Effects of inorganic nutrients and environmental factors on the removal of n-propylbenzene and isopropylbenzene in seawater by cryptophytes Rhinomonas reticulata S6A

To effectively remove n-propylbenzene(n-PBZ)and isopropylbenzene(i-PBZ)leaked into seawater using Rhinomonas reticulata S6A(a newly isolated marine microalga),the effects of three inorganic nutrients and four environmental factors on their degradation were determined after 7 d of inoculation.Results show that NaNO_(3) at 300 mg/L caused a higher removal efficiency of both n-PBZ and i-PBZ(44.79%and 39.26%),while for NaH_(2) PO_(4)·H_(2) O,greater removal rates of two PBZs(47.30%and 42.23%)were achieved at 30 and 20 mg/L,respectively.NaHCO_(3) supplementation(500-750 mg/L)resulted in a large reduction(43.67%-45.04%)in i-PBZ concentration.The change in seawater pH(from 6 to 9)did not affect the elimination of n-PBZ and i-PBZ.The most suitable salinity and temperature were 30 and 25-30℃,respectively,leading to the PBZs removal of~40%.Light intensity exhibited significant influence on elimination of PBZs,and the maximum removal efficiencies of 56.07%(n-PBZ)and 55.00%(i-PBZ)were recorded under 200 and 600μmol/(m^(2)·s),respectively.In addition,the microalga could still remove PBZs when it failed to grow well due to darkness,strong light,low temperature,or low salinity,which might mean that good growth of alga is not always a necessary condition for PBZs removal.Therefore,attention should be paid to the suitability of nutrient levels and environmental conditions(excluding pH)in seawater when using microalgae for bioremediating PBZs-contaminated seawater.

Marine ecological risk assessment for the herbicide sulfometuron-methyl based on species sensitivity distribution approach

In recent years,herbicide sulfometuron-methyl(SM)has been used to kill the invasive plant Spartina alterniflora in some coastal areas of China,which may lead to the toxic effects on non-target marine organisms.The 96-h median effective concentrations(96-h EC50)of SM on six species of marine microalgae were measured in growth inhibition tests,and were then compared with other published toxicity data,based on which a method of species sensitivity distribution(SSD)was built to estimate the hazardous concentration of SM for 5%of species(HC5)and potentially affected fraction(PAF)for a certain concentration.Results indicate that SM exhibited a high toxicity to two species of green algae(Chlorella pacifica and Dunaliella salina)with a 96-h EC50 of 0.11 and 0.13 mg/L respectively,had a medium toxicity to two species of golden algae(Diacronema viridis and Isochrysis galbana)with a 96-h EC50 of 14.24 and 21.48 mg/L respectively,and showed a low toxicity to two species of diatoms(Skeletonema costatum and Phaeodactylum tricornutum)with a 96-h EC50 of 148.99 and>100 mg/L,respectively.The estimated values of HC5 and the predicted no-effect concentrations(PNEC)for SM were 0.077 and 0.015 mg/L,respectively.According to the current dosage for killing S.alterniflora in tidal flats in Fujian Province,China,SM entering the sea by spraying might cause the acute injury or death of 14%of marine species.This hazard could last for about a month for those sensitive species.Therefore,on the premise of inhibiting the growth of this invasive plant,the dosage of SM should be reduced as much as possible to avoid severe damage to the marine ecosystem.The results provide a valuable information for marine ecological risk assessment on SM and for marine environmental management.

Fusion protein of single-chain variable domain fragments for treatment of myasthenia gravis

Single-chain variable domain fragment （scFv） 637 is an antigen-specific scFv of myasthenia gravis. In this study, scFv and human serum albumin genes were conjugated and the fusion pro-tein was expressed in Pichia pastoris. The afifnity of scFv-human serum albumin fusion protein to bind to acetylcholine receptor at the neuromuscular junction of human intercostal muscles was detected by immunolfuorescence staining. The ability of the fusion protein to block myas-thenia gravis patient sera binding to acetylcholine receptors and its stability in healthy serum were measured by competitive ELISA. The results showed that the inhibition rate was 2.0-77.4%, and the stability of fusion protein in static healthy sera was about 3 days. This approach suggests the scFv-human serum albumin is a potential candidate for speciifc immunosuppressive therapy of myasthenia gravis.

