Engineering Three-Dimensional Interconnected Pores with Plentiful Edge Sites via a Confined Space for Enhanced Oxygen Reduction.

N-Doped carbon sheets based on edge engineering provide more opportunities for improving oxygen reduction reaction (ORR) active sites. However, with regard to the correlation between porous structural configurations and performances, it remains underexplored. Herein, a silica-assisted localized etching method was employed to create two-dimensional mesoporous carbon materials with customizable pore structures, abundant edge sites, and nitrogen functionalities. The mesoporous carbon exhibited superior electrocatalytic performance for the ORR compared to that of a 20 wt % Pt/C catalyst, achieving a half-wave potential of 0.88 V versus RHE, situating them in the leading level of the reported carbon electrocatalysts. Experimental data suggest that the edge graphitic nitrogen sites played a crucial role in the ORR process. The three-dimensional interconnected pores provided a high density of active sites for the ORR and facilitated the efficient transport of electrons. These unique properties make the carbon sheets a promising candidate for highly efficient air cathodes in rechargeable Zn-air batteries.

Clinical and genetic architecture of a large cohort with auditory neuropathy.

Auditory neuropathy (AN) is a unique type of language developmental disorder, with no precise rate of genetic contribution that has been deciphered in a large cohort. In a retrospective cohort of 311 patients with AN, pathogenic and likely pathogenic variants of 23 genes were identified in 98 patients (31.5% in 311 patients), and 14 genes were mutated in two or more patients. Among subgroups of patients with AN, the prevalence of pathogenic and likely pathogenic variants was 54.4% and 56.2% in trios and families, while 22.9% in the cases with proband-only; 45.7% and 25.6% in the infant and non-infant group; and 33.7% and 0% in the bilateral and unilateral AN cases. Most of the OTOF gene (96.6%, 28/29) could only be identified in the infant group, while the AIFM1 gene could only be identified in the non-infant group; other genes such as ATP1A3 and OPA1 were identified in both infant and non-infant groups. In conclusion, genes distribution of AN, with the most common genes being OTOF and AIFM1, is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups.

Characterization of an Emergent Chicken H3N8 Influenza Virus in Southern China: a Potential Threat to Public Health.

Although influenza A viruses of several subtypes have occasionally infected humans, to date only those of the H1, H2, and H3 subtypes have led to pandemics and become established in humans. The detection of two human infections by avian H3N8 viruses in April and May of 2022 raised pandemic concerns. Recent studies have shown the H3N8 viruses were introduced into humans from poultry, although their genesis, prevalence, and transmissibility in mammals have not been fully elucidated. Findings generated from our systematic influenza surveillance showed that this H3N8 influenza virus was first detected in chickens in July 2021 and then disseminated and became established in chickens over wider regions of China. Phylogenetic analyses revealed that the H3 HA and N8 NA were derived from avian viruses prevalent in domestic ducks in the Guangxi-Guangdong region, while all internal genes were from enzootic poultry H9N2 viruses. The novel H3N8 viruses form independent lineages in the glycoprotein gene trees, but their internal genes are mixed with those of H9N2 viruses, indicating continuous gene exchange among these viruses. Experimental infection of ferrets with three chicken H3N8 viruses showed transmission through direct contact and inefficient transmission by airborne exposure. Examination of contemporary human sera detected only very limited antibody cross-reaction to these viruses. The continuing evolution of these viruses in poultry could pose an ongoing pandemic threat. IMPORTANCE A novel H3N8 virus with demonstrated zoonotic potential has emerged and disseminated in chickens in China. It was generated by reassortment between avian H3 and N8 virus(es) and long-term enzootic H9N2 viruses present in southern China. This H3N8 virus has maintained independent H3 and N8 gene lineages but continues to exchange internal genes with other H9N2 viruses to form novel variants. Our experimental studies showed that these H3N8 viruses were transmissible in ferrets, and serological data suggest that the human population lacks effective immunological protection against it. With its wide geographical distribution and continuing evolution in chickens, other spillovers to humans can be expected and might lead to more efficient transmission in humans.

