sheep, and ticks, respectively. All positive samples were sequenced, and BLASTn analysis of the ompA gene sequences of SFG Rickettsia showed that all positive samples from animals and ticks had 99.04-100% identity with yak and horse isolates from Qinghai Province, China. BLASTn analysis of the sca4 gene sequences of SFG Rickettsia showed that all positive samples had 97.60-98.72% identity with tick isolates from Ukraine. In addition, the phylogenetic analysis showed that all the SFG Rickettsia ompA and sca4 sequences obtained from this study belong to the same clade as Rickettsia raoultii isolated from livestock and ticks from China and other countries. Molecularly, this study detected and characterized SFG Rickettsia both in the tick vectors and animals, suggesting that the relationship between SFG Rickettsia , tick species and animal hosts should be explored to understand their interrelationships, which provide a theoretical basis for preventing control of this pathogen., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Li, Sun, Kang, He, Guo, Ma, Wei, Li, Chen, Chen, Li, Qi, Yang, Zhang, Wang, Cai, Zhao, Hu, Chen and Li.)

Intervertebral disc degeneration (IDD) constitutes the pathological foundation of most musculoskeletal disorders of the spine. Previous studies have noted that cell proliferation is a common feature of IDD. Bioinformatics indicated that aberrantly expressed long non-coding RNAs (lncRNAs) were involved in the development of IDD. In this study, we aimed to investigate the function of lncRNA HOTAIR in the proliferation of human nucleus pulposus (NP) cells of IDD in vitro and further clarified its mechanism. The expression of HOTAIR and miR-130b was quantified by qRT-PCR in nucleus pulposus (NP) tissues. Furthermore, NP cells proliferation were assayed by CCK8 and Immunostaining. Dual-luciferase reporter and RIP assay were used to examine the expression of HOTAIR, PTEN, and their co-target gene miR-130b. Western blotting was used to test AKT expression. Our in vitro experiments on human normal NP cells observed that HOTAIR was significantly dysregulated in IDD. Further, HOTAIR can suppress proliferation by directly targeting miR-130b. In addition, Both HOTAIR and PTEN were confirmed to target miR-130b, and miR-130b upregulation reversed the phenomenon of ectopic expression of HOTAIR. More importantly, HOTAIR upregulation significantly reduced CyclinD1 protein expression by PTEN/AKT signaling pathway. Our findings suggest that HOTAIR may bind to miR-130b and subsequently increased CyclinD1 expression via PTEN/Akt pathway. Thereby, HOTAIR could become a potential target for the treatment of IDD. Abbreviations : IDD; intervertebral disc degeneration ncRNAs; non-coding RNAs lncRNAs; long non-coding RNAs miRNAs; microRNAs NP; nucleus pulposus qRT-PCR; quantitative reverse transcription-PCR LBP; Low back pain ORF; open reading frame HOTAIR; Hox transcript antisense intergenic RNA FAF1; Fas-associated protein factor-1 Erk; extracellular signal-regulated kinase TUG1; Taurine Up-regulated Gene 1 HIF1A hypoxia-inducible factor 1-alpha PI3K; phosphoinositide-3 kinase AIS; adolescent idiopathic scoliosis ECM; extracellular matrix LN;lupus nephritis CT;computed tomography MRI; magnetic resonance imaging PBS; phosphate-buffered salin PBS; phosphate-buffered salin PVDF; polyvinylidene fluoride TBST; Tris-buffered saline Tween ECL; enhanced chemiluminescence RIP; RNA immunoprecipitation.

The double cropping system has been widely applied in many subtropical viticultural regions. In the 2-year study of 2014-2015, four grape varieties were selected to analyze their fruit volatile compounds in four consecutive seasons in the Guangxi region of South China, which had a typical subtropical humid monsoon climate. Results showed that berries of winter seasons had higher concentrations of terpenes, norisoprenoids, and C6/C9 compounds in "Riesling," "Victoria," and "Muscat Hamburg" grapes in both of the two vintages. However, in the "Cabernet Sauvignon" grapes, only the berries of the 2014 winter season had higher terpene concentrations, but lower norisoprenoid concentrations than those of the corresponding summer season. The Pearson correlation analysis showed the high temperature was the main climate factor that affected volatile compounds between the summer and winter seasons. Hexanal, γ-terpinene, terpinen-4-ol, cis -furan linalool oxide, and trans -pyran linalool oxide were all negatively correlated with the high-temperature hours in all of the four varieties. Transcriptome analysis showed that the upregulated VviDXSs , VviPSYs , and VviCCDs expressions might contribute to the accumulations of terpenes or norisoprenoids in the winter berries of these varieties. Our results provided insights into how climate parameters affected grape volatiles under the double cropping system, which might improve the understanding of the grape berries in response to the climate changes accompanied by extreme weather conditions in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Chen, Wang, Bai, Cheng, Duan, Wang and He.)

