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Abstract Chiral assemblies have become one of the most active research areas due to their versatility, playing an increasingly important role in bio-detection, imaging and therapy. In this work, chiral UCNPs/CuxOS@ZIF nanoprobes are prepared by encapsulating upconversion nanoparticles (UCNPs) and CuxOS nanoparticles (NPs) into zeolitic imidazolate framework-8 (ZIF-8). The novel excited-state energy distribution-modulated upconversion nanostructure (NaYbF4@NaYF4: Yb, Er) is selected as the fluorescence source and energy donor for highly efficient fluorescence resonance energy transfer (FRET). CuxOS NP is employed as chiral source and energy acceptor to quench upconversion luminescence (UCL) and provide circular dichroism (CD) signal. Utilizing the natural adsorption and sorting advantages of ZIF-8, the designed nanoprobe can isolate the influence of other common disruptors, thus achieve ultra-sensitive and highly selective UCL/CD dual-mode quantification of H2S in aqueous solution and in living cells. Notably, the nanoprobe is also capable of in vivo intra-tumoral H2S tracking. Our work highlights the multifunctional properties of chiral nanocomposites in sensing and opens a new vision and idea for the preparation and application of chiral nanomaterials in biomedical and biological analysis.

Abstract Resilience is one of the main features of smart distribution networks, and a microgrid (MG) access to the distribution network provides an effective way to improve resilience. MG and distribution network belong to different interests, so it is necessary that MGs and flexible resources are actively guided through price leverage. In this way, MGs take part in the post‐disaster restoration and enhance its resilience. Firstly, this paper proposes a dynamic restoration electricity price response mechanism after extreme disasters and constructs a power response model for loads and electric vehicles within the MGs. Secondly, the optimal scheduling model of the distribution network with multiple‐microgrids (MMG) is proposed to improve the restoration rate of critical loads (RRCL). Single microgrid achieves the largest microgrid revenue and restoration contribution, and MMG uses the power headroom index to optimize the dynamic restoration electricity price to achieve the smallest power purchase cost of distribution network. Finally, the optimal scheduling method for resilience enhancement of distribution networks with MMG considering dynamic restoration electricity price response mechanism is validated by dual microgrid access to an IEEE 33‐node distribution system. The simulation results show that the proposed optimization method effectively improves the RRCL of distribution network.

In recent years, the deep integration of basic research and clinical translational research of nanotechnology and oncology has led to the emergence of a new branch, namely integrated nano-oncology. This is an emerging and important interdisciplinary field, which plays an irreplaceable role in the diagnosis, treatment, early warning, monitoring and prevention of tumors, and has become a new interdisciplinary frontier. Here main advances of integrated nano-oncology was reviewed, mainly included controlled preparation of nanomaterials, ultra-sensitive detection of tumor biomarkers, multi-functional nanoimaging probes and integrated diagnosis and treatment technology, innovative nano drugs and nano drug delivery system, DNA nanotechnology, RNA nanotechnology, nano self-assembly technology, nanosensors, intelligent nanorobots, nanotherapeutic machines. The terms, concepts, trends and challenges are also discussed with the aim of promoting the application of nanotechnology in integrated oncology and solving the scientific and key technical problems in basic and clinical translational research of cancer.

Abstract Background Cancer‐associated cachexia (CAC) is a debilitating syndrome associated with poor quality of life and reduced life expectancy of cancer patients. CAC is characterized by unintended body weight reduction due to muscle and adipose tissue loss. A major hallmark of CAC is systemic inflammation. Several non‐steroidal anti‐inflammatory drugs (NSAIDs) have been suggested for CAC treatment, yet no single medication has proven reliable. R‐ketorolac (RK) is the R‐enantiomer of a commonly used NSAID. The effect of RK on CAC has not yet been evaluated. Methods Ten‐ to 11‐week‐old mice were inoculated with C26 or CHX207 cancer cells or vehicle control (phosphate‐buffered saline [PBS]). After cachexia onset, 2 mg/kg RK or PBS was administered daily by oral gavage. Body weight, food intake and tumour size were continuously measured. At study endpoints, blood was drawn, mice were sacrificed and tissues were excised. Immune cell abundance was analysed using a Cytek® Aurora spectral flow cytometer. Cyclooxygenase (COX) activity was determined in lung homogenates using a fluorometric kit. Muscle tissues were analysed for mRNA and protein expression by quantitative real‐time PCR and western blotting analysis, respectively. Muscle fibre size was determined on histological slides after haematoxylin/eosin staining. Results Ten‐day survival rate of C26‐bearing animals was 10% while RK treatment resulted in a 100% survival rate (P = 0.0009). Chemotherapy resulted in a 10% survival rate 14 days after treatment initiation, but all mice survived upon co‐medication with RK and cyclophosphamide (P = 0.0001). Increased survival was associated with a protection from body weight loss in C26 (−0.61 ± 1.82 vs. −4.48 ± 2.0 g, P = 0.0004) and CHX207 (−0.49 ± 0.33 vs. −2.49 ± 0.93 g, P = 0.0003) tumour‐bearing mice treated with RK, compared with untreated mice. RK ameliorated musculus quadriceps (−1.7 ± 7.1% vs. −27.8 ± 8.3%, P = 0.0007) and gonadal white adipose tissue (−18.8 ± 49% vs. −69 ± 15.6%, P = 0.094) loss in tumour‐bearing mice, compared with untreated mice. Mechanistically, RK reduced circulating interleukin‐6 (IL‐6) concentrations from 334 ± 151 to 164 ± 123 pg/mL (P = 0.047) in C26 and from 93 ± 39 to 35 ± 6 pg/mL (P = 0.0053) in CHX207 tumour‐bearing mice. Moreover, RK protected mice from cancer‐induced T‐lymphopenia (+1.8 ± 42% vs. −49.2 ± 12.1% in treated vs. untreated mice, respectively). RK was ineffective in ameliorating CAC in thymus‐deficient nude mice, indicating that the beneficial effect of RK depends on T‐cells. Conclusions RK improved T‐lymphopenia and decreased systemic IL‐6 concentrations, resulting in alleviation of cachexia and increased survival of cachexigenic tumour‐bearing mice, even under chemotherapy and independent of COX inhibition. Considering its potential, we propose that the use of RK should be investigated in patients suffering from CAC.