The composition and function of bacterial communities in Bombyx mori (Lepidoptera: Bombycidae) changed dramatically with infected fungi: A new potential to culture Cordyceps cicadae.

Cordyceps cicadae (Hypocreales: Cordycipitaceae) is a renowned entomopathogenic fungus used as herbal medicine in China. However, wild C. cicadae resources have been threatened by heavy harvesting. We hypothesised that Bombyx mori L. (Lepidoptera: Bombycidae) could be a new alternative to cultivate C. cicadae due to the low cost of rearing. Bacterial communities are crucial for the formation of Cordyceps and for promoting the production of metabolites. To better understand the bacterial community structure associated with Cordyceps, three Claviciptaceae fungi were used to explore the pathogenicity of the silkworms. Here, fifth-instar silkworms were infected with C. cicadae, Cordyceps cateniannulata (Hypocreales: Cordycipitaceae) and Beauveria bassiana (Hypocreales: Cordycipitaceae). Subsequently, we applied high-throughput sequencing to explore the composition of bacterial communities in silkworms. Our results showed that all three fungi were highly pathogenic to silkworms, which suggests that silkworms have the potential to cultivate Cordyceps. After fungal infection, the diversity of bacterial communities in silkworms decreased significantly, and the abundance of Staphylococcus increased in mummified larvae, which may play a role in the death process when the host suffers infection by entomopathogenic fungi. Furthermore, there were high similarities in the bacterial community composition and function in the C. cicadae and C. cateniannulata infected samples, and the phylogenetic analysis suggested that these similarities may be related to the fungal phylogenetic relationship. Our findings reveal that infection with different entomopathogenic fungi affects the composition and function of bacterial communities in silkworms and that the bacterial species associated with Cordyceps are primarily host dependent, while fungal infection affects bacterial abundance.

Global research landscape on the contribution of de novo mutations to human genetic diseases over the past 20 years: bibliometric analysis.

As the contribution of de novo mutations (DNMs) to human genetic diseases has been gradually uncovered, analyzing the global research landscape over the past 20 years is essential. Because of the large and rapidly increasing number of publications in this field, understanding the current landscape of the contribution of DNMs in the human genome to genetic diseases remains a challenge. Bibliometric analysis provides an approach for visualizing these studies using information in published records in a specific field. This study aimed to illustrate the current global research status and explore trends in the field of DNMs underlying genetic diseases. Bibliometric analyses were performed using the Bibliometrix Package based on the R language version 4.1.3 and CiteSpace version 6.1.R2 software for publications from 2000 to 2021 indexed under the Web of Science Core Collection (WoSCC) about DNMs underlying genetic diseases on 17 September 2022. We identified 3435 records, which were published in 731 journals by 26,538 authors from 6052 institutes in 66 countries. There was an upward trend in the number of publications since 2013. The USA, China, and Germany contributed the majority of the records included. The University of Washington, Columbia University, and Baylor College of Medicine were the top-producing institutions. Evan E Eichler of the University of Washington, Stephan J Sanders of the Yale University School of Medicine, and Ingrid E Scheffer of the University of Melbourne were the most high-ranked authors. Keyword co-occurrence analysis suggested that DNMs in neurodevelopmental disorders and intellectual disabilities were research hotspots and trends. In conclusion, our data show that DNMs have a significant effect on human genetic diseases, with a noticeable increase in annual publications over the last 5 years. Furthermore, potential hotspots are shifting toward understanding the causative role and clinical interpretation of newly identified or low-frequency DNMs observed in patients.

Atomic Insights into the Relationship between Molecular Structure and Dispersion Performance of Phenyl Polymer on Graphene Oxide.

The adsorption of organic polymers onto the surface of graphene oxide is known to improve its dispersibility in cement-based materials. However, the mechanism of this improvement at the atomic level is not yet fully understood. In this study, we employ a combination of DFT static calculation and umbrella sampling to explore the reactivity of polymers and investigate the effects of varying amounts of phenyl groups on their adsorption capacity on the surface of graphene oxide. Quantitative analysis is utilized to study the structural reconstruction and charge transfer caused by polymers from multiple perspectives. The interfacial reaction between the polymer and graphene oxide surface is further clarified, indicating that the adsorption process is promoted by hydrogen bond interactions and π-π stacking effects. This study sheds light on the adsorption mechanism of polymer-graphene oxide systems and has important implications for the design of more effective graphene oxide dispersants at the atomic level.

Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from Penicillium chrysogenum C-7-2-1 and Their Interconversion Properties.

Xanthone-chromanone homo- or heterodimers are regarded as a novel class of topoisomerase (Topo) inhibitors; however, limited information about these compounds is currently available. Here, 14 new (1-14) and 6 known tetrahydroxanthone chromanone homo- and heterodimers (15-20) are reported as isolated from Penicillium chrysogenum C-7-2-1. Their structures and absolute configurations were unambiguously demonstrated by a combination of spectroscopic data, single-crystal X-ray diffraction, modified Mosher's method, and electronic circular dichroism analyses. Plausible biosynthetic pathways are proposed. For the first time, it was discovered that tetrahydroxanthones can convert to chromanones in water, whereas chromone dimerization does not show this property. Among them, compounds 5, 7, 8, and 16 exhibited significant cytotoxicity against H23 cell line with IC50 values of 6.9, 6.4, 3.9, and 2.6 µM, respectively.

Elevated serum neurofilament light chain levels are associated with hepatic encephalopathy in patients with cirrhosis.

Increasing evidences implicate vital role of neuronal damage in the development of hepatic encephalopathy (HE). Neurofilament light chain (NfL) is the main frame component of neurons and is closely related to axonal radial growth and neuronal structural stability. We hypothesized that NfL as a biomarker of axonal injury may contribute to early diagnosis of HE. This study recruited 101 patients with liver cirrhosis, 10 healthy individuals, and 7 patients with Parkinson's disease. Minimal hepatic encephalopathy (MHE) was diagnosed using psychometric hepatic encephalopathy score. Serum NfL levels were measured by the electrochemiluminescence immunoassay. Serum NfL levels in cirrhotic patients with MHE were significantly higher than cirrhotic patients without MHE, and increased accordingly with the aggravation of HE. Serum NfL levels were associated with psychometric hepatic encephalopathy score, Child-Pugh score, model for end-stage liver disease score, and days of hospitalization. Additionally, serum NfL was an independent predictor of MHE (odds ratio of 1.020 (95% CI 1.005-1.034); P = 0.007). The discriminative abilities of serum NfL were high for identifying MHE (AUC of 0.8134 (95% CI 0.7130-0.9219); P ˂ 0.001) and OHE (AUC of 0.8852 (95% CI 0.8117-0.9587); P ˂ 0.001). Elevated serum NfL levels correlated with the presence of MHE and associated with the severity of HE, are expected to be a biomarker in patients with cirrhosis. Our study suggested that neuronal damage may play a critical role in the development of HE.

Comprehensively evaluating the relationships between marital status and other family factors with cardiovascular disease and long-term overall mortality in the elderly: a study of 48 510 Chinese individuals.

BACKGROUND: Marital status is associated with cardiovascular disease (CVD) incidence and overall mortality, yet limited research on this topic in elderly individuals is available. Our aim was to comprehensively assess the impact of marital status and other family factors on CVD incidence and long-term mortality among elderly people. METHODS: Data from the Chinese Longitudinal Healthy Longevity Survey (2002/2005/2008-2018) for participants aged ≥60 years were analysed. A cross-sectional study initially examined the correlation between spouses, offspring, living arrangements, and CVD using logistic regression. Subsequently, a retrospective cohort study investigated the long-term associations of these factors with overall mortality via Kaplan-Meier and Cox regression analyses. RESULTS: The study involved 48 510 subjects (average age: 87 years). The cross-sectional analysis revealed a correlation between living with a spouse and an increased incidence of heart disease (adjusted OR 1.27, 95% CI 1.04-1.55) and cerebrovascular disease/stroke (adjusted OR 1.26, 95% CI 1.11-1.42). According to the retrospective cohort analysis, living with a spouse significantly reduced overall mortality (adjusted HR 0.84, 95% CI 0.80-0.87), irrespective of marital relationship quality. Conversely, living with offspring (adjusted HR 1.12, 95% CI 1.08-1.16), having more children (adjusted Pnonlinearity = 0.427) or cohabitants (adjusted Pnonlinearity < 0.0001) were associated with increased overall mortality. CONCLUSION: In the elderly population, being married and living with a spouse were not significantly associated with a decrease in CVD incidence but were associated with a reduction in long-term overall mortality. Living with offspring, having more children, or having a larger family size did not replicate the protective effect but indicated greater overall mortality.

