Building Fe atom–cluster composite sites using a site occupation strategy to boost electrochemical oxygen reduction

The high-temperature pyrolysis process for preparing M–N–C single-atom catalyst usually results in high heterogeneity in product structure concurrently contains multiscale metal phases from single atoms(SAs),atomic clusters to nanoparticles.Therefore,understanding the interactions among these components,especially the synergistic effects between single atomic sites and cluster sites,is crucial for improving the oxygen reduction reaction(ORR)activity of M–N–C catalysts.Accordingly,herein,we constructed a model catalyst composed of both atomically dispersed FeN4 SA sites and adjacent Fe clusters through a site occupation strategy.We found that the Fe clusters can optimize the adsorption strength of oxygen reduction intermediates on FeN4 SA sites by introducing electron-withdrawing–OH ligands and decreasing the d-band center of the Fe center.The as-developed catalyst exhibits encouraging ORR activity with halfwave potentials(E1/2)of 0.831 and 0.905 V in acidic and alkaline media,respectively.Moreover,the catalyst also represents excellent durability exceeding that of Fe–N–C SA catalyst.The practical application of Fe(Cd)–CNx catalyst is further validated by its superior activity and stability in a metalair battery device.Our work exhibits the great potential of synergistic effects between multiphase metal species for improvements of singleatom site catalysts.

SiO_(2) Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.

一种薄管板简化有限元模型

分析了锅壳锅炉薄管板受力情况,认为扳边是设备应力最大部位。针对薄管板受力特点,提出了一种对薄管板扳边部位应力进行数值分析计算的简化模型。在两种工况下对简化模型与3D结构离散化模型进行了有限元应力分析对比,结果表明两种模型对扳边部位应力的计算精度基本相当,满足工程实践的需求。薄管板应力计算简化模型结构简单,易于建模,而且模型规模远小于无简化模型,可以大幅减少计算时间,在直径大、换热管数量多的设备分析中优势更为明显。

The role of Epstein-Barr virus in multiple sclerosis:from molecular pathophysiology to in vivo imaging

Multiple sclerosis(MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus(EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory B-cells, the primary reservoir site where EBV latency occurs. In addition, EBV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EBV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on B-cells and in vivo imaging. Addressing the potential link between EBV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to B-cell depleting intervention.

Diabetes mellitus is a risk factor of acute kidney injury in liver transplantation patients

Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate(e GFR), the model for end-stage liver disease(MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients(35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of e GFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of e GFR within the first year after surgery.

H5N1禽流感病毒继续流行和变异——H5N1病毒正以不可预测的方式继续发生变异，对鸟类和人类构成严重威胁

高致病H5N1流感病毒的变体从亚洲传播到印度、欧洲和非洲,并持续在中国的东南部进化,产生了新的突变体,研究者担心由此引发病毒传播到各地及在全球野生鸟类中流行。到目前为止,在感染H5N1病毒的250例中,半数以上死亡。为控制病毒传播,亚洲有2亿多的家禽被宰杀。HSN1病毒打破了有关流感病毒的一些观念,包括何种鸟可以平安地传播病毒,何种鸟中病毒能致病和致死,以及何种猫可被感染并且能够传播病毒等。一旦在一个地区内一株特别的流感病毒在鸟类中广泛传播时,对家禽扑杀的控制措施应当扩大,同时配合使用疫苗。

Advances in interscale and interdisciplinary approaches to the South China Sea

The South China Sea(SCS)connects the Pacific Ocean and the Indian Ocean,and acts as an important part in regional and global climate systems(e.g.,Qu et al.,2009;Wang et al.,2009).Multi-scale dynamic and biogeochemical processes in the SCS,comprising a hot spot in marginal sea studies,have attracted great attentions from researchers(e.g.,Chen et al.,2020;Hu et al.,2020).The South China Sea Annual Meeting(SCSAM)2021,recently held on October 22–24 in Zhanjiang,China,focused on academic exchanges of the newly research results and progresses in the interdisciplinary multi-scale processes in the SCS.The SCSAM 2021 is the eighth international workshop of the series,which started in April 2013(Zhu,2013)and renamed as SCSAM in 2018.There were 90 oral presentations and 57 posters in the meeting this year,which attracted attentions of more than 2000 audiences both on line and on site.This short article summaries the cutting-edge advances in interscale and interdisciplinary approaches to the SCS from the meeting presentations and the associated research.

Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A

Objective To explore whether age,disease severity,cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance.Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study.Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients,respectively(P < 0.05).Moreover,the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients(P < 0.01).The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells.Additionally,the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells.Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods,which may partially be attributed to the impaired Th17 cell response.