Abstract Echovirus 25 (E25), a member of the Enterovirus B (EV-B) species, can cause aseptic meningitis (AM), viral meningitis (VM), and acute flaccid paralysis (AFP). However, systematic studies on the molecular epidemiology of E25, especially those concerning its evolution and recombination, are lacking. In this study, 18 strains of E25, isolated from seven provinces of China between 2009 and 2018, were collected based on the Chinese hand, foot, and mouth disease (HFMD) surveillance network, and 95 sequences downloaded from GenBank were also screened. Based on the phylogenetic analysis of 113 full-length VP1 sequences worldwide, globally occurring E25 strains were classified into 9 genotypes (A–I), and genotype F was the dominant genotype in the Chinese mainland. The average nucleotide substitution rate of E25 was 6.08 × 10–3 substitutions/site/year, and six important transmission routes were identified worldwide. Seventeen recombination patterns were determined, of which genotype F can be divided into 9 recombination patterns. A positive selector site was found in the capsid protein region of genotype F. Recombination analysis and pressure selection analysis for genotype F showed multiple recombination patterns and evolution characteristics, which may be responsible for it being the dominant genotype in the Chinese mainland. This study provides a theoretical basis for the subsequent prevention and control of E25.

Abstract Background Parents of children with autism spectrum disorder (ASD) are at a higher risk of depression than parents of typically developing children and those of children with other developmental disorders. Depression affects the well-being and quality of life of parents of children with ASD and has serious consequences for the long-term health outcomes of children with ASD. Therefore, this study explored the current status of depressive symptoms in parents of children with ASD in eastern China and further analyzed multiple aspects of the predictors of depressive symptoms. Methods A multicenter cross-sectional survey was conducted among parents of children with ASD in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China. A structured questionnaire that focused on child-related factors, parent-related factors, depressive symptoms, courtesy stigma, and social support was used to obtain data. Binary logistic regression was used to identify the independent predictors of depressive symptoms in parents of children with ASD. Results A total of 409 parents of children with ASD were recruited, of whom 18.8% had depressive symptoms. Parents of children with ASD who raised a child who spoke few to no words (odds ratio [OR]: 2.747, 95% confidence interval [CI]: 1.026–7.357), claimed a high economic burden (OR: 3.215, 95% CI: 1.234–8.379), reported no change or increased severity of ASD in their children (OR: 2.518, 95% CI: 1.108–5.720), and those with a higher courtesy stigma score (OR: 1.189, 95% CI: 1.093–1.294) were more likely to have depressive symptoms. Conversely, parents of children with ASD who were employed (OR: 0.427, 95% CI: 0.201–0.907), satisfied with their current marital status (OR: 0.429, 95% CI: 0.221–0.834), and those with a higher social support score (OR: 0.973, 95% CI: 0.950–0.996) were less likely to have depressive symptoms. Conclusions Depressive symptoms are common in parents of children with ASD in eastern China. Therefore, screening and intervention for depressive symptoms in parents of children with ASD is necessary, especially for those with high-risk factors.

ABSTRACTRemote sensing technology has been widely used for marine monitoring. However, due to the limitations of sensor technologies and data sources, effective monitoring of marine ships at night remains challenging. To address these challenges, our study developed SDGST, a high-resolution glimmer marine ship dataset from SDGSAT-1 satellite and proposed a ship detection and identification method based on the YOLOv5s model, the Glimmer YOLO model. Considering the characteristics of glimmer images, our model has made several effective improvements to the original YOLOv5s model. In particular, the improved model incorporates a new layer for detecting small targets and integrates the CA (Coordinate Attention) mechanism. To enhance the original feature fusion strategy, we introduced BiFPN (Bi-directional Feature Pyramid Network). We also adopted the EIOU Loss function and replaced the initially defined anchors with clustering results, thus improving detection performance. The mean Average Precision (mAP%) reaches 96.7%, which is a 5.1% improvement over the YOLOv5s model. Notably, it significantly improves the detection of small ships. This model demonstrates superior performance in ship detection under glimmer conditions compared to the original YOLOv5s model and other popular target detection models, and may serve as a valuable reference for achieving high-precision nighttime marine monitoring.

Abstract Digital public goods (DPGs), if implemented with effective policies, can facilitate the realization of the United Nations Sustainable Development Goals (SDGs). However, there are ongoing deliberations on how to define DPGs and assure that society can extract the maximum benefit from the growing number of digital resources. The International Research Center of Big Data for Sustainable Development Goals (CBAS) sees DPGs as an important mechanism to facilitate information-driven policy and decision-making processes for the SDGs. This article presents the results of a CBAS survey of 51 respondents from around the world spanning multiple scientific fields, who shared their expert opinions on DPGs and their thoughts about challenges related to their practical implementation in supporting the SDGs. Based on the survey results, the paper presents core principles in a proposed strategy, including establishment of international standards, adherence to open science and open data principles, and scalability in monitoring SDG indicators. A community-driven strategy to develop DPGs is proposed to accelerate DPG production in service of the SDGs while adhering to the core principles identified in the survey.

We present GeoGlue, a novel method using high-resolution UAV imagery for accurate feature matching, which is normally challenging due to the complicated scenes. Current feature detection methods are performed without guidance of geometric priors (e.g., geometric lines), lacking enough attention given to salient geometric features which are indispensable for accurate matching due to their stable existence across views. In this work, geometric lines are firstly detected by a CNN-based geometry detector (GD) which is pre-trained in a self-supervised manner through automatically generated images. Then, geometric lines are naturally vectorized based on GD and thus non-significant features can be disregarded as judged by their disordered geometric morphology. A graph attention network (GAT) is utilized for final feature matching, spanning across the image pair with geometric priors informed by GD. Comprehensive experiments show that GeoGlue outperforms other state-of-the-art methods in feature-matching accuracy and performance stability, achieving pose estimation with maximum rotation and translation errors under 1% in challenging scenes from benchmark datasets, Tanks & Temples and ETH3D. This study also proposes the first self-supervised deep-learning model for curved line detection, generating geometric priors for matching so that more attention is put on prominent features and improving the visual effect of 3D reconstruction.

Forest is the largest carbon reservoir and carbon absorber on earth. Thus, mapping forest cover change accurately is of great significance to achieving the global carbon neutrality goal. Accurate forest change information could be acquired by deep learning methods using high-resolution remote sensing images. However, deforestation detection based on deep learning on a large-scale region with high-resolution images required huge computational resources. Therefore, there was an urgent need for a fast and accurate deforestation detection model. In this study, we proposed an interesting but effective re-parameterization deforestation detection model, named RepDDNet. Unlike other existing models designed for deforestation detection, the main feature of RepDDNet was its decoupling feature, which means that it allowed the multi-branch structure in the training stages to be converted into a plain structure in the inference stage, thus the computation efficiency can be significantly improved in the inference stage while maintaining the accuracy unchanged. A large-scale experiment was carried out in Ankang city with 2-meter high-resolution remote sensing images (the total area of it was over 20,000 square kilometers), and the result indicated that the model computation efficiency could be improved by nearly 30% compared with the model without re-parameterization. Additionally, compared with other lightweight models, RepDDNet also displayed a trade-off between accuracy and computation efficiency.

