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Since the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in 2019, the public health system has faced enormous challenges. Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality. With the increasing of asymptomatic infections, it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing. However, due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes, neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2. We recruited 4 human leukocyte antigen A2 (HLA-A2) infections, 15 individuals who received three doses of inactivated vaccines, and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8+ T cells in the peripheral blood of close contacts, including accurate HLA typing based on ribonucleic acid (RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8+ T cells. From individuals who received three doses of inactivated vaccine, we observed that the CD8+ T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes, and the fold change of CD8+ T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1. The enzyme-linked immunospot (ELISpot) results further validate this result. This study forms a “method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8+ T cells in the peripheral blood of subjects”, covering up to 46 % of the population, including HLA-A2+ and HLA-A24+ donors, providing a novel method for SARS-CoV-2 infected case tracing.

ABSTRACTFor kinematic relative positioning users between two moving platforms, limited communication bandwidth and computation ability usually cannot support real-time transmission of high-rate (≥10 Hz) BeiDou Navigation Satellite System (BDS) data. The performance of Ambiguity Resolution (AR) is also a major challenge in signal blocked and loss of lock environments. Based on BDS and Inertial Navigation System (INS) data, we develop a novel mode of INS-aided BDS kinematic relative positioning between two moving platforms, aiming to realize real-time, high-rate and precise positioning with low-cost communication modules in challenge environments. To achieve this goal, the INS-aided high-rate relative kinematic positioning and INS-aided BDS AR re-initialization methods are proposed. In this mode, the baseline bias caused by the different position datum is first defined and resolved. Then, high-rate INS data are assisted to obtain kinematic relative position when real-time kinematic positioning results are unavailable within 1 second. Once the BDS data are available, the predicted relative position is used as additional constraint to facilitate AR re-initialization and improve the kinematic positioning performance. The performance of these methods is discussed in a set of experiments with 1 Hz BDS data and 100 Hz INS data, and compared with the conventional method by sending raw BDS/INS measurements. The results show that the proposed methods can achieve an accuracy of about 5 cm for the INS-aided 100 Hz relative positioning in baseline components and lengths, which is equal to the conventional method, but the transmitted data have been sharply reduced by an average of nearly 80%. With the assistance of INS-predicted baseline constraint, the relative positioning performance has been further improved. The accuracy of baseline length errors is less than 4 cm, and the AR fixing rates keep larger than 95% during the experiment, while the wrongly fixed rates are reduced to less than 0.5%.

BackgroundFor medical diagnosis, clinicians typically begin with a patient’s chief concerns, followed by questions about symptoms and medical history, physical examinations, and requests for necessary auxiliary examinations to gather comprehensive medical information. This complex medical investigation process has yet to be modeled by existing artificial intelligence (AI) methodologies. ObjectiveThe aim of this study was to develop an AI-driven medical inquiry assistant for clinical diagnosis that provides inquiry recommendations by simulating clinicians’ medical investigating logic via reinforcement learning. MethodsWe compiled multicenter, deidentified outpatient electronic health records from 76 hospitals in Shenzhen, China, spanning the period from July to November 2021. These records consisted of both unstructured textual information and structured laboratory test results. We first performed feature extraction and standardization using natural language processing techniques and then used a reinforcement learning actor-critic framework to explore the rational and effective inquiry logic. To align the inquiry process with actual clinical practice, we segmented the inquiry into 4 stages: inquiring about symptoms and medical history, conducting physical examinations, requesting auxiliary examinations, and terminating the inquiry with a diagnosis. External validation was conducted to validate the inquiry logic of the AI model. ResultsThis study focused on 2 retrospective inquiry-and-diagnosis tasks in the emergency and pediatrics departments. The emergency departments provided records of 339,020 consultations including mainly children (median age 5.2, IQR 2.6-26.1 years) with various types of upper respiratory tract infections (250,638/339,020, 73.93%). The pediatrics department provided records of 561,659 consultations, mainly of children (median age 3.8, IQR 2.0-5.7 years) with various types of upper respiratory tract infections (498,408/561,659, 88.73%). When conducting its own inquiries in both scenarios, the AI model demonstrated high diagnostic performance, with areas under the receiver operating characteristic curve of 0.955 (95% CI 0.953-0.956) and 0.943 (95% CI 0.941-0.944), respectively. When the AI model was used in a simulated collaboration with physicians, it notably reduced the average number of physicians’ inquiries to 46% (6.037/13.26; 95% CI 6.009-6.064) and 43% (6.245/14.364; 95% CI 6.225-6.269) while achieving areas under the receiver operating characteristic curve of 0.972 (95% CI 0.970-0.973) and 0.968 (95% CI 0.967-0.969) in the scenarios. External validation revealed a normalized Kendall τ distance of 0.323 (95% CI 0.301-0.346), indicating the inquiry consistency of the AI model with physicians. ConclusionsThis retrospective analysis of predominantly respiratory pediatric presentations in emergency and pediatrics departments demonstrated that an AI-driven diagnostic assistant had high diagnostic performance both in stand-alone use and in simulated collaboration with clinicians. Its investigation process was found to be consistent with the clinicians’ medical investigation logic. These findings highlight the diagnostic assistant’s promise in assisting the decision-making processes of health care professionals.

c-FLIP functions as a dual regulator of apoptosis and inflammation, yet its implications in Zika virus (ZIKV) infection remain partially understood, especially in the context of ZIKV-induced congenital Zika syndrome (CZS) where both apoptosis and inflammation play pivotal roles. Our findings demonstrate that c-FLIP promotes ZIKV infection in placental cells and myeloid-derived macrophages, involving inflammation and caspase-8/3-mediated apoptosis. Moreover, our observations reveal that c-FLIP augments ZIKV infection in multiple tissues, including blood cell, spleen, uterus, testis, and the brain of mice. Notably, the partial deficiency of c-FLIP provides protection to embryos against ZIKV-induced CZS, accompanied by a reduction in caspase-3-mediated apoptosis. Additionally, we have found a distinctive parental effect of c-FLIP influencing ZIKV replication in fetal heads. In summary, our study reveals the critical role of c-FLIP as a positive regulator in caspase-8/3-mediated apoptosis during ZIKV infection, significantly contributing to the development of CZS.

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

The most common method for interpreting strata with seismic data is to relate the peaks and troughs of adjacent traces based on the seismic waveform characteristics. This can be captured by machine learning and deep learning methods to stratigraphic segmentation as many people investigated in industry. However, the spatial variability and instability of the peaks and troughs of seismic signals increases the difficulty of applying this technology. In addition, the nonlinear relationship and complicated subsurface geological setting make it more difficult. Thus, we propose a new seismic attribute extraction method based on the Gabor wavelet transform and linear dimensionality reduction. This method does not use the peaks or troughs of the seismic signal and instead focuses on the energy change in the seismic signal at the strata interface. It uses the characteristics of the energy change to identify strata. A sliding window Fourier transforms (STFTs) pretreatment is applied to convert the seismic signal to a spectrum energy form. On this basis, the local texture information of the spectrum can be processed by the Gabor wavelet transform to obtain the Gabor attribute of the seismic signal. The seismic Gabor attributes extracted using the above method contain time, frequency, and energy features, solving the problem of single seismic amplitude data features. Finally, the validity of the extracted seismic attributes is verified by a field data. In this process, the seismic amplitude, spectrum data and Gabor attributes are used as sample data for the support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost) models and deep residual shrinkage network (DRSN) for comparison. The results show that when the seismic Gabor attributes are used, the accuracy and root mean square error (RMSE) of the stratigraphic identification with the SVM, RF and XGBoost models are significantly better than those of the seismic amplitude and spectrum data only.