Insulation degradation and fracture cracks of mechanical impacted thermal-ageing oil-impregnated papers

In order to elucidate mechanical impacts affecting the insulation strength of thermalageing oil-impregnated pressboards,we perform mechanical degradation experiments of impacting forces that are represented as the winding-suffered stresses on thermalageing oil-paper insulation in transient short-circuit of transformer.Water content,degree of polymerisation(DP),partial discharge inception voltage and AC breakdown field strength are tested and analysed for diverse thermal-ageing levels.An analytical model of mechanical degradation is established by relating dielectric breakdown strength to mechanical impact.Mechanical impacts result in less water content in thermal-aging oilimpregnated pressboards while causing reduction and increment of DP,respectively,in mildly and severely aged oil-impregnated pressboards.Partial discharge inception voltage and dielectric breakdown strength vary significantly with the numbers of impact cycles,showing a maximum value under low-intensity impact and decreasing monotonously under high-intensity impact.High-intensity mechanical impacts will evidently exacerbate the thermal deterioration process of oil-impregnated pressboards,which is primarily attributed to cellulose fibre fractures in pressboard cracks produced by equivalent tensile stress of mechanical impacts.It is acceptable for mildly aged oil-impregnated pressboards to suffer low-intensity mechanical impacts that will alleviate insulation degradation by restraining partial discharge in smaller oil-gaps and prolonging breakdown discharge pathways along impact-caused cracks.

A SARS-CoV-2-specific CAR-T-cell model identifies felodipine,fasudil,imatinib,and caspofungin as potential treatments for lethal COVID-19

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019(COVID-19)severity and lethality.However,drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed.Here,we constructed a SARS-CoV-2 spike protein-specific CAR,and human T cells infected with this CAR(SARS-CoV-2-S CAR-T)and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients,causing cytokine storm and displaying a distinct memory,exhausted,and regulatory T-cell phenotype.THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture.Based on this"two-cell"(CAR-T and THP1 cells)model,we screened an FDA-approved drug library and found that felodipine,fasudil,imatinib,and caspofungin were effective in suppressing the release of cytokines,which was likely due to their ability to suppress the NF-kB pathway in vitro.Felodipine,fasudi,imatinib,and caspofungin were further demonstrated,although to different extents,to attenuate lethal inflammation,ameliorate severe pneumonia,and prevent mortality in a SARS-CoV-2-infected Syrian hamster model,which were also linked to their suppressive role in inflammation.In summary,we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner.The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe,inexpensive,and easily accessible for immediateuseinmostcountries.

The emergence of pandemic influenza viruses

Pandemic influenza has posed an increasing threat to public health worldwide in the last decade.In the 20th century,three human pandemic influenza outbreaks occurred in 1918,1957 and 1968,causing significant mortality.A number of hypotheses have been proposed for the emergence and development of pandemic viruses,including direct introduction into humans from an avian origin and reassortment between avian and previously circulating human viruses,either directly in humans or via an intermediate mammalian host.However,the evolutionary history of the pandemic viruses has been controversial,largely due to the lack of background genetic information and rigorous phylogenetic analyses.The pandemic that emerged in early April 2009 in North America provides a unique opportunity to investigate its emergence and development both in human and animal aspects.Recent genetic analyses of data accumulated through long-term influenza surveillance provided insights into the emergence of this novel pandemic virus.In this review,we summarise the recent literature that describes the evolutionary pathway of the pandemic viruses.We also discuss the implications of these findings on the early detection and control of future pandemics.

Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness.To experimentally demonstrate the epidemiological results,we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2.Remarkably,high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss,weakness,piloerection,hunched back and abdominal respiration,as well as severe pneumonia,pulmonary edema,consolidation,and fibrosis.In contrast with the males,the female hamsters showed much lower shedding viral titers,moderate symptoms,and relatively mild lung pathogenesis.The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.

Dexamethasone ameliorates severe pneumonia but slightly enhances viral replication in the lungs of SARS-CoV-2-infected Syrian hamsters

The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 230 million cases and over four million deaths worldwide.Furthermore,multiple emerging SARS-CoV-2 variants have shown enhanced infectivity,transmissibility,pathogenicity and ability to escape neutralization by vaccine-induced humoral immunity[1].The antibody resistance of SARS-CoV-2 variants constitutes a challenge for current vaccines and therapeutic antibodies.No specific antiviral is currently available for coronavirus in humans[2].Although remdesivir was approved by the FDA for the treatment of SARS-CoV-2 infection,the therapeutic effect is limited,particularly for critical cases with severe pneumonia.

