Predicting Lung Cancers Using Epidemiological Data:A Generative-Discriminative Framework

Predictive models for assessing the risk of developing lung cancers can help identify high-risk individuals with the aim of recommending further screening and early intervention.To facilitate pre-hospital self-assessments,some studies have exploited predictive models trained on non-clinical data(e.g.,smoking status and family history).The performance of these models is limited due to not considering clinical data(e.g.,blood test and medical imaging results).Deep learning has shown the potential in processing complex data that combine both clinical and non-clinical information.However,predicting lung cancers remains difficult due to the severe lack of positive samples among follow-ups.To tackle this problem,this paper presents a generative-discriminative framework for improving the ability of deep learning models to generalize.According to the proposed framework,two nonlinear generative models,one based on the generative adversarial network and another on the variational autoencoder,are used to synthesize auxiliary positive samples for the training set.Then,several discriminative models,including a deep neural network(DNN),are used to assess the lung cancer risk based on a comprehensive list of risk factors.The framework was evaluated on over 55000 subjects questioned between January 2014 and December 2017,with 699 subjects being clinically diagnosed with lung cancer between January 2014 and August 2019.According to the results,the best performing predictive model built using the proposed framework was based on DNN.It achieved an average sensitivity of 76.54%and an area under the curve of 69.24%in distinguishing between the cases of lung cancer and normal cases on test sets.

Advances in the development of amorphous solid dispersions:The role of polymeric carriers

Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To prepare the solid dispersions,there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations.Polymer selection is of great importance because it influences the stability,solubility and dissolution rates,manufacturing process,and bioavailability of the ASD.This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers,formulation designs and preparation methods.Furthermore,considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.

Analysis of the Status Quo and Influencing Factors of Readiness for Hospital Discharge of Patients Undergoing Hysteromyomectomy

Objective: To evaluate the status quo and influencing factors of readiness for hospital discharge of patients undergoing hysteromyomectomy. Methods: A total of 240 patients with uterine fibroid undergoing hysteromyomectomy from 2 hospitals in Jingzhou were investigated using a self-designed general information questionnaire, the Readiness for Hospital Discharge Scale and the Quality of Discharge Teaching Scale. Results: The total score of readiness for hospital discharge was (91.36 ± 18.46), the multiple linear regression analysis showed that the quality of discharge guidance, the scope of myomectomy, pain degree of incision and the average monthly income per family were the main influencing factors of readiness for hospital discharge. Conclusion: The readiness for hospital discharge was at a medium level in patients with uterine fibroid undergoing hysteromyomectomy, medical personnel should give specific discharge guidance according to the specific conditions of patients to ensure the safety of patients after discharge.

重庆市12～15岁中学生口腔健康知识、态度、行为的问卷调查分析

目的对重庆市12~15岁中学生口腔健康知识、态度、行为等情况进行抽样调查并分析,为有针对性地对中学生开展口腔健康指导计划提供依据。方法采用多阶段分层抽样的方法抽取重庆市4个区县(主城区和郊区各2个)12~15岁4个年龄组中学生,通过问卷方式调查其口腔健康知识、态度及行为等方面的情况。全部数据使用Epidata双录入,使用SPSS 21.0软件进行统计学分析。结果共计回收有效问卷3902份,有良好刷牙习惯的比例为39.7%(1548人),平均口腔健康知识正确率为58.9%,平均口腔健康正性态度为88.6%,有就医经历的中学生为54.5%(2127人),在学校接受过口腔健康教育的为17.5%(681人)。刷牙习惯存在性别和地区性的差异。结论重庆市12~15岁中学生口腔健康知识知晓情况和口腔卫生行为有待提高,应加强针对中学生的口腔健康教育和口腔健康行为指导,并加强远郊和农村地区的口腔健康教育工作。