Little studies evaluated the effectiveness of booster vaccination of inactivated COVID-19 vaccines against being infected (susceptibility), infecting others (infectiousness), and spreading the disease from one to another (transmission). Therefore, we conducted a retrospective cohort study to evaluate the effectiveness of booster vaccination of inactivated COVID-19 vaccines against susceptibility, infectiousness, and transmission in Shenzhen during an Omicron BA.2 outbreak period from 1 February to 21 April 2022. The eligible individuals were classified as four sub-cohorts according to the inactivated COVID-19 vaccination status of both the close contacts and their index cases: group 2-2, fully vaccinated close contacts seeded by fully vaccinated index cases (reference group); group 2-3, booster-vaccinated close contacts seeded by fully vaccinated index cases; group 3-2, fully vaccinated close contacts seeded by booster-vaccinated index cases; and group 3-3, booster-vaccinated close contacts seeded by booster-vaccinated index cases. Univariate and multivariate logistic regression analyses were applied to estimate the effectiveness of booster vaccination. The sample sizes of groups 2-2, 2-3, 3-2, and 3-3 were 846, 1,115, 1,210, and 2,417, respectively. We found that booster vaccination had an effectiveness against infectiousness of 44.9% (95% CI: 19.7%, 62.2%) for the adults ≥ 18 years, 62.2% (95% CI: 32.0%, 78.9%) for the female close contacts, and 60.8% (95% CI: 38.5%, 75.1%) for the non-household close contacts. Moreover, booster vaccination had an effectiveness against transmission of 29.0% (95% CI: 3.2%, 47.9%) for the adults ≥ 18 years, 38.9% (95% CI: 3.3%, 61.3%) for the female close contacts, and 45.8% (95% CI: 22.1%, 62.3%) for the non-household close contacts. However, booster vaccination against susceptibility did not provide any protective effect. In summary, this study confirm that booster vaccination of the inactivated COVID-19 vaccines provides low level of protection and moderate level of protection against Omicron BA.2 transmission and infectiousness, respectively. However, booster vaccination does not provide any protection against Omicron BA.2 susceptibility.

To minimize the global pandemic COVID-19 spread, understanding the possible transmission routes of SARS-CoV-2 and discovery of novel antiviral drugs are necessary. We describe here that the virus can infect ocular surface limbal epithelial, but not other regions. Limbal supports wild type and mutant SARS-CoV-2 entry and replication depending on ACE2, TMPRSS2 and possibly other receptors, resulting in slight CPE and arising IL-6 secretion, which symbolizes conjunctivitis in clinical symptoms. With this limbal model, we have screened two natural product libraries and discovered several unreported drugs. Our data reveal important commonalities between COVID-19 and ocular infection with SARS-CoV-2, and establish an ideal cell model for drug screening and mechanism research.

Abstract We report a 36-year-old male patient died of V. vulnificus-induced septicaemia and multiple organ failure syndrome after oyster consumption at a restaurant. We isolated and identified V. vulnificus vv16015 from the patient’s blood sample and antibiotic susceptibility tests indicated sensitivity to all 21 antibiotics. Oyster samples were subsequently collected from the restaurant’s supplier and three strains of V. vulnificus were isolated. Whole genome sequencing and analysis revealed vv16015 to be distantly related to these strains and confirmed that V. vulnificus contamination was present in the seafood of the restaurant and supplier. Using a Galleria mellonella larvae infection model, the virulence of vv16015 was determined to be higher than that of comparison strains isolated from a surviving patient (vv15018) and an oyster (vv220015). The human and environment distribution of V. vulnificus in Shenzhen is sporadic and heterogeneous, and vv16015 is highly virulent compared to other strains.

This paper comprehensively analyses the first-ever monkeypox outbreak in Shenzhen, China, encompassing clinical symptomatology, therapeutic approaches, epidemiological research, and comprehensive laboratory tests, aiming to establish a robust reference for future monkeypox mitigation and management strategies. The investigation involved a thorough investigation of all identified positive cases, including extensive molecular analysis by nucleic acid detection and whole-genome sequencing of the monkeypox virus. Contact tracing and containment of the infected individuals were also undertaken. Three distinct monkeypox cases were identified in this unique outbreak, exhibiting mild and atypical clinical manifestations, primarily fever and rash. All cases were associated with a single transmission chain, primarily facilitated through close contact and homosexual behavior, indicative of a high-risk factor for monkeypox transmission.

Objectives: The Omicron BA.2 variant is probably the main epidemic strain worldwide at present. Comparing the epidemiological characteristics, transmissibility, and influencing factors of SARS-CoV-2, the results obtained in this paper will help to provide theoretical support for disease control. Methods: This study was a historical information analysis, using the R programming language and SPSS 24.0 for statistical analysis. The Geoda and Arc GIS were used for spatial autocorrelation analysis. Results: Local spatial autocorrelations of the incidence rate were observed in Delta and Omicron BA.1 outbreaks, whereas Omicron BA.2 outbreaks showed a random distribution in incidence rate. The time-dependent reproduction number of Delta, Omicron BA.1, and Omicron BA.2 were 3.21, 4.29, and 2.96, respectively, and correspondingly, the mean serial interval were 4.29 days (95% confidence interval [CI]: 0.37-8.21), 3.84 days (95% CI: 0-8.37), and 2.77 days (95% CI: 0-5.83). The asymptomatic infection rate of cases in Delta, Omicron BA.1, and Omicron BA.2 outbreaks were 21.71%, 6.25%, and 4.35%, respectively. Conclusion: The Omicron BA.2 variant had the greatest serial interval, transmissibility, and transmission speed, followed by BA.1, and then Delta. Compared with Delta and Omicron BA.1 variants, the Omicron BA.2 variant may be less pathogenic and more difficult to control than Omicron BA.1 and Delta.

We conducted a retrospective cohort study to evaluate the transmission risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 variant and the effectiveness of inactivated COVID-19 vaccine boosters in Shenzhen during a BA.2 outbreak period from 1 February to 21 April 2022. A total of 1,248 individuals were infected with the BA.2 variant, and 7,855 close contacts were carefully investigated. The risk factors for the high secondary attack rate of SARS-CoV-2 infection were household contacts [adjusted odds ratio (aOR): 1.748; 95% confidence interval (CI): 1.448, 2.110], younger individuals aged 0–17 years (aOR: 2.730; 95% CI: 2.118, 3.518), older persons aged ≥60 years (aOR: 1.342; 95% CI: 1.135, 1.588), women (aOR: 1.442; 95% CI: 1.210, 1.718), and the subjects exposed to the post-onset index cases (aOR: 8.546; 95% CI: 6.610, 11.050), respectively. Compared with the unvaccinated and partially vaccinated individuals, a relatively low risk of secondary attack was found for the individuals who received booster vaccination (aOR: 0.871; 95% CI: 0.761, 0.997). Moreover, a high transmission risk was found for the index cases aged ≥60 years (aOR: 1.359; 95% CI: 1.132, 1.632), whereas a relatively low transmission risk was observed for the index cases who received full vaccination (aOR: 0.642; 95% CI: 0.490, 0.841) and booster vaccination (aOR: 0.676; 95% CI: 0.594, 0.770). Compared with full vaccination, booster vaccination of inactivated COVID-19 vaccine showed an effectiveness of 24.0% (95% CI: 7.0%, 37.9%) against BA.2 transmission for the adults ≥18 years and 93.7% (95% CI: 72.4%, 98.6%) for the adults ≥60 years, whereas the effectiveness was 51.0% (95% CI: 21.9%, 69.3%) for the individuals of 14 days to 179 days after booster vaccination and 51.2% (95% CI: 37.5%, 61.9%) for the non-household contacts. The estimated mean values of the generation interval, serial interval, incubation period, latent period, and viral shedding period were 2.7 days, 3.2 days, 2.4 days, 2.1 days, and 17.9 days, respectively. In summary, our results confirmed that the main transmission route of Omicron BA.2 subvariant was household contact, and booster vaccination of the inactivated vaccines was relatively effective against BA.2 subvariant transmission in older people.

