Clinical features of hand, foot and mouth disease caused by Coxsackievirus A6 in Xi'an, China, 2013-2019: A multicenter observational study.

PURPOSE: To investigate the clinical features of hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6) and this work may help early diagnose of atypical HFMD. METHODS: From January 2013 to December 2019, a total of 7,208 patients with a clinical diagnosis of HFMD in Xi'an Children's Hospital, Xi'an Central Hospital, and Xi'an Jiaotong University Second Affiliated Hospital, were included in this observational study. The clinical data, specimens and follow-up results were collected. Real-time RT‒PCR was performed for the detection and typing of enterovirus nucleic acids. RESULTS: Of the 7,208 clinically diagnosed HFMD patients, 5,622 were positive for enterovirus nucleic acids, and the positive proportions of CVA6, enterovirus 71 (EV-A71), coxsackievirus A16 (CVA16), and other enteroviruses were 31.0% (1,742/5,622), 27.0% (1,518/5,622), 35.0% (1,968/5,622), and 7.0% (394/5,622), respectively. Based on the etiology, patients were divided into CVA6 group, EV-A71group, and CVA16 group. The mean age at onset was significantly higher in the CVA6 group (4.62±2.13 years) than in the EV-A71 group and CVA16 group (3.45±2.25 years and 3.35±2.13 years, respectively; both P < 0.05). The male/female ratio was 1.45 (1,031/711) in the CVA6 group and was not significantly different from the other two groups. The incidence of fever was significantly higher in the CVA6 group [82.5% (1,437/1,742)] than in the EV-A71 group [51.3% (779/1,518)] and the CVA16 group [45.9% (903/1,968)] (P < 0.05). In the CVA6 group, the rashes were more frequently on the trunk and elbows/knees and were significantly different from the other two groups (P < 0.05). The number of patients with two or more rash morphologies was significantly higher in the CVA6 group than in the other two groups (P < 0.05). The incidence of bullous rash in the CVA6 group [20.2%; n = 352] was higher than in the EV-A71 group [0.33%; n = 5] and CVA16 group [0.66%; n = 13] (P < 0.05). The incidence of neurological complications was significantly higher in the EV-A71 group [52.1% (791/1,518)] than in the CVA16 group [5.1% (100/1,968)] and the CVA6 group [0.8% (14/1,742)] (P < 0.05). In the follow-up period, 160 patients (9.2%) with CVA6 HFMD experienced onychomadesis, but no onychomadesis was observed in the EV-A71 and CVA16 groups. The average WBC count was significantly higher in the CVA6 group than in the CVA16 group (P < 0.05). The number of patients with increased CRP was significantly larger in the CVA6 group than in the CVA16 group but was significantly smaller than that in the EV-A71 group (P < 0.05). CONCLUSIONS: CVA6 has become one of the main pathogens of HFMD in the Xi'an area during 2013-2019. The main clinical manifestations were slightly different from those of HFMD caused by EV-A71 or CVA16, with a higher frequency of fever, diverse morphologies and diffuse distribution of rashes, fewer neurological complications and some onychomadesis.

Visible-light-mediated C-H amidation of imidazoheterocycles with N-amidopyridiniums.

C-3 amidated imidazoheterocycles were synthesized via a visible light-promoted reaction of imidazoheterocycles with N-amidopyridinium salts catalyzed by 4CzIPN under mild conditions. For imidazoheterocycles and N-amidopyridinium salts with various substituents, the reaction proceeded smoothly to give the corresponding products in moderate to good yields. The reaction provides a new strategy for the synthesis of secondary amides with the imidazo[1,2-a]pyridine core.

Clinical Observation of Posterior-Chamber Phakic Implantable Collamer Lens V4c Implantation in Myopic Patients with Shallow Anterior Chamber Depth: A Retrospective, Consecutive Observational Study.

