β-cyclopiazonic acid binds iron demonstrating siderophorelike activity and promotes growth in Pseudomonas aeruginosa

This chemical study reports a novel siderophore-like compound,β-cyclopiazonic acid(1,β-CPA)extracted from marine fungus Aspergillus flavus.The chemical structure ofβ-CPA was elucidated by a combination of extensive spectroscopic analyses and TDDFT-ECD calculations.The iron-binding ability and CAS assays demonstrate thatβ-CPA is a novel siderophore that features a different chemical structure from those of traditional siderophores.Theβ-CPA has no obvious influence on the growth of bacterium Pseudomonas aeruginosa PAO1.However,its iron chelator could promote the growth of P.aeruginosa PAO1,suggesting that P.aeruginosa employed siderophores to sequester iron,which is vital for their survival.The study provides the physiochemical evaluation ofβ-CPA,an unusual skeletonstructure siderophore,which for the first time,was proven to have the ability to bind iron and affect P.aeruginosa growth.This new discovery of siderophore provides an opportunity for developing novel anti-P.aeruginosa drugs.

Highly efficient production of 2,5-dihydroxymethylfuran from biomass-derived 5-hydroxymethylfurfural over an amorphous and mesoporous zirconium phosphonate catalyst

The development of high-efficiency and low-cost catalysts is very crucial for the MeerweinPonndorf-Verley (MPV) reduction of biomass-derived 5-hydroxymethylfurfural (HMF) into 2,5-dihydroxymethylfuran (DHMF). In this work, an amorphous and mesoporous zirconium phosphonate catalyst (Zr-DTMP), which is a zirconium-containing organic-inorganic nanohybrid, was successfully designed and synthesized by the simple assembly of zirconium tetrachloride (ZrCl4) and diethylene triaminepenta(methylene phosphonic acid)(DTMP). Satisfactorily, when Zr-DTMP was employed for the MPV reduction of HMF in the presence of 2-butanol (secBuOH), DHMF yield could be achieved as 96.5% in 3 h under a relatively mild reaction temperature of 140℃. Systematic investigations indicated that this high catalytic activity should be mainly due to the cooperative role of enhancive Lewis acid site (Zr4+) and Lewis base site (O2-) in activating the carbonyl group of HMF and dissociating the hydroxyl group of secBuOH, respectively. Additionally, Zr-DTMP showed excellent catalytic stability, when it was successively used 5 recycles, its surface characteristics and textural properties still remained almost unchanged, and so, the catalytic activity was not obviously affected. More interestingly, Zr-DTMP could also be applied for the selective reduction of other biomass-derived carbonyl compounds, such as 5-methylfurfural (MF), furfural (FF), levulinic acid (LA), ethyl levulinate (EL) and cyclohexanone (CHN), into the corresponding products with high yields, which is beneficial to the effective synthesis of various valuable bio-based chemicals.

Epidemiology and Mechanisms of Ceftazidime-Avibactam Resistance in Gram-Negative Bacteria

Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms(CRO) are frequently associated with significant morbidity and mortality. Ceftazidime–avibactam(CAZ–AVI) is a novel cephalosporin/β-lactamase inhibitor combination offering an important advance in the treatment of CRO infections. CAZ–AVI has been reported to inhibit the activities of Ambler classes A, C, and some class D enzymes. However, bacterial resistance has been emerging shortly after the introduction of this combination in clinical use, with an increasing trend. Understanding these resistance mechanisms is crucial for guiding the development of novel treatments and aiding in the prediction of underlying resistance mechanisms. This review aims to systematically summarize the epidemiology of CAZ–AVI-resistant strains and recently identified resistance mechanisms of CAZ–AVI, with a focus on the production of β-lactamase variants, the hyperexpression of β-lactamases, reduced permeability, and overexpressed efflux pumps. The various mechanisms of CAZ–AVI resistance that have emerged within a short timescale emphasize the need to optimize the use of current agents, as well as the necessity for the surveillance of CAZ–AVI-resistant pathogens.

Development and Validation of a Prognostic Risk Score System for COVID-19 Inpatients:A Multi-Center Retrospective Study in China

Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients.Here,we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital,Wuhan,China(development cohort)and externally validated with data from two other centers:141 inpatients from Jinyintan Hospital,Wuhan,China(validation cohort 1)and 432 inpatients from The Third People’s Hospital of Shenzhen,Shenzhen,China(validation cohort 2).The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death.The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90%accuracy across all cohorts.Moreover,the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low,intermediate,or high risk,with an area under the curve(AUC)score of 0.9551.In summary,a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);it has also been validated in independent cohorts.

