A truncated protein product of the germline variant of the DUOX2 gene leads to adenomatous polyposis

Objective:In some patients with adenomatous polyposis,an identifiable pathogenic variant of known associated genes cannot be found.Researchers have studied this for decades;however,few new genes have been identified.Methods:Adenomatous polyposis coli(APC)negative polyposis patients were identified through next-generation sequencing and multiplex ligation-dependent probe amplification.Then,whole-exome sequencing(WES)was used to determine candidate genes harboring pathogenic variants.Functional experiments were performed to explore their effects.Subsequently,using Sanger sequencing,we found other polyposis patients carrying variants of the DUOX2 gene,encoding dual oxidase 2,and analyzed them.Results:From 88 patients with suspected familial adenomatous polyposis,25 unrelated APC negative polyposis patients were identified.Based on the WES results of 3 patients and 2 healthy relatives from a family,the germline nonsense variant(c.1588 A>T;p.K530 X)of the DUOX2 gene was speculated to play a decisive role in the pedigree in relation to adenomatous polyposis.During functional experiments,we observed that the truncated protein,h Duox2 K530,was overexpressed in the adenoma in a carrier of the DUOX2 nonsense variant,causing abnormal cell proliferation through endoplasmic reticulum(ER)retention.In addition,we found two unrelated APC negative patients carrying DUOX2 missense variants(c.3329 G>A,p.R1110 Q;c.4027 C>T,p.L1343 F).Given the results of the in silico analysis,these two missense variants might exert a negative influence on the function of h Duox2.Conclusions:To our knowledge,this is the first study that reports the possible association of DUOX2 germline variants with adenomatous polyposis.With an autosomal dominant inheritance,it causes ER retention,inducing an unfolded protein response.

Long-term exposure to fine particulate matter modifies the association between physical activity and hypertension incidence

Background:The trade-off between the benefits of regular physical activity(PA)and the potentially detrimental effects of augmented exposure to air pollution in highly polluted regions remains unclear.This study aimed to examine whether ambient fine particulate matter(PM_(2.5))exposure modified the impacts of PA volume and intensity on hypertension risk.Methods:We included 54,797 participants without hypertension at baseline in a nationwide cohort of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR)project.PA volume and intensitywere assessed by questionnaire,and high-resolution(1 km×1 km)PM_(2.5)estimates were generated using a satellite-based model.Results:During 413,516 person-years of follow-up,12,100 incident hypertension cases were identified.PM_(2.5)significantly modified the relationship between PA and hypertension incidence(p_(interaction)<0.001).Increased PA volume was negatively associated with incident hypertension in the low PM_(2.5)stratum(<59.8μg/m^(3),ptrend<0.001),with a hazard ratio of 0.81(95%confidence interval(95%CI):0.74-0.88)when comparing the fourth with the first quartile of PA volume.However,the health benefits were not observed in the high PM_(2.5)stratum(≥59.8μg/m^(3),p_(trend)=0.370).Moreover,compared with light PA intensity,vigorous intensity was related to a 20%(95%CI:9%-29%)decreased risk of hypertension for participants exposed to low PM_(2.5),but a 17%(95%CI:4%-33%)increased risk for those with high PM_(2.5)levels.Conclusion:PA was associated with a reduced risk of hypertension only among participants with low PM_(2.5)exposure.Our findings recommended regular PA to prevent hypertension in less polluted regions and reinforced the importance of air quality improvement.

Erratum to A truncated protein product of the germline variant of the DU0X2 gene leads to adenomatous polyposis

In the published paper1,the author's organization information on page 215 contained errors.The author information has been updated to correct the errors.The errors do not affect the conclusions of this article.We apologize for the errors and for any confusion they may have caused.