Purpose: The reference range for the preoperative anterior chamber angle width for ICL surgery is unclear. Our objective was to assess the clinical effect and the range of anterior chamber angle width of posterior-chamber implantable collamer lens V4c (ICL V4c) implantation in patients with anterior chamber depth (ACD) < 2.8 mm. Methods: Patients who underwent ICL V4c implantation with shallow ACD were included in this retrospective study. The patients' uncorrected and corrected distance visual acuity, angle of trabecular-iris (TIA), angle-opening distance (AOD500), trabecular-iris space area (TISA500), corneal endothelial cell density, vault, retinal nerve fiber layer thickness, intraocular pressure, visual field, and complications were analyzed. Results: Forty-one patients (68 eyes) completed at least 12 months of follow-up (median follow-up, 30 months). The effectiveness and safety indices were 1.09 ± 0.13 and 1.04 ± 0.21, respectively. The preoperative TIA values on the nasal and temporal sides were 39.78 ± 7.68 degree (range, 25.8-65.1 degree) and 41.54 ± 8.03 degree (range, 28.5-63.00 degree). Forty-seven eyes had uncorrected distance visual acuity ≥1.0, and 55 had corrected distance visual acuity ≥1.0 at the last follow-up visit. The TIA, AOD500, and TISA500 on the nasal and temporal sides were significantly reduced compared to those before surgery (all P < 0.01); no eye had an angle closure or elevated intraocular pressure. The ICL V4c vault was 290.88 ± 153.36 µm (range, 60.0-880.0 µm). No severe complications occurred in any patient. Conclusions: In patients with myopia with shallow ACD (2.55-2.79 mm), a preoperative TIA >25.8° is safe and effective for a relatively long time after surgery; however, an extended long-term close follow-up is needed.

Preparation of Polyaniline-Modified Cellulose/PDMS Composite Triboelectric Material and Application of Its Pretreatment in MOW Pulp.

Self-powered electronic equipment has rapidly developed in the fields of sensing, motion monitoring, and energy collection, posing a greater challenge to triboelectric materials. Triboelectric materials need to enhance their electrical conductivity and mechanical strength to address the increasing demand for stability and to mitigate unpredictable physical damage. In this study, polyaniline-modified cellulose was prepared by means of in situ polymerization and compounded with polydimethylsiloxane, resulting in a triboelectric material with enhanced strength and conductivity. The material was fabricated into a tubular triboelectric nanogenerator (TENG) (G-TENG), and an electrocatalytic pretreatment of mixed office waste paper (MOW) pulp was performed using papermaking white water as the flowing liquid to improve the deinking performance. The electrical output performance of G-TENG is highest at a flow rate of 400 mL/min, producing a voltage of 22.76 V and a current of 1.024 µA. Moreover, the deinking effect of MOW was enhanced after the electrical pretreatment. This study explores the potential application of G-TENG as a self-powered sensor power supply and emphasizes its prospect as an energy collection device.

A near-infrared fluorescent probe for the detection of Cu2+ in Chinese herbal medicine and imaging in living cells.

Copper is one of the common among the heavy metal pollution in Chinese herbal medicine (CHM). So, it is essential to develop rapid and accurate testing method to quantify the Cu2+ content in CHM. Herein, we prepared a coordination-based near-infrared fluorescent probe (NRh6G-FA) by introducing a hemicyanine dye in rhodamine 6G scaffold. NRh6G-FA had a high sensitivity, anti-interference performance, fast response (within 60 s), visualization (from light yellow to green) for Cu2+ and excellent sensing performance for the detection of Cu2+ at low concentrations (LOD = 0.225 µM). The most likely mechanism was verified on the basis of Job's plot, ESI-HRMS and DFT calculations. NRh6G-FA could be successfully applied for the detection and "naked eye" recognition of Cu2+ in CHM samples. Moreover, NRh6G-FA was used to visualize Cu2+ in living MCF-7 cells by confocal fluorescence imaging.

VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.

BACKGROUND: Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se. METHODS: VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis. RESULTS: VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis. CONCLUSIONS: VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.

Irisin attenuates type 1 diabetic cardiomyopathy by anti-ferroptosis via SIRT1-mediated deacetylation of p53.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.

TRIM21 reduces H1N1-induced inflammation and apoptosis by regulating the TBK1-IRF3 signaling pathway in A549 cells.

