Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells

Background:Inhibitor of NF-κB kinase-interacting protein(IKIP)is known to promote proliferation of glioblastoma(GBM)cells,but how it affects migration and invasion by those cells is unclear.Methods:We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases.We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays,and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved.Results:Based on data from our clinical samples and from public databases,IKIP was overexpressed in GBM tumors,and its expression level correlated inversely with survival.IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays,whereas IKIP knockdown exerted the opposite effects.IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue.The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling.Conclusions:IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.

Filtration assisted pretreatment for rapid enrichment and accurate detection of Salmonella in vegetables

Rapid detection of target foodborne pathogens plays more and more significant roles in food safety,which requires the efficiency,sensitivity,and accuracy.In this research,we proposed a new st rategy of isothermal-molecular-amplification integrated with lateral-flow-strip for rapid detection of Salmonella without traditional enrichment-culture.Th e designed syringe-assisted-filtration can contribute to simultaneous collection and concentration of target bacterium from vegetable samples in just 3 min,resolving the drawbacks of traditional random sampling protocols.After simple and convenient ultrasonication,samples can be directly amplified at 39℃ in 25 min and the amplicons are qualitatively and quantitatively analyzed with the designed lateral-flow-strip in 5 min.Finally,satisfied results have been achieved within 40 min,which greatly improve the efficiency while the accuracy is also guaranteed.Furthermore,all detection steps can be completed under instrument-free conditions.This method will hold great promise for target pathogen detection in the resource-limited district,or for emergency on-site identification.

Advances in Diagnosis and Treatment of Lupus Nephritis(Class V)

Membranous lupus nephritis(MLN),class V,is a distinct LN characterized by immune complex deposition on subepithelial kidney biopsy.MLN is often associated with nephrotic syndrome.The histology of MLN is very similar to idiopathic(primary)membranous nephropathy(pMN).However,MLN usually has abundant mesa-glomerular deposits absent in primary membranous nephropathy.The clinical manifestations,management,and prognosis of MLN differ from other types of LN(type III,IV,or mixed type III/IV+V).Although immunosuppressive therapy is often necessary for MLN,the optimal treatment regimen is yet to be determined.This review summarizes the progress in the diagnosis and treatment of MLN and discusses the selection of immunosuppressants for MLN.

Isolation and Identification of Alkali-Resistant 1,3-Propanediol Producing Strain

1,3-Propanediol is a promising renewable resource produced by microbial production. It is mainly used in many synthetic reactions, particularly applied to the polymer synthesis and cosmetics industry. We described here the isolation of strain ZH-1, which has the ability of high production with 1,3-propanediol, from Fenhe River in China. It was classified as a member of K. pneumoniae after the study of phenotypic, physio-logical, biochemical and phylogenetic (16S rDNA). The initial glycerol concentration, fermentation time and pH value of strain ZH-1 were determined to be 50 g·L-1, 36 h and 8.0. Under these conditions, the practical yield of 1,3-PD was 18.53 g·L-1 and a molar yield (mol1,3-PD molGlycerol-1 of 1,3-propanediol to glycerol of 0.497. In addition, we found that for the strain ZH-1, the optimum grown pH was 9.0, so we can deter-mine that it is a new member of alkali-resistant strains.

Esophageal cancer:Epidemiology,risk factors and screening

More than 600,000 people are diagnosed with esophageal cancer(EC)every year globally,and the five-year survival rate of EC is less than 20%.Two common histological subtypes of EC,esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),have great geographical variations in incidence rates.About half of the world’s EC was diagnosed in China and a majority of which belong to ESCC.Globally,the overall incidence rate of EC is decreasing.In some high-risk Asian regions,such as China,the incidence rate of ESCC has generally declined,potentially due to economic growth and improvement of diet habits.In some European high-income countries and the United States,the decline is mainly attributed to the decrease in smoking and drinking.The risk factors of EC are not well understood,and the importance of environmental and genetic factors in the pathogenesis is also unclear.The incidence and mortality of advanced EC can be reduced through early diagnosis and screening.White light endoscopy is still the gold standard in the current screening technology.This article reviews the epidemiology,risk factors,and screening strategies of EC in recent years to help researchers determine the most effective management strategies to reduce the risk of EC.