Structural and optical properties of AlN sputtering deposited on sapphire substrates with various orientations

AlN thin films were deposited on c-,a-and r-plane sapphire substrates by the magnetron sputtering technique.The in-fluence of high-temperature thermal annealing(HTTA)on the structural,optical properties as well as surface stoichiometry were comprehensively investigated.The significant narrowing of the(0002)diffraction peak to as low as 68 arcsec of AlN after HTTA implies a reduction of tilt component inside the AlN thin films,and consequently much-reduced dislocation densities.This is also supported by the appearance of E2(high)Raman peak and better Al-N stoichiometry after HTTA.Furthermore,the in-creased absorption edge after HTTA suggests a reduction of point defects acting as the absorption centers.It is concluded that HTTA is a universal post-treatment technique in improving the crystalline quality of sputtered AlN regardless of sapphire orienta-tion.

基于血清学指标的联合模型诊断代偿期肝硬化轻微型肝性脑病的价值

目的探讨血清学指标对代偿期肝硬化轻微型肝性脑病(MHE)的诊断价值,构建基于血清学指标的联合模型并评估其对MHE的诊断价值。方法前瞻性、多中心研究。选取2021年10月至2022年8月来自我国15个省(自治区、直辖市)的23家医院就诊的代偿期肝硬化患者263例。收集患者临床资料及实验室检查结果,并计算终末期肝病模型(MELD)评分。使用基线血氨测量值/正常参考值上限(AMM-ULN)集中校正各中心血氨测量结果,以我国《肝硬化肝性脑病诊疗指南》标准,数字连接试验-A、数字符号试验均异常作为诊断MHE的标准。基于R语言caret包将患者随机(7∶3)分为训练集(n=185)和验证集(n=78)。通过Logistic回归构建诊断MHE的联合模型;受试者工作特征曲线下面积(AUC)、Hosmer-Lemeshow拟合优度检验及校准曲线图评估诊断性能,并用Bootstrap法(n=200)进行内部验证;Delong检验比较AUC之间的差异。结果训练集中,MHE占37.8%(70/185),MHE组AMM-ULN、白蛋白、血小板、碱性磷酸酶、国际标准化比值、终末期肝病模型评分以及教育年限与无MHE组比较,差异有统计学意义(P均<0.05)。多因素Logistic回归分析显示,AMM-ULN(OR=1.78,95%CI 1.05~3.14,P=0.038)和MELD评分(OR=1.11,95%CI 1.04~1.20,P=0.002)是MHE的独立危险因素,AUC分别为0.663和0.625。联合AMM-ULN、MELD评分和教育年限的联合模型诊断MHE的AUC为0.755,特异度和敏感度分别为85.2%和55.7%。Hosmer-Lemeshow拟合优度检验表明模型具有较好的校准度(P=0.733),联合模型内部验证AUC为0.752。Delong检验显示联合模型诊断效能优于单独使用血氨(P=0.020)和MELD评分(P=0.003)。验证集中,联合模型诊断MHE的AUC为0.794,Hosmer-Lemeshow拟合优度检验显示有较好的校准度(P=0.841)。结论基于AMM-ULN、MELD评分和教育年限的联合模型可提高对MHE的诊断价值。

Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19:a phase 1 clinical trial

No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients:a randomized,double-blind,placebo-controlled phase 2 trial

Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.

Comparative study on virus shedding patterns in nasopharyngeal and fecal specimens of COVID-19 patients

Dear Editor,An acute viral pneumonia(COVID-19),caused by the novel coronavirus known as SARS-CoV-2,was first identified during December 2019 in China(Zhu et al.,2020).SARSCoV-2 was found to be highly transmissible in humans(Wang et al.,2020)and is now a pandemic spreading to over 140 countries and causing over 150,000 infections and 6,000 deaths as of March 15,2020.Diagnosis is critical for confirmation and treatment of COVID-19.Currently the primary criterion for diagnosis of COVID-19 is viral RNA detection for respiratory samples.Recently,two studies on virus loads in clinical samples reported that viral loads in nasal and throat swabs and sputum specimens peaked at 3–7 days after illness onset(d.a.o.)and virtually disappeared before 15 d.a.o.(Pan et al.,2020;Zou et al.,2020).Another study showed that the median duration of virus shedding in throat swabs was 20 d.a.o.in survivors and was detectable until death in non-survivors(Zhou et al.,2020).Additionally,live viruses have been isolated in the feces and urine samples of COVID-19 patients.However,the viral dynamics in these types of specimens has not yet been clearly elucidated,as well as comparative studies on virus shedding in the upper respiratory,intestinal,and urinary tracts.