Oncolytic Activity of Wild-type Newcastle Disease Virus HK84 Against Hepatocellular Carcinoma Associated with Activation of Type I Interferon Signaling

Background and Aims:Hepatocellular carcinoma(HCC)is listed as one of the most common causes of cancer-related death.Oncolytic therapy has become a promising treatment because of novel immunotherapies and gene editing technology,but biosafety concerns remain the biggest limitation for clinical application.We studied the the antitumor activity and biosafety of the wild-type Newcastle disease virus HK84 strain(NDV/HK84)and 10 other NDV strains.Meth-ods:Cell proliferation and apoptosis were determined by cell counting Kit-8 and fluorescein isothiocyanate Annexin V apoptosis assays.Colony formation,wound healing,and a xenograft mouse model were used to evaluate in vivo and in vitro oncolytic effectiveness.The safety of NDV/HK84 was tested in nude mice by an in vivo luciferase imaging system.The replication kinetics of NDV/HK84 in normal tis-sues and tumors were evaluated by infectious-dose assays in eggs.RNA sequencing analysis was performed to explore NDV/HK84 activity and was validated by quantitative real-time PCR.Results:The cell counting Kit-8 assays of vi-ability found that the oncolytic activity of the NDV strains differed with the multiplicity of infection(MOI).At an MOI of 20,the oncolytic activity of all NDV strains except the DK/JX/21358/08 strain was>80%.The oncolytic activities of the NDV/HK84 and DK/JX/8224/04 strains were>80%at both MOI=20 and MOI=2.Only NDV/HK84 had>80%oncolytic activities at both MOI=20 and MOI=2.We chose NDV/HK84 as the candidate virus to test the oncolytic effect of NDV in HCC in the in vitro and in vivo experiments.NDV/HK84 killed human SK-HEP-1 HCC cells without affecting healthy cells.Conclusions:Intratumor infection with NDV/HK84 strains compared with vehicle controls or positive controls indicated that NDV/HK84 strain specifically inhib-ited HCC without affecting healthy mice.High-throughput RNA sequencing showed that the oncolytic activity of NDV/HK84 was dependent on the activation of type I interferon signaling.

Female sex hormone, progesterone, ameliorates the severity of SARS-CoV-2-caused pneumonia in the Syrian hamster model

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 260 million people worldwide and causes coronavirus disease 2019(COVID-19)with clinical spectrum ranging from mild to severe pneumonia.Recent clinical trials and experimental animal studies demonstrated that the severity of COVID-19 is lower in the females than in males.

Persisting lung pathogenesis and minimum residual virus in hamster after acute COVID-19

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 200 million people,causing coronavirus disease 2019(COVID-19)worldwide.Lungs are the primary target organ of SARS-CoV-2 infection.The mild COVID-19 cases develop symptoms of fever,fatigue,muscle weakness,chest pain,headache and cough(Chen et al.,2020;Wang et al.,2020;Zhu et al.,2020),while severe COIVD-19 cases might have pneumonia,breathing difficulties,multiple organ failure and death(Chen et al.,2020;Wang et al.,2020;Zhu et al.,2020).Both the clinicians and researchers have largely focused on the acute phase of COVID-19,but the long-term health consequences of the COVID-19 patients after clinical recovery remain less investigated.Several clinical cohorts demonstrated that some patients discharged from hospital still experience symptoms including fatigue,muscle weakness,chest pain,cough and breathing difficulties(Carfi et al.,2020;Lim et al.,2020;Huang et al.,2021).Moreover,severely impaired pulmonary diffusion capacities and abnormal chest imaging manifestations were observed in some convalescent patients(Huang et al.,2021).Surprisingly,residual virus(An et al.,2020;Yao et al.,2020;Kim et al.,2021)were detected in some convalescent patients.

Infection,pathology and interferon treatment of the SARS-CoV-2 Omicron BA.1 variant in juvenile,adult and aged Syrian hamsters

The new predominant circulating SARS-CoV-2 variant,Omicron,can robustly escape current vaccines and neutralizing antibodies.Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants,its pathogenicity in different age groups has not been well elucidated.Here,we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters,with more body weight loss,respiratory tract viral burden,and lung injury in these hamsters than in adult hamsters.Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection,whereas aged hamsters show excessive proinflammatory cytokine expression,delayed viral clearance,and aggravated lung injury.Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters.Overall,the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.