Establishment of primary cultures of craniopharyngioma cells

Craniopharynigoma samples were collected from 36 patients. Out of the 36 samples, 29 achieved successful sub-culturing, with a success rate of 80.6%. Immunohistochemistry staining showed that cytokeratin-7 was positively expressed in the cytomembrane and cytoplasm of craniopharyngioma cells at 6-8 passages, confirming that all cultured cells were squamous epithelial cells. The doubling time of craniopharyngioma cells was 3 days, as confirmed by the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay. In this study, craniopharyngioma cells cultured in vitro were established; however, establishment of immortalized craniopharyngioma cell lines requires further research.

Rapid and easy determination of morphine in chafing dish condiments with colloidal gold labeling based lateral flow strips

In order to enhance the flavor of chafing dish and increase the attraction of consumers,the poppy shell is reported to be illegally added to the condiments of chafing dish.In this research,a rapid,simple,and convenient method based on the classic immunochromatographic lateral flow strip(LFS)with gold nanoparticles(GNPs)labeling was developed for easy monitoring of morphine(MOP),an effective component of poppy shell.Under optimized conditions,this developed LFS can well realize the detection of target MOP in the condiments of chafing dish in less than 10 min without any complicated pre-treatments.The limit of detection(LOD)can be achieved as low as 0.1 ppb for standard MOP or the MOP spiked condiments of chafing dish.All these results of the research strongly demonstrate that this established LFS method can be successfully applied in practical rapid and accurate on-site screening of poppy shell in condiments of chafing dish.

Thermal Error Modeling Method with the Jamming of Temperature-Sensitive Points'Volatility on CNC Machine Tools

Aiming at the deficiency of the robustness of thermal error compensation models of CNC machine tools, the mechanism of improving the models＇ robustness is studied by regarding the Leaderway-V450 machining center as the object. Through the analysis of actual spindle air cutting experimental data on Leaderway-V450 machine, it is found that the temperature-sensitive points used for modeling is volatility, and this volatility directly leads to large changes on the collinear degree among modeling independent variables. Thus, the forecasting accuracy of multivariate regression model is severely affected, and the forecasting robustness becomes poor too. To overcome this effect, a modeling method of establishing thermal error models by using single temperature variable under the jamming of temperature-sensitive points＇ volatility is put forward. According to the actual data of thermal error measured in different seasons, it is proved that the single temperature variable model can reduce the loss of fore- casting accuracy resulted from the volatility of tempera- ture-sensitive points, especially for the prediction of cross quarter data, the improvement of forecasting accuracy is about 5 μm or more. The purpose that improving the robustness of the thermal error models is realized, which can provide a reference for selecting the modelingindependent variable in the application of thermal error compensation of CNC machine tools.

Semi-active Control with Variable Damper for Pier-Beam Transversal Vibration

In this paper, the method of semi-active control with variable damper is presented to deal with the relatively poor transversal seismic condition of bridge. Based on the LQR control algorithm the control effectiveness for transverse vibration of pier-beam structure of bridge are discussed. Taking the structure as a multiple-degree of freedom system, the calculating model of structure-variable damper system is set up and the differential equation is derived, combined with practical example the control system is simulated and studied by various semi-active control algorithms and passive strategy with MATLAB. The results show that the semi-active control with variable damper can decrease the transverse vibration effectively and the control effect is obvious.