重庆市主城区学龄前儿童患龋情况及口腔卫生服务需要、利用情况和影响因素的研究

目的对重庆市主城区学龄前儿童口腔健康状况及其口腔卫生服务的需要和口腔卫生服务实际利用情况进行调查,分析其可能的影响因素,为重庆地区有针对性开展学龄前儿童口腔预防保健工作提供参考。方法参考第四次全国口腔健康流行病学调查实施方案,采用整群随机抽样的方法抽取主城9区中的3区12个街道24所幼儿园共1 300名3～4岁儿童进行口腔检查,并根据安德森卫生服务利用行为模型设计调查问卷并发放给家长填写。对口腔卫生服务利用情况采用卡方检验和logistic逐步回归分析。结果重庆市主城区学龄前儿童患龋率为55.4%,龋失补牙面数为6 696,龋面均为5.2,龋齿充填构成比为2.3%。有效问卷共1 173份,结果显示过去1年治疗性口腔就诊率为6.31%(74/1 173),预防性口腔就诊率为22.93%(269/1 173)。照顾者的受教育程度、受口腔问题困扰、每天何时刷牙和过去1年牙疼史为口腔就诊率的影响因素。结论重庆市学龄前儿童的口腔卫生服务需要仍普遍,口腔卫生服务利用不足,口腔医疗保健任务仍然十分艰巨,应进一步制定有针对性的口腔预防政策。

干细胞局部应用对缺损面神经再生效果的系统评价

目的系统评价干细胞对面神经缺损的修复效果。方法在Pubmed、Cochrane Library、Web of Science、Embase、Scopus及中国生物医学文献数据库检索关于评价干细胞对动物面神经再生效果的所有原始研究,2名专业人员独立完成文献筛选、数据提取及偏倚风险评估。使用RevMan 5.3软件及随机效应模型进行统计分析,分析结果以均数差(MD)及95%可信区间(CI)的形式呈现。对面神经的功能性评估(胡须运动评分、面瘫评分)及组织学评估(有髓纤维密度、纤维直径、髓鞘厚度、G比值)结果进行Meta分析。结果从6个数据库共检索出4614篇文献,15篇被纳入了Meta分析。干细胞组的胡须运动评分、面瘫评分、有髓纤维密度、髓鞘厚度均高于非干细胞组(P<0.05),G比值小于非干细胞组(P=0.001),纤维直径二者无统计学差异(P=0.08)。结论干细胞具有促进面神经再生的潜能。

Cytomegalovirus glycoprotein B sequence variation in Chinese liver transplant recipients

Objective: To investigate human cytomegalovirus infec-tion and genetic variations in glycoprotein B(gB) inliver transplant recipients in south-east China.Methods:EDTA-blood samples were obtained from 21liver transplant recipients. The semi-nested PCR wasused to amplify a region of high sequence variabilityin the gB gene of human cytomegalovirus (HCMV)followed by direct sequence analysis.Results: Out of the 21 liver transplant recipients, 5were proved HCMV positive 62 to 180 days aftertransplantation. The nucleotide and encoded aminoacid sequences were compared with published se-quences of AD169 and Towne laboratory strains.Within the region sequenced, 2 out of 5 strains pos-sessed a peptide configuration similar to that of strainAD169, while another 2 strains displayed a peptideconfiguration similar to that of strain Towne. Onestrain had amino acid substitution, which was differ-ent from those of both AD169 and Towne in thecleavage site.Conclusion: Our results provide molecular epidemio-logical data for HCMV strains circulating among trans-plant recipients in south-east China.

Impact of physical activity on the prevalence of hypertension among the older adults in Beijing communities

This study aims to evaluate the impact of physical activity (PA) on the prevalence of hypertension among older adults in Beijing community. As economy growing rapidly in China, the occurrence of hypertension increases among older people in China as well. Epidemiological studies have shown that physical activity may significantly related to lower risk of hypertension. Taking PA maybe an instructive factor to reduce the risk of being hypertensive. We randomly selected Beijing community residents aged 65 and above (n = 400), collected data comprising level of PA (low, moderate, high), blood pressure, and a host of potentially confounding variables indicated by the literature. Five logistic regression models adjusted for different modifiers were used to estimate the association between hypertension and PA. The prevalence of hypertension was 96.88%, 78.57% and 73.66% among subjects with low, moderate and high level of PA respectively. Lower diastolic BP was observed for elder people with higher level of PA (p<0.01). We observed a strong and statistically significant association between moderate (OR=0.09, 95% CI: 0.01 to 0.74) or high (OR=0.08, 95% CI: 0.01 to 0.57) level of PA and lower risk of hypertension (p < 0.05). PA is a protective factor for hypertension among older Beijing people, which suggests elderly people be encouraged to actively engage in PA, if body conditions permit.