PurposeTo explore the clinical characteristics of Micrococcus luteus bloodstream infection in an infant and characterize the phenotype and genotype of the isolated strains, as well as seek suitable infection models for assessing virulence.MethodsClinical data was collected from an infant patient diagnosed with M. luteus bloodstream infection. Metagenomic sequencing was performed on the isolated blood sample. The strain was isolated and underwent mass spectrometry, biochemical tests, antibiotic susceptibility assays, and whole-genome sequencing. The Galleria mellonella infection model was used to assess M. luteus virulence.ResultsPatient responded poorly to cephalosporins, but recovered after Linezolid treatment. Metagenomic sequencing identified M. luteus as the predominant species in the sample, confirming infection. They were identified as M. luteus with a high confidence level of 98.99% using mass spectrometry. The strain showed positive results for Catalase, Oxidase, and Urea tests, and negative results for Mannose, Xylose, Lactose, Mannitol, Arginine, and Galactose tests, consistent with the biochemical profile of M. luteus reference standards. M. luteus susceptibility to 15 antibiotics was demonstrated and no resistance genes were detected. Predicted virulence genes, including clpB, were associated with metabolic pathways and the type VI secretion system. The infection model demonstrated dose-dependent survival rates.ConclusionThe infant likely developed a bloodstream infection with M. luteus due to compromised immunity. Although the isolated strain is sensitive to cephalosporin antibiotics and has low pathogenicity in infection models, clinical treatment with cephalosporins was ineffective. Linezolid proved to be effective, providing valuable guidance for future clinical management of such rare infections.

Environmental supervision is significantly disrupted by local economic development and typically characterized by a lack of independence in China. This paper investigates the impacts and mechanisms of the vertical management reform of environmental protection department in China on urban air quality. We construct a principal–agent model suitable for explaining the interactions between the central and local governments and elaborate the intrinsic mechanism of EVM on strengthening environmental supervision. Using manually collected data, we conduct EVM as a quasi-experiment and construct a time-varying difference-in-difference (DID) model. Our empirical results show that the EVM significantly strengthens regional environmental supervision and reduces urban air pollution, bringing abatement in the PM2.5 concentration. The mechanism shows that EVM increases enterprises’ green innovation and attracts new entrants, further promoting industrial upgrading. Our study provides a new perspective on environmental governance and urban air quality in emerging countries such as China.

In China, the human papillomavirus (HPV) vaccination coverage among age-eligible girls is rather low, and parent’s attitude often plays a determinant role in their girls’ HPV vaccination. To accelerate HPV vaccination coverage, several cities and Guangdong province in China offered different HPV vaccine types with different reimbursement methods. In April 2022, we conducted a province-wide survey to investigate parents of children aged 9–15 in Guangdong province, and analyzed factors associated with their preference for HPV vaccine type and vaccination strategy. Of the 4,967 surveyed respondents, 2,610 (58.1%) have not yet vaccinated their children. Among these parents, 67.9% preferred to vaccinate their children with the nine-valent vaccine, while only 8.1% preferred the quadrivalent vaccine and 7.4% preferred the bivalent vaccine. More parents preferred fixed subsidies with free choices of HPV vaccine type over the domestic bivalent vaccine provided by the government (58.1% vs. 39.3%). The multinomial logistic regression showed that parents’ relationship with children, educational level, household income, and vaccination status were significantly associated with parents’ preference for HPV vaccine type. Parent’s relationship with children, workplace, household income, vaccination status, and age of children, were significantly associated with parents’ preference for HPV vaccination strategy. Our findings suggest that policymakers may consider adjusting the current vaccination strategy by offering more vaccination choices. More health education on HPV vaccine and vaccination should also be provided to parents of age-eligible girls. Future research should examine which HPV vaccination strategy is more effective in promoting HPV vaccine uptakes in China.

Background: MicroRNA (miRNA) and mRNA levels in matching specimens were used to identify miRNA–mRNA interactions. We aimed to integrate transcriptome, immunophenotype, methylation, mutation, and survival data analyses to examine the profiles of miRNAs and target mRNAs and their associations with breast cancer (BC) diagnosis. Methods: Based on the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), differentially expressed miRNAs and targeted mRNAs were screened from experimentally verified miRNA-target interaction databases using Pearson's correlation analysis. We used real-time quantitative reverse transcription polymerase chain reaction to verify BC and benign disease samples, and logistic regression analysis was used to establish a diagnostic model based on miRNAs and target mRNAs. Receiver operating characteristic curve analysis was performed to test the ability to recognize the miRNA-mRNA pairs. Next, we investigated the complex interactions between miRNA-mRNA regulatory pairs and phenotypic hallmarks. Results: We identified 27 and 359 dysregulated miRNAs and mRNAs, respectively, based on the GEO and TCGA databases. Using Pearson's correlation analysis, 10 negative miRNA-mRNA regulatory pairs were identified after screening both databases, and the related miRNA and target mRNA levels were assessed in 40 BC tissues and 40 benign breast disease tissues. Two key regulatory pairs (miR-205-5p/High mobility group box 3 (HMGB3) and miR-96-5p/Forkhead Box O1 (FOXO1)) were selected to establish the diagnostic model. They also had utility in survival and clinical analyses. Conclusions: A diagnostic model including two miRNAs and their respective target mRNAs was established to distinguish between BC and benign breast diseases. These markers play essential roles in BC pathogenesis.