Downregulated miR-451a as a feature of the plasma cfRNA landscape reveals regulatory networks of IL-6/IL-6R-associated cytokine storms in COVID-19 patients

Rapidly spreading coronavirus disease 2019(COVID-19)is currently affecting the world.Specifically,cytokine storms are a key feature in a substantial num ber of COVID-19 patients,1 and studies from our group and others suggest that the IL-6/IL-6R cascade plays a dom inant role in symptom-correlated cytokine storms.

Natural attenuation characteristics and comprehensive toxicity changes of C9 aromatics under simulated marine conditions

Microcosmic experiments were performed under a simulated marine environment to investigate the natural attenuation of C9 aromatics using nine components(propylbenzene,isopropylbenzene,2-ethyltoluene,3-ethyltoluene,4-ethyltoluene,1,2,3-trimethylbenzene,1,2,4-trimethylbenzene,1,3,5-trimethylbenzene,and indene).This research aims to assess the contribution of biodegradation and abiotic activity to total attenuation of C9 aromatics and ascertain the changes in the comprehensive toxicity of seawater in the natural environment.The process of natural attenuation indicates the agreement with pseudo-first-order kinetics for all nine components in microcosmic experiments.The half-lives of the nine main compounds in C9 aromatics ranged between 0.34 day and 0.44 day under optimal conditions.The experiments showed that the natural attenuation of nine aromatic hydrocarbonsmainly occurred via abiotic processes.Seawater samples significantly inhibited the luminescence of P.phosphoreum(the luminescence inhibition ratio reached 100%)at the beginning of the experiment.In addition,the toxicity declined slowly and continued for 25 days.The attenuation kinetics and changes in toxicity could be applied to explore the natural attenuation of C9 aromatics in the marine environment.

Clinical Epidemiology,Illness Profiles,and the Implication of COVID-19 Before and After the Nationwide Omicron Outbreak During the Winter of 2022

China.In this study,we aimed to investigate the clinical characteristics and outcomes of patients with coronavirus disease 2019(COVID-19)in the Beijing region.Methods:In this retrospective study,we enrolled inpatients admitted for COVID-19 in the Fifth Medical Center of Chinese PLA General Hospital in Beijing between November 10,2022,and January 30,2023.Demographic and clinical features and treatment outcomeswere comprehensively analyzed.We used logistic regression and linear regression analyses to explore the risk factors associated with disease severity and time of nucleic acid conversion,respectively.Results:A total of 1010 hospitalized patients with COVID-19 were enrolled.The median age was 43.0 years(interquartile range,28.0–63.0),and patients aged<60 years and≥60 years comprised 71.2%and 28.8%of total included patients,respectively.The clinical classification of mild(74.6%,753/1010),moderate(21.0%,212/1010),severe(2.7%,27/1010),and unidentified(1.8%,18/1010)was separately recorded;1005 patients were discharged,and 5 patients died in the hospital.The outbreak of the emerging epidemic witnessed an evident increase in the proportion of moderate(42.9%vs.16.4%)and severe(10.3%vs.1.1%)cases after December 7,2022.Patients with a moderate/severe classification had higher levels of procalcitonin,IL-6,serum ferritin,C-reactive protein,lactic dehydrogenase,serum urea nitrogen,and D-dimer and lower counts of CD4+T,CD8+T,and B cells(all P<0.001).Multivariable regression analysis revealed that increased odds of disease severity were associated with the following factors:age≥60 years,IL-6>7 pg/mL,lactic dehydrogenase level>245 U/L,cough,and fever at admission.Age≥80 years and chronic lung diseasewere independent risk factors in the nonmild group in elderly patients.In addition,the duration for nucleic acid to turn negativewas approximately 5.0 d(interquartile range,3.0–7.0).Prolonged time of nucleic acid conversion was associated with age≥60 years,serum urea nitrogen level>8.2 mmol/L,neutrophil count>7×10^(9)/L,and the presence of a chronic lung disease or carcinoma.Finally,unvaccinated patients accounted for 37.3%of enrolled patients;children and the elder people accounted for approximately half of that.The univariable analysis found that booster doses reduced disease severity and shortened the time of nucleic acid conversion in elderly patients.Conclusions:The outbreak ofOmicron rapidly increased the number of patientswith COVID-19 in Beijing.In elderly patients,booster doses may reduce disease severity and shorten the time of nucleic acid conversion.Healthcare systems should be optimized before an emerging epidemic outbreak.