With the advancement of technology and the spread of the COVID19 epidemic, learning can no longer only be done through face-to-face teaching. Numerous digital learning materials have appeared in large numbers, changing people's learning mode. In the era of information explosion, how to capture the learners' attention to teaching videos and improve learning effectiveness is the common goal of every designer of e-leaning teaching content. Previous researches focused on the analysis of learning effectiveness and satisfaction. Instructional designers only provided design elements with high learning effectiveness or high satisfaction, and lacked in-depth analysis of the learners' perspectives. The opinions of these e-learning users are often the key to the success of online teaching videos. Therefore, this study aims at the design elements that will be used in the teaching film. The operation mode of the piano mechanism will be employed as the content of the teaching film. Based on eight elements including arrow cueing, dynamic arrow cueing, spreading-color cueing, contrary to cueing, font style, color application, anthropomorphic, and audiovisual complementarity, we use Refined Kano Model to analyze learners' needs of categorization of each element, and discover learners' expectations for teaching videos. In addition, this study also conducts in-depth data analysis through decision trees algorithm, and stratification analyses using different variables (such as design expertise, using frequency, and usage experience, etc.) to find out the key design factors that affect learners' learning. Depending on the learner's background, the use of e-learning experience, using frequency, and the length of the learning video, our results could provide for reference when designing teaching videos. Instructional designers can better understand how to effectively use design elements, so that the teaching videos can achieve the best learning effect., Competing Interests: Conflicts of interestTo the best of our knowledge, the named authors have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

This study investigates the catechin composition and protective effect of green tea extract on senescence-mediated redox imbalance in the livers and kidneys of aged mice. The results showed that the seven catechins in the green tea extract analyzed in this study could be completely separated within 30 min and the main components of catechins in green tea extract were EGCG, EGC and ECG. In terms of the anti-senescence effects of green tea extract, green tea extract supplementation at doses of 125, 625 and 1250 mg/kg for 4 weeks significantly alleviated the senescence-mediated redox imbalance, as exhibited from significantly ( p < 0.05) reduced thiobarbituric acid-reactive substances (TBARS) and protein carbonyls levels in the serum, and increased glutathione (GSH) and total thiols contents in the plasma. Additionally, hepatic and renal protein carbonyls levels were significantly diminished ( p < 0.05) and the activities of superoxide dismutase (SOD), catalase, glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) in the liver and kidney were remarkably elevated ( p < 0.05). Overall, these results clearly show that green tea extract exhibits extremely potent protective effects against senescence-mediated redox imbalance in the livers and kidneys of mice by inhibiting oxidative damage of lipids and proteins and increasing the activities of antioxidant enzymes in organs.

Under the double cropping system, berries usually showed significant quality variations in the summer and winter seasons. In the two-year/four-consecutive-season study, two table grapes of 'Muscat Hamburg' and 'Victoria' were investigated to determine the phenolic compounds in their berries. Different from those of the summer season, the berries in the winter season suffered no high-temperature stress since veraison to harvest in 2014 and 2015. The variations in the season temperatures led to a higher anthocyanin concentration in the winter season berries of 'Muscat Hamburg' grapes than that in the summer berries, while the summer season berries had higher proportions of acylated and methylated anthocyanins than those in the winter season berries. Similar to the anthocyanins, the winter season berries also had a higher flavonol concentration in both varieties. Transcriptome analysis showed that the upregulated genes involved in the flavonoid pathway in the winter season berries were agreed with the changes found in the metabolites. However, the influence of the growing seasons on the flavanols was not consistent in the two varieties, and the variations in VviLARs between the grapes of 'Muscat Hamburg' and 'Victoria' might be the cause. This research helped us better understand the double cropping system and how the climate factors affected the phenolic compounds in the double cropping system.