Background: We report here the clinical and genetic features of KMT5B-related neurodevelopmental disorder caused by a novel heterozygous frameshift variant in KMT5B in a Chinese family. Case presentation: A 7-year-old Chinese boy with mild-to-moderate intellectual disability, significant language impairment, motor disability, and coordination difficulties presented to our hospital because he “could not speak and did not look at others.” He was diagnosed with autism spectrum disorder previously owing to developmental delays in cognition, language expression, and understanding. The child also had variable nonspecific features including macrocephaly, wide button-hole space and nasal bridge, low ear, social behavior disorder, and foot deformities. Exome sequencing (ES) revealed that both the proband and his younger brother had inherited a novel heterozygous frameshift variant c.438_439ins[ASD; KT192064.1:1_310] of the KMT5B gene from their father. Bioinformatics analysis showed that the novel mutation affected the structure of the KMT5B pre-SET domain, mainly in the α-helix region. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this type of variant was eventually determined to be likely pathogenic (PVS1+PM2_P). Conclusions: Our investigation expands the mutation spectrum of KMT5B to help us to better understand KMT5B-related neurodevelopmental disorder.

Environmental surveillance (ES) is a useful approach for monitoring circulating viruses, including polioviruses (PVs) and non-polio enteroviruses (NPEVs). In this study, the results of nine years of ES from 2013 to 2021 at six sampling sites in three cities in Fujian Province, China, were summarized. It showed that the sewage samples contained abundant viruses, but the positive rate was affected by different sampling sites. From the 520 samples, 431 PVs, 1,713 NPEVs, and 281 human adenoviruses (HAdVs) were isolated. PV isolates had been markedly affected following the adjustment of the immunization strategy. All but one PV isolate were Sabin-like strains without wild PVs. One isolate was vaccine-derived PV type 3 with 10 variation points in the VP1 region. After May 2016, PV type 2 was no longer detected, and PV type 3 became a superior serotype. Of 1,713 NPEVs, 24 serotypes were identified, including echovirus11 (E11), E6, coxsackievirus B3 (CVB3), CVB5, E7, and E3 were the predominant serotypes (37.65%, 20.96%, 11.50%, 8.87%, 8.23%, and 7.06%, respectively). The temporal dynamic of the six common serotypes was inconsistent. E3 was frequently isolated, but the number of isolates was low, with no obvious peaks. E6, E7, and CVB3 exhibited periodic changes with a high peak every three to four years, and E11 only had one high peak lasting four years. Summer-fall peaks of the echoviruses and spring-winter peaks of CVB were observed in the monthly distribution of virus isolation. The infectious isolates of various serotypes of different species identified from the sewage samples showed that ES is an essential part of pathogen surveillance.

ABSTRACTBig Earth Data refers to the multidimensional integration and association of scientific data, including geography, resources, environment, ecology, and biology. An effective data classification system and label management strategy are important foundations for long-term management of data resources. The objective of this study was to construct a classification system and realize multidimensional semantic data label management for the Big Earth Data Science Engineering Program (CASEarth). This study constructed two sets of classification and coding systems that realize classification by mapping each other; namely, the geosphere-level and Sustainable Development Goals (SDGs) indicator classifications. This technique was based on natural language processing technology and solved problems with subject-word segmentation, weight calculation, and dynamic matching. A prototype system for classification and label management was constructed based on existing CASEarth datasets of more than 1,100. Furthermore, we expect our study to provide the methodology and technical support for user-oriented classification and label management services for Big Earth Data.

This study aimed to compare the sensitivity of two-phase separation and the filtration method using a mixed cellulose ester (MCE) membrane to detect enteroviruses in sewage samples. From December 2015 to July 2016, four domestic sewage samples (1 L/sample) were collected monthly from the Guangzhou Liede Sewage Treatment Plant, and each sewage sample was divided into two aliquots (500 mL). The sewage sample was concentrated using the two-phase separation and the filtration method using an MCE membrane, and the treated solutions were inoculated into cells for enterovirus isolation. Polymerase chain reaction amplification, VP1 sequencing, and enterovirus molecular typing were performed on the positive isolates. The detection rates of poliovirus (PV) and non-polio enterovirus (NPEV) obtained using the filtration method using an MCE membrane were higher than those using the two-phase separation method. McNemar's test showed that the detection rates of PV, NPEV, type 1 Sabin-like (SL1), type 2 Sabin-like (SL2), and type 3 Sabin-like (SL3) strain were not statistically significant (P > 0.05). In Guangdong Province, China, the detection rates for PV and NPEV were 53.13% and 62.50% (20/32), respectively. Twenty-seven PVs were isolated, three highly variable strains of the type 1 vaccine, with seven nucleotide substitutions in the VP1 region, compared with the type 1 Sabin strains. Eighty-seven strains of NPEV were isolated and nine serotypes were identified, among which coxsackievirus B3 (CVB3), echovirus 6(E6), and echovirus 11(E11) were the dominant strains. The filtration method using an MCE membrane is more sensitive than two-phase separation and can be used as a robust, sensitive, and cost-effective method to isolate enteroviruses from sewage.

Industrial heat sources (IHSs) are key contributors to anthropogenic heat, air pollution, and carbon emissions. Accurately and automatically detecting their production areas (IHSPAs) on a large scale is vital for environmental monitoring and decision making, yet this is challenged by the lack of high-resolution thermal data. Sustainable Development Science Satellite 1 (SDGSAT-1) thermal infrared spectrometer (TIS) data with the highest resolution (30 m) in the civilian field and a three-band advantage were first introduced to detect IHSPAs. In this study, an IHSPA identification model using multi-features extracted from SDGSAT-1 TIS and Landsat OLI data and support vector machine (SVM) was proposed. First, three brightness temperatures and four thermal radiation indices using SDGSAT-1 TIS and Landsat OLI data were designed to enlarge the temperature difference between IHSPAs and the background. Then, 10 features combined with three indices from Landsat OLI images with the same spatial resolution (30 m) and stable data were extracted. Second, an IHSPA identification model based on SVM and multi-feature extraction was constructed to identify IHSPAs. Finally, the IHS objects were manually delineated and verified using the identified IHSPAs and Google Earth images. Some conclusions were obtained from different comparisons in Wuhai, China: (1) IHSPA identification based on SVM using thermal and optical features can detect IHSPAs and obtain the best results compared with different features and identification models. (2) The importance of using thermal features from the SDGSAT-1 TIS to detect IHSPAs was demonstrated by different importance analysis methods. (3) Our proposed method can detect more IHSs, with greater spatial coverage and smaller areas, compared with the methods of Ma and Liu. This new way to detect IHSPAs can obtain higher-spatial-resolution emissions of IHSs on a large scale and help decision makers target environmental monitoring, management, and decision making in industrial plant processing.