基于ZigBee的无线照明系统设计

为了改变传统室内照明系统布线复杂,不易控制、无法满足环境采集和线性调光要求的缺点,采用ZigBee技术来操控LED灯。本论文对ZigBee网络特点,ZigBee中各层的协议,数据传输方式及网络拓扑结构进行了分析,根据系统需求提出了总体设计方案和系统硬件结构框架,完成了电源控制电路、串口通信电路、LED照明控制电路、光敏电路等硬件设计。在研究传统智能照明控制系统的基础上,以ZigBee协议为平台通过光照强度和ZigBee协调器来控制LED,以光照感应技术和协调器为基础的整体系统方案,确定将ZigBee网络作为系统的通信基础。即采用两块ZigBee功能板,一块为终端导入光敏传感器,用作信号发射,另一个用作协调器建立网络,设定为手动模式下LED灯的开关。在自动模式下当光照强度不足时,LED灯将自动变亮。在手动模式下通过协调器改变LED的亮灭。

Transposition Flaps for Reconstruction of Perianal Skin Defects After Tumor Resection

Objective To investigate the application of transposition flaps in the reconstruction of perianal skin defects after tumor resection.Methods From September 2018 to December 2019,16 cases of perianal skin defects were repaired with unilateral or bilateral transposition flaps.The wound size before closure ranged from 4 cm×8 cm to 7 cm×10 cm.Fourteen patients achieved primary healing.Wound dehiscence occurred in one patient at the flap tip,whereas a slight infection occurred in another patient,which healed after a dressing change.During the follow-up period of 3–6 months,all patients were satisfied with the perianal area both aesthetically and functionally.Conclusion Transposition flaps are a promising option for the repair of perianal skin defects after tumor removal.Owing to the simplicity of the flap design,the wide popularity of this flap type among surgeons is anticipated.

Current advance of nanotechnology in diagnosis and treatment for malignant tumors

Cancer remains a significant risk to human health.Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation.Nanomedicine shows great potential for cancer diagnosis and treatment.Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations.Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors.The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers.Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes,thus enhancing treatment outcomes while minimizing harm to healthy tissues.Simultaneously,nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors.This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors.According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites,we review the most recent developments in nanotechnology applications.Finally,we briefly discuss the prospects and challenges of nanotechnology in cancer.

Simultaneous determination of 6 carbamate pesticides and relevant metabolites in oilseeds and oil with the modified fast QuEChERS method by ultra-performance liquid chromatography-tandem mass spectrometry

A sensitive and reliable method was developed and validated for the simu1taneous determination of 6 carbamate pesticides and relevant metabolites based on the modified fast QuEChERS(quick,easy,cheap,effective,rugged and safe)method combined with ultra-performance 1iquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The method was also applied in the analysis of 23 commonly consumed oilseeds and oil samples.The sample was extracted with acetonitrile for three times and then the extracted solution was filtered directly though 250 mg precipitated silica adsorbent(PSA)and 250 mg Cis The mobile phase was water(containing 0.1%formic acid)and acetonitrile.The extemal standard protocols were adopted to validate the method in terms of recovery,1inearity,precision,sensitivity,and relative standard deviation(RSD)under the optimized conditions.The linear calibration curves with different ranges were established with R^(2)>0.9973,limit of detections(LODs)ranged from 0.100μg/kg to 20000μg/kg and limit of quantitations(LOQs)ranged from 0.300μg/kg to 6.000μg/kg.The LODs meets the detection requirement for the maximum residue limits in practical samples.Meanwhile,the recoveries ranged from 60.2%to 116.6%with associated RSDs ranged from 0.33%to 5.35%in 10 oilseeds matrices and ranged from 61.9%to 116.9%with RSDs ranged from 0.30%to 5.02%in 13 oil matrices.These features do make the UPLC-MSMS an ideal analytical platform for accurate and high throughput analysis of carbamates residues in the complex matrix.