Abstract Background Pancreatic adenocarcinoma (PAAD) remains a lethal malignancy making the detection of novel prognostic biomarkers urgent. Limited studies have investigated the predictive capability of immune checkpoints in PAAD. Method Gene expression data and correlative clinical information of PAAD cohort were obtained from public databases, including TCGA, ICGC, GTEX and GEO databases. Risk factors were screened and used to establish a risk score model through LASSO and Cox regression analyses. The prognostic ability of the risk score model was demonstrated. The association between risk score with immune cells infiltration, immune checkpoint genes expression, immunogenic cell death, somatic mutations and signaling pathways enrichment were analysed. scRNA-seq data were collected to confirmed the immune checkpoints expression in PAAD samples. The prognosis prediction ability of OX40/TNFRSF4 was identified. The mRNA and protein expression of OX40 in our clinical specimens were examined by RT-PCR and IHC method and its prognosis ability was verified. Results First of all, the difference of immune microenvironment between pancreatic cancer and adjacent tissues was shown. A risk score system based on three immune checkpoints (OX40, TNFSF14 and KIR3DL1) was established. The risk score model was an independent prognostic factor and performed well regarding overall survival (OS) predictions among PAAD patients. A nomogram was established to facilitate the risk model application in clinical prognosis. Immune cells including naive B cells, CD8+ T cells and Tregs were negatively correlated with the risk score. The risk score was associated with expression of immune checkpoint genes, immunogenic cell death related genes and somatic mutations. Glycolysis processes, IL-2-STAT5, IL-6-STAT3, and mTORC1 signaling pathways were enriched in the high-risk score group. Furthermore, scRNA-seq data confirmed that TNFRSF4, TNFSF14 and KIR3DL1 were expressed on immune cells in PAAD samples. We then identified OX40 as an independent prognosis-related gene, and a higher OX40 expression was associated with increased survival rate and immune environment change. In 84 PAAD clinical specimens collected from our center, we confirmed that higher OX40 mRNA expression levels were related to a good prognosis. The protein expression of OX40 on tumor-infiltrating immune cells (TIICs), endothelial cells and tumor cells was verified in PAAD tissues by immunohistochemistry (IHC) method. Conclusions Overall, our findings strongly suggested that the three-immune checkpoints score system might be useful in the prognosis and design of personalized treatments for PAAD patients. Finally, we identified OX40 as an independent potential biomarker for PAAD prognosis prediction.

We analyzed variations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome during a flight-related cluster outbreak of coronavirus disease 2019 (COVID-19) in Shenzhen, China, to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations (iSNVs) in a confined space. Thirty-three patients with COVID-19 were sampled, and 14 were resampled 3–31 days later. All 47 nasopharyngeal swabs were deep-sequenced. iSNVs and similarities in the consensus genome sequence were analyzed. Three SARS-CoV-2 variants of concern, Delta (n = 31), Beta (n = 1), and C.1.2 (n = 1), were detected among the 33 patients. The viral genome sequences from 30 Delta-positive patients had similar SNVs; 14 of these patients provided two successive samples. Overall, the 47 sequenced genomes contained 164 iSNVs. Of the 14 paired (successive) samples, the second samples (T2) contained more iSNVs (median: 3; 95% confidence interval [95% CI]: 2.77–10.22) than did the first samples (T1; median: 2; 95% CI: 1.63–3.74; Wilcoxon test, P = 0.021). 38 iSNVs were detected in T1 samples, and only seven were also detectable in T2 samples. Notably, T2 samples from two of the 14 paired samples had additional mutations than the T1 samples. The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event. Intra-host diversity increased gradually with time, and new site mutations occurred in vivo without a population transmission bottleneck. Therefore, we could not determine the generational relationship from the mutation site changes alone.

Aiming at the local, global and temporal morphological characteristics of faults in seismic profiles, this paper proposes the MCD-ABiLSTM method for fault identification. The method uses multi-channel, convolution kernels of different sizes and convolution of different depths to extract multi-scale seismic profile features, and makes full use of the extracted features to enhance the model’s sensitivity to small faults. By combining Bi-directional Long Short-Term Memory (BiLSTM) with multi-scale dense convolution (MCD), the spatial and temporal characteristics of seismic signals are extracted successively, so that the seismic attribute features can be better represented in space and time. In order to solve the problem of extreme imbalance between label data and background data, an improved Weighted Cross Entropy is adopted as the loss function of MCD-ABiLSTM, which alleviates the imbalance between label data and background data. Then, the label data is expanded to establish a fault label data set suitable for deep learning, which further alleviates the problem of imbalance between fault label data and background data. The comparison results show that compared with FCN, U-net, U-net++ and Deeplap V3, the method proposed in this paper improves the precision by 6.27%, 3.65%, 2.94% and 4%.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent subtype of pancreatic cancer and one of the most malignant tumors worldwide. Due to the heterogeneity of its genomics and proteomics, the prognosis of PDAC remains disappointing despite advances in surgery and medicines. Recently, a novel form of programmed cell death, cuproptosis, was proposed, although its role in PDAC has not been investigated. This study aimed to quantify the expression of cuproptosis-related genes and characterize the novel subtypes of PDAC. Methods: To evaluate the pattern of cuproptosis in PDAC, the gene expression data and clinical information of 372 samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus cluster analysis was performed using the transcriptional levels, genetic alterations, and individual prognostic values of seven pre-selected cuproptosis-related genes (DLAT, LIPT1, FDX1, DLD, PDHB, PDHA1, and LIAS) to identify the novel subtypes associated with cuproptosis in PDAC. A univariate Cox regression analysis was used to determine the significant prognostic indicators and cuproptosis scores among the differentially expressed genes (DEGs) between the dividing subclusters, followed by a principal component analysis. The prognostic values, immune profiles, treatment sensitivities, and cuproptosis scores were evaluated between the different subgroups. Results: Seven cuproptosis-related genes showed aberrant expression levels and genetic alterations in the PDAC tumor microenvironment. Among them, LIPT1, LIAS, DLAT, PDHA1, and DLD were significantly correlated with overall survival. Based on the expression profiles of the seven cuproptosis-related genes, three cuproptosis clusters (Clusters A, B, and C) were identified, which were represented by different clinicopathologic features, gene expression levels, and biological processes. A total of 686 DEGs were identified among the three cuproptosis clusters, of which 35 prognosis-related DEGs were selected to further classify the PDAC samples into two subgroups with different survival rates, clinicopathologic features, immune infiltration levels, and drug sensitivities. Higher cuproptosis scores were associated with a significantly poorer prognosis. Conclusion: The cuproptosis subtypes, scores, and relevant genes represent valuable information for assessing the heterogeneity, treatment, and prognosis of PDAC.

Abstract Background To promote influenza vaccination coverage, a Chinese megacity, Shenzhen provides free influenza vaccination to its residents aged 60 years and above through community health centres (CHCs) since October 2016. A community health centre-based experiment was conducted by asking primary care physicians (PCPs) working in the intervention health centres to proactively recommend influenza vaccination to their patients aged 60 and above during their patients’ visits. Methods This study used an experimental design and a survey design. The experimental design evaluated the effect of PCP recommendation on influenza vaccination. A total of 24 CHCs were randomly selected as the intervention (involving 3814 participants) and control (3072 participants) group evenly. The intervention study period was during the 2017–2018 flu season. The 2016–2017 flu season was considered as the baseline comparison. The survey design examined changes in knowledge, attitude, and practice of influenza vaccination among older participants before and after the free influenza vaccination implementation. We randomly invited 1200 participants aged 60 and above during their visits to CHCs in October 2016 and followed them up until October 2017; among them, 958 participants completed the follow-up survey using the same questionnaire. Results In the 2017–2018 flu season, 1,100 more patients got vaccinated in the intervention group under PCP recommendation compared with the 2016–2017 flu season. Among the 958 older adults in the post-implementation period, 77.5% had heard about the influenza vaccine, which was 24.7% higher than in the pre-implementation period; 84.8% of participants were aware where to take influenza vaccines, with the most improvement of 37.2% among all knowledge related questions; 62.5% of them agreed that patients with chronic diseases should have influenza vaccine, which was 19.1% higher than those being surveyed before the implementation period. About 83.6% of participants agreed older adults should have influenza vaccine, but there were still 58.4% who considered themselves too healthy to get vaccinated. Conclusion PCP recommendation improved influenza vaccine uptake and knowledge, attitude, and practice levels regarding influenza vaccination among older adults. More health policies and health education should be made to raise vaccination willingness and improve vaccination coverage among older adults.