The biochemical behavior and mechanism of uranium(Ⅵ)bioreduction induced by natural Bacillus thuringiensis

For a broader understanding of uranium migration affected by microorganisms in natural anaerobic environment,the bioreduction of uranium(Ⅵ)(U(Ⅵ))was revealed in Bacillus thuringiensis,a dominant bacterium strain with potential of uranium-tolerant isolated from uranium contaminated soil.The reduction behavior was systematically investigated by the quantitative analysis of U(Ⅳ)in bacteria,and mechanism was inferred from the pathway of electron transmission.Under anaerobic conditions,appropriate biomass and sodium lactate as electron donor,reduction behavior of U(Ⅵ)induced by B.thuringiensis was restricted by the activity of lactate dehydrogenase,which was directly affected by the initial pH,temperature and initial U(Ⅵ)concentration of bioreduction system.Bioreduction of U(Ⅵ)was driven by the generation of nicotinamide adenine dinucleotide(NADH)from enzymatic reaction of sodium lactate with various dehydrogenase.The transmission of the electrons from bacteria to U(Ⅵ)was mainly supported by the intracellular NADH dehydrogenase-ubiquinone system,this process could maintain the biological activity of cells.

自动乳腺超声联合免疫组化早期预测乳腺癌新辅助化疗病理完全缓解的临床价值

目的探讨自动乳腺超声(ABUS)联合免疫组化早期预测乳腺癌患者新辅助化疗(NAC)后获得病理完全缓解(pCR)的临床价值。方法收集2019年3月至2022年6月于空军军医大学第一附属医院(西京医院)乳腺外科收治的420例女性乳腺癌患者,所有患者均经穿刺病理证实为浸润性乳腺癌,患者在行NAC前均行ABUS检查,根据术后病理结果将乳腺癌患者分为pCR组153例和非病理完全缓解(npCR)组267例。采用多因素Logistic回归分析乳腺癌pCR的独立预测因素,构建3种预测模型分别为ABUS特征预测模型、免疫组化预测模型、ABUS联合免疫组化的联合预测模型。绘制3种模型的ROC曲线评估模型效能,通过DeLong检验比较模型的ROC曲线下面积,选择最优模型构建列线图。通过Hosmer-Lemeshow检验分析模型拟合度,采用Bootstrap法对模型进行内部验证,绘制校准度曲线对模型性能进行评估,使用决策曲线评估预测模型的临床获益。结果乳腺癌NAC前pCR组与npCR组肿瘤的雌激素受体(ER)状态、孕激素受体(PR)状态、人表皮生长因子受体-2(HER-2)状态、Ki67状态和分子分型差异有统计学意义(P均<0.05);NAC前pCR组与npCR组肿瘤的皮肤侵犯、形态、后方回声、冠状面汇聚征、冠状面白墙征差异有统计学意义(P均<0.05)。多因素Logistic回归分析显示,HER-2状态(OR值:4.396,95%CI:2.089~9.250)、分子分型(HER-2过表达型OR值:4.124,95%CI:2.069~8.219;三阴性型OR值:4.775,95%CI:2.188~10.422)、皮肤侵犯(OR值:0.110,95%CI:0.038~0.318)、冠状面汇聚征(OR值:0.416,95%CI:0.220~0.787)、冠状面白墙征(OR值:11.192,95%CI:5.316~23.561)是pCR的独立预测因子(P均<0.05)。DeLong检验表明基于ABUS模型和免疫组化特征构建的联合模型的ROC曲线下面积(AUC=0.855)显著高于免疫组化模型(AUC=0.758)和ABUS模型(AUC=0.774),差异均有统计学意义(Z=5.11,P<0.001;Z=5.49,P<0.001);ABUS模型的ROC曲线下面积(AUC=0.774)略高于免疫组化模型(AUC=0.758),但差异无统计学意义(Z=0.55,P=0.58)。Hosmer-Lemeshow检验表明联合模型拟合度良好(χ^(2)=6.175,P=0.519);内部验证结果显示,C-指数为0.856(95%CI:0.810~0.886),表明模型稳定性良好;校准曲线表明联合模型的预测概率与实际概率一致性良好;决策曲线表明在广泛阈值范围内,联合模型具有较好的临床获益。结论基于NAC前肿瘤的ABUS特征联合免疫组化构建联合模型可以早期准确预测乳腺癌NAC后pCR,可为乳腺癌患者临床治疗方案的制定提供依据。