Study on the COVID-19 epidemic in China's Mainland between November 2022 and January 2023,with prediction of its tendency

The prediction system EpiSIX was used to study the COVID-19 epidemic in China's Mainland between November 2022 and January 2023,based on reported data from December 9,2022,to January 30,2023,released by The Chinese Center for Disease Control and Prevention on February 1,2023.Three kinds of reported data were used for model fitting:the daily numbers of positive nucleic acid tests and deaths,and the daily number of hospital beds taken by COVID-19 patients.It was estimated that the overall infection rate was 87.54%and the overall case fatality rate was 0.078%–0.116%(median 0.100%).Assuming that a new COVID-19 epidemic outbreak would start in March or April of 2023,induced by a slightly more infectious mutant strain,we predicted a possible large rebound between September and October 2023,with a peak demand of between 800,000 and 900,000 inpatient beds.If no such new outbreak was induced by other variants,then the current COVID-19 epidemic course in China's Mainland would remain under control until the end of 2023.However,it is suggested that the necessary medical resources be prepared to manage possible COVID-19 epidemic emergencies in the near future,especially for the period between September and October 2023.

COVID-19 transmission driven by age-group mathematical model in Shijiazhuang City of China

Background:A COVID-19 outbreak in the rural areas of Shijiazhuang City was attributed to the complex interactions among vaccination,host,and non-pharmaceutical interventions(NPIs).Herein,we investigated the epidemiological characteristics of all reported symptomatic cases by picking Shijiazhuang City,Hebei Province in Northern China as research objective.In addition,we established an age-group mathematical model to perform the optimal fitting and to investigate the dynamical profiles under three scenarios.Methods:All reported symptomatic cases of Shijiazhuang epidemic(January 2-February 3,2021)were investigated in our study.The cases were classified by gender,age group and location,the distributions were analyzed by epidemiological characteristics.Furthermore,the reported data from Health Commission of Hebei Province was also analyzed by using an age-group mathematical model by two phases and three scenarios.Results:Shijiazhuang epidemic caused by SARS-CoV-2 wild strain was recorded with the peak 84 cases out of 868 reported symptomatic cases on January 11,2021,which was implemented with strong NPIs by local government and referred as baseline situation in this study.The research results showed that R0 under baseline situation ranged from 4.47 to 7.72,and Rt of Gaocheng Distinct took 3.72 with 95%confidence interval from 3.23 to 4.35 on January 9,the declining tendencies of Rt under baseline situation were kept till February 3,the value of Rt reached below 1 on January 19 and remained low value up to February 3 for Gaocheng District and Shijiazhuang City during Shijiazhuang epidemic.This indicated Shijiazhuang epidemic was under control on January 19.However,if the strong NPIs were kept,but remote isolation operated on January 11 was not implemented as of February 9,then the scale of Shijiazhuang epidemic reached 9,482 cases from age group who were 60 years old and over out of 31,017 symptomatic cases.The investigation also revealed that Shijiazhuang epidemic reached 132,648 symptomatic cases for age group who were 60 years old and over(short for G2)under risk-based strategies(Scenario A),58,048 symptomatic cases for G2 under late quarantine strategies(Scenario B)and 207,124 symptomatic cases for G2 under late quarantine double risk strategies(Scenario C),and that the corresponding transmission tendencies of Rt for three scenarios were consistently controlled on Jan 29,2021.Compared with baseline situation,the dates for controlling Rt below 1 under three scenarios were delayed 10 days.Conclusions:Shijiazhuang epidemic was the first COVID-19 outbreak in the rural areas in Hebei Province of Northern China.The targeted interventions adopted in early 2021 were effective to halt the transmission due to the implementation of a strict and village-wide closure.However we found that age group profile and NPIs played critical rules to successfully contain Shijiazhuang epidemic,which should be considered by public health policies in rural areas of China's Mainland during the dynamic zero-COVID policy.