Triple motif protein 21 (TRIM21) has an antiviral function that inhibits various viral infections. However, its role in the progress of influenza A virus (IAV) infection is unclear. In this study, we investigated the role and molecular mechanism of TRIM21 in IAV infection. RT-qPCR was used to determine the level of TRIM21 mRNA, and ELISA was used to measure the levels of IFN-α, IFN-ß, IL-6, and TNF-α. The levels of the TRIM21, NP, TBK1, IRF3, p-TBK1, and p-IRF3 proteins were estimated by Western blot. The results showed that, after IAV infection, TRIM21 was upregulated in clinical patient serum and A549 cells, and this was correlated with the IFN response. Overexpression of TRIM21 reduced IAV replication and transcription in in vitro cell experiments. TRIM21 also increased IFN-α and IFN-ß levels and decreased IL-6 and TNF-α levels in A549 cells. In addition, overexpression of TRIM21 inhibited IAV-induced apoptosis. Further experiments demonstrated that TBK1-IRF3 signaling was activated by TRIM21 and was involved in the inhibitory effect of TRIM21 on virus replication. In summary, our study suggests that TRIM21 inhibits viral replication by activating the TBK1-IRF3 signaling pathway, further inhibiting the infection process of IAV.

Novel tetranuclear grid-like Zn(II) complexes derived from dihydrazone pyrimidine derivatives as antitumor agents.

Due to the antitumor properties, Zn(II) complexes have attracted more and more attention. Herein, three novel tetranuclear Zn(II) complexes 1-3 based on dihydrazone pyrimidine derivatives H2L1-H2L3 were synthesized and characterized using IR spectroscopy, 1H NMR spectroscopy, single crystal X-ray diffraction analysis, XRD, TG and elemental analysis. Single crystal X-ray diffraction analysis revealed that 1-3 all displayed a [2 × 2] grid-like topology. The stability in solution, lipophilicity, confocal imaging and antitumor activities were investigated. Complexes 1-3 displayed high structural stability, membrane permeability and different lipophilicities. They can target mitochondria due to the cation charge. The MTT assay indicated that all of them exhibited stronger antiproliferative activity than the corresponding derivatives H2L1-H2L3 and the well-known cisplatin against all the selected tumor cells (BGC-823, BEL-7402, MCF-7 and A549), with IC50 values ranging from 2.83 µM to 7.97 µM. AO/EB double staining, flow cytometry and ROS detection suggested that complexes 1 and 2 could induce BGC-823 apoptosis in a dose-dependent manner. UV-Vis spectra, CD spectra, viscosity analysis and molecular docking revealed that complexes 1 and 2 interact with DNA mainly via partial intercalation and groove binding. Tetranuclear [2 × 2] grid-like Zn(II) complexes have the potential to be promising antitumor agents in the future.

Patient-Family Caregiver Concordance of Symptom Assessment for Esophageal Cancer Patients Undergoing Esophagectomy.

BACKGROUND: Esophageal cancer patients suffer from multiple and severe symptoms during the postoperative recovery period. Family caregivers play a vital role in assisting patients to cope with their symptoms. OBJECTIVE: To examine the concordance of esophageal cancer patients and their caregivers on assessing patients' symptoms after surgery and identify predictors associated with the symptom concordance. METHODS: In this cross-sectional study, 213 patient-caregiver dyads completed general information questionnaires, the Memorial Symptom Assessment Scale, the Depression Subscale of Hospital Anxiety and Depression Scale, the Mutuality Scale, and the Zarit Burden Interview (for caregivers). Data were analyzed using intraclass correlation coefficients, paired t tests, and binary logistic regression. RESULTS: At the dyad level, agreement of patients' and caregivers' reported symptoms ranged from poor to fair. At the group level, patients reported significantly higher scores than caregivers in most symptoms. Of the 213 dyads, 119 (55.9%) were identified as concordant on symptom assessment. Patients' nasogastric tube, perceived mutuality, caregivers' educational background, and dyad's communication frequency with each other could predict their concordance of symptom assessment. CONCLUSIONS: There were relatively low agreements between esophageal cancer patients and caregivers on assessing patients' symptoms, and caregivers tended to underestimate patients' symptoms. The dyad's symptom concordance was influenced by patient-, caregiver-, and dyad-related factors. IMPLICATIONS FOR PRACTICE: Having an awareness of the incongruence on assessing symptoms between esophageal cancer patients and caregivers may help healthcare professionals to comprehensively interpret patients' symptoms and develop targeted dyadic interventions to improve their concordance, contributing to optimal symptom management and health outcomes.

Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF-κB and AP-1 pathway.

Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.

Marital transitions and frailty among middle-aged and older adults in China: The roles of social support.

Background: This study explored the association of marital transitions and frailty among Chinese middle-aged and older people and whether this association differs by social support. Methods: We used a sample of 12,388 adults aged ≥45 years who participated in the China Health and Retirement Longitudinal Study (CHARLS) between 2015 and 2018. Between-wave changes in marital status ("married at both times", "unmarried to married", "married to unmarried", "unmarried at both times") were used to explore the changes in frailty measured by the frailty index (FI), which was constructed from 55 health variables. Social support was evaluated based on social engagement and intergenerational support. The associations among marital transitions, social support and frailty were analyzed using generalized estimating equations (GEEs). Results: The mean FI of 12,388 participants was 0.23 (SD = 0.13). Participants who were married to unmarried (ß = 0.014, B = 0.005, P = 0.012) and unmarried at both times (ß = 0.022, B = 0.003, P < 0.001) had significant a positive impact on FI compared with participants who were married at both times. Social engagement, financial support by children and providing care to grandchildren had an interactive effect with marital transitions in influencing FI. Conclusions: Being unmarried may increase frailty among Chinese middle-aged and older adults. Financial support by children may mitigate the adverse effects of being unmarried on frailty.

eEF2 improves dense connective tissue repair and healing outcome by regulating cellular death, autophagy, apoptosis, proliferation and migration.

Outcomes following human dense connective tissue (DCT) repair are often variable and suboptimal, resulting in compromised function and development of chronic painful degenerative diseases. Moreover, biomarkers and mechanisms that guide good clinical outcomes after DCT injuries are mostly unknown. Here, we characterize the proteomic landscape of DCT repair following human Achilles tendon rupture and its association with long-term patient-reported outcomes. Moreover, the potential regulatory mechanisms of relevant biomarkers were assessed partly by gene silencing experiments. A mass-spectrometry based proteomic approach quantified a large number (769) of proteins, including 51 differentially expressed proteins among 20 good versus 20 poor outcome patients. A novel biomarker, elongation factor-2 (eEF2) was identified as being strongly prognostic of the 1-year clinical outcome. Further bioinformatic and experimental investigation revealed that eEF2 positively regulated autophagy, cell proliferation and migration, as well as reduced cell death and apoptosis, leading to improved DCT repair and outcomes. Findings of eEF2 as novel prognostic biomarker could pave the way for new targeted treatments to improve healing outcomes after DCT injuries.Trial registration: NCT02318472 registered 17 December 2014 and NCT01317160 registered 17 March 2011, with URL http://clinicaltrials.gov/ct2/show/NCT02318472 and http://clinicaltrials.gov/ct2/show/study/NCT01317160 .

Small population of the largest water strider after the late Pleistocene and the implications for its conservation.

Climate oscillation and its synergistic impacts on habitat fragmentation have been identified as threatening the survival of some extant species. However, the mechanisms by which semi-aquatic insects impacted by such events remain poorly understood. Herein, we studied the largest water strider in the world, Gigantometra gigas, to explore the effect of these two factors on its evolutionary history. The sequences of mitogenomic and nrDNA cluster were utilized to reconstruct phylogenetic relationship among G. gigas populations and its demographic history. Mitochondrial genes were separately reconstructed topologies of that populations and detected remarkable differences. We found that G. gigas populations conform to the isolation-by-distance model, and decline occurred at about 120 ka, which was probably influenced by the climate change during the late Pleistocene and eventually maintained a small effective population size (Ne) around 85,717. The populations in Guangdong Province of China are worthy of note in that they exhibit low genetic diversity, a small Ne around 18,899 individuals, and occupy an area with little suitable future habitat for G. gigas. This work recommends that conservation efforts are implemented to ensure the long-term survival of small G. gigas populations, and notes that further evaluation of their extinction risk under the impacts of human activities is required.

Sirtuin3 Alleviated Influenza A Virus-Induced Mitochondrial Oxidative Stress and Inflammation in Lung Epithelial Cells via Regulating Poly (ADP-Ribose) Polymerase 1 Activity.

