Prevotella copri alleviates hyperglycemia and regulates gut microbiota and metabolic profiles in mice.

Prevotella copri is the dominant species of the Prevotella genus in the gut, which is genomically heterogeneous and difficult to isolate; hence, scarce research was carried out for this species. This study aimed to investigate the effect of P. copri on hyperglycemia. Thirty-nine strains were isolated from healthy individuals, and three strains (HF2123, HF1478, and HF2130) that had the highest glucose consumption were selected to evaluate the effects of P. copri supplementation on hyperglycemia. Microbiomics and non-target metabolomics were used to uncover the underlying mechanisms. Oral administration of P. copri in diabetic db/db mice increased the expression and secretion of glucagon-like peptide-1 (GLP-1), significantly improved hyperglycemia, insulin resistance, and lipid accumulation, and alleviated the pathological morphology in the pancreas, liver, and colon. P. copri changed the composition of the gut microbiota of diabetic db/db mice, which was characterized by increasing the ratio of Bacteroidetes to Firmicutes and increasing the relative abundance of genera Bacteroides, Akkermansia, and Faecalibacterium. After intervention with P. copri, fecal metabolic profiling showed that fumaric acid and homocysteine contents decreased, and glutamine contents increased. Furthermore, amino acid metabolism and cAMP/PKA signaling pathways were enriched. Our findings indicate that P. copri improved glucose metabolism abnormalities in diabetic db/db mice. Especially, one of the P. copri strains, HF2130, has shown superior performance in improving hyperglycemia, which may have the potential as a probiotic against hyperglycemia. IMPORTANCE: As a core member of the human intestinal ecosystem, Prevotelal copri has been associated with glucose metabolic homeostasis in previous studies. However, these results have often been derived from metagenomic studies, and the experimental studies have been based solely on the type of strain DSM 18205T. Therefore, more experimental evidence from additional isolates is needed to validate the results according to their high genomic heterogeneity. In this study, we isolated different branches of strains and demonstrated that P. copri could improve the metabolic profile of hyperglycemic mice by modulating microbial activity. This finding supports the causal contribution of P. copri in host glucose metabolism.

Functional Networks of Reward and Punishment Processing and Their Molecular Profiles Predicting the Severity of Young Adult Drinking.

Alcohol misuse is associated with altered punishment and reward processing. Here, we investigated neural network responses to reward and punishment and the molecular profiles of the connectivity features predicting alcohol use severity in young adults. We curated the Human Connectome Project data and employed connectome-based predictive modeling (CPM) to examine how functional connectivity (FC) features during wins and losses are associated with alcohol use severity, quantified by Semi-Structured Assessment for the Genetics of Alcoholism, in 981 young adults. We combined the CPM findings and the JuSpace toolbox to characterize the molecular profiles of the network connectivity features of alcohol use severity. The connectomics predicting alcohol use severity appeared specific, comprising less than 0.12% of all features, including medial frontal, motor/sensory, and cerebellum/brainstem networks during punishment processing and medial frontal, fronto-parietal, and motor/sensory networks during reward processing. Spatial correlation analyses showed that these networks were associated predominantly with serotonergic and GABAa signaling. To conclude, a distinct pattern of network connectivity predicted alcohol use severity in young adult drinkers. These "neural fingerprints" elucidate how alcohol misuse impacts the brain and provide evidence of new targets for future intervention.

ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma.

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

Machine Learning Identification of Nutrient Intake Variations across Age Groups in Metabolic Syndrome and Healthy Populations.

This study undertakes a comprehensive examination of the intricate link between diet nutrition, age, and metabolic syndrome (MetS), utilizing advanced artificial intelligence methodologies. Data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018 were meticulously analyzed using machine learning (ML) techniques, specifically extreme gradient boosting (XGBoost) and the proportional hazards model (COX). Using these analytic methods, we elucidated a significant correlation between age and MetS incidence and revealed the impact of age-specific dietary patterns on MetS. The study delineated how the consumption of certain dietary components, namely retinol, beta-cryptoxanthin, vitamin C, theobromine, caffeine, lycopene, and alcohol, variably affects MetS across different age demographics. Furthermore, it was revealed that identical nutritional intakes pose diverse pathogenic risks for MetS across varying age brackets, with substances such as cholesterol, caffeine, and theobromine exhibiting differential risks contingent on age. Importantly, this investigation succeeded in developing a predictive model of high accuracy, distinguishing individuals with MetS from healthy controls, thereby highlighting the potential for precision in dietary interventions and MetS management strategies tailored to specific age groups. These findings underscore the importance of age-specific nutritional guidance and lay the foundation for future research in this area.

LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein.

Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.

PJA1-mediated suppression of pyroptosis as a driver of docetaxel resistance in nasopharyngeal carcinoma.

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.

Aflatoxin B1-induced liver pyroptosis is mediated by disturbing the gut microbial metabolites: The roles of pipecolic acid and norepinephrine.

The disturbed gut microbiota is a key factor in activating the aflatoxin B1 (AFB1)-induced liver pyroptosis by promoting inflammatory hepatic injury; however, the pathogen associated molecular pattern (PAMP) from disturbed gut microbiota and its mechanism in activating liver pyroptosis remain undefined. By transplanting AFB1-originated fecal microbiota and sterile fecal microbial metabolites filtrate, we determined the association of PAMP in AFB1-induced liver pyroptosis. Notably, AFB1-originated sterile fecal microbial metabolites filtrate were more active in triggering liver pyroptosis in mice, as compared to parental fecal microbiota. This result supported a critical role of the metabolic homeostasis of gut microbiota in AFB1-induced liver pyroptosis, rather than an injurious response to direct exposure of AFB1 in liver. Among the gut-microbial metabolites, pipecolic acid and norepinephrine were proposed to bind TLR4 and NLRP3, the upstream proteins of pyroptosis signaling pathway. Besides, the activations of TLR4 and NLRP3 were linearly correlated with the concentrations of pipecolic acid and norepinephrine in the serum of mice. In silenced expression of TLR4 and NLRP3 in HepG2 cells, pipecolic acid or norepinephrine did not able to activate hepatocyte pyroptosis. These results demonstrated the necessity of gut microbial metabolism in sustaining liver homeostasis, as well as the potential to provide new insights into targeted intervention for AFB1 hepatotoxicity.

Biomedical application of materials for external auditory canal: History, challenges, and clinical prospects.

Biomaterials play an integral role in treatment of external auditory canal (EAC) diseases. Regarding the special anatomic structure and physiological characteristics of EAC, careful selection of applicable biomaterials was essential step towards effective management of EAC conditions. The bioactive materials can provide reasonable biocompatibility, reduce risk of host pro-inflammatory response and immune rejection, and promote the healing process. In therapeutic procedure, biomaterials were employed for covering or packing the wound, protection of the damaged tissue, and maintaining of normal structures and functions of the EAC. Therefore, understanding and application of biomaterials was key to obtaining great rehabilitation in therapy of EAC diseases. In clinical practice, biomaterials were recognized as an important part in the treatment of different EAC diseases. The choice of biomaterials was distinct according to the requirements of various diseases. As a result, awareness of property regarding different biomaterials was fundamental for appropriate selection of therapeutic substances in different EAC diseases. In this review, we firstly introduced the characteristics of EAC structures and physiology, and EAC pathologies were summarized secondarily. From the viewpoint of biomaterials, the different materials applied to individual diseases were outlined in categories. Besides, the underlying future of therapeutic EAC biomaterials was discussed.

The Effects of Vitamin D and Gene Polymorphisms on Susceptibility to Thyroid Peroxidase Antibody Positivity.

BACKGROUND: The etiology of Hashimoto's thyroiditis (HT) involves genetic and environmental factors. There is a lack of clarity regarding the relationship between Vitamin D and HT. This study aimed to investigate the effect of Vitamin D and gene polymorphisms on thyroid peroxidase antibody (TPOAb) positivity. METHODS: A total of 9,966 participants were included from a survey conducted in East China from 2014 to 2016. We measured the levels of 25(OH)D, thyroid hormones and autoimmune antibodies. rs11675434, rs9277555, and rs301799 were genotyped. Based on these 3 SNPs, a weighted genetic risk score was calculated for TPOAb. RESULTS: The proportion of females in the TPOAb-positive group was greater than that in the TPOAb-negative group (74.2% vs. 57.2%, P<0.001). Vitamin D levels were lower in the TPOAb-positive group than in the TPOAb-negative group (40.07±11.87 vs. 40.80±12.84, P=0.01). The GG genotype of rs9277555 and the TT genotype of rs11675434 were correlated with the risk of TPOAb positivity (OR=1.34, 95% CI 1.13-1.59, P=0.001; OR=1.29, 95% CI 1.06-1.58, P=0.01). TPOAb-GRS was associated with TPOAb positivity (OR=3.17, 95% CI 1.72-5.84; P<0.001). When stratified by Vitamin D group, the association between TPOAb-GRS and TPOAb positivity existed only in the Vitamin D deficiency group (OR=3.41, 95% CI 1.73-6.70 P<0.001) but not in the control group (OR=2.45, 95% CI 0.59-10.19, P=0.22). CONCLUSIONS: This study suggested that TPOAb-GRS was associated with TPOAb positivity in the Han Chinese population, mainly due to rs9277555 and rs11675434. The hereditary effect of TPOAb positivity differed depending on Vitamin D status.