This work aims to build a comprehensive and effective fire emergency management system based on the Internet of Things (IoT) and achieve an actual intelligent fire rescue. A smart fire protection information system was designed based on the IoT. A detailed analysis was conducted on the problem of rescue vehicle scheduling and the evacuation of trapped persons in the process of fire rescue. The intelligent fire visualization platform based on the three-dimensional (3D) Geographic Information Science (GIS) covers project overview, equipment status, equipment classification, equipment alarm information, alarm classification, alarm statistics, equipment account information, and other modules. The live video accessed through the visual interface can clearly identify the stage of the fire, which facilitates the arrangement of rescue equipment and personnel. The vehicle scheduling model in the system primarily used two objective functions to solve the Pareto Non-Dominated Solution Set Optimization: emergency rescue time and the number of vehicles. In addition, an evacuation path optimization method based on the Improved Ant Colony (IAC) algorithm was designed to realize the dynamic optimization of building fire evacuation paths. The experimental results indicate that all the values of detection signals were significantly larger in the smoldering fire scene at t = 17s than the initial value. In addition, the probability of smoldering fire and the probability of open fire were relatively large according to the probability function of the corresponding fire situation, demonstrating that this model could detect fire. The IAC algorithm reported here avoided the passages near the fire and spreading areas as much as possible and took the safety of the trapped persons as the premise when planning the evacuation route. Therefore, the IoT-based fire information system has important value for ensuring fire safety and carrying out emergency rescue and is worthy of popularization and application.

IntroductionThe experience and perception of stigma is a common problem among primary caregivers of children with autism spectrum disorder (ASD), and has a profound adverse impact on primary caregivers and children with ASD; however, few studies have explored courtesy stigma among primary caregivers of children with ASD in the Chinese context. The aim of this study was to explore the status of courtesy stigma among primary caregivers of children with ASD in Lianyungang, Jiangsu Province, Eastern China, and to conduct in-depth analysis of its predictors from multiple perspectives.MethodsAn institution-based multi-center cross-sectional survey was conducted in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China, from October 2022 to February 2023. A structured questionnaire to assess child-related factors, primary caregiver-related factors, courtesy stigma, general self-efficacy, and social support, was used to collect data. Predictors of courtesy stigma among primary caregivers of children with ASD were identified by linear regression.ResultsA total of 428 primary caregivers of children with ASD were recruited. The mean ± standard deviation (SD) score for courtesy stigma was 7.49 ± 4.13. Multiple linear regression analysis revealed that primary caregivers of children with ASD who were not too satisfied with their current marital status (β = 1.21, 95% CI: 0.34–2.08, p

Metabolic associated fatty liver disease (MAFLD) ranks among the most prevalent chronic liver conditions globally. At present, the mechanism of MAFLD has not been fully elucidated. Tripartite motif (TRIM) protein is a kind of protein with E3 ubiquitin ligase activity, which participates in highly diversified cell activities and processes. It not only plays an important role in innate immunity, but also participates in liver steatosis, insulin resistance and other processes. In this review, we focused on the role of TRIM family in metabolic associated fatty liver disease. We also introduced the structure and functions of TRIM proteins. We summarized the TRIM family’s regulation involved in the occurrence and development of metabolic associated fatty liver disease, as well as insulin resistance. We deeply discussed the potential of TRIM proteins as targets for the treatment of metabolic associated fatty liver disease.

Summary: In 2013, a case of immunodeficiency vaccine-derived poliovirus (iVDPV) was identified in Jiangxi Province, China. In this study, we purified 14 type 3 original viral isolates from this case and characterized the molecular evolution of these iVDPVs for 298 days. Genetic variants were found in most of the original viral isolates, with complex genetic and evolutionary relationships among the variants. A phylogenetic tree constructed based on the P1 region showed that these iVDPVs were classified into lineage A and B. The dominant lineage B represents a major trend in virus evolution. The nucleotide substitution rate at the third codon position (3CP) estimated by the BEAST program was 1.76 × 10−2 substitutions/site/year (95% HPD: 1.23-2.39 × 10−2). The initial OPV dose was given dating back to March 2013, which was close to the time of the last OPV vaccination, suggesting that OPV infection may have originated with the last dose of vaccine. Recombinant analysis showed that these iVDPVs were inter-vaccine recombinants with two recombination patterns, S3/S2/S1 and S3/S2/S3/S2/S1. Whole genome sequence analysis revealed that key nucleotide sites (C472U, C2034U, U2493C) associated with the attenuated phenotype of Sabin 3 have been replaced. Temperature sensitivity test showed that all tested strains were temperature-sensitive, except for the variant Day11-5. Interestingly, we observed that the variant Day11-5 temperature resistance properties may be associated with the Lys to Met substitution at the VP2-162 site. Serological test and whole genome sequence analysis showed that the seropositivity rate remained high, and mutations in the antigenic sites did not significantly alter neutralization ability.

Abstract Background Vaccine-derived poliovirus (VDPV) is a potential threat to polio eradication because they can reintroduce into the general population and cause paralytic polio outbreaks, a phenomenon that has recently emerged as a prominent public health concern at the end of global polio eradication. This study aimed to describe the epidemiology and genetic characteristics of the first VDPV identified from a patient with acute flaccid paralysis (AFP), with four doses of inactivated polio vaccine immunization in Henan Province, China in 2017. Methods The patient was diagnosed with type 3 VDPV. Subsequently, a series of epidemiological approaches was implemented, including a retrospective search of AFP cases, rate of vaccination assessment, study of contacts, and supplementary immunization activities. Fecal samples were collected, viral isolation was performed, and the viral isolates were characterized using full-length genomic sequencing and bioinformatic analysis. Results Phylogenetic analysis showed that the viral isolates from the patient were different from other reported genetic clusters of type 3 VDPV worldwide. They were identified as a Sabin 3/Sabin 1 recombinant VDPV with a crossover site in the P2 region. Nucleotide substitutions, including U → C (472) and C → U (2493), have been identified, both of which are frequently observed as reversion mutations in neurovirulent type 3 poliovirus. A unique aspect of this case is that the patient had been vaccinated with four doses of inactive polio vaccine, and the serum neutralizing antibody for Sabin types 1 and 3 were 1∶16 and 1∶512, respectively. Thus, the patient was speculated to have been infected with type 3 VDPV, and the virus continued to replicate and be excreted for at least 41 d. Conclusions The existence of this kind of virus in human population is a serious risk and poses a severe challenge in maintaining a polio-free status in China. To the best of our knowledge, this is the first report of VDPV identified in the Henan province of China. Our results highlight the importance of maintaining a high-level vaccination rate and highly sensitive AFP case surveillance system in intercepting VDPV transmission.