INTRODUCTION: Influenza A virus (IAV) infection causes severe lung inflammation and injury, particularly in children. Sirtuin3 (Sirt3) was confirmed to be effective in protecting the lung against injury. This study aims to explore the function and mechanism of Sirt3 on influenza development in children. METHODS: The Sirt3 level in serum samples from IAV-infected children and lung epithelial cells were detected using RT-qPCR, ELISA, and Western blot assays. Cell viability and apoptosis were determined by MTT and flow cytometry assays. Virus titration was conducted by determining TCID50. Cell inflammatory response was detected by a battery of inflammatory cytokines. The contents of ROS and ATP, mitochondrial membrane potential level, and oxygen-consumption rate were examined to reflect on oxidative stress and mitochondrial dysfunction. The activity of poly (ADP-ribose) polymerase 1 (PARP-1) was measured by colorimetry. RESULTS: Sirt3 was downregulated in IAV-infected children's serum samples and BEAS-2B cells. Overexpression of Sirt3 alleviated IAV replication and IAV-induced inflammatory injury, oxidative stress, and mitochondrial dysfunction in lung epithelial cells. Moreover, upregulation of Sirt3 deacetylated SOD2 and PARP-1 and inhibited the PARP-1 activity. Notably, the Sirt3 inhibitor (3-TYP) and PARP-1 activity agonist (nicotinamide) reversed the effects of Sirt3 overexpression on IAV replication and IAV-induced injury. CONCLUSION: Overexpression of Sirt3 attenuated IAV-evoked inflammatory injury and mitochondrial oxidative stress through the inhibition of PARP-1 activity in lung epithelial cells.

Efficacy of non-pharmacological interventions in females with overactive bladder: A systematic review and network meta-analysis.

AIMS AND OBJECTIVES: To compare and rank the effectiveness of non-pharmacological interventions for symptoms of Overactive Bladder (OAB) in network meta-analysis. BACKGROUND: Overactive Bladder affects many patients, which often generates bothersome symptoms and debilitates the quality of life. Non-pharmacological therapies have been widely used in OAB. However, due to insufficient evidence, it remains unclear which strategies are most suitable for OAB. METHODS: We integrated randomised controlled trials (RCTs), which were searched up to 1 January 2021, from 8 databases (PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc). Studies that met the eligible criteria were assessed the risk of bias. Then, network meta-analyses were conducted by STATA, R, and OpenBUGS. The review followed PRISMA statement. RESULTS: A total of 24 studies comprising 2347 patients with OAB were included in this review, most of which were low to moderate risk of bias. The results of network meta-analysis implied that electric stimulation (ES) was the most effective intervention to reduce voided frequency and nocturia frequency of OAB. CONCLUSIONS: Electric stimulation ranked the best in the management of OAB, and future studies should pay more attention to ES.

HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection.

The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection with M. tuberculosis isn't well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection with M. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant for M. tuberculosis control. Vhl cKO mice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility to M. tuberculosis infection and the impaired responses of Vhl-deficient T cells are HIF-1-dependent.

Risk Assessment of Chlorothalonil as a Probable Human Carcinogen on Selected Vegetables in an Eastern China Province.

Objectives: This study aimed to provide an assessment of chlorothalonil's possible carcinogenic risk posed to the public. In combination and comparison with the non-carcinogenic risk, the results hopefully could provide useful insights, early warning, and references for policy formulation. Methods: This study firstly investigated the occurrence of chlorothalonil on selected key vegetables for different scenarios, and then conducted an exposure assessment with officially published data. Lastly, both the non-carcinogenic and carcinogenic risk of chlorothalonil were calculated by using Monte-Carlo simulation. Results: Even though mean non-carcinogenic risks of chlorothalonil for all scenarios were below threshold value, the mean carcinogenic risks for maximum-risk scenario and most-likely risk scenario were mostly above threshold value. High probabilities of exceedance of threshold value existed for carcinogenic risk under all scenarios. Conclusion: Potential threat to public health existed for conventionally 'safe' pesticide if considering the possible carcinogenicity. Extra caution should be taken and the potential carcinogenic effects should be included into consideration for better protection of public health during the policy formulation process.