A Novel Tongue Coating Segmentation Method Based on Improved TransUNet.

BACKGROUND: As an important part of the tongue, the tongue coating is closely associated with different disorders and has major diagnostic benefits. This study aims to construct a neural network model that can perform complex tongue coating segmentation. This addresses the issue of tongue coating segmentation in intelligent tongue diagnosis automation. METHOD: This work proposes an improved TransUNet to segment the tongue coating. We introduced a transformer as a self-attention mechanism to capture the semantic information in the high-level features of the encoder. At the same time, the subtraction feature pyramid (SFP) and visual regional enhancer (VRE) were constructed to minimize the redundant information transmitted by skip connections and improve the spatial detail information in the low-level features of the encoder. RESULTS: Comparative and ablation experimental findings indicate that our model has an accuracy of 96.36%, a precision of 96.26%, a dice of 96.76%, a recall of 97.43%, and an IoU of 93.81%. Unlike the reference model, our model achieves the best segmentation effect. CONCLUSION: The improved TransUNet proposed here can achieve precise segmentation of complex tongue images. This provides an effective technique for the automatic extraction in images of the tongue coating, contributing to the automation and accuracy of tongue diagnosis.

Two-Site Enhanced Porphyrinic Metal-Organic Framework Nanozymes and Nano-/Bioenzyme Confined Catalysis for Colorimetric/Chemiluminescent Dual-Mode Visual Biosensing.

The rational design of efficient nanozymes and the immobilization of enzymes are of great significance for the construction of high-performance biosensors based on nano-/bioenzyme catalytic systems. Herein, a novel V-TCPP(Fe) metal-organic framework nanozyme with a two-dimensional nanosheet morphology is rationally designed by using V2CTx MXene as a metal source and iron tetrakis(4-carboxyphenyl)porphine (FeTCPP) ligand as an organic linker. It exhibits enhanced peroxidase- and catalase-like activities and luminol-H2O2 chemiluminescent (CL) behavior. Based on the experimental and theoretical results, these excellent enzyme-like activities are derived from the two-site synergistic effect between V nodes and FeTCPP ligands in V-TCPP(Fe). Furthermore, a confined catalytic system is developed by zeolitic imidazole framework (ZIF) coencapsulation of the V-TCPP(Fe) nanozyme and bioenzyme. Using the acetylcholinesterase (AChE) as a model, our constructed V-TCPP(Fe)/AChE@ZIF confined catalytic system was successfully used for the colorimetric/CL dual-mode visual biosensing of organophosphorus pesticides. This work is expected to provide new insights into the design of efficient nanozymes and confined catalytic systems, encouraging applications in catalysis and biosensing.

Malignant transformation rate of oral leukoplakia in the past 20 years: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the rate of malignant transformation (MT) of oral leukoplakia (OL) and to study potential risk factors for the MT of OL into oral squamous cell carcinoma (OSCC). METHOD: We performed a bibliographic search on nine electronic databases, including PubMed, MEDLINE, and Wanfang Data, for data on the MT rate of OL. Possible risk factors were calculated using Comprehensive Meta-Analysis and Open Meta [Analyst] software. RESULTS: The pooled proportion of OL MT for the total population described in the 26 selected studies was 7.20% (95% confidence interval: 5.40-9.10%). Nonhomogeneous type lesions, higher grades of dysplasia, the location of the lesion (tongue and multifocal), and female sex had significant effects on the MT of OL. CONCLUSION: OL tended to develop into OSCC (7.2%), and those with significant MT risk factors should be subjected to regular follow-up and observation. However, we require large-scale prospective studies to validate these results, together with unified clinicopathological diagnostic criteria, standardized risk factor recording/assessment methods, and long-term follow-up guidelines.