Cornus officinalis Extract Enriched with Ursolic Acid Ameliorates UVB-Induced Photoaging in Caenorhabditis elegans.

Ultraviolet B (UVB) exposure can contribute to photoaging of skin. Cornus officinalis is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the Cornus officinalis extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of Cornus officinalis. The effect of COE on UVB damage was assessed using Caenorhabditis elegans. The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of C. elegans exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the skn-1 downstream gene and the extension of the lifespan in skn-1 mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in C. elegans via the SKN-1/Nrf2 pathway.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Investigation on the Epidemic Situation of Epidemic Hemorrhagic Fever in an Island Industrial Park in Zhoushan, China.

Objective: To investigate the epidemic factors of hemorrhagic fever with renal syndrome (HFRS) and compare the S and M gene sequences of hantavirus (HV) between rodents and the infected cases. Methods: Detailed epidemiological investigations were conducted on the cases' working and living areas. Captured rodents were classified by night trapping method, and their lungs and blood were collected for virus carriage detection after aseptic dissection. Viral S and M fragments of HV RNA were amplified and sequenced from positive samples of cases and mice, and their homology was analyzed. Results: After reconstruction, the geographic and living environment changed significantly, altering rodent behaviors. The industrial park, characterized by high population density, poor living conditions, and frequent contact of rodent (feces) and humans, had a high rodent density and HV virus infection ratio. Four workers infected with HV were positive for anti-HV immunoglobulin G (IgG) and IgM. Among the positive samples, HV RNA was detected in all two cases, and four Rattus norvegicus specimens were Seoul type HV S3 subtype. The virus had the closest relationship with Rod/2012/QHD/4/Gc (Hebei, China) and RuianRn180 (Zhejiang, China), with the 100% homology of M gene segment. The homology of viral S gene segment exhibited the closest relationship with the Jiangxi isolated JiangxiXinjianRn-09-2011, ranging from 99.6% to 99.8%. Conclusion: The HV sequencing showed a strong epidemiological relationship between the cases and host rodents. Improving living environmental health conditions, administering HFRS vaccine, and reducing rodent density and human-rodent contact can mitigate the risk of HFRS.

Three species of rape responded to cadmium and melatonin alleviating Cd-toxicity in species-specific strategy.

Cadmium (Cd) pollution has been a significant concern in heavy metal pollution, prompting plants to adopt various strategies to mitigate its damage. While the response of plants to Cd stress and the impact of exogenous melatonin has received considerable attention, there has been limited focus on the responses of closely related species to these factors. Consequently, our investigation aimed to explore the response of three different species of rape to Cd stress and examine the influence of exogenous melatonin in this scenario. The research findings revealed distinctive responses among the investigated rape species. B. campestris showed the resistance to Cd and exhibited lower Cd absorption and sustained its physiological activity under Cd stress. In contrast, B. juncea accumulated much Cd and increased the amount of anthocyanin to mitigate the Cd-damage. Furthermore, B. napus showed the tolerance to Cd and tended to accumulate Cd in vacuoles under Cd stress, thereby decreasing the Cd damage and leading to higher activity of antioxidant enzymes and photosynthesis. Moreover, the application of exogenous melatonin significantly elevated the melatonin level in plants and mitigated Cd toxicity by promoting the activity of antioxidant enzymes, reducing Cd absorption, enhancing the chelating capacity with Cd, decreasing Cd accumulation in organelles, and reducing its fluidity. Specifically, exogenous melatonin increased the FHAc content in B. campestris, elevated the phytochelatins (PCs) level in B. napus, and stimulated photosynthesis in B. juncea. In summary, the findings underscore the species-specific responses of the three species of rape to both Cd stress and exogenous melatonin, highlighting the potential for tailored mitigation strategies based on the unique characteristics of each species.

Niche convergence and biogeographic history shape elevational tree community assembly in a subtropical mountain forest.