We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the Orf1ab and Spike genes was found.

This study conducts an empirical investigation into the decarbonization effects of urban polycentric structures, exploring their mechanisms and varied influences. Our findings reveal key insights. First, urban polycentric structures effectively reduce carbon emission intensity, a conclusion supported by robust tests and endogeneity analysis. Second, our analysis shows that polycentric structures significantly alleviate downtown overcrowding, reducing carbon emission intensity. These structures also impact carbon emissions through factors like labor allocation across industries and the entry of high-productivity enterprises. Third, our analysis shows that the impact of the polycentric structure on carbon emission intensity follows a ‘U-shaped’ pattern. In this ‘U-shaped’ pattern, the growth of an urban population scale can offset the potential negative impacts of this structure. Finally, government support, urban transportation networks, and communication technologies are crucial in enhancing the effectiveness of polycentric decarbonization. Our research contributes to the literature on polycentric structures and carbon emissions and offers policy implications for addressing climate change, applicable not only to China but also to other economies.

Background: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. Methods: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. Discussion: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

The primary objective of this investigation was to study the effect of altitude on fish swimming ability. Different species were tested to ensure that the differences observed are not associated with a single species. Fish critical swimming speed and burst speed were determined using stepped-velocity tests in a Brett-type swimming respirometer. Based on the effects of water temperature and dissolved oxygen, it is clear that the swimming ability of fish decreases as altitude increases. Further, because the effects of high altitude on fish physiology go beyond the effects of lower temperature and dissolved oxygen, we recommend that fish swimming ability be tested at an altitude similar to the target fishway site to ensure the validity of fish data used for fishway design.

Background Tumor-associated tertiary lymphoid structures (TLSs) are functional immune-responsive niches that are not fully understood in pancreatic ductal adenocarcinoma (PDAC).Methods Fluorescent multiplex immunohistochemistry was performed on sequential sections of surgically resected tumor tissues from 380 PDAC patients without preoperative treatment (surgery alone (SA)) and 136 patients pretreated with neoadjuvant treatment (NAT). Multispectral images were processed via machine learning and image processing platforms, inForm V.2.4 and HALO V.3.2; TLS regions were segmented, and the cells were identified and quantified. The cellular composition and immunological properties of TLSs and their adjacent tissues in PDAC were scored and compared, and their association with prognosis was further examined.Results Intratumoral TLSs were identified in 21.1% (80/380) of patients in the SA group and 15.4% (21/136) of patients in the NAT group. In the SA group, the presence of intratumoral TLSs was significantly associated with improved overall survival (OS) and progression-free survival. The existence of intratumoral TLSs was correlated with elevated levels of infiltrating CD8+T, CD4+T, B cells and activated immune cells in adjacent tissues. A nomogram model was generated with TLS presence as a variable, which successfully predicted PDAC patient OS in an external validation cohort (n=123). In the NAT group, samples exhibited a lower proportion of B cells and a higher proportion of regulatory T cells within intratumoral TLSs. Additionally, these TLSs were smaller in size, with a lower overall maturation level and reduced immune cell activation, and the prognostic value of TLS presence was insignificant in the NAT cohort.Conclusion Our study systematically revealed the cellular properties and prognostic values of intratumoral TLSs in PDAC and described the potential impact of NAT on TLS development and function.

BackgroundChlamydia psittaci is a small bacterium often found in birds, including poultry, and domesticated mammals, which causes psittacosis (or parrot fever) in humans. Different strains of C. psittaci respond variably to antibiotics, suggesting a possible risk of antibiotic resistance. In general, different genotypes of C. psittaci have relatively stable hosts and different pathogenicity.MethodsMacrogenomic sequencing was performed using nucleic acids extracted from psittacosis patients’ alveolar lavage fluid samples and analyzed for genetic variability and antibiotic resistance genes. Nucleic acid amplification sequences specific to the core coding region of the C. psittaci ompA gene were used, and a phylogenetic tree was constructed with C. psittaci genotypic sequences from other sources, including Chinese published sources. The C. psittaci found in each patient were genotyped by comparing ompA gene sequences. In addition, to better illustrate the relationship between genotype and host of C. psittaci, 60 bird fecal samples were collected from bird-selling stores for screening and C. psittaci typing.ResultsMacrogenomic sequence alignment revealed the presence of resistance genes in varying abundance in samples from all three patients, including C. psittaci resistance gene sequences from two patients that matched those previously published on NCBI. Based on ompA genotyping, two patients were infected with C. psittaci genotype A and one patient was infected with genotype B. All five C. psittaci-positive samples obtained from bird-selling stores were genotype A. Both genotypes are reported to be infectious to humans. The host origin of the samples and the previously reported main sources of each genotype suggested that all but one of the C. psittaci genotype A in this study were derived from parrots, while genotype B was probably derived from chickens.ConclusionThe presence of bacterial resistance genes in psittacosis patients may affect the efficacy of clinical antibiotic therapy. Focusing on the developmental progression of bacterial resistance genes and differences in the therapeutic efficacy may facilitate effective treatment of clinical bacterial infections. Pathogenicity genotypes (e.g., genotype A and genotype B) are not limited to one animal host, suggesting that monitoring the development and changes of C. psittaci may help prevent transmission to humans.

Abstract Background Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs. Methods We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy. Results The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup. Conclusions Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy.

Phage contamination is a persistent problem in industrial biotechnology processes employing bacterial strains. Here, the authors report the construction of E. coli host strains with broad antiphase activities via the genomic integration of the Ssp defense system and mutations of components essential for phage infection cycles.

Functional succinate dehydrogenase (SDH) complex is vital to mitochondrial homeostasis. Here the authors show that disruption of SDH assembly in the heart causes dilated cardiomyopathy via impairing the mitochondrial integrity and metabolism and that mitochondrial interventions can be an effective approach to ameliorate the disease progression.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a well-known lethal and heterogeneous disease. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) is an important mutagenic driver that has seldom been investigated in PDAC. Therefore, this study investigated the significance of APOBEC3C in PDAC. First, cytosine deamination-associated mutation signatures were identified in the PDAC cohorts from TCGA and Fudan University Shanghai Cancer Center (FUSCC) datasets, and C > X-enriched kataegis regions were identified in the FUSCC cohort (12 to 27 counts per sample). Patients were stratified according to APOBEC3C expression, and high APOBEC3C expression was found to correlate with a higher motif enrichment score of 5’-CC-3’ and an elevated kataegis count within PCSK5 and NES genes. Second, we compared APOBEC expression in PDAC and normal pancreatic tissues and found that APOBEC3C was substantially upregulated in PDAC. APOBEC3C-overexpressing cell lines were generated to substantiate the effects of APOBEC3C on PDAC genome, including alterations in single-nucleotide variant (SNV) classes (higher proportion of C > T conversions) and the formation of kataegis regions (newly occurring kataegis regions detected in ACHE and MUC6 genes). Three different PDAC cohorts (FUSCC, TCGA, and QCMG) were analysed to evaluate the prognostic value of APOBEC3C, and APOBEC3C overexpression predicted shorter survival. Finally, the APOBEC3C overexpression correalted with the PDAC tumour microenvironment (TME) remodelling, APOBEC3C expression was associated with the invasion of CD4 + T lymphocytes and CD8 + T lymphocytes (cytotoxic T lymphocytes, CTLs), indicating enhanced immune activity and validating the practicality of APOBEC3C for guiding immunotherapy.