Impact of long-term care insurance on the health status of middle-aged and older adults.

With the increase of aging population, long-term care insurance (LTCI) systems have become important for improving individuals' health. However, the effect of LTCI on health is unclear, especially in developing countries, owing to the lack of random policy shocks and comprehensive databases. This study investigates the Chinese LTCI pilot program, using four waves of the China Health and Retirement Longitudinal Study database (sample aged ≥45 years) from 2011 to 2018. The recent difference-in-differences approaches for staggered design, which are capable of dealing with the negative weights issue, are used to investigate changes in health status, measured by self-rated health (SRH), (instrumental) activities of daily living, self-rated depression, and cognition, in pilot and non-pilot cities before and after LTCI implementation. Long-term care insurance has a significant average effect on SRH improvement and a long-term positive effect on cognition for middle-aged and older populations. This study provides the first evaluation of LTCI policy on health outcomes using the recent difference-in-differences approaches. It provides evidence for the overall health improvement achieved through the LTCI and offers positive reinforcement and potential areas for improvement in establishing LTCI worldwide.

The Frequency of Common Deafness-Associated Variants Among 3,555,336 Newborns in China and 141,456 Individuals Across Seven Populations Worldwide.

OBJECTIVES: Genetic screening can benefit early detection and intervention for hearing loss. The frequency of common deafness-associated variants in general populations is highly important for genetic screening and genetic counseling tailored to different ethnic backgrounds. We aimed to analyze the frequency of common deafness-associated variants in a large population-based Chinese newborn cohort and to explore the population-specific features in diverse populations worldwide. DESIGN: This population-based cohort study analyzed the frequency of common deafness-associated variants in 3,555,336 newborns in the Chinese Newborn Concurrent Hearing and Genetic Screening cohort. Participants were newborn infants born between January 2007 and September 2020. Limited genetic screening for 20 variants in 4 common deafness-associated genes and newborn hearing screening were offered concurrently to all newborns in the Chinese Newborn Concurrent Hearing and Genetic Screening cohort. Sequence information of 141,456 individuals was also analyzed from seven ethnic populations from the Genome Aggregation Database for 20 common deafness-related variants. Statistical analysis was performed using R. RESULTS: A total of 3,555,326 Chinese neonates completed the Newborn Concurrent Hearing and Genetic Screening were included for analysis. We reported the distinct landscape of common deafness-associated variants in this large population-based cohort. We found that the carrier frequencies of GJB2 , SLC26A4 , GJB3 , and MT-RNR were 2.53%, 2.05%, 0.37%, and 0.25%, respectively. Furthermore, GJB2 c.235delC was the most common variant with an allele frequency of 0.99% in the Chinese newborn population. We also demonstrated nine East-Asia-enriched variants, one Ashkenazi Jewish-enriched variant, and one European/American-enriched variant for hearing loss. CONCLUSIONS: We showed the distinct landscape of common deafness-associated variants in the Chinese newborn population and provided insights into population-specific features in diverse populations. These data can serve as a powerful resource for otolaryngologists and clinical geneticists to inform population-adjusted genetic screening programs for hearing loss.

Traditional Chinese medicine for treating aplastic anemia.

Aplastic anemia (AA) is a bone marrow failure disease caused by T cell hyperfunction. Although the overall response rate has been improved by immunosuppressive therapy (IST) plus Eltrombopag, 30% of patients have either no response or relapse. We therefore attempted to find other ways to improve the outcomes of AA patients. Traditional Chinese medicine has the advantages of low cost, reasonable effects, and few side effects. More and more clinical studies have confirmed that traditional Chinese medicine has a beneficial role in treating AA patients. This article reviews the potential mechanism of traditional Chinese medicine or its active ingredients in the treatment of AA. These include improving the bone marrow microenvironment, regulating immunity, and affecting the fate of hematopoietic stem cells. This provides useful information for further treatment of AA with integration of traditional Chinese and Western medicine and the development of new treatment strategies.