Niche convergence or conservatism have been proposed as essential mechanisms underlying elevational plant community assembly in tropical mountain ecosystems. Subtropical mountains, compared to tropical mountains, are likely to be shaped by a mixing of different geographic affinities of species and remain somehow unclear. Here, we used 31 0.1-ha permanent plots distributed in subtropical forests on the eastern and western aspects of the Gaoligong Mountains, southwest China between 1498 m and 3204 m a.sl. to evaluate how niche-based and biogeographic processes shape tree community assembly along elevational gradients. We analyzed the elevational patterns of taxonomic, phylogenetic and functional diversity, as well as of individual traits, and assessed the relative importance of environmental effects on these diversity measures. We then classified tree species as being either tropical affiliated or temperate affiliated and estimated their contribution to the composition of biogeographic affinities. Species richness decreased with elevation, and species composition showed apparent turnover across the aspects and elevations. Most traits exhibited convergent patterns across the entire elevational gradient. Phylogenetic and functional diversity showed opposing patterns, with phylogenetic diversity increasing and functional diversity decreasing with elevation. Soil nutrients, especially phosphorus and nitrogen, appeared to be the main abiotic variables driving the elevational diversity patterns. Communities at lower elevations were occupied by tropical genera, while highlands contained species of tropical and temperate biogeographic affinities. Moreover, the high phylogenetic diversity at high elevations were likely due to differences in evolutionary history between temperate and tropical species. Our results highlight the importance of niche convergence of tropical species and the legacy of biogeographic history on the composition and structure of subtropical mountain forests. Furthermore, limited soil phosphorus caused traits divergence and the partitioning for different forms of phosphorus may explain the high biodiversity found in phosphorus-limited subtropical forests.

Groundwater chemical evolution characteristics and human health risk assessment in Shicheng County, Jiangxi Province.

Groundwater plays a pivotal role in the water resources of Shicheng County; however, the issue of excessive fluoride content in groundwater and its associated health risks often goes unnoticed. Groundwater assumes a crucial role in the hydrological dynamics of Shicheng County; nevertheless, the matter concerning elevated levels of fluoride within groundwater and its accompanying health hazards frequently evades attention. The hydrogeochemical analysis, obscure comprehensive water quality assessment based on cloud model, and probabilistic human health risk assessment using Monte Carlo simulation were conducted on 34 collected water samples. The findings indicate that the predominant groundwater hydrochemical types are SO4·Cl-Na and HCO3-Na. The processes of rock weathering and cation exchange play crucial roles in influencing water chemistry. Groundwater samples generally exhibit elevated concentrations of F-, surpassing the drinking water standard, primarily attributed to mineral dissolution. The concentrations of F- in more than 52.94% and 23.53% of the groundwater samples exceeded the acceptable non-carcinogenic risk limits for children and adults, respectively. Considering the inherent uncertainty in model parameters, it is anticipated that both children and adults will have a probability exceeding 49.36% and 30.50%, respectively, of being exposed to elevated levels of F ions in groundwater. The utilization of stochastic simulations, in contrast to deterministic methods, enables a more precise depiction of health risks. The outcomes derived from this investigation possess the potential to assist policymakers in formulating strategies aimed at ensuring the provision of secure domestic water supplies.

Correction to "Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression".

[This corrects the article DOI: 10.1021/acsomega.3c09667.].

Endocrine toxicity of atrazine and its underlying mechanisms.

Atrazine (ATR) is one of the most widely utilized herbicides globally and is prevalent in the environment due to its extensive use and long half-life. It can infiltrate the human body through drinking water, ingestion, and dermal contact, and has been recognized as an environmental endocrine disruptor. This study aims to comprehensively outline the detrimental impacts of ATR on the endocrine system. Previous research indicates that ATR is harmful to various bodily systems, including the reproductive system, nervous system, adrenal glands, and thyroi d gland. The toxic effects of ATR on the endocrine system and its underlying molecular mechanisms are summarized as follows: influencing the expression of kisspeptin in the HPG axis, consequently affecting steroid synthesis; disrupting DNA synthesis and meiosis, as well as modifying DNA methylation levels, leading to reproductive and developmental toxicity; impacting dopamine by altering Nurr1, VMAT2, and DAT expression, consequently affecting dopamine synthesis and transporter expression, and influencing other neurotransmitters, resulting in neurotoxicity; and changing adipose tissue synthesis and metabolism by reducing basal metabolism, impairing cellular oxidative phosphorylation, and inducing insulin resistance. Additionally, a compilation of natural products used to mitigate the toxic effects of ATR has been provided, encompassing melatonin, curcumin, quercetin, lycopene, flavonoids, vitamin C, vitamin E, and other natural remedies. It is important to note that existing research predominantly relies on in vitro and ex vivo experiments, with limited population-based empirical evidence available.