Evolutionary analysis of Omicron variant BF.7 and BA.5.2 pandemic in China

On December 7,2022,China adjusted public health control measures,there have been widespread of SARS-CoV-2 infections in Chinese mainland.As the number of infected people increased,the mutation probability of SARS-CoV-2 is also raised.Therefore,it is of great importance to monitor SARS-CoV-2 variants and its mutations in China.In this current study,665 SARS-CoV-2 genomes from China deposited in the public database were used to analyze the proportion of different variants;to determine the composition of variants in China across different provinces;and analyze specific mutation frequency,focusing on 12 immune escape residues.The results showed that no new mutations were generated on the 12 immune escape residues.The evolutionary analysis of the BF.7 variant circulating in China showed that there is an independent evolutionary branch with unique mutation sites,officially named BF.7.14 by PANGO.This variant may have been imported from Russia to Inner Mongolia at the end of September 2022 and continued its spread in China.The evolutionary analysis of BA.5.2 variant shows that the variant is composed of two sub-variants,named BA.5.2.48 and BA.5.2.49 by PANGO,respectively.This variant may have been imported from abroad to Beijing at the beginning of September 2022 and formed two sub-variants after domestic transmission.Finally,this study showed that current epidemic variants in China were already circulating in other countries,and there were no additional mutations on immune escape residues that could pose a threat to other countries.

One-step co-doping of ZnO and Zn^(2+)in osteoinductive calcium phosphate ceramics with synergistic antibacterial activity for regenerative repair of infected bone defect

How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelitis.The present study introduced a novel one-step route to realizing the co-doping of zinc oxide(ZnO)and zinc ion(Zn^(2+))in biphasic calcium phosphate(BCP)ceramics to utilize their synergistic antibacterial.Compared with the conventional BCP ceramics(BCP-Ca),the ZnO/Zn^(2+)co-doping ones(BCP-Zn)possessed strong antibacterial ability on E.coli and S.aureus as well as stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)effectively.The synergistic antibacterial mechanism of ZnO and Zn^(2+)was also investigated.BCP-Zn showed excellent osteoinductivity and angiogenesis at three months postoperatively in the canine intramuscular implantation model.Moreover,BCP-Zn exhibited excellent anti-infective ability and bone regenerative repair compared to BCP-Ca and control groups in the infected bone defect model of rat femur.Collectively,these findings suggest that the simultaneous introduction of ZnO/Zn^(2+)could have immense potential to expand the application of osteoinductive BCP ceramics in the regenerative repair of infected bone defects.

Landscape of emerging and re-emerging infectious diseases in China： impact of ecology, climate, and behavior

For the past several decades, the infectious disease profile in China has been shifting with rapid developments in social and economic aspects, environment, quality of food, water, housing, and public health infrastructure. Notably, 5 notifiable infectious diseases have been almost eradicated, and the incidence of 18 additional notifiable infectious diseases has been significantly reduced. Unexpectedly, the incidence of over 10 notifiable infectious diseases, including HIV, brucellosis, syphilis, and dengue fever, has been increasing. Nevertheless, frequent infectious disease outbreaks/events have been reported almost every year, and imported infectious diseases have increased since 2015. New pathogens and over 100 new genotypes or serotypes of known pathogens have been identified. Some infectious diseases seem to be exacerbated by various factors, including rapid urbanization, large numbers of migrant workers, changes in climate, ecology, and policies, such as returning farmland to forests. This review summarizes the current experiences and lessons from China in managing emerging and re-emerging infectious diseases, especially the effects of ecology, climate, and behavior, which should have merits in helping other countries to control and prevent infectious diseases.

Transforming bacterial disease surveillance and investigation using whole-genome sequence to probe the trace

Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the strains in the same species has been revealed. In recent years, genome sequencing techniques and bioinformatics have developed rapidly, which has resulted in transformation and expedited the application of strategy and methodology for bacterial genome comparison used in dissection of infectious disease epidemics. Bacterial whole-genome sequencing and bioinformatic computing allow genotyping to satisfy the requirements of epidemiological study in disease control. In this review, we outline the significance and summarize the roles of bacterial genome sequencing in the context of bacterial disease control and prevention. We discuss the applications of bacterial genome sequencing in outbreak detection, source tracing, transmission mode discovery, and new epidemic clone identification. Wide applications of genome sequencing and data sharing in infectious disease surveillance networks will considerably promote outbreak detection and early warning to prevent the dissemination of bacterial diseases.