Role of the cathode chamber in microbial electrosynthesis:A comprehensive review of key factors

The consumption of non-renewable fossil fuels has directly contributed to a dramatic rise in global carbon dioxide(CO_(2))emissions,posing an ongoing threat to the ecological security of the Earth.Microbial electrosynthesis(MES)is an innovative energy regeneration strategy that offers a gentle and efficient approach to converting CO_(2) into high-value products.The cathode chamber is a vital component of an MES system and its internal factors play crucial roles in improving the performance of the MES system.Therefore,this review aimed to provide a detailed analysis of the key factors related to the cathode chamber in the MES system.The topics covered include inward extracellular electron transfer pathways,cathode materials,applied cathode potentials,catholyte pH,and reactor configuration.In addition,this review analyzes and discusses the challenges and promising avenues for improving the conversion of CO_(2) into high-value products via MES.

Electricity generation by Pseudomonas putida B6-2 in microbial fuel cells using carboxylates and carbohydrate as substrates

Microbial fuel cells(MFCs)employing Pseudomonas putida B6-2(ATCC BAA-2545)as an exoelectrogen have been developed to harness energy from various conventional substrates,such as acetate,lactate,glucose,and fructose.Owing to its metabolic versatility,P.putida B6-2 demonstrates adaptable growth rates on diverse,cost-effective carbon sources within MFCs,exhibiting distinct energy production characteristics.Notably,the anode chamber’s pH rises with carboxylates’(acetate and lactate)consumption and decreases with carbohydrates’(glucose and fructose)utilization.The MFC utilizing fructose as a substrate achieved the highest power density at 411 mW m^(−2).Initial analysis revealed that P.putida B6-2 forms biofilms covered with nanowires,contributing to bioelectricity generation.These microbial nanowires are likely key players in direct extracellular electron transport through physical contact.This study established a robust foundation for producing valuable compounds and bioenergy from common substrates in bioelectrochemical systems(BESs)utilizing P.putida as an exoelectrogen.

Potentiating CD8^(+) T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity.However,cholesterol metabolism as a key component of this regulation remains largely unexplored.Herein,we found that the low-density lipoprotein receptor(LDLR),which has been previously identified as a transporter for cholesterol,plays a pivotal role in regulating CD8+T cell antitumor activity.Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion,we also found a non-canonical function of LDLR in CD8+T cells:LDLR interacts with the T-cell receptor(TCR)complex and regulates TCR recycling and signaling,thus facilitating the effector function of cytotoxic T-lymphocytes(CTLs).Furthermore,we found that the tumor microenvironment(TME)downregulates CD8+T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9(PCSK9)which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs.Moreover,genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+T cells by alleviating the suppressive effect on CD8+T cells and consequently inhibit tumor progression.While previously established as a hypercholesterolemia target,this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well.

Correction to:Potentiating CD8^(+)T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling

Figure 1.LDLR deficiency hinders the antitumor activity of CD8^(+)T cells.(A)Transcriptional level of genes involved in cholesterol transport in naïve CD8^(+)T cells,CTLs and CD8^(+)TILs(isolated at Day3 or Day7 post CTLs adoptive transfer),(n=4).(B)LDLR expression level on CTLs and CD8^(+)TILs(isolated at Day3 post CTLs adoptive transfer),(n=4).