Enhanced Biohydrogen Production by Accelerating the Hydrolysis of Macromolecular Components of Waste Activated Sludge Using TiO₂Photocatalysis as a Pretreatment

The effects of TiO2 photocatalysis on the hydrolysis of protein of waste activated sludge (WAS) and its biodegradability were investigated in this study. After 12-h UV irradiation, the removal ratio of protein by TiO2 photocatalysis reached 98.1%. The optimal condition for photocatalytic degradation of protein is TiO2 dosage of 5.0 mg·L–1 under 2.4 w·m–2 UV light irradiation. TiO2 photocatalysis in comparison with other pretreatments obviously accelerated the hydrolysis of WAS and improved the conversion of total COD (tCOD) to soluble COD (sCOD). The sCOD/tCOD ratio of WAS pretreated by TiO2 photocatalysis, UV photolysis and TiO2 adsorption and that of the control were 92.8%, 32.5%, 18.0% and 16.6%, respectively. TiO2 photocatalytic pretreatment accelerated the biohydrogen production from 10-fold diluted WAS. The bioreactors containing UV photolysis and TiO2 adsorption pretreated WASs and the control reactor require 0.5-d, 0.9-d and 0.7-d start-up period for biohydrogen production, respectively. While the bioreactor containing TiO2 photocatalysis pretreated WAS obtained a hydrogen yield of 0.5 mL-H2/g-VS merely after 0.5-d mesophilic fermentation. The cumulative biohydrogen production from TiO2 photocatalysis pretreated WAS during 4-d mesophilic fermentation reached 11.7 mL-H2/g-VS, which was 1.2 times higher than that from the control. TiO2 photocatalytic pretreatment enhanced the biohydrogen production from WAS via accelerating the hydrolysis of its macromolecular components to smaller molecule weight hydrolysates.

Systematical analysis of sludge treatment and disposal technologies for carbon footprint reduction

This study aims to comprehensively analyze the Greenhouse Gases(GHGs)emissions from current sewage sludge treatment and disposal technologies(buildingmaterial,landfill,land spreading,anaerobic digestion,and thermochemical processes)based on the database of Science Citation Index(SCI)and Social Science Citation Index(SSCI)from 1998 to 2020.The general patterns,spatial distribution,and hotspotswere provided by bibliometric analysis.A comparative quantitative analysis based on life cycle assessment(LCA)put forward the current emission situation and the key influencing factors of different technologies.The effective GHG emissions reduction methods were proposed to mitigate climate change.Results showed that incineration or building materials manufacturing of highly dewatered sludge,and land spreading after anaerobic digestion have the best GHG emissions reduction benefits.Biological treatment technologies and thermochemical processes have great potential for reducing GHGs.Enhancement of pretreatment effect,co-digestion,and newtechnologies(e.g.,injection of carbon dioxide,directional acidification)are major approaches to facilitate substitution emissions in sludge anaerobic digestion.The relationship between the quality and efficiency of secondary energy in thermochemical process and GHGs emission still needs further study.Solid sludge products generated by bio-stabilization or thermochemical processes are considered to have a certain carbon sequestration value and can improve the soil environment to control GHG emissions.The findings are useful for future development and processes selection of sludge treatment and disposal facing carbon footprint reduction.

Bio-immobilization and recovery of chromium using a denitrifying biofilm system: Identification of reaction zone, binding forms and end products

Chromium is an important resource in strategic metals.Different from most studies focusing on the bio-reduction of hexavalent chromium[Cr(VI)],this study aims to achieve the immobilization and recovery of chromium using a sequencing batch biofilm reactor.Results showed that Cr(VI) removal efficiency remained more than 99%,and 97%of reduced Cr(III) was immobilized in the biofilm.Immobilization zone,chromium forms and extracellular polymeric substances composition changes were combined to reveal the mechanism of Cr(VI) reduction and immobilization.The chromium distribution in biofilm demonstrated that intercellular layer was the main active zone with an immobilization amount of 891.70±126.32 mg/g-VSS.The reduced products analysis confirmed that trivalent chromium[Cr(III)]chelated with carboxyl,amino and other functional groups and immobilized in the form of organic Cr(III).The digestion method realized a chromium recovery efficiency of 74.59%.This study provides an alternative method for the bioremediation and resources recovery in chromium polluted wastewater.