The recent emergence of COVID-19 variants has necessitated the development of new vaccines that stimulate the formation of high levels of neutralizing antibodies against S antigen variants. A new strategy involves the intradermal administration of heterologous vaccines composed of one or two doses of inactivated vaccine and a booster dose with the mutated S1 protein (K-S). Such vaccines improve the immune efficacy by increasing the neutralizing antibody titers and promoting specific T cell responses against five variants of the RBD protein. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that both administration schedules (i.e. “1 + 1” and “2 + 1”) ensured protection against this strain. These results suggest that the aforementioned strategy is effective for protecting against new variants and enhances the anamnestic immune response in the immunized population.

It is crucial to detect and classify industrial heat sources for sustainable industrial development. Sustainable Development Science Satellite 1 (SDGSAT-1) thermal infrared spectrometer (TIS) data were first introduced for detecting industrial heat source production areas to address the difficulty in identifying factories with low combustion temperatures and small scales. In this study, a new industrial heat source identification and classification model using SDGSAT-1 TIS and Landsat 8/9 Operational Land Imager (OLI) data was proposed to improve the accuracy and granularity of industrial heat source recognition. First, multiple features (thermal and optical features) were extracted using SDGSAT-1 TIS and Landsat 8/9 OLI data. Second, an industrial heat source identification model based on a support vector machine (SVM) and multiple features was constructed. Then, industrial heat sources were generated and verified based on the topological correlation between the identification results of the production areas and Google Earth images. Finally, the industrial heat sources were classified into six categories based on point-of-interest (POI) data. The new model was applied to the Beijing–Tianjin–Hebei (BTH) region of China. The results showed the following: (1) Multiple features enhance the differentiation and identification accuracy between industrial heat source production areas and the background. (2) Compared to active-fire-point (ACF) data (375 m) and Landsat 8/9 thermal infrared sensor (TIRS) data (100 m), nighttime SDGSAT-1 TIS data (30 m) facilitate the more accurate detection of industrial heat source production areas. (3) Greater than 2~6 times more industrial heat sources were detected in the BTH region using our model than were reported by Ma and Liu. Some industrial heat sources with low heat emissions and small areas (53 thermal power plants) were detected for the first time using TIS data. (4) The production areas of cement plants exhibited the highest brightness temperatures, reaching 301.78 K, while thermal power plants exhibited the lowest brightness temperatures, averaging 277.31 K. The production areas and operational statuses of factories could be more accurately identified and monitored with the proposed approach than with previous methods. A new way to estimate the thermal and air pollution emissions of industrial enterprises is presented.

Objective: The purpose of this study was to evaluate the efficacy and safety of Zishen Yutai Pill combined with western medicine for the treatment of women with threatened miscarriage during the first trimester of pregnancy. Methods: Randomized controlled trials published before the end of Apr 1, 2023 on Zishen Yutai Pill and threatened miscarriage were systematically retrieved from China National Knowledge Infrastructure, Wanfang, Sinomed, VIP, PubMed, EMBASE, Web of Science and the Cochrane Library. The international clinical trial registration platform and the Chinese clinical trial registration platform of clinical trials was searched from their inception until Apr 1, 2023. Meta analysis of random effect model was used to combine the research data. Chi-squared test and I2 statistics were used for heterogeneity test. Results: Twenty-three trials (enrolling 2411 participants) were included in the review. Zishen Yutai pill combined with western medicine therapy showed significant improvement on human chorionic gonadotropin [MD 19.33 IU/ml, 95% CI (15.84, 22.81)], the total effective rate [RR 1.19, 95% CI (1.15–1.23)], progesterone [MD 7.14 ng/ml, 95% CI (6.14, 8.13)], estradiol [MD 33.69 pg/ml, 95% CI (27.42, 39.96)], duration of abdominal pain [MD -2.36 d, 95% CI (- 3.54, - 1.18)], duration of vaginal bleeding [MD -1.94 d, 95% CI (- 2.93, - 0.94)], and fibrinogen [MD -0.34 g/L, 95% CI (- 0.57, - 0.11)]. There was no significant difference in hematocrit [MD 0.68%, 95% CI (- 0.08, 1.44)] between the experimental and the control group. Zishen Yutai Pill may improve the clinical symptoms in women with threatened miscarriage, such as human chorionic gonadotropin the total effective rate, progesterone, estradiol, duration of abdominal pain, duration of vaginal bleeding, and fibrinogen. Especially for progesterone, the effect of treatment ≦2 weeks is significantly better than treatment of >2 weeks. For estradiol, the effect of treatment >2 weeks is significantly better than treatment of ≦ 2 weeks. Conclusion: Zishen Yutai Pill, as a complementary therapy, significantly improved human chorionic gonadotropin, the total effective rate, progesterone, estradiol, abdominal pain, vaginal bleeding, and fibrinogen in patients with threatened miscarriage in first-trimester pregnancy. However, the systematic review has some limitations, such as degraded information quality, no blinding of patients or doctors, etc. Due to the small sample size and low quality of research, it needs to be further confirmed by large sample and high-quality randomized controlled trials, such as blinding of patients, doctors and outcome assessment should be complemented, clinical follow-up, live birth rate, fetal growth should be supplemented. Systematic review registration: INPLASY202320039.