[Percutaneous pedicle screw anchored vertebral augmentation for the treatment of Kümmell disease without neurological symptoms].

OBJECTIVE: To explore the clinical effect of percutaneous pedicle screw anchored vertebral augmentation(PPSAVA) in the treatment of asymptomatic Kümmell disease without neurological symptoms. METHODS: The clinical data of 20 patients with Kümmell disease without neurological symptoms treated with PPSAVA in our hospital from January 2019 to December 2021 were analyzed retrospectively, including 5 males and 15 females, aged 56 to 88 (74.95±9.93) years old. and the course of disease was 7 to 60 days with an average of (21.35±14.46) days. All patients were treated with PPSAVA. The time of operation, the amount of bone cement injected and the leakage of bone cement were recorded. The visual analogue scale(VAS), Oswestry disability index(ODI), vertebral body angle(VBA), anterior edge height and midline height of vertebral body were compared among the before operation, 3 days after operation and during the final follow-up. The loosening and displacement of bone cement were observed during the final follow-up. RESULTS: All the 20 patients completed the operation successfully. The operation time was 30 to 56 min with an average of (41.15±7.65) min, and the amount of bone cement injection was 6.0 to 12.0 ml with an average of (9.30±1.49) ml. Bone cement leakage occurred in 6 cases and there were no obvious clinical symptoms. The follow-up time was 6 to 12 months with an average of (8.43±2.82) months. The VBA, anterior edge height and midline height of of injured vertebral body were significantly improved 3 days after operation and the final follow-up(P<0.05), and the VBA, anterior edge height and midline height of of injured vertebral body were lost in different degrees at the final follow-up (P<0.05). The VAS and ODI at 3 days after operation and at the final follow-up were significantly lower than those at preoperatively(P<0.05), but the VAS score and ODI at the final follow-up were not significantly different from those at 3 d after operation(P>0.05). At the last follow-up, no patients showed loosening or displacement of bone cement. CONCLUSION: PPSAVA is highly effective in treating Kümmell disease without neurological symptoms, improving patients' pain and functional impairment, and reducing the risk of cement loosening and displacement postoperatively.

Boron modification promoting electrochemical surface reconstruction of NiFe-LDH for efficient and stable freshwater/seawater oxidation catalysis.

Transition metal-based electrocatalysts generally take place surface reconstruction in alkaline conditions, but little is known about how to improve the reconstruction to a highly active oxyhydroxide surface for an efficient and stable oxygen evolution reaction (OER). Herein, we develop a strategy to accelerate surface reconstruction by combining boron modification and cyclic voltammetry (CV) activation. Density functional theory calculations and in-situ/ex-situ characterizations indicate that both B-doping and electrochemical activation can reduce the energy barrier and contribute to the surface evolution into highly active oxyhydroxides. The formed oxyhydroxide active phase can tune the electronic configuration and boost the OER process. The reconstructed catalyst of CV-B-NiFe-LDH displays excellent alkaline OER performance in freshwater, simulated seawater, and natural seawater with low overpotentials at 100 mA cm-2 (η100: 219, 236, and 255 mV, respectively) and good durability. This catalyst also presents outstanding Cl- corrosion resistance in alkalized seawater electrolytes. The CV-B-NiFe-LDH||Pt/C electrolyzer reveals prominent performance for alkalized freshwater/seawater splitting. This study provides a guideline for developing advanced OER electrocatalysts by promoting surface reconstruction.

Conditional reprogrammed human limbal epithelial cell model for anti-SARS-CoV-2 drug screening.

To minimize the global pandemic COVID-19 spread, understanding the possible transmission routes of SARS-CoV-2 and discovery of novel antiviral drugs are necessary. We describe here that the virus can infect ocular surface limbal epithelial, but not other regions. Limbal supports wild type and mutant SARS-CoV-2 entry and replication depending on ACE2, TMPRSS2 and possibly other receptors, resulting in slight CPE and arising IL-6 secretion, which symbolizes conjunctivitis in clinical symptoms. With this limbal model, we have screened two natural product libraries and discovered several unreported drugs. Our data reveal important commonalities between COVID-19 and ocular infection with SARS-CoV-2, and establish an ideal cell model for drug screening and mechanism research.