New potential transporter CIPAS8 enhances cadmium hypersensitivity and cobalt tolerance.

KEY MESSAGE: CIPAS8 is a novel Cd-influx and Co-efflux transporters, and Ser86 and Cys128 might play a decisive role in Co-binding and translocation. Cadmium (Cd) is among the most toxic heavy metals and is a widespread environmental pollutant. Cobalt (Co) is a mineral nutrient that is essential for plant growth and development, but high concentrations may be toxic. Cadmium-induced protein AS8 (CIPAS8) is widely distributed among plant species and might be induced by heavy metals, but its function has not been studied previously. In this study, Populus euphratica PeCIPAS8 and Salix linearistipularis SlCIPAS8 were investigated. The transcription of both genes was significantly enhanced under Cd and Co stresses. PeCIPAS8 and SlCIPAS8 conferred sensitivity to Cd in transgenic yeast, allowing higher quantities of Cd to accumulate within the cells, whereas SlCIPAS8 also conferred tolerance to Co and reduced Co accumulation. The determinants of substrate selectivity of the SlCIPAS8 protein were examined by site mutagenesis, which indicated that the Ser at 86th (S86) substituted for Arg (R) [S86R] and Cys at 128th (C128) substituted for Ser [C128S] mutations limited the protein's capability for Co translocation. These results suggested that PeCIPAS8 and SlCIPAS8 may be involved in Cd uptake into the plant cell. SlCIPAS8 can reduce excess Co accumulation to maintain intracellular Co homeostasis, and the site mutations S86R and C128S were essential for Co transport. These findings provide insight into the function of CIPAS8 and highlight its potential for utilization in phytoremediation applications.

Comparative Analysis of Doppler Ultrasound Combined with Serum PAPP-A in Diagnosis and Pathology of Placenta Accreta.

Objective: To explore the value of Doppler ultrasound combined with the serum pregnancy associated plasma protein A (PAPP-A) in the diagnosis and pathology of placenta accreta. Methods: For the method of retrospective study, the data of 250 pregnant women with cesarean section delivery in our hospital from February 2020 to February 2021 were analyzed, and the prenatal examination of pregnant women was performed by Doppler ultrasound and the serum PAPP-A level was determined by serology detection. They were divided into the placenta accreta group (n=152) and non-placenta accreta group (n=98) according to the pathological results after delivery to compare the imaging data and the serum PAPP-A levels in the two groups. The receiver operating characteristic curve (ROC curve) was drawn with the pathological results as the gold standard. Results: The serum PAPP-A level in the placenta accreta group was overtly lower than that in the non-placenta accreta group (698.65±9.65 vs 910.57±9.65, t = 169.52, P < .001). In the placenta accreta group, there were 126 cases (82.89%) with irregular gyrate liquid dark area formed in the placenta of pregnant women, 78 cases (51.32%) with partial or all disappearance of posterior placenta space, 22 cases (14.74%) with the attenuation or disappearance of myometrium in the placental attachment, and 20 cases (13.16%) with abnormal placental thickening. The sensitivity, specificity, positive predictive value and negative predictive value of the Doppler ultrasound combined with serum diagnosis of PAPP-A were 86.84%, 79.59%, 86.84% and 79.59%, respectively. ROC analysis showed that the area under the curve (AUC) of Doppler ultrasound combined with serum diagnosis of PAPP-A was 0.835, with the asymptotic Sig.b < .001 and an asymptotic 95% confidence interval (CI) of 0.780-0.891. Conclusion: Doppler ultrasound could analyze the pathological manifestations of placenta accreta, and serum PAPP-A could be combined to improve the detection rate of placenta accreta, with a certain clinical application value.

Association between ambient temperature and varicella among adults in Qingdao, China during 2008-2019.