DeceFL:a principled fully decentralized federated learning framework

Traditional machine learning relies on a centralized data pipeline for model training in various applications;however,data are inherently fragmented.Such a decentralized nature of databases presents the serious challenge for collaboration:sending all decentralized datasets to a central server raises serious privacy concerns.Although there has been a joint effort in tackling such a critical issue by proposing privacy-preserving machine learning frameworks,such as federated learning,most state-of-the-art frameworks are built still in a centralized way,in which a central client is needed for collecting and distributing model information(instead of data itself)from every other client,leading to high communication burden and high vulnerability when there exists a failure at or an attack on the central client.Here we propose a principled decentralized federated learning algorithm(DeceFL),which does not require a central client and relies only on local information transmission between clients and their neighbors,representing a fully decentralized learning framework.It has been further proven that every client reaches the global minimum with zero performance gap and achieves the same convergence rate O(1=T)(where T is the number of iterations in gradient descent)as centralized federated learning when the loss function is smooth and strongly convex.Finally,the proposed algorithm has been applied to a number of applications to illustrate its effectiveness for both convex and nonconvex loss functions,time-invariant and time-varying topologies,as well as IID and Non-IID of datasets,demonstrating its applicability to a wide range of real-world medical and industrial applications.

（＊, ~）-Good Congruences on Regular Ortho-lc-monoids

The aim of this paper is to characterize the （＊, ~）-good congruences on regular ortho-lc-monoids by making use of the compatible congruence systems on the semi-spined product components of regular ortho-lc-monoids.

On f-Disjunctive Languages, f-Disjunctive Domains and Solid Codes(Dedicated to the late Professor Xu Yonghua (1932-2019))

Every language is either the disjoint union or the intersection of two disjunctive languages.The family of f-disjunctive languages is a natural generalization of the family of disjunctive languages.Disjunctive domains(f-disjunctive domains)are defined as the languages which can be checked whether a given language is disjunctive(f-disjunctive)or not.The f-disjunctive domains were first studied by Guo et al.around 1986-1989.We continue their study on f-disjunctive domains.Some new results for f-disjunctive domains,containing a relation between disjunctive domains and f-disjunctive domains,are introduced.In this respect,we also make an appropriate opening for the completely dense languages and solid codes.

Effect of Hepatitis C Treatment on Renal Function in Liver Transplant Patients

Background andAims:Hepatitis C Virus(HCV)is uniformly recurrent after liver transplant(LT)and recurrence is associated with an increased risk of mortality.Immunosuppressive medications increase the risk of chronic kidney disease,and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients.The aim of this study was to assess changes in glomerular filtration rates(GFRs)of LT recipients receiving HCV treatment.Methods:This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016(n=60).The outcomes of interest were differences in serum creatinine levels and in GFR,measured at treatment initiation and at 24 weeks after treatment.The average age of the patients was 59 years-old,and 17%were cirrhotic and 67%were treatment-experienced.All patients received sofosbuvir/ledipasvir without ribavirin.Results:All patients achieved sustained virologic response at 12 weeks after treatment(SVR12).At baseline,55%of patients had GFR<60 mL/min per 1.73 m2.Among those patients,GFR did not change in 18%,33%had improved GFR,and 48%had worsened GFR.Up to 45%of the patients had a GFR>60 mL/min per 1.73 m2.Among those patients,GFR did not change in 81%,and 19%had worsened GFR.In the entire cohort,65%of patients had improved or stable GFR and 35%had worsened GFR.The average change in serum creatinine between baseline and 24 weeks was 0.10(p=0.18).Conclusions:This study showed improved or unchanged GFR in 65%and worsened GFR in 35%of LT recipients who achieved SVR12.Worsening of GFR was more frequently encountered in those with impaired renal function at baseline.Caution should be used when treating HCV in LT recipients,especially those with baseline status of renal impairment.

A Hua-like Theorem in Semirings＊

In this paper, we establish a Hua-Like theorem in some kind of semirings. This can be regarded as a generalized version of Hua＇s theorem from rings to semirings.

Data-driven discovery of a clinical route for severity detection of COVID-19 paediatric cases

In this retrospective COVID-19 study on 105 infected children admitted to Wuhan Children's Hospital,we have revealed two biomarkers(DBIL and ALT)to promptly screen out the severe ones from all the cases with the assistance of a proposed supervised decision-tree classifier.This clinical route achieves a 100%F1-score in the present investigation,which can be expected to facilitate early diagnosis and intervention for pediatric COVID-19 case.