Fenton-reaction-triggered metabolism of acetaminophen for enhanced cancer therapy

Acetaminophen(APAP), a classic nonsteroidal anti-inflammatory drug(NSAID), has attracted much attention due to the overdose-induced hepatotoxicity in the past several decades. N-Acetyl-p-benzoquinone imine(NAPQI), the P450-dependent metabolism of APAP, leads to GSH depletion, protein binding, mitochondrial oxidative stress, and eventually the liver injury. Herein, we develop a Fe-based metal-organic framework(MOF) to deliver and transform acetaminophen into toxic “chemo” drug through the cascade reaction for enhanced cancer therapy. In the acidic tumor microenvironment, the Fe-based MOF collapses and releases abundant Fe ions to generate hydroxyl radicals(·OH) via Fenton reaction, subsequently catalyzing nontoxic APAP into toxic NAPQI. Meanwhile, NAPQI depletes intracellular glutathione(GSH) rapidly, leading to alleviating the antioxidant ability of cancer cells and amplifying Fenton activity. The intracellular oxidative stress and the toxic metabolite of APAP can provide a synergistic effect on antitumor activity.

Multi-Label Feature Selection Based on Improved Ant Colony Optimization Algorithm with Dynamic Redundancy and Label Dependence

The world produces vast quantities of high-dimensional multi-semantic data.However,extracting valuable information from such a large amount of high-dimensional and multi-label data is undoubtedly arduous and challenging.Feature selection aims to mitigate the adverse impacts of high dimensionality in multi-label data by eliminating redundant and irrelevant features.The ant colony optimization algorithm has demonstrated encouraging outcomes in multi-label feature selection,because of its simplicity,efficiency,and similarity to reinforcement learning.Nevertheless,existing methods do not consider crucial correlation information,such as dynamic redundancy and label correlation.To tackle these concerns,the paper proposes a multi-label feature selection technique based on ant colony optimization algorithm(MFACO),focusing on dynamic redundancy and label correlation.Initially,the dynamic redundancy is assessed between the selected feature subset and potential features.Meanwhile,the ant colony optimization algorithm extracts label correlation from the label set,which is then combined into the heuristic factor as label weights.Experimental results demonstrate that our proposed strategies can effectively enhance the optimal search ability of ant colony,outperforming the other algorithms involved in the paper.

用于甲醛催化氧化的锰基催化剂及协同效应的影响

甲醛作为主要的室内空气污染气体,正在严重威胁着人类的健康。甲醛的治理引起了人们的广泛关注,其中催化氧化技术是目前最有效和环境友好的手段之一。因氧化锰结构多变和氧化能力强的特点,围绕锰基催化剂在甲醛深度氧化中应用的研究日渐成为热点。本文主要从单一组分MnOx催化剂、锰基复合氧化物催化剂、多孔材料负载MnOx催化剂以及MnOx负载贵金属催化剂四方面归纳总结了近年来锰基催化剂在甲醛氧化方面的研究进展,阐述了以Mars-van Krevelen机理为基础的甲醛催化氧化机制。在具体反应过程中,不同的表面氧物种和活性位点产生特定的中间相。重点分析了催化剂组分之间存在的协同作用对催化剂的影响,组分间的相互活化以及不同组分在多步反应中分别或依次发挥催化作用是实现锰基催化剂协同的主要方式。最后,展望了锰基催化剂在甲醛氧化反应中的未来发展方向和趋势。

Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications

Pharmaceutical cocrystals are multicomponent systems in which at least one component is an active pharmaceutical ingredient and the others are pharmaceutically acceptable ingredients.Cocrystallization of a drug substance with a coformer is a promising and emerging approach to improve the performance of pharmaceuticals,such as solubility,dissolution profile,pharmacokinetics and stability.This review article presents a comprehensive overview of pharmaceutical cocrystals,including preparation methods,physicochemical properties,and applications.Furthermore,some examples of drug cocrystals are highlighted to illustrate the effect of crystal structures on the various aspects of active pharmaceutical ingredients,such as physical stability,chemical stability,mechanical properties,optical properties,bioavailability,sustained release and therapeutic effect.This review will provide guidance for more efficient design and manufacture of pharmaceutical cocrystals with desired physicochemical properties and applications.

Advances in coamorphous drug delivery systems

In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient(API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics,physical stability, in vitro and in vivo performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.