Little concern has been paid to the relationship between temperature and varicella among adults. Daily meteorological data and varicella cases in Qingdao among adults from 1 January 2008 to 31 December 2019 were collected. A combination of quasi-Poisson generalized additive model (GAM) and distributed lag non-linear model (DLNM) was conducted to assess the temperature-lag-varicella relationship. We also estimated the lag-response curves for different temperatures and the exposure-response relationships for different lag days. The number of varicella cases was 10,296. Compared with the minimum-varicella temperature (25°C), we found the largest effect of temperature on varicella within 21 lag days was at 1°C (RR, 6.72; 95% CI, 2.90-15.57), and then the effect declined as the temperature increased. A similar trend of rising first and then falling was found in temperature-response curves for different lag days. A reverse U-shape lag pattern was found for different levels of temperatures. Temperature may affect varicella.

Copper-Catalyzed Chemoselective Asymmetric Hydrogenation of C=O Bonds of Exocyclic α,ß-Unsaturated Pentanones.

A highly chemoselective earth-abundant transition metal copper catalyzed asymmetric hydrogenation of C=O bonds of exocyclic α,ß-unsaturated pentanones was realized using H2 . The desired products were obtained with up to 99 % yield and 96 % ee (enantiomeric excess) (99 % ee, after recrystallization). The corresponding chiral exocyclic allylic pentanol products can be converted into several bioactive molecules. The hydrogenation mechanism was investigated via deuterium-labelling experiments and control experiments, which indicate that the keto-enol isomerization rate of the substrate is faster than that of the hydrogenation and also show that the Cu-H complex can only catalyze chemoselectively the asymmetric reduction of the carbonyl group. Computational results indicate that the multiple attractive dispersion interactions (MADI effect) between the catalyst with bulky substituents and substrate play important roles which stabilize the transition states and reduce the generation of by-products.

Carbon tetrachloride induced mitochondrial division, respiratory chain damage, abnormal intracellular [H+] and apoptosis are due to the activation of 5-HT degradation system in hepatocytes.

Previously we found that acute liver injury (ALI) with inflammation caused by carbon tetrachloride (CCl4) was associated with the activation of the 5-HT degradation system (5DS), which includes monoamine oxidase A (MAO-A), the 5-HT2A receptor, and 5-HT synthases in hepatocytes. This study aimed to determine the role of 5DS in mitochondrial damage and apoptosis. In hepatocyte LO2 cells, CCl4 activated 5-HT2A receptor at the gene level, and then 5-HT2A receptor mediated the expression of 5-HT synthase and MAO-A at the gene level. Suppression of 5DS with the 5-HT2A receptor antagonist, MAO-A inhibitor, or gene silencing MAO-A significantly reduced the CCl4-induced production of mitochondrial reactive oxygen species (ROS). The ROS-associated upregulation of mitochondrial division proteins (FIS1 and DRP1); downregulation of mitochondrial fusion-associated protein 1, respiratory chain proteins (ND1 and CYTB), and ATP6; and decrease of ATP levels were reversed. Moreover, ROS-associated abnormal levels of caspase pathway-associated proteins (Bcl-2, Bax, cleaved-caspase3 and cleaved-caspase9) and apoptosis were suppressed. Notably, a combination of 5-HT2A receptor antagonist and MAO-A inhibitor almost abolished CCl4 cytotoxicity; abolished mitochondrial membrane potential (MMP) depolarization, mitochondrial structural abnormality, and high mitochondrial pH, with low pH states of the nucleus and cytoplasm. The effects of both were more significant than either alone. LO2 cells exposed to H2O2 or depleted mitochondrial ROS showed that ROS induced mitochondrial division and apoptosis and inhibited the levels of respiratory chain proteins. CCl4-induced abnormalities of ATP generation and MMP were dependent on both ROS and other 5DS-associated factors, probably NH3. Investigation of CCl4-induced ALI mice showed that hepatic injury and apoptosis occur at the site of 5DS activation and are significantly inhibited by the 5-HT2A receptor antagonist and 5-HT synthetic inhibitor in a synergistic manner, as well as mitochondrial damage. Together, we revealed the close relationship between CCl4-induced activation of 5DS and mitochondrial damage, abnormal intracellular [H+], and apoptosis in hepatocytes.