Nuclear factor E2-related factor 2 (Nrf2) is fundamental to the maintenance of redox homeostasis within cells via the regulation of a series of phase II antioxidant enzymes. The unique olive-derived phenolic compound hydroxytyrosol (HT) is recognized as an Nrf2 activator, but knowledge of the HT derivative hydroxytyrosol acetate (HTac) on Nrf2 activation remains limited. In this study, we observed that an HT pretreatment could protect the cell viability, mitochondrial membrane potential, and redox homeostasis of ARPE-19 cells against a t-butyl hydroperoxide challenge at 50 μM. HTac exhibited similar benefits at 10 μM, indicating a more effective antioxidative capacity compared with HT. HTac consistently and more efficiently activated the expression of Nrf2-regulated phase II enzymes than HT. PI3K/Akt was the key pathway accounting for the beneficial effects of HTac in ARPE-19 cells. A further RNA-Seq analysis revealed that in addition to the consistent upregulation of phase II enzymes, the cells presented distinct expression profiles after HTac and HT treatments. This indicated that HTac could trigger a diverse cellular response despite its similar molecular structure to HT. The evidence in this study suggests that Nrf2 activation is the major cellular activity shared by HTac and HT, and HTac is more efficient at activating the Nrf2 system. This supports its potential future employment in various disease management strategies.

Abstract Purpose MicroRNA (miRNA) is a class of short non-coding RNA molecules that functions in RNA silencing and post-transcriptional regulation of gene expression. This study aims to identify critical miRNA-mRNA regulation pairs contributing to bladder cancer (BLCA) pathogenesis. Patients and methods MiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. The tool of GEO2R and R packages were used to screen differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) and DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The miRNA-mRNA regulation pair were screened from the experimentally validated miRNA-target interactions databases (miRTarbase and TarBase). Twenty-eight pairs of BLCA tissues were used to further verify the screened DE-miRNAs and DE-mRNAs by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). The correlation analysis between the selected miRNA-mRNAs regulation pair and clinical, survival and tumor-related phenotypes was performed in this study. Results After miRTarBase, the analysis of 2 miRNA datasets, 6 mRNA datasets, and TCGA-BLCA dataset, a total of 13 miRNAs (5 downregulated and 8 upregulated in BLCA tissues) and 181 mRNAs (72 upregulated and 109 downregulated in BLCA tissues) were screened out. The pairs of miR-17-5p (upregulated in BLCA tissues) and TGFBR2 (downregulated in BLCA tissues) were verified in the external validation cohort (28 BLCA vs. 28 NC) using qRT-PCR. Areas under the ROC curve of the miRNA-mRNA regulation pair panel were 0.929 (95% CI: 0.885–0.972, p < 0.0001) in TCGA-BLCA and 0.767 (95% CI: 0.643–0.891, p = 0.001) in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing BLCA from normal controls. Correlation analysis showed that miR-17-5p and TGFBR2 correlated with tumor immunity. Conclusions The research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of BLCA.

Pogostemon cablin is an important aromatic medicinal herb widely used in the pharmaceutical and perfume industries. However, our understanding of the phytochemical compounds and metabolites within P. cablin remains limited. To our knowledge, no integrated studies have hitherto been conducted on the metabolites of the aerial parts of P. cablin. In this study, twenty-three volatile compounds from the aerial parts of P. cablin were identified by GC-MS, predominantly sesquiterpenes. Quantitative analysis showed the highest level of patchouli alcohol in leaves (24.89 mg/g), which was 9.12 and 6.69-fold higher than in stems and flowers. UHPLC-QTOFMS was used to analyze the non-volatile compounds of leaf, stem and flower tissues. The differences in metabolites between flower and leaf tissues were the largest. Based on 112, 77 and 83 differential metabolites between flower-leaf, flower-stem and leaf-stem, three tissue-specific biomarkers of metabolites were identified, and the differential metabolites were enriched in several KEGG pathways. Furthermore, labeling differential metabolites in the primary and secondary metabolic pathways showed that flowers accumulated more lipids and amino acids, including proline, lysine and tryptophan; the leaves accumulated higher levels of terpenoids, vitamins and flavonoids, and stems contained higher levels of carbohydrate compounds. Based on the role of acetyl coenzyme A, the distribution and possible exchange mechanism of metabolites in leaves, stems and flowers of P. cablin were mapped for the first time, laying the groundwork for future research on the metabolites in P. cablin and their regulatory role.

Summary: Background: Motor disturbances and non-motor disturbances such as constipation are the main factors affecting the quality of life in patients with Parkinson's disease (PD). We investigated the efficacy and safety of electroacupuncture combined with conventional pharmacological treatment on motor dysfunction and constipation in PD. Methods: In this multi-centre randomised controlled trial, we enrolled 166 eligible participants between September 19, 2018 and September 25, 2019 in four hospitals in China. Participants were randomly assigned (1:1) to the electroacupuncture (EA) group and the waitlist control group. Each participant in both groups received the conventional pharmacological treatment, EA group received 3 sessions of electroacupuncture per week for 12 weeks. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to week 12. The secondary outcomes included the evaluation of functional disability in motor symptoms and constipation, the adherence and adverse events were also recorded. Registered with Chictr.org.cn, ChiCTR1800019517. Findings: At week 12, the change in the UPDRS score of the EA group was significantly higher than that of the control group, with a difference of −9.1 points (95% CI, −11.8 to −6.4), and this difference continued into weeks 16 and 24. From baseline to week 12, the 39-item Parkinson Disease Question (PDQ-39) decreased by 10 points (interquartile range, IQR −26.0 to 0.0) in the EA group and 2.5 points (IQR: −11.0 to 4.0) in the control group, the difference was statistically significant. The time and steps for the 20-m walk at week 12, as well as the changes from baseline in the EA group, were comparable with that in the control group. But the EA group had a greater decrease than the control group from baseline in the times for 20-m walks at weeks 16 and 24. From week 4 to week 24, the median values of spontaneous bowel movements (SBMs) per week in the EA group were higher than that in the control group, the differences were all statistically significant. The incidence of EA-related adverse events during treatment was low, and they are mild and transient. Interpretation: The findings of our study suggested that compared with conventional pharmacological treatment, conventional pharmacological treatment combined with electroacupuncture significantly enhances motor function and increased bowel movements in patients with PD, electroacupuncture is a safe and effective treatment for PD. Funding: Shanghai “Science and Technology Innovation Action Plan” Clinical Medicine Field Project (18401970700), Shanghai Special Project on Aging and Women's and Children's Health Research (020YJZX0134), Shanghai Clinical Research Centre for Acupuncture and Moxibustion (20MC1920500).

Evidence is limited on the actual uptake of the coronavirus disease 2019 (COVID-19) vaccine among older adults, especially those with chronic diseases, during the pandemic. To examine COVID-19 vaccine uptake, reasons, and associated factor among older adults, a cross-sectional survey was conducted between September 24 and October 20, 2021 among older adults aged 60 and above in Shenzhen, China. Logistic regression analysis was used to examine associations of COVID-19 vaccine uptake with sociodemographic characteristics, pneumonia vaccination history, and participation in health education activities among older adults and among those with chronic diseases. Of the 951 participants, 82.8% reported being vaccinated against COVID-19 during the study period, but this proportion was relatively lower among adults aged 80 and above (62.7%) and those with chronic diseases (77.9%). The top-rated reasons for not being vaccinated included doctors not recommending it due to underlying diseases (34.1%), not being ready for it (18.3%), and failure to make an appointment (9.1%). General older adults who were aged below 70, had a high school and above education, were permanent residents of Shenzhen, were with good health and had pneumonia vaccination history were more likely to take the COVID-19 vaccination. Yet, among older adults with chronic diseases, other than age and permanent residency status, health status was the only significant indicator of COVID-19 vaccine uptake. Our study added to evidence that health condition is the critical barrier to the actual uptake of the COVID-19 vaccine among Chinese older adults, especially those aged 80 and above and those with chronic diseases.

BackgroundMetal exposure affects human health. Current studies mainly focus on the individual health effect of metal exposure on hypertension (HTN), and the results remain controversial. Moreover, the studies assessing overall effect of metal mixtures on hypertension risk are limited.MethodsA cross-sectional study was conducted by recruiting 1,546 Chinese adults who attended routine medical check-ups at the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen. The plasma levels of 13 metals were measured using inductively coupled plasma mass spectrometry. Multivariate logistic regression model, restricted cubic spline (RCS) model and the Bayesian Kernel Machine Regression (BKMR) model were applied to explore the single and combined effect of metals on the risk of HTN.ResultsA total of 642 (41.5%) participants were diagnosed with HTN. In the logistic regression model, the adjusted odds ratios (ORs) were 0.71 (0.52, 0.97) for cobalt, 1.40 (1.04, 1.89) for calcium, 0.66 (0.48, 0.90), and 0.60 (0.43, 0.83) for aluminum in the second and third quartile, respectively. The RCS analysis showed a V-shaped or an inverse V-shaped dose-response relationship between metals (aluminum or calcium, respectively) and the risk of HTN (P for non-linearity was 0.017 or 0.009, respectively). However, no combined effect was found between metal mixture and the risk of hypertension.ConclusionsPlasma levels of cobalt, aluminum and calcium were found to be associated with the risk of HTN. Further studies are needed to confirm our findings and their potential mechanisms with prospective studies and experimental study designs.

Background: Metal exposure were assumed to be closely related with declined renal function, but the conclusions were controversial. We employed diverse statistical models and assessed the association between metal mixture exposure and mild renal impairment. Methods: A total of 13 plasma metals were measured in 896 general population from Southern China. Subjects with estimated glomerular filtration rate within 60–89 ml/min/1.73 m2 and urinary albumin-creatinine ratio

Influenza is prevalent globally, leading to severe morbidity and mortality. During the pandemic, knowledge, attitude, and practice (KAP) towards influenza virus and vaccination were less investigated among southern Chinese older adults. A cross-sectional study was conducted through the structured questionnaire among community healthcare centers in selected districts in Shenzhen, southern China from September to October 2021. KAP towards influenza virus and vaccination were analyzed. A multivariable logistic regression model was used to identify associated factors. Among 975 participants, 55.6% were reported to have received influenza vaccination ever, and 46.6% had taken influenza vaccination in 2020 during the pandemic. Only one-fifth of participants knew severe comorbidities happen among severe influenza cases. A total of 88.3% thought older adults should have influenza vaccination. COVID-19 vaccination history was associated with receiving influenza vaccination (OR 1.92, 95% CI 1.32–2.80). People with a high-level income had better KAP towards influenza virus and vaccination. COVID-19 vaccination history was associated with the positive actions of influenza vaccination during the pandemic. Efforts should be made to promote the free influenza vaccination program widely and launch health education events on influenza and its vaccination regularly to improve KAP among older adults.

Silicosis is one of the most important occupational diseases worldwide, caused by inhalation of silica particles or free crystalline silicon dioxide. As a disease with high mortality, it has no effective treatment and new therapeutic targets are urgently needed. Recent studies have identified FCER1A, encoding α-subunit of the immunoglobulin E (IgE) receptor FcεRI, as a candidate gene involved in the biological pathways leading to respiratory symptoms. FcεRI is known to be important in allergic asthma, but its role in silicosis remains unclear. In this study, serum IgE concentrations and FcεRI expression were assessed in pneumoconiosis patients and silica-exposed mice. The role of FcεRI was explored in a silica-induced mouse model using wild-type and FcεRI-deficient mice. The results showed that serum IgE concentrations were significantly elevated in both pneumoconiosis patients and mice exposed to silica compared with controls. The mRNA and protein expression of FcεRI were also significantly increased in the lung tissue of patients and silica-exposed mice. FcεRI deficiency significantly attenuated the changes in lung function caused by silica exposure. Silica-induced elevations of IL-1β, IL-6, and TNF-α were significantly attenuated in the lung tissue and bronchoalveolar lavage fluid (BALF) of FcεRI-deficient mice compared with wild-type controls. Additionally, FcεRI-deficient mice showed a significantly lower score of pulmonary fibrosis than wild-type mice following exposure to silica, with significantly lower hydroxyproline content and expression of fibrotic genes Col1a1 and Fn1. Immunofluorescent staining suggested FcεRI mainly on mast cells. Mast cell degranulation took place after silica exposure, as shown by increased serum histamine levels and β-hexosaminidase activity, which were significantly reduced in FcεRI-deficient mice compared with wild-type controls. Together, these data showed that FcεRI deficiency had a significant protective effect against silica-induced pulmonary inflammation and fibrosis. Our findings provide new insights into the pathophysiological mechanisms of silica-induced pulmonary fibrosis and a potential target for the treatment of silicosis.

Public health decision-making may have great uncertainty especially in dealing with emerging infectious diseases, so it is necessary to establish a collaborative mechanism among modelers, epidemiologists, and public health decision-makers to reduce the uncertainty as much as possible. We searched the relevant studies on transmission dynamics modeling of infectious diseases, SARS, MERS, and COVID-19 as of March 1, 2021 based on PubMed. We compared the key health decision-making time points of SARS, MERS, and COVID-19 prevention and control, and the publication time points of modeling research, to reveal the collaboration between infectious disease modeling and public health decision-making in the context of the COVID-19 pandemic. Searching with infectious disease and mathematical model as keywords, there were 166, 81 and 1 289 studies on the modeling of infectious disease transmission dynamics of SARS, MERS, and COVID-19 were retrieved respectively. Based on the modeling application framework of public health practice proposed in the current study, the collaboration among modelers, epidemiologists and public health decision-makers should be strengthened in the future.

ABSTRACT Antibiotic resistance genes (ARGs) are recognized as contaminants due to their potential risk for human and environment. The aim of the present study is to investigate the effects of pyroligneous acid (PA), a waste of biochar production, on fermentation characteristics, diversity, and dynamics of ARGs during ensiling of alfalfa using metagenomic analysis. The results indicated that PA decreased (P

ObjectiveThis study aimed to develop an artificial intelligence model for predicting the pathological complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) of locally advanced rectal cancer (LARC) using digital pathological images.BackgroundnCRT followed by total mesorectal excision (TME) is a standard treatment strategy for patients with LARC. Predicting the PCR to nCRT of LARC remine difficulty.Methods842 LARC patients treated with standard nCRT from three medical centers were retrospectively recruited and subgrouped into the training, testing and external validation sets. Treatment response was classified as pCR and non-pCR based on the pathological diagnosis after surgery as the ground truth. The hematoxylin & eosin (H&E)-stained biopsy slides were manually annotated and used to develop a deep pathological complete response (DeepPCR) prediction model by deep learning.ResultsThe proposed DeepPCR model achieved an AUC-ROC of 0.710 (95% CI: 0.595, 0.808) in the testing cohort. Similarly, in the external validation cohort, the DeepPCR model achieved an AUC-ROC of 0.723 (95% CI: 0.591, 0.844). The sensitivity and specificity of the DeepPCR model were 72.6% and 46.9% in the testing set and 72.5% and 62.7% in the external validation cohort, respectively. Multivariate logistic regression analysis showed that the DeepPCR model was an independent predictive factor of nCRT (P=0.008 and P=0.004 for the testing set and external validation set, respectively).ConclusionsThe DeepPCR model showed high accuracy in predicting pCR and served as an independent predictive factor for pCR. The model can be used to assist in clinical treatment decision making before surgery.

Cities in China do not constitute a few global metropolises, but are characterized by heterogeneity. Studying counties can give us a comprehensive picture of urban sprawl in China. This study measured the sprawl index of 1880 counties in China from 2005 to 2020 for the first time and then revealed the evolution of their spatiotemporal characteristics and driving mechanisms. The results revealed the following. (1) China’s counties had a noticeable sprawling trend from 2005 to 2020, and their evolutionary process was characterized by spatiotemporal heterogeneity. (2) From 2005 to 2020, the counties’ sprawl gradually evolved into a spatial distribution pattern of high in the east and low in the west. The spatial distribution of sprawl in county and municipal districts had the characteristics of an interlocking distribution. (3) High–high cluster areas of CSI are mainly distributed in plains, and hilly, basin, and plateau areas tend to be low–low cluster areas. High–low outliers were distributed in a “point–line” pattern along the railroad lines and a cluster pattern near railroad intersections and central cities. Low–high outliers had the trend of encircling the high–high cluster areas. (4) The coefficient of the natural drivers was higher but tended to decrease, while the coefficient of economic and spatial drivers was lower but gradually increased. This study is the first to refine the study of urban sprawl to the county scale, which provides a reference for decision making to optimize the spatial structure of counties and thus promote high-quality development.

Abstract Background The novel coronavirus disease 2019 (COVID-19) confirmed cases overseas have continued to rise in the last months, and many people overseas have chosen to return to China. This increases the risk of a large number of imported cases which may cause a relapse of the COVID-19 outbreak. In order to prevent imported infection, the Shenzhen government has implemented a closed-loop management strategy using nucleic acid testing (NAT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and requiring 14 days of medical observation for individuals with an overseas tour history (Hong Kong, Macao, Taiwan province and other countries). Our study aims to describe the status of COVID-19 infection among people entering Shenzhen, and to evaluate the effect of the closed-loop management strategy. Methods We undertook a descriptive study and risk analysis by the entry time, time of reporting, and local confirmed cases in countries of origin. The NAT were completed in Shenzhen Center for Disease Control and Prevention (CDC), ten district-level CDCs, and fever clinics. Results A total of 86,844 people from overseas entered Shenzhen from January 1 to April 18, 2020; there were 39 imported COVID cases and 293 close contacts. The infection rate of people entering was 4.49‰ [95% Confidence interval (CI): 3.26‰–6.05‰]. Fourteen imported cases (35.9%) came from the UK, and nine (23.08%) came from the USA. People entering from the USA since March 9 or from the UK since March 13 are the high-risk population. As of July 17, there have been no new confirmed cases in Shenzhen for 153 days, and the numbers of confirmed case, close contacts, and asymptomatic cases are 0. Conclusions The closed-loop management has been effective in preventing imported infection and controlling domestic relapse. The distribution of entry time and report time for imported cases overseas was similar. This shows that it is important to implement closed-loop management at the port of entry.

Purpose: MicroRNA (miRNA) binds to target mRNA and inhibit post-transcriptional gene expression. It plays an essential role in regulating gene expression, cell cycle, and biological development. This study aims to identify potential miRNA-mRNA regulatory networks that contribute to the pathogenesis of lung squamous cell carcinoma (LUSC).Patients and Methods: MiRNA microarray and RNA-Seq datasets were obtained from the gene expression omnibus (GEO) databases, the cancer genome atlas (TCGA), miRcancer, and dbDEMC. The GEO2R tool, “limma” and “DEseq” R packages were used to perform differential expression analysis. Gene enrichment analysis was conducted using the DAVID, DIANA, and Hiplot tools. The miRNA-mRNA regulatory networks were screened from the experimentally validated miRNA-target interactions databases (miRTarBase and TarBase). External validation was carried out in 30 pairs of LUSC tissues by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Receiver operating characteristic curve (ROC) and decision curve analysis (DCA) were conducted to evaluate the diagnostic value. Clinical, survival and phenotypic analysis of miRNA-mRNA regulatory networks were further explored.Results: We screened 5 miRNA and 10 mRNA expression datasets from GEO and identified 7 DE-miRNAs and 270 DE-mRNAs. After databases screening and correlation analysis, four pairs of miRNA-mRNA regulatory networks were screened out. The miRNA-mRNA network of miR-205-5p (up) and PTPRM (down) was validated in 30 pairs of LUSC tissues. MiR-205-5p and PTPRM have good diagnostic efficacy and are expressed differently in different clinical features and are related to tumor immunity.Conclusion: The research identified a potential miRNA-mRNA regulatory network, providing a new way to explore the genesis and development of LUSC.

Dominant optic atrophy (DOA) is one of the most common type of hereditary optic atrophy. Here, we describe the generation and characterization of a human induced pluripotent stem cell (hiPSC) line of DOA patient with an OPA1 mutation. The reprogramming of this iPSC line was performed from peripheral blood mononuclear cells (PBMCs) using the non-integrative Sendai virus. The established hiPSC line retained the disease-associated mutation and showed normal karyotype, pluripotency, and differentiation capacity.

Choroideremia (CHM) is a rare monogenic, X-linked recessive inherited chorioretinal dystrophy caused by loss of function variants in the CHM gene. We successfully generated a novel human induced pluripotent stem cell (hiPSC) line from a CHM patient with CHM variant using the Sendai-virus based approach. These cells will provide a disease model for further studies on the disease pathogenesis and potential interventions.

RDH12 mutations have been identified in patients diagnosed with severe early-onset retinal dystrophy, including Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD). Here, we describe the generation and characterization of a human induced pluripotent stem cell (hiPSC) line of a patient with RDH12 mutations. Blood sample was obtained, and peripheral blood mononuclear cells (PBMCs) were reprogrammed using the non-integrative Sendai virus to generate the iPSC line. The hiPSCs were characterized according to standard protocols including karyotyping, pluripotency marker expression and differentiation towards the three germ layers.