Edible mushrooms as a potent therapeutics of subclinical thyroid dysfunction among adults,especially in obese individuals:a prospective cohort study

Background:Mushrooms are a good source of many nutrients which are potentially beneficial for chronic diseases.We speculated that due to its abundant nutrients edible mushrooms might have a beneficial effect on the prevention of subclinical thyroid dysfunction(SCTD).Therefore,we designed a large-scale cohort study to examine whether mushrooms consumption is a protective factor for SCTD in adults.Methods:This prospective cohort study investigated 6631 participants(mean age:(45.0±10.2)years;55.1%men).Edible mushrooms consumption was measured at baseline using a validated food frequency questionnaire.SCTD was defined as abnormal serum thyroid-stimulating hormone levels and normal free thyroxine.Cox proportional hazards regression models were used to examine the association of edible mushrooms consumption with incident SCTD.Results:During follow-up period,a total of 262 new cases of SCTD were identified,the incidence rate of subclinical hypothyroidism was 8.9/1000 person-years and subclinical hyperthyroidism was 7.2/1000 person-years.After adjusting potential confounding factors,the multivariable hazard ratios(95%confidence intervals)for subclinical hypothyroidism were 1.00(reference)for almost never,0.53(0.29,0.97)for 1-3 times/week and 0.30(0.10,0.87)for≥4 times/week(P for trend=0.02).It also showed edible mushrooms consumption was inversely associated with subclinical hypothyroidism in obese individuals but not non-obese individuals,the final hazard ratios(95%confidence intervals)were 0.14(0.03,0.73)(P for trend<0.01).Conclusions:This population-based prospective cohort study has firstly demonstrated that higher edible mushrooms consumption was significantly associated with lower incidence of subclinical hypothyroidism among general adult population,especially in obese individuals.

The Short-term Effects of Temperature on Infectious Diarrhea among Children under 5 Years Old in Jiangsu,China:A Time-series Study(2015-2019)

The association between meteorological factors and infectious diarrhea has been widely studied in many countries.However,investigation among children under 5 years old in Jiangsu,China remains quite limited.Data including infectious diarrhea cases among children under five years old and daily meteorological indexes in Jiangsu,China from 2015 to 2019 were collected.The lag-effects up to 21 days of daily maximum temperature(Tmax)on infectious diarrhea were explored using a quasi-Poisson regression with a distributed lag non-linear model(DLNM)approach.The cases number of infectious diarrhea was significantly associated with seasonal variation of meteorological factors,and the burden of disease mainly occurred among children aged 0-2 years old.Moreover,when the reference value was set at 16.7°C,Tmax had a significant lag-effect on cases of infectious diarrhea among children under 5 years old in Jiangsu Province,which was increased remarkably in cold weather with the highest risk at 8℃.The results of DLNM analysis implicated that the lag-effect of Tmax varied among the 13 cities in Jiangsu and had significant differences in 8 cities.The highest risk of Tmax was presented at 5 lag days in Huaian with a maximum RR of 1.18(95% CI:1.09,1.29).Suzhou which had the highest number of diarrhea cases(15830 cases),had a maximum RR of 1.04(95%CI:1.03,1.05)on lag 15 days.Tmax is a considerable indicator to predict the epidemic of infectious diarrhea among 13 cities in Jiangsu,which reminds us that in cold seasons,more preventive strategies and measures should be done to prevent infectious diarrhea.

Translocation of IGF-1R in endoplasmic reticulum enhances SERCA2 activity to trigger Ca_(ER)^(2+)perturbation in hepatocellular carcinoma

The well-known insulin-like growth factor 1(IGF1)/IGF-1 receptor(IGF-1R)signaling pathway is overexpressed in many tumors,and is thus an attractive target for cancer treatment.However,results have often been disappointing due to crosstalk with other signals.Here,we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma(HCC)cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)activity.In response to ligand binding,IGF-1Rβis translocated into the ER byβ-arrestin2(β-arr2).Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ.SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβlevels.ER IGF-1Rβphosphorylates SERCA2 on Tyr^(990)to enhance its activity.Mutation of SERCA2-Tyr^(990)disrupted the interaction of ER IGF-1Rβwith SERCA2,and therefore ER IGF-1Rβfailed to promote SERCA2 activity.The enhancement of SERCA2 activity triggered Ca_(ER)^(2+)perturbation,leading to an increase in autophagy.Thapsigargin blocked the interaction between SERCA2and ER IGF-1Rβand therefore SERCA2 activity,resulting in inhibition of HCC growth.In conclusion,the translocation of IGF-1R into the ER triggers Ca_(ER)^(2+)perturbation by enhancing SERCA2 activity through phosphorylating Tyr^(990)in HCC.

Activation of insulin-like growth factor-1 receptor (IGF-1R) promotes growth of colorectal cancer through triggering the MEX3A-mediated degradation of RIG-Ⅰ

Insulin-like growth factor-1 receptor(IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers.However,targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings.Here,we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I.The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A.In response to ligands,IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250,opening the middle loop(Leu130-Cys141) to the RING domain of MEX3A through the conformational changes of βarr2.The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I.The assay of the mutants βarr2Y64Aand βarr2Y250Afurther confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A.The truncated-βarr2 and the peptide ATQAIRIF,which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes,thus blocking the IGF-1R-triggered RIG-I degradation.Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway.Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I.In summary,we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.

Surveillance of emerging infectious diseases for biosecurity

Emerging infectious diseases, such as COVID-19, continue to pose significant threats to human beings and their surroundings. In addition, biological warfare, bioterrorism, biological accidents, and harmful consequences arising from dual-use biotechnology also pose a challenge for global biosecurity. Improving the early surveillance capabilities is necessary for building a common biosecurity shield for the global community of health for all. Furthermore, surveillance could provide early warning and situational awareness of biosecurity risks. However, current surveillance systems face enormous challenges, including technical shortages, fragmented management, and limited international cooperation. Detecting emerging biological risks caused by unknown or novel pathogens is of particular concern. Surveillance systems must be enhanced to effectively mitigate biosecurity risks. Thus, a global strategy of meaningful cooperation based on efficient integration of surveillance at all levels, including interdisciplinary integration of techniques and interdepartmental integration for effective management, is urgently needed. In this paper, we review the biosecurity risks by analyzing potential factors at all levels globally. In addition to describing biosecurity risks and their impact on global security, we also focus on analyzing the challenges to traditional surveillance and propose suggestions on how to integrate current technologies and resources to conduct effective global surveillance.

Control strategies and their effects on the COVID-19 pandemic in 2020 in representative countries

COVID-19 is the most severe pandemic globally since the 1918 influenza pandemic.Effectively responding to this once-in-a-century global pandemic is a worldwide challenge that the international community needs to jointly face and solve.This study reviews and discusses the key measures taken by major countries in 2020 to fight against COVID-19,such as lockdowns,social distancing,wearing masks,hand hygiene,using Fangcang shelter hospitals,large-scale nucleic acid testing,close-contacts tracking,and pandemic information monitoring,as well as their prevention and control effects.We hope it can help improve the efficiency and effectiveness of pandemic prevention and control in future.