Influence of induced ciprofloxacin resistance on efflux pump activity of Klebsiella pneumoniae

Objective:The efflux pump(EP) is one of the major mechanisms of antibiotic resistance in Klebsiella pneumoniae.However,there are few reports on the effect of the abuse of antibiotic use on the activity of EPs.To determine whether the use of low efficacy antibiotics has any effect on the activity of EPs and induces drug resistance in K.pneumoniae,we investigated the effect of ciprofloxacin on the activity of EPs in K.pneumoniae strains.Methods:Sixteen susceptible K.pneumoniae strains were isolated from patients and their minimum inhibitory concentrations(MICs) of ciprofloxacin were measured in the absence and presence of the pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone(CCCP).The strains were then induced with a gradient of ciprofloxacin until the MICs of the strains showed no further increase,to obtain induced resistant strains.The EP activities of the strains before and after induction were compared using EP inhibition and ethidium bromide(EtBr) accumulation assays.Results:The MIC values of the strains were 16 256 times higher after induction than before induction.In the presence of CCCP,the MIC values of 50% of the induced strains were 2 4-fold lower than that in the absence of this inhibitor.The EtBr accumulation assay showed that the fluorescence of EtBr in the induced cells was lower than that in the cells before induction.Conclusions:EPs are widespread in susceptible and drug-resistant K.pneumoniae strains.Induction with ciprofloxacin may increase the activity of EPs in K.pneumoniae.The EtBr accumulation assay is more sensitive than the EP inhibition assay in evaluating the activity of EPs in K.pneumoniae.

Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model

Chloroquine(CQ)phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019(COVID-19).To develop a physiologically-based pharmacokinetic(PBPK)model for predicting tissue distribution of CQ and apply it to optimize dosage regimens,a PBPK model,with parameterization of drug distribution extrapolated from animal data,was developed to predict human tissue distribution of CQ.The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism.Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships.The model was also validated by clinical data from Chinese patients with COVID-19.The novel PBPK model allows indepth description of the pharmacokinetics of CQ in several key organs(lung,heart,liver,and kidney),and was applied to design dosing strategies in patients with acute COVID-19(Day 1:750 mg BID,Days 2-5:500 mg BID,CQ phosphate),patients with moderate COVID-19(Day 1:750 mg and 500 mg,Days 2-3:500 mg BID,Days 4-5:250 mg BID,CQ phosphate),and other vulnerable populations(e.g.,renal and hepatic impairment and elderly patients,Days 1-5:250 mg BID,CQ phosphate).A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

ILC3-derived OX40L is essential for homeostasis of intestinal Tregs in immunodeficient mice

OX40L is one of the co-stimulatory molecules that can be expressed by splenic lymphoid tissue inducer(Lti)cells,a subset of group 3 innate lymphoid cells(ILC3s).OX40L expression in subsets of intestinal ILC3s and the molecular regulation of OX40L expression in ILC3s are unknown.Here,we showed intestinal ILC3s marked as an OX40L high population among all the intestinal leukocytes and were the dominant source of OX40L in Rag1–/–mice.All ILC3 subsets expressed OX40L,and NCR–ILC3s were the most abundant source of OX40L.The expression of OX40L in ILC3s could be upregulated during inflammation.In addition to tumor necrosis factor(TNF)-like cytokine 1A(TL1A),which has been known as a trigger for OX40L,we found that Poly(I:C)representing viral stimulus promoted OX40L expression in ILC3s via a cell-autonomous manner.Furthermore,we demonstrated that IL-7-STAT5 signaling sustained OX40L expression by ILC3s.Intestinal regulatory T cells(Tregs),most of which expressed OX40,had defective expansion in chimeric mice,in which ILC3s were specifically deficient for OX40L expression.Consistently,co-localization of Tregs and ILC3s was found in the cryptopatches of the intestine,which suggests the close interaction between ILC3s and Tregs.Our study has unveiled the crosstalk between Tregs and ILC3s in mucosal tissues through OX40–OX40L signaling,which is crucial for the homeostasis of intestinal Tregs.