Abstract Background To assess the correlation between ocular residual astigmatism and anterior corneal astigmatism in children with low and moderate myopia. Methods Refractive astigmatism was determined by subjective manifest refraction. Anterior corneal astigmatism was determined by IOL Master. Thibos vector analysis was used to calculate ocular residual astigmatism. Correlation analysis was used to assess the relationship between the amounts of ocular residual astigmatism and anterior corneal astigmatism. The relationship between the vectors of ocular residual astigmatism and anterior corneal astigmatism was evaluated by a physical method. Results The study analysed 241 right eyes of 241 children aged 8 to 18 years old. In this study, the median magnitude of ocular residual astigmatism was 1.02 D, with an interquartile range was of 0.58 D. Against-the-rule ocular residual astigmatism was seen in 232 eyes (96.3%). There was a significant and moderate correlation between ocular residual astigmatism and anterior corneal astigmatism (r = 0.50, P

Abstract Background Echovirus 9 (E9) is associated with a wide variety of diseases and medical conditions, and the clinical symptoms of sporadic cases caused by E9 often are severe. With a high global prevalence, E9 has caused multiple outbreaks worldwide. However, little is known about the genetic and geographic population dynamics of E9. Method A total of 131 VP1 gene sequences, including15 generated in this study and 116 obtained from GenBank, were used to coestimate time-resolved phylogenies to infer viral evolution and transmission in worldwide. Overlapping fragments representing whole genomes were amplified by reverse transcription polymerase chain reaction (RT-PCR) using specific primers. Then, we reported the genetic characteristics of fifteen E9 strains in the Chinese Mainland. Similarity plots and bootscanning analysis were used to determine recombination patterns of E9. Results The estimated mean evolutionary rate of global E9 VP1 gene was 4.278 × 10−3 substitutions per site per year (95% confidence interval [CI], 3.822 × 10−3/site/year to 4.710 × 10−3/site/year), and the common ancestor of E9 likely emerged around 1868 (95% CI, 1840 to 1892). The full-length genomic sequences of the fifteen E9 strains showed 76.9–79.6% nucleotide identity and 95.3–95.9% amino acid identity with E9 Barty strain. 11 of 15 E9 whole genome sequence present four recombination patterns, and E9 recombinants have extensive genetic exchanges in the 2C and P3 regions with other Enterovirus B (EV-B) circulated in China. Four of six E9 strains were temperature sensitive, and two were temperature resistant, and a comparative genomics analysis suggested that 411, 865 and 867 amino acid substitution in the P1 region was related to temperature sensitivity. Conclusion This study highlights a persistent transmission network of E9 in worldwide, provides valuable information regarding the molecular epidemiology of E9.

As the proportion of non-enterovirus 71 and non-coxsackievirus A16 which proportion of composition in the hand, foot, and mouth pathogenic spectrum gradually increases worldwide, the attention paid to other enteroviruses has increased. As a member of the species enterovirus A, coxsackievirus A14 (CVA14) has been epidemic around the world until now since it has been isolated. However, studies on CVA14 are poor and the effective population size, evolutionary dynamics, and recombination patterns of CVA14 are not well understood. In this study, 15 CVA14 strains were isolated from HFMD patients in mainland China from 2009 to 2019, and the complete sequences of CVA14 in GenBank as research objects were analyzed. CVA14 was divided into seven genotypes A-G based on an average nucleotide difference of the full-length VP1 coding region of more than 15%. Compared with the CVA14 prototype strain, the 15 CVA14 strains showed 84.0–84.7% nucleotide identity in the complete genome and 96.9–97.6% amino acid identity in the encoding region. Phylodynamic analysis based on 15 CVA14 strains and 22 full-length VP1 sequences in GenBank showed a mean substitution rate of 5.35 × 10−3 substitutions/site/year (95% HPD: 4.03–6.89 × 10−3) and the most recent common ancestor (tMRCA) of CVA14 dates back to 1942 (95% HPD: 1930–1950). The Bayesian skyline showed that the effective population size had experienced a decrease–increase–decrease fluctuation since 2004. The phylogeographic analysis indicated two and three possible migration paths in the world and mainland China, respectively. Four recombination patterns with others of species enterovirus A were observed in 15 CVA14 strains, among which coxsackievirus A2 (CVA2), coxsackievirus A4 (CVA4), coxsackievirus A6 (CVA6), coxsackievirus A8 (CVA8), and coxsackievirus A12 (CVA12) may act as recombinant donors in multiple regions. This study has filled the gap in the molecular epidemiological characteristics of CVA14, enriched the global CVA14 sequence database, and laid the epidemiological foundation for the future study of CVA14 worldwide.

Abstract The C4 sub-genotype of Enterovirus 71 (EV71) has been identified as the most dominant sub-genotype circulating in the Chinese mainland since 1998. The circulation situation of EV71 before 1998 is not well established due to insufficient experimental data. The C1 subgenotype of EV71 has not yet been reported in the Chinese mainland by now. Based on the AFP surveillance system of the mainland of China, this study conducted a retrospective study of AFP cases for 1985–1999: a strain of EV-A71 C1 subgenotype was found. To our knowledge, this strain (SD92-41) is the first C1 sub-genotype reported in the Chinese mainland. This study demonstrates that the C1 gene subtype also appeared in the Chinese mainland, but it is unknown whether it is an imported or a local epidemic strain. With sufficient information known from retrospective studies, the source of the SD92-41 strain will be identified and the prevalence of EV-A71 in the Chinese mainland before 1998 will be clearer.

Abstract Background Coxsackievirus B3 (CVB3) has emerged as an active pathogen in myocarditis, aseptic meningitis, hand, foot, and mouth disease (HFMD), and pancreatitis, and is a heavy burden on public health. However, CVB3 has not been systematically analyzed with regard to whole-genome diversity and recombination. Therefore, this study was undertaken to systematically examine the genetic characteristics of CVB3 based on its whole genome. Methods We combined CVB3 isolates from our national HFMD surveillance and global sequences retrieved from GenBank. Phylogenetic analysis was performed to examine the whole genome variety and recombination forms of CVB3 in China and worldwide. Results Phylogenetic analysis showed that CVB3 strains isolated worldwide could be classified into clusters A–E based on the sequence of the entire VP1 region. The predominant CVB3 strains in China belonged to cluster D, whereas cluster E CVB3 might be circulated globally compared to other clusters. The average nucleotide substitution rate in the P1 region of CVB3 was 4.82 × 10–3 substitutions/site/year. Myocarditis was more common with cluster A. Clusters C and D presented more cases of acute flaccid paralysis, and cluster D may be more likely to cause HFMD. Multiple recombination events were detected among CVB3 variants, and there were twenty-three recombinant lineages of CVB3 circulating worldwide. Conclusions Overall, this study provides full-length genomic sequences of CVB3 isolates with a wide geographic distribution over a long-term time scale in China, which will be helpful for understanding the evolution of this pathogen. Simultaneously, continuous surveillance of CVB3 is indispensable to determine its genetic diversity in China as well as worldwide.