Evaluating the impact of sulfamethoxazole on hydrogen production during dark anaerobic sludge fermentation

The impact of antibiotics on the environmental protection and sludge treatment fields has been widely studied.The recovery of hydrogen from waste activated sludge(WAS)has become an issue of great interest.Nevertheless,few studies have focused on the impact of antibiotics present in WAS on hydrogen production during dark anaerobic fermentation.To explore the mechanisms,sulfamethoxazole(SMX)was chosen as a representative antibiotic to evaluate how SMX influenced hydrogen production during dark anaerobic fermentation of WAS.The results demonstrated SMX promoted hydrogen production.With increasing additions of SMX from 0 to 500 mg/kg TSS,the cumulative hydrogen production elevated from 8.07±0.37 to 11.89±0.19 mL/g VSS.A modified Gompertz model further verified that both the maximum potential of hydrogen production(Pm)and the maximum rate of hydrogen production(R_(m))were promoted.SMX did not affected sludge solubilization,but promoted hydrolysis and acidification processes to produce more hydrogen.Moreover,the methanogenesis process was inhibited so that hydrogen consumption was reduced.Microbial community analysis further demonstrated that the introduction of SMX improved the abundance of hydrolysis bacteria and hydrogen-volatile fatty acids(VFAs)producers.SMX synergistically influenced hydrolysis,acidification and acetogenesis to facilitate the hydrogen production.

Prevalence of familial hypercholesterolemia and its association with coronary artery disease:A Chinese cohort study

Background:Familial hypercholesterolemia(FH)is underrecognized,and its association with coronary artery disease(CAD)remains limited,especially in China.We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort.Methods:FH was defined using the Make Early Diagnosis to Prevent Early Death(MEDPED)criteria.The crude and age-sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR)project during 2007−2008.The associations of FH with incident CAD and its major subtypes were estimated with the cohort-stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow-up(2018−2020).Results:Among 98,885 included participants,190 participants were defined as FH.Crude and age−sex standardized prevalence and 95%confidence interval(CI)of FH were 0.19%(0.17%-0.22%)and 0.13%(0.10%-0.16%),respectively.The prevalence varied across age groups and peaked in the group of 60-<70 years(0.28%),and the peak prevalence(0.18%)in males was earlier,yet lower than the peak crude prevalence in females(0.41%).During a mean follow-up of 10.7 years,2493 cases of incident CAD were identified.After multivariate adjustment,FH patients had a 2.03-fold greater risk of developing CAD compared to non-FH participants.Conclusions:The prevalence of FH was estimated to be 0.19%in the participants,and it was associated with an elevated risk of incident CAD.Our study suggests that early screening of FH has certain public health significance for the prevention of CAD.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk:a single-center study

Low-density lipoprotein cholesterol(LDL-C)is an independent risk factor for atherosclerotic cardiovascular disease(ASCVD).Even after lipid-lowering therapy(LLT)with statins or statin–ezetimibe,a large proportion of patients at very high risk still do not reach the LDL-C targets(<1.4 mmol/L and≥50%reduction).[1,2]Proprotein convertase subtilisin/kexin type 9 inhibitor(PCSK9i)is recommended for patients at high or very high cardiovascular risk inwhom LDL-C reduction is not adequate with statin therapy or in those with statin intolerance.Limited data are available regarding the use of PCSK9i in China.

Environmental sustainability opportunity and socio-economic cost analyses of phosphorus recovery from sewage sludge

Although phosphorus(P)recovery and management from sewage sludge are practiced in North America and Europe,such practices are not yet to be implemented in China.Here,we evaluated the environmental sustainability opportunity and socio-economic costs of recovering P from sewage sludge by replacing the current-day treatments(CT;sludge treatment and landfill)and P chemical fertilizer application(CF)in China using life cycle assessment and life cycle costing methods.Three potential P recovery scenarios(PR1‒PR3:struvite,vivianite,and treated sludge)and corresponding current-day scenarios(CT1‒CT3 and CF)were considered.Results indicated that PR1 and PR2 have smaller environmental impacts than the current-day scenarios,whereas PR3 has larger impacts in most categories.PR3 has the lowest net costs(sum of internal costs and benefits,39.1-54.7 CNY per kg P),whereas PR2 has the lowest external costs(366.8 CNY per kg P).Societal costs for production and land use of 1 kg P by P recovery from sewage sludge(e.g.,∼527 CNY for PR1)are much higher than those of P chemical fertilizers(∼20 CNY for CF).However,considering the costs in the current-day treatments(e.g.,∼524 CNY for CT1),societal costs of P recovery scenarios are close to or slightly lower than those of current-day scenarios.Among the three P recovery scenarios,we found that recovering struvite as P fertilizer has the highest societal feasibility.This study will provide valuable information for improved sewage sludge management and will help promote the sustainable supply of P in China.