Can Ursodeoxycholic Acid Prevent SARS-CoV-2 Infection or Reduce the COVID-19 Severity? Current Knowledge and Unresolved Issues

A recent study revealed that the inhibition of the farnesoid X receptor using ursodeoxycholic acid(UDCA)significantly reduces angiotensin-converting enzyme 2(ACE2)expression.Therefore,considerable attention has been paid to the use of UDCA to prevent severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and reduce the severity of the disease.This review compre-hensively summarizes the role of ACE2 in SARS-CoV-2 infection and the potential role and mechanisms of UDCA in the prevention of SARS-CoV-2 infection or reinfection.It also discusses unresolved issues and the potential use of UDCA in the treatment of patients with coronavirus disease.

Prevalence and risk factors for minimal hepatic encephalopathy in cirrhotic patients with different etiologies

Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with cirrhosis of different etiologies and whether the etiology directly influences the occurrence of MHE.Methods:This multicenter,cross-sectional study enrolled 1879 patients with confirmed cirrhosis at 40 hospitals from October 25,2021,to January 10,2023(Trial registration:https://clinicaltrials.gov/[NCT05140837]).The patients'demographics,etiologies of cirrhosis,and laboratory test results were collected.The psychometric hepatic encephalopathy score(PHES)was determined in all patients to screen for MHE.Multivariate logistic analyses were performed to identify the risk factors for MHE.Results:In total,736 patients with cirrhosis were analyzed.The prevalence of MHE was 42.0%(n=309).The primary etiology among all patients was hepatitis B virus(HBV)-related cirrhosis(71.9%[529/736]).The prevalence of MHE was significantly higher in patients with alcoholic cirrhosis(57.1%[40/70])than in those with HBV-related cirrhosis(40.6%[215/529],p=0.009)or hepatitis C virus(HCV)-related cirrhosis(38.2%[26/68],p=0.026).Age(odds ratio[OR],1.042;95%confidence interval[CI],1.024-1.059;p<0.001),duration of education(OR,0.935;95%CI,0.899-0.971;p=0.001),etiology(OR,1.740;95%CI,1.028-2.945;p=0.039),and high MELD-Na scores(OR,1.038;95%CI,1.009-1.067;p=0.009)were independent risk factors for MHE.When patients with cirrhosis of different etiologies were analyzed separately,the results showed that age(OR,1.035;95%CI,1.014-1.057;p=0.001)and duration of education(OR,0.924;95%CI,0.883-0.966;p=0.001)were risk factors for MHE among patients with HBV-related cirrhosis,whereas age(OR,1.138;95%CI,1.033-1.254;p=0.009)and creatinine concentration(OR,16.487;95%CI,1.113-244.160;p=0.042)were risk factors for MHE in patients with HCV-related cirrhosis.No risk factors for MHE were found in patients with autoimmune cirrhosis.For patients with alcoholic cirrhosis,the platelet count(OR,1.014;95%CI,1.000-1.027;p=0.045)was a risk factor for MHE.The PHES subtest results were inconsistent among patients who had MHE with cirrhosis of different etiologies.Patients with HBV-related cirrhosis performed better on Number Connection Test B and the serial dotting test than those with alcoholic cirrhosis(p=0.007 and p<0.001),better on Number Connection Test B than those with HCV-related cirrhosis(p=0.020),and better on the line tracing test than those with autoimmune cirrhosis(p=0.037).Conclusion:The etiology of cirrhosis affected the prevalence of MHE and risk factors for MHE.The domains of major cognitive impairment varied among patients with cirrhosis of different etiologies.Further studies are required to verify these findings.

Legionella sainthelensi Pneumonia with Abdominal Symptoms as Prominent Manifestations:A Case Report

Fewstudies have reported Legionella sainthelensi infection.This infection primarily presents with respiratorymanifestations.Here,we report an immunocompromised patient with cavitary pneumonia caused by L.sainthelensi who mainly had abdominal symptoms.The timely administration of moxifloxacin provided clinical improvement and resolution of symptoms.To our knowledge,this is one of the rare cases of L.sainthelensi infection presenting uniquelywith abdominal distension and liver function impairment butwithout obvious respiratory symptoms.