Coxsackievirus A12 (CVA12) is an enterovirus that has been isolated in many countries in recent years. However, studies on CVA12 are limited, and its effective population size, evolutionary dynamics and recombination patterns have not been clarified now. In this study, we described the phylogenetic characteristics of 16 CVA12 strains isolated from pediatric HFMD patients in mainland China from 2010 to 2019. Comparison of the nucleotide sequences and amino acid sequences with the CVA12 prototype strain revealed that the 16 CVA12 strains are identical in 78.8–79% and 94–94.2%, respectively. A phylodynamic analysis based on the 16 full-length VP1 sequences from this study and 21 sequences obtained from GenBank revealed a mean substitution rate of 6.61 × 10−3 substitutions/site/year (95% HPD: 5.16–8.20 × 10−3), dating the time to most recent common ancestor (tMRCA) of CVA12 back to 1946 (95% HPD: 1942–1947). The Bayesian skyline plot showed that the effective population size has experienced twice dynamic fluctuations since 2007. Phylogeographic analysis identified two significant migration pathways, indicating the existence of cross-provincial transmission of CVA12 in mainland China. Recombination analysis revealed two recombination patterns between 16 CVA12 strains and other EV-A, suggesting that there may be extensive genetic exchange between CVA12 and other enteroviruses. In summary, a total of 16 full-length CVA12 strains were reported in this study, providing valuable references for further studies of CVA12 worldwide.

The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.

This study determined the global genetic diversity and transmission dynamics of enterovirus B83 (EV-B83) and proposed future disease surveillance directions. Blood samples were collected from a patient with viral myocarditis, and viral isolation was performed. The complete genome sequence of the viral isolate was obtained using Sanger sequencing. A dataset of 15 sequences (from three continents) that had sufficient time signals for Bayesian phylogenetic analysis was set up, and the genetic diversity and transmission dynamics of global EV-B83 were analyzed using bioinformatics methods, including evolutionary dynamics, recombination event analysis, and phylogeographic analysis. Here, we report the complete genome sequence of an EV-B83 strain (S17/YN/CHN/2004) isolated from a patient with acute viral myocarditis in Yunnan Province, China. All 15 EV-B83 strains clustered together in a phylogenetic tree, confirming the classification of these isolates as a single EV type, and the predicted time for the most recent common ancestor appeared in 1998. Recombinant signals were detected in the 5’-untranslated region and 2A–3D coding regions of the S17 genome. The phylogeographic analysis revealed multiple intercontinental transmission routes of EV-B83. This study indicates that EV-B83 is globally distributed. Our findings add to the publicly available EV-B83 genomic sequence data and deepen our understanding of EV-B83 epidemiology.

Abstract Background Parechoviruses (PeV-As), which constitute a new genus within the family Picornaviridae, have been associated with numerous localized outbreaks of serious diseases, such as coryza, pneumonia, maculopapular exanthem, and conjunctivitis. However, to the best of our knowledge, only a few laboratories worldwide conduct tests for the identification of this group of viruses. Therefore, in this study, we aimed to develop and validate a real-time RT-PCR assay for the identification of PeV-As. Methods To design and validate a real-time PCR primer–probe targeting the 5′-UTR region of PeV-As, the 5′-UTR sequences of PeV-As available in GenBank were aligned using the MUSCLE algorithm in MEGA v7.0. Thereafter, the highly conserved 5′-UTR region was selected, and its primer–probe sequence was designed using Primer Premier v5.0. This primer–probe sequence was then evaluated for specificity, sensitivity, and repeatability, and for its validation, it was tested using fecal samples from 728 healthy children living in Beijing (China). Results The PeV-A real-time RT-PCR assay detected only the RNA-positive standards of PeV-A genotypes (1–8, 14, 17, and 18), whereas 72 serotypes of non-PeV-A EV viruses were undetected. In addition, the VP1 region of these 11 PeV-A genotypes that tested positive were amplified using the primers designed in this study. Typing results indicated that eight, one, and two strains of the 11 were PeV-A1, PeV-A4, and PeV-A6, respectively. We also determined and presented the genetic characterization and phylogenetic analyses results corresponding to these 11 VP1 region sequences. Furthermore, real-time RT-PCR assay showed good sensitivity with LOD of 102 copies/μL. Positive results in eight parallel experiments at each concentration gradient from 107 copies/μL to 102 copies/μL, indicating good repeatability. Conclusion Our findings suggested that the real-time RT-PCR assay developed in this study can be applied for routine PeV-A identification. We detected PeV-A1, 4 and 6 genotypes in the 728 faecal samples using this method. Additionally, we believe that our results will serve as a foundation for further studies on PeV-As and facilitate the expansion of the gene sequence information available in GenBank.

The limited driving range and the unavailability or insufficiency of battery charging/swapping stations cause the so-called range anxiety issue for traffic assignment involving battery electric vehicle (BEV) users. In addition, expected utility theory-based stochastic user equilibrium (EUT-SUE) model generates the perfectly rational issue when the travellers make route choice decisions. To tackle these two problems, this article improves the cumulative prospect theory-based stochastic user equilibrium (CPT-SUE) model in a degradable transport network through incorporating the constraints of multiple user classes and distance limit. In this degradable network, the travellers experience stochastic travel times due to network link capacity degradations. For this improved CPT-SUE model, the equivalent variational inequality (VI) model and associated method of successive averages (MSA) based solution are provided. The improved CPT-SUE model is tested and compared with the EUT-SUE model with distance limit, with results showing that the improved CPT-SUE model can handle jointly the range anxiety issue and the perfectly rational issue.

ABSTRACT Enterovirus A71 (EV-A71) is one of the main pathogens causing hand, foot, and mouth disease (HFMD) outbreaks in Asian children under 5 years of age. In severe cases, it can cause neurological complications and be life-threatening. In this study, 200 newly sequenced EV-A71 whole-genome sequences were combined with 772 EV-A71 sequences from GenBank for large-scale analysis to investigate global EV-A71 epidemiology, phylogeny, and Bayesian phylodynamic characteristics. Based on the phylogenetic analysis of the EV-A71 3Dpol region, six new evolutionary lineages (lineages B, J, K, O, P, and Q) were found in this study, and the number of evolutionary lineages was expanded from 11 to 17. Temporal dynamics and recombination breakpoint analyses based on genotype C revealed that recombination of nonstructural protein-coding regions, including 3Dpol, is an important reason for the emergence of new lineages. The EV-A71 epidemic in the Asia-Pacific region is complex, and phylogeographic analysis found that Vietnam played a key role in the spread of subgenotypes B5 and C4. The origin of EV-A71 subgenotype C4 in China is East China, which is closely related to the prevalence of subgenotype C4 in the south and throughout China. Selection pressure analysis revealed that, in addition to VP1 amino acid residues VP1-98 and VP1-145, which are associated with EV-A71 pathogenicity, amino acid residues VP1-184 and VP1-249 were also positively selected, and their functions still need to be determined by biology and immunology. This study aimed to provide a solid theoretical basis for EV-A71-related disease surveillance and prevention, antiviral research, and vaccine development through a comprehensive analysis. IMPORTANCE EV-A71 is one of the most important pathogens causing HFMD outbreaks; however, large-scale studies of EV-A71 genomic epidemiology are currently lacking. In this study, 200 new EV-A71 whole-genome sequences were determined. Combining these with 772 EV-A71 whole-genome sequences in the GenBank database, the evolutionary and transmission characteristics of global and Asian EV-A71 were analyzed. Six new evolutionary lineages were identified in this study. We also found that recombination in nonstructural protein-coding regions, including 3Dpol, is an important cause for the emergence of new lineages. The results provided a solid theoretical basis for EV-A71-related disease surveillance and prevention, antiviral research, and vaccine development.