Enhanced anaerobic digestion of waste activated sludge with periodate-based pretreatment

The potential of periodate(PI)in sludge anaerobic digestion is not tapped,although it has recently attracted great research interest in organic contaminants removal and pathogens inactivation in wastewater treatment.This is the first work to demonstrate significant improvement in methane generation from waste activated sludge(WAS)with PI pretreatment and to provide underlying mechanisms.Biochemical methane potential tests indicated that methane yield enhanced from 100.2 to 146.3 L per kg VS(VS,volatile solids)with PI dosages from 0 to 100 mg per g TS(TS,total solids).Electron spin resonance showed PI could be activated without extra activator addition,which might be attributed to the native transition metals(e.g.,Fe2t)in WAS,thereby generating hydroxyl radical(-OH),superoxide radicals(-O2-),and singlet oxygen(1O2).Further scavenging tests demonstrated all of them synergistically promoted WAS disintegration,and their contributions were in the order of-O2->-OH>1O2,leading to the release of substantial biodegradable substances(i.e.,proteins and polysaccharides)into the liquid phase for subsequent biotransformation.Moreover,fluorescence and ultraviolet spectroscopy analyses indicated the recalcitrant organics(especially lignocellulose and humus)could be degraded by reducing their aromaticity under oxidative stress of PI,thus readily for methanogenesis.Microbial community analysis revealed some microorganisms participating in hydrolysis,acidogenesis,and acetoclastic methanogenesis were enriched after PI pretreatment.The improved key enzyme activities and up-regulated metabolic pathways further provided direct evidence for enhanced methane production.This research was expected to broaden the application scope of PI and provide more diverse pretreatment choices for energy recovery through anaerobic digestion.

Fruit and vegetable intake and the risk of arterial hypertension in China:A prospective cohort study

Background:Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent.This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new-onset hypertension.Methods:Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR),58,981 Chinese adults without hypertension at baseline were included.Information on fruit and vegetable intake was collected using a food-frequency questionnaire.Cox proportional hazards models were performed to estimate the hazard ratios(HRs)and 95%confidence intervals(CIs)of incident hypertension.Results:During 640,795 person-years of follow-up,21,008 new cases of hypertension were recorded.Compared with participants in the lowest quintile(Q1)of total fruit and vegetable(TFV)intake,the HRs(95%CIs)of incident hypertension were 0.90(0.86-0.95),0.85(0.81-0.90),0.82(0.78-0.86),and 0.83(0.78-0.88)for the Q2 to Q5 group(ptrend<0.001),respectively.In further analyses categorizing participants according to the recommended intake level(500 g/day),we found that increasing the intake of TFV,even though it was still insufficient for the recommendation,also had a protective effect against the incident hypertension.When considering the intake of fruit or vegetable separately,we found similar trends as the TFV intake.Conclusion:These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults.

久坐行为增加心血管疾病发病风险

西方发达国家的研究提示久坐行为增加心血管病发病风险,但是尚无来自中国等发展中国家的证据.此外,久坐行为替换为身体活动的心血管健康获益尚不明确.本研究的三项队列均来自于中国动脉粥样硬化性心血管病风险预测研究(China-PAR),共纳入基线无心血管病的研究对象93,110人.采用Cox比例风险模型计算心血管疾病的风险比和95%置信区间,采用等时替换模型计算替换久坐行为的健康效应.经过平均5.8年的随访,共发生心血管事件3799例.与久坐<5小时/天者相比,久坐5~<83 8~<10,≥10小时/天者发生心血管病的风险分别增加7%,27%和51%;其中,久坐≥10小时/天且中重度身体活动<150分钟/周者心血管病发病风险最高.对于久坐≥5小时/天者,将1小时的久坐替换为轻、中、高强度身体活动可以分别降低5%,6%,8%的心血管病发病风险.本研究首次报道久坐行为增加中国人群心血管病发病风险,并且发现将久坐行为替换为不同强度身体活动均可降低心血管病发病风险,为"少坐多动"健康生活方式的预防策略提供了中国证据.

Associations of egg consumption with incident cardiovascular disease and all-cause mortality

Eggs are nutrient-dense while also loaded with abundant cholesterol, thus making the public hesitant about their consumption.We conducted the study to investigate if egg consumption is associated with incident cardiovascular disease(CVD) and all-cause mortality. Using the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China, we included 102,136 adults free of CVD and assessed their egg consumption with food-frequency questionnaires. CVD endpoints and all-cause mortality were confirmed during follow-ups by interviewing participants or their proxies and checking hospital records/death certificates.The HRs(95% CIs) were calculated using the cohort-stratified Cox regression models. During 777,163 person-years of followup, we identified 4,848 incident CVD and 5,511 deaths. U-shaped associations of egg consumption with incident CVD and allcause mortality were observed. Compared with consumption of 3–<6/week, the multivariable-adjusted HRs(95% CIs) of <1/week and ≥10/week for incident CVD were 1.22(1.11 to 1.35) and 1.39(1.28 to 1.52), respectively. The corresponding HRs(95% CIs) for all-cause mortality were 1.29(1.18 to 1.41) and 1.13(1.04 to 1.24). Our findings identified that both low and high consumption were associated with increased risk of incident CVD and all-cause mortality, highlighting that moderate egg consumption of 3–<6/week should be recommended for CVD prevention in China.

利用多轴3D打印系统制造锥形生物可吸收支架

Coronary artery disease(CAD)is the leading cause of death worldwide.Implantation of traditional cylindrical stents into the stenotic coronary arteries is widely used in patients with CAD.However,because most coronary arteries taper in diameter by at least 0.5 mm over a length of 20 mm[1],natural size mismatch is common between a cylindrical stent and a tapered coronary artery.This stent-vessel mismatch may directly cause either increased stress on both stent and vessel or incomplete stent apposition,followed by vessel injury,in-stent restenosis,or stent thrombosis[2,3].

A WEDGE DISCLINATION DIPOLE INTERACTING WITH A COATED CYLINDRICAL INHOMOGENEITY

A three-phase composite cylinder model is utilized to study the interaction of a wedge disclination dipole with a coated cylindrical inhomogeneity. The explicit expression of the force acting on the wedge disclination dipole is calculated. The motilities and the equilibrium po- sitions of the disclination dipole near the coated inhomogeneity are discussed for various material combinations, relative thicknesses of the coating layer and the features of the disclination dipole. The results show that the material properties of the coating layer have a major part to play in alteringi the strengthening effect or toughening effect produced by the coated inhomogeneity.

Longitudinal association of egg consumption habits with blood lipids among Chinese adults: results from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project

To the Editor:According to guidelines from western countries as well as China,dietary patterns with low intake of cholesterol have been widely recommended for maintaining ideal lipid levels.As one of the major sources of both high-quality protein and dietary cholesterol,eggs have always been the focus in terms of diet.Although increased lipid levels induced by high egg intake have been revealed by randomized controlled trials(RCTs),they may not be sufficient to reflect the impacts of habitual egg intake due to high doses of egg intake of more than 7 eggs/week or even 14 eggs/week.Further,RCTs typically have shorter intervention periods of about 3 months,which may not observe a stable association due to homeostasis in cholesterol metabolism of human beings.[1,2]Up to now,only three cohorts assessed the associations of egg intake with lipid levels or dyslipidemia,and the findings were still controversial.One recent cohort study has reported the non-significant association between higher egg intake(≥7 vs.1 eggs/week)and lipid profiles.On the other hand,another cohort from Spain found that compared with<1 egg/week,>4 eggs/week had no significant influence on total cholesterol(TC)and triglyceride(TG),but significantly decreased high-density lipoprotein cholesterol(HDL-C)levels.[4]However,none of these cohorts were from developing countries,and the association between moderate egg intake and lipid profiles has not been well illustrated.Egg consumption in China,a representative of developing countries,is relatively higher,and it may be possible to better explore the appropriate range of egg intake.