Genomic epidemiology of CVA10 in Guangdong, China, 2013-2021.

Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness primarily affecting children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-Enterovirus A71 (EV-A71) and non-Coxsackievirus A16 (CVA16) enteroviruses (EVs). Our study conducts a retrospective examination of 36,461 EV-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, Coxsackievirus A6 (CVA6) and Coxsackievirus A10 (CVA10) have emerged as the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, cases of CVA10 infection were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, possibly indicating accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2 A protein, contributing to a predominant subcluster within genogroup C of CVA10 circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of EV genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of EV genotypes. Moreover, given the shifting dominance of EV genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily target EV-A71.

Accurate determination of plasma temperature and electron density using a reference target: one-point calibration LIBS elemental analysis of alloy samples.

Elemental analysis of aluminum alloy samples with calibration-free laser-induced breakdown spectroscopy (CF-LIBS) encounters two difficulties: the inconvenience of determining accurate temperature and electron density of the plasma and the influence of self-absorption of the observed aluminum lines. To solve this problem, target-enhanced orthogonal double-pulse laser-induced breakdown spectroscopy in the reheating regime combined with the one-point calibration method was proposed in this work. A mixture of copper powders and K H C O 3 grains was pressed to a pellet and used as the target. Accurate determination of plasma temperature and electron density can be obtained using a reference target. The plasma temperature could be determined with Saha-Boltzmann plot of copper, and the electron density of the plasma could be determined according to the Stark broadening of the H α line of hydrogen. Aluminum alloy samples were analyzed with a relative error of better than 0.02% for a major element. This approach provides a convenient way to determine the temperature and electron density of the plasma more accurately and is able to reduce the influence of self-absorption, which is helpful for realizing quantitative elemental analysis of different samples while using a calibration-free algorithm.

Experience of diet in patients with inflammatory bowel disease: A thematic synthesis of qualitative studies.

AIM: To synthesise the dietary expesriences of patients with inflammatory bowel disease by reviewing relevant qualitative studies. BACKGROUND: Diet plays a crucial role in the development and progression of inflammatory bowel disease (IBD). There is no specific diet that can be recommended for all patients. We conducted a synthesis of qualitative studies to gain a comprehensive understanding of the dietary management experience of patients with IBD, aiming to provide better dietary guidance in the future. DESIGN: A qualitative synthesis was conducted following the Thomas and Harden method and reported following the ENTREQ statement. METHODS: Qualitative studies were systematically searched in five electronic databases: PubMed, PsycINFO, Embase, CINAHL, and Web of Science. There was no time limit for publication, and all database searches were up to 10 May, 2023. The Joanna Briggs Institute Qualitative Assessment and Review Instrument was utilised to appraise the quality of the included studies. Data for inclusion in articles were extracted and analysed using a thematic synthesis method. RESULTS: Six studies involving 119 patients were eventually included. The studies were conducted in six different countries. Four major themes were identified: the diet of patients with IBD is completely different from the normal one; manage symptoms and live with the disease by modifying diet; psychological adjustment to eating (be frustrated; worried and afraid; feel ashamed; growth and resilience); barriers and challenges (barriers from perceived social support; conflicts between diet and nutrition; challenges from food hedonism and cravings). CONCLUSIONS: Patients with IBD highlighted the distinction between their diet and the normal diet. Dietary modifications were used as a way to manage symptoms and live with the disease. In addition to physical symptoms, patients experienced diet-related psychological changes. Dietary modifications in patients with IBD encounters difficulties and challenges, necessitating prompt guidance and intervention. (1) The implementation of dietary modifications in patients with IBD encounters numerous obstacles and complexities, necessitating prompt guidance and intervention. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REGISTRATION: The protocol was registered with PROSPERO (CRD42023391545).

Preparation of Stereo-Divergent Compounds from the Natural Product Drupacine Based on Complexity-to-Diversity Strategy.

The Complexity-to-Diversity (CtD) strategy was applied to synthesize a 23-member compound collection from the natural product drupacine, including 21 novel compounds. An unusual benzo [d] cyclopenta [b] azepin skeleton was constructed by Von Braun reaction to cleave C-N bond of drupacine. Moreover, compound 10 has potential cytotoxicity to human colon cancer cells with low toxicity to the normal human colon mucosal epithelial cell lines.

Drug Delivery and Therapy Strategies for Osteoporosis Intervention.

With the advent of the aging society, osteoporosis (OP) risk increases yearly. Currently, the clinical usage of anti-OP drugs is challenged by recurrent side effects and poor patient compliance, regardless of oral, intravenous, or subcutaneous administration. Properly using a drug delivery system or formulation strategy can achieve targeted drug delivery to the bone, diminish side effects, improve bioavailability, and prolong the in vivo residence time, thus effectively curing osteoporosis. This review expounds on the pathogenesis of OP and the clinical medicaments used for OP intervention, proposes the design approach for anti-OP drug delivery, emphatically discusses emerging novel anti-OP drug delivery systems, and enumerates anti-OP preparations under clinical investigation. Our findings may contribute to engineering anti-OP drug delivery and OP-targeting therapy.

Influencing factors of medical device-related pressure ulcers in medical personnel during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVE: To determine the influencing factors of medical device related pressure injury (MDRPU) in medical staff by meta-analysis. METHODS: A comprehensive literature search was conducted by PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, CBM, and WanFang Data (from inception to July 27, 2022). Two researchers independently performed literature screening, quality evaluation and data extraction, and meta-analysis was conducted with RevMan 5.4 and Stata12.0 software. RESULTS: Total of 11215 medical staff were included in 9 articles. Meta analysis showed that gender, occupation, sweating, wearing time, single working time, department of COVID-19, preventive measures, and level 3 PPE were the risk factors for MDRPU in medical staff (P < 0.05). CONCLUSION: The outbreak of COVID-19 led to the occurrence of MDRPU among medical staff, and the influencing factors should be focused on. The medical administrator can further improve and standardize the preventive measures of MDRPU according to the influencing factors. Medical staff should accurately identify high-risk factors in the clinical work process, implement intervention measures, and reduce the incidence of MDRPU.

["To be meridian or collateral" in meridian-collateral differentiation].

Identifying the study subject, "to be in meridian or collateral", is the first step of meridian-collateral differentiation. Combined with the ancient literature and clinical practice of acupuncture and moxibustion, the methods of identifying "to be in meridian or collateral" and its values are elaborated. Through analyzing the onset location of symptoms and the body layers of lesions, as well as the palpation and observation in meridian-collateral detection, "to be meridian" or "to be collateral" is identified in disease diagnosis. It may guide the choice of techniques of acupuncture and moxibustion. Identifying "to be meridian or collateral" is crucial in meridian-collateral differentiation, which not only contributes to improving the therapeutic effect of acupuncture and moxibustion, but also to better recognizing diseases and understanding the relevant concepts of techniques of acupuncture and moxibustion in view of acupuncture and moxibustion, and perfecting the system of meridian-collateral differentiation.

Evaluating the therapeutic potential of moxibustion on polycystic ovary syndrome: a rat model study on gut microbiota and metabolite interaction.

Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion's impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, 1H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of UCG-005 and Turicibacter, as well as decreasing the abundance of Desulfovibrio. Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites.

Pokemon inhibits Bim transcription to promote the proliferation, anti-anoikis, invasion, histological grade, and dukes stage of colorectal neoplasms.

PURPOSE: This study aims to determine whether Pokemon regulates Bim activity in colorectal carcinoma (CRC) carcinogenesis. METHODS: Clinical tissue samples were analyzed to detect the expression and clinicopathological significance of Pokemon and Bim in CRC. Proliferation, apoptosis, and invasion assays were conducted to identify the regulatory effect of Pokemon on Bim. The combined treatment effects of Pokemon knockdown and diamminedichloroplatinum (DDP) were also examined. RESULTS: Immunohistochemical analysis of 80 samples of colorectal epithelia (CRE), 80 cases of colorectal adenoma (CRA), and 160 of CRC samples revealed protein expression rates of 23.8%, 38.8%, and 70.6% for Pokemon, and 88.8%, 73.8%, and 31.9% for Bim, respectively. A significant negative correlation was observed between Pokemon and Bim expression across the CRE, CRA, and CRC lesion stages. In CRC, higher Pokemon and lower Bim expression correlated with higher histological grades, advanced Dukes stages, and increased cancer invasion. In both LoVo and HCT116 cells, overexpression of Pokemon significantly reduced Bim expression, leading to increased proliferation, resistance to anoikis, and cell invasion. Additionally, Pokemon overexpression significantly decreased DDP-induced Bim expression, reduction of anti-apoptosis and invasion, whereas Pokemon knockdown resulted in the opposite effects. CONCLUSION: These findings suggest that Pokemon inhibits Bim transcription, thereby promoting CRC proliferation, resistance to apoptosis, invasion, and advancing histological grade and Dukes staging. Pokemon knockdown enhances the therapeutic efficacy of DDP in the treatment of CRC.

Characterizing Infections in Two Epidemic Waves of SARS-CoV-2 Omicron Variants: A Cohort Study in Guangzhou, China.

BACKGROUND: After the adjustment of COVID-19 epidemic policy, mainland China experienced two consecutive waves of Omicron variants within a seven-month period. In Guangzhou city, as one of the most populous regions, the viral infection characteristics, molecular epidemiology, and the dynamic of population immunity are still elusive. METHODS: We launched a prospective cohort study in the Guangdong Provincial CDC from December 2022 to July 2023. Fifty participants who received the same vaccination regimen and had no previous infection were recruited. RESULTS: 90% of individuals were infected with Omicron BA.5* variants within three weeks in the first wave. Thirteen cases (28.26%) experienced infection with XBB.1* variants, occurring from 14 weeks to 21 weeks after the first wave. BA.5* infections exhibited higher viral loads in nasopharyngeal sites compared to oropharyngeal sites. Compared to BA.5* infections, the XBB.1* infections had significantly milder clinical symptoms, lower viral loads, and shorter durations of virus positivity. The infection with the BA.5* variant elicited varying levels of neutralizing antibodies against XBB.1* among different individuals, even with similar levels of BA.5* antibodies. The level of neutralizing antibodies specific to XBB.1* determined the risk of reinfection. CONCLUSIONS: The rapid large-scale infections of the Omicron variants have quickly established herd immunity among the population in mainland China. In the future of the COVID-19 epidemic, a lower infection rate but a longer duration can be expected. Given the large population size and ongoing diversified herd immunity, it remains crucial to closely monitor the molecular epidemiology of SARS-CoV-2 for the emergence of new variants of concern in this region. Additionally, the timely evaluation of the immune status across different age groups is essential for informing future vaccination strategies and intervention policies.

Molecular epidemiology and population immunity of SARS-CoV-2 in Guangdong (2022-2023) following a pivotal shift in the pandemic.

The SARS-CoV-2 Omicron variant sparked the largest wave of infections worldwide. Mainland China eased its strict COVID-19 measures in late 2022 and experienced two nationwide Omicron waves in 2023. Here, we investigated lineage distribution and virus evolution in Guangdong, China, 2022-2023 by comparing 5813 local viral genomes with the datasets from other regions of China and worldwide. Additionally, we conducted three large-scale serological surveys involving 1696 participants to measure their immune response to the BA.5 and XBB.1.9 before and after the corresponding waves. Our findings revealed the Omicron variants, mainly the BA.5.2.48 lineage, causing infections in over 90% of individuals across different age groups within a month. This rapid spread led to the establishment of widespread immunity, limiting the virus's ability to further adaptive mutation and dissemination. While similar immune responses to BA.5 were observed across all age groups after the initial wave, children aged 3 to 11 developed a stronger cross immune response to the XBB.1.9 strain, possibly explaining their lower infection rates in the following XBB.1 wave. Reinfection with Omicron XBB.1 variant triggered a more potent neutralizing immune response among older adults. These findings highlight the impact of age-specific immune responses on viral spread in potential future waves.

Weibo users and Academia's foci on tourism safety: Implications from institutional differences and digital divide.

Tourism safety is essential for tourists and tourism practitioners. This study conducted a bibliometric analysis using VOSviewer and CiteSpace for 2018 articles indexed on the Web of Science (WoS). It also analysed 7293 Weibo posts between 1977 and 2022 using Python, MYSQL, AI sentiment, and Tableau. The first tourism safety publication on WoS appeared in 1977, while the first Weibo microblog dated was dated back to 2011. Compared to the information posted on Weibo, the annual publications about tourism safety on WoS recorded a stable increment. On Web of Science (WoS), the academic staff and universities produced the largest number of tourism safety posts. On the flip side, the most productive organisations on Weibo are government agencies in popular tourism destinations. "Accident", "medical tourism", "environment", "mediating role", and "hospitality" were important burst nodes in tourism safety on WoS. "Quality", "accident", and health-related words were the foci on both Weibo and WoS. On Web of Science, the top 10 most popular keywords of tourism safety-related articles could be classified into two groups: health ("Covid-19", "restoration", "pandemics", "Sars-Cov-2", "Sars", "mental health") and IT terminologies ("big data", "artificial intelligence"). It has been concluded that "artificial intelligence (AI)" is more likely to be included in the keywords on tourism researched by academia. In contrast, the public may not know about or use AI in the tourism industry. Besides, the top 10 most popular keywords on Weibo related to tourism risks and hazards were drowning and traffic risks and hazards, such as drowning and traffic risks. The digital divide may explain such a difference: the academic circle benefits more from the digital age than laypersons. It may also be the result of institutional differences and information asymmetry.

Evaluation of evidence of prevention and management of facial pressure injuries in medical staff.

AIM: This systematic review evaluated the quality of evidence for the prevention and management of facial pressure injuries in medical staff. DESIGN: This review was presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: We retrieved the relevant studies from 19 databases. Using the literature evaluation standards and evidence grading system of the Australian Joanna Briggs Institute Evidence-Based Health Care Center, we evaluated the quality of the literature encompassing different types of research and assessed their levels of evidence. RESULTS: A total of 13 studies were included, including seven expert consensuses, two recommended practices, one clinical decision, one best practice information booklet, one systematic review and one randomized controlled trial. In the end, 31 best evidence were summarized, including skin cleaning and care, PPE placement and movement, reasonable use of dressings, treatment measures and education and training.

Highly-oxidizing Au@MnO2-X nanozymes mediated homogeneous electrochemical detection of organophosphorus independent of dissolved oxygen.

Traditional oxidase-like (OXD) nanozymes rely primarily on O2-mediated superoxide anion (O2·-) process for catalytic oxidation and organophosphorus (Ops) detection. While during the actual detection process, the concentration of O2 is inconstant that can be easily changed with the external environment, distorting detection results. Herein, highly-oxidizing Au@MnO2-X nanozymes with core-shell nanostructure are designed which trigger substantial electron transfer from inner Au core to outer ultrathin MnO2-X layer. According to experimental and theoretical calculations, the core-shell nanostructure and ultrathin MnO2-X of Au@MnO2-X result in the large surface defects, high oxygen vacancies and MnIII ratios. The specially structured Au@MnO2-X nanozymes are therefore highly-oxidizing and the catalytic oxidation can be completed merely through electrons transferring instead of the O2-mediated O2·- process. Based on this, an oxygen independent and ultrasensitive nanozyme-based sensor is established using homogeneous electrochemistry (HEC), its Ops is detected at a LOD of 0.039 ng mL-1. Combined with the UV-vis spectrum of 3,3',5,5'-tetramethylbenzidine (TMB), the linear discriminant analysis of five Ops i.e., Ethion, Omethoate, Diazinon, Chlorpyrifos methyl and Dipterex has achieved superior discrimination results. Therefore, HEC based on strong oxidizing nanozymes provide a new avenue for the development of high-performance electrochemical sensors and demonstrate potential applicability to pesticide residue determination in real samples.

New N-oxide alkaloids from the stems of Sinomenium acutum.

Six new alkaloids (1-6) and six known alkaloids (7-12) were obtained from the stems of Sinomenium acutum. Among them, compounds 1-3 and 6 were four N-oxide alkaloids. The structures and absolute configurations of these new alkaloids were elucidated through comprehensive data of 1D and 2D NMR, HRESIMS and ECD spectra. All isolated compounds were evaluated in vitro for their inhibitory activities against nitric oxide (NO) production and inhibitory effects on AChE. Among them, the sinomenine N-oxide (9) was the most potent NO production inhibitor, with an IC50 value of 23.04 µM.

[Effect of transcutaneous electrical acupoint stimulation on learning and memory ability of chronic fatigue syndrome rats and its mechanisms].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the histomorphological manifestations of hippocampal CA1 region and the expression of extracellular regulatory protein kinase (ERK), cyclic adenosine response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in chronic fatigue syndrome (CFS) rats, so as to explore the mechanisms of TEAS in improving the learning and memory abilities of CFS rats. METHODS: Forty male Wistar rats were randomly divided into normal group (10 rats) and modeling group (30 rats); then after modeling, they were selected and randomly divided into model group (10 rats) and TEAS group (10 rats). CFS rats model was prepared by sleep deprivation combined with weight-bearing swimming. Rats in the TEAS group were stimulated with Han's acupoint nerve stimulator at bilateral "Zusanli" (ST36) and "Shenshu" (BL23) (2 Hz/15 Hz, 1-2 mA), 20 min each time, once a day for 4 weeks with 1 d rest every 6 d. The score of general conditions of rats was evaluated. The learning and memory ability was tested with Morris water maze. The morphology and ultrastructure of hippocampal CA1 region were observed by HE staining and transmission electron microscopy. The expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were detected by real time quantitative PCR and Western blot, respectively. RESULTS: Compared with the normal group, the score of general condition was increased (P<0.01); the escape latency was prolonged (P<0.05, P<0.01) and the times of crossing the original platform was decreased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were decreased (P<0.05, P<0.01) in the model group. Compared with the model group, the scores of general condition on the 42nd and 49th day were decreased (P<0.05, P<0.01); the escape latency was shortened (P<0.01, P<0.05)and the times of crossing the original platform were increased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were increased (P<0.01, P<0.05) in the TEAS group. The morphology of neurons in hippocampal CA1 region was normal in the normal group. In the model group, the number of neurons in hippocampal CA1 region decreased, the arrangement of nerve cells was scattered, the number of apoptotic cells increased, some nuclear structures disappeared, nuclear heterochromatin increased, the cell membrane wrinkled, the chromatin appeared empty bright area, and the crista was incomplete. Compared with the model group, the nerve cells morphology in hippocampal CA1 region was more regular, the number of apoptotic cells decreased, the chromatin and the cytoplasm were uniformly distributed, and the crista was relatively intact in the TEAS group. CONCLUSION: TEAS can improve the learning and memory ability of CFS rats, the mechanisms may be related to improving the neural structure of hippocampal CA1 region and up-regulating the expression levels of ERK/CREB/BDNF.

Personalized nutrition intervention improves nutritional status and quality of life of colorectal cancer survivors in the community: A randomized controlled trial.

OBJECTIVES: This study aimed to evaluate the effects of personalized nutrition intervention combined with telephone-based education on the nutritional status of colorectal cancer survivors and their quality of life. METHODS: In this randomized, parallel-controlled trial, 60 colorectal cancer survivors who met the eligibility criteria were recruited from a community in Shanghai and randomly assigned 1:1 into nutrition intervention and routine care groups. The routine care group received a follow up by telephoneafter 6 months. The nutrition intervention group received personalized nutritional interventions and telephone-based education through the WeChat app for 6 mo. Nutrition status, dietary intake, and quality of life were measured and compared between the groups. RESULTS: Of the enrolled participants, 56 participants were included in the modified intent-to-treat analysis for comparison. After the 6-mo intervention, the nutrition group had a statistically lower patient-generated subjective global assessment score and higher energy and protein intake compared with the routine care group. Moreover, the nutrition intervention group gained more weight (2.00 kg; 95% confidence interval, 0.25-3.00) than the routine care group (0.00 kg; 95% confidence interval, -1.75 to 0.00). Meanwhile, compared with the routine care group, the nutrition intervention group had significantly higher global health status, as well as physical, role, emotional, cognitive, and social functioning (P < 0.05). CONCLUSIONS: Personalized nutrition interventions, combined with telephone-based education, provided by community health service centers can improve colorectal cancer survivors' nutritional status and quality of life. Personalized nutrition intervention for cancer survivors warrants further investigation in confirmatory studies.

Waterborne zinc bioaccumulation influences glucose metabolism in orange-spotted grouper embryos.

Fish embryos, as an endogenous system, strictly regulate an energy metabolism that is particularly sensitive to environmental pressure. This study used orange-spotted grouper embryos and stable isotope 67Zn to test the hypothesis that waterborne Zn exposure had a significant effect on energy metabolism in embryos. The fish embryos were exposed to a gradient level of waterborne 67Zn, and then sampled to quantify 67Zn bioaccumulation and mRNA expressions of key genes involved glucose metabolism. The results indicated that the bioaccumulated 67Zn generally increased with increasing waterborne 67Zn concentrations, while it tended to be saturated at waterborne 67Zn > 0.7 mg L-1. As we hypothesized, the expression of PK and PFK gene involved glycolysis pathway was significantly up-regulated under waterborne 67Zn exposure >4 mg L-1. Waterborne 67Zn exposure >2 mg L-1 significantly suppressed PCK and G6PC gene expression involved gluconeogenesis pathway, and also inhibited the AKT2, GSK-3beta and GLUT4 genes involved Akt signaling pathway. Our findings first characterized developmental stage-dependent Zn uptake and genotoxicity in fish embryos. We suggest fish embryos, as a small-scale modeling biosystem, have a large potential and wide applicability for determining cytotoxicity/genotoxicity of waterborne metal in aquatic ecosystem.

Anti-influenza A Virus Effects and Mechanisms of Emodin and Its Analogs via Regulating PPARα/γ-AMPK-SIRT1 Pathway and Fatty Acid Metabolism.

The peroxisome proliferator-activated receptor (PPAR) α/γ-adenosine 5'-monophosphate- (AMP-) activated protein kinase- (AMPK-) sirtuin-1 (SIRT1) pathway and fatty acid metabolism are reported to be involved in influenza A virus (IAV) replication and IAV-pneumonia. Through a cell-based peroxisome proliferator responsive element- (PPRE-) driven luciferase bioassay, we have investigated 145 examples of traditional Chinese medicines (TCMs). Several TCMs, such as Polygonum cuspidatum, Rheum officinale Baillon, and Aloe vera var. Chinensis (Haw.) Berg., were found to possess high activity. We have further detected the anti-IAV activities of emodin (EMO) and its analogs, a group of common important compounds of these TCMs. The results showed that emodin and its several analogs possess excellent anti-IAV activities. The pharmacological tests showed that emodin significantly activated PPARα/γ and AMPK, decreased fatty acid biosynthesis, and increased intracellular ATP levels. Pharmaceutical inhibitors, siRNAs for PPARα/γ and AMPKα1, and exogenous palmitate impaired the inhibition of emodin. The in vivo test also showed that emodin significantly protected mice from IAV infection and pneumonia. Pharmacological inhibitors for PPARα/γ and AMPK signal and exogenous palmitate could partially counteract the effects of emodin in vivo. In conclusion, emodin and its analogs are a group of promising anti-IAV drug precursors, and the pharmacological mechanism of emodin is linked to its ability to regulate the PPARα/γ-AMPK pathway and fatty acid metabolism.