BackgroundThe diversity in currently documented viruses and their morphological characteristics indicates the need for understanding the evolutionary characteristics of viruses. Notably, further studies are needed to obtain a comprehensive landscape of virome, the virome of host species in Yunnan province, China.Materials and methodsWe implemented the metagenomic next-generation sequencing strategy to investigate the viral diversity, which involved in 465 specimens collected from bats, pangolins, monkeys, and other species. The diverse RNA viruses were analyzed, especially focusing on the genome organization, genetic divergence and phylogenetic relationships.ResultsIn this study, we investigated the viral composition of eight libraries from bats, pangolins, monkeys, and other species, and found several diverse RNA viruses, including the Alphacoronavirus from bat specimens. By characterizing the genome organization, genetic divergence, and phylogenetic relationships, we identified five Alphacoronavirus strains, which shared phylogenetic association with Bat-CoV-HKU8-related strains. The pestivirus-like virus related to recently identified Dongyang pangolin virus (DYPV) strains from dead pangolin specimens, suggesting that these viruses are evolving. Some genomes showed higher divergence from known species (e.g., calicivirus CS9-Cali-YN-CHN-2020), and many showed evidence of recombination events with unknown or known strains (e.g., mamastroviruses BF2-astro-YN-CHN-2020 and EV-A122 AKM5-YN-CHN-2020). The newly identified viruses showed extensive changes and could be assigned as new species, or even genus (e.g., calicivirus CS9-Cali-YN-CHN-2020 and iflavirus Ifla-YN-CHN-2020). Moreover, we identified several highly divergent RNA viruses and estimated their evolutionary characteristics among different hosts, providing data for further examination of their evolutionary dynamics.ConclusionOverall, our study emphasizes the close association between emerging viruses and infectious diseases, and the need for more comprehensive surveys.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the existing prognosis systems based on clinical variables are difficult to stratify patients accurately. Nutritional indices play a meaningful role in prognosis of solid tumors, whereas the effect on DLBCL is still equivocal. This retrospective study aimed to develop a novel model based on nutritional indices and other clinical variables to accurately differentiate the prognosis of DLBCL.MethodsA total of 129 patients pathologically diagnosed with DLBCL in Affiliated Hospital of Xuzhou Medical University from 2014 to 2018 were retrospectively recruited. The total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) at the third lumbar vertebra level spine were obtained by computed tomography (CT) to assess the effect of nutritional status on the prognosis of DLBCL. Principal component analysis was used to reduce the dimension of nutritional indices, and continuous variables were evaluated according to X-Tile and Restricted cubic spline. Univariable and multivariable Cox proportional hazard analyses were performed on potential variables. Kaplan-Meier method was utilized to evaluate survival probabilities and the differences between groups were assessed by log-rank test.ResultsX-Tile analysis divided VFA and albumin into two and three groups when applying 114.7 cm2 of VFA, 38.3 and 42.4 g/L of albumin as the optimal cut-off points, respectively. The final scoring model of nutrition-related prognostic index (NPI) comprised four independent prognostic variables. The C-index of the final model was 0.823 [95% CI (0.749~0.897)] by bootstrap resampling. Finally, a maximum score of 6 points was obtained. Compared with IPI, NCCN-IPI and GELTAMO-IPI, NPI showed better accuracy in discerning the prognostic risk of patients.ConclusionVFA and albumin were associated with the prognosis of DLBCL, and the NPI model based on nutritional indices could better stratify the prognosis of DLBCL.

A booster vaccination is called for constraining the evolving epidemic of SARS-CoV-2. However, the necessity of a new COVID-19 vaccine is currently unclear. To compare the effect of an Omicron-matched S DNA vaccine and an ancestral S DNA vaccine in boosting cross-reactive immunities, we firstly immunized mice with two-dose of a DNA vaccine encoding the spike protein of the ancestral Wuhan strain. Then the mice were boosted with DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8+ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron-matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-protective immunities.

A variety of methods have been explored to increase delivery efficiencies for DNA vaccine. However, the immunogenicity of DNA vaccines has not been satisfactorily improved. Unlike most of the previous attempts, we provided evidence suggesting that changing the injection site successively (successively site-translocated inoculation, SSTI) could significantly enhance the immunogenicity of DNA vaccines in a previous study. To simplify the strategy and to evaluate its impact on candidate SARS-CoV-2 vaccines, we immunized mice with either a SARS-CoV-2 spike-based DNA vaccine or a spike protein subunit vaccine via three different inoculation strategies. Our data demonstrated that S protein specific antibody responses elicited by the DNA vaccine or the protein subunit vaccine showed no significant difference among different inoculation strategies. Of interest, compared with the conventional site fixed inoculation (SFI), both successive site-translocating inoculation (SSTI) and the simplified translocating inoculation (STI) strategy improved specific T cell responses elicited by the DNA vaccine. More specifically, the SSTI strategy significantly improved both the monofunctional (IFN-γ+IL-2-TNF-α-CD8+) and the multifunctional (IFN-γ+IL-2-TNF-α+CD8+, IFN-γ+IL-2-TNF-α+CD4+, IFN-γ+IL-2+TNF-α+CD4+) T cell responses, while the simplified translocating inoculation (STI) strategy significantly improved the multifunctional CD8+ (IFN-γ+IL-2-TNF-α+CD8+, IFN-γ+IL-2+TNF-α+CD8+) and CD4+ (IFN-γ+IL-2-TNF-α+CD4+, IFN-γ+IL-2+TNF-α+CD4+) T cell responses. The current study confirmed that changing the site of intra muscular injection can significantly improve the immunogenicity of DNA vaccines.

Anti-CD30 CAR-T is a potent candidate therapy for relapsed/refractory (r/r) CD30+ lymphomas with therapy limitations, and the efficacy needed to be further improved. Herein a multi-center phase II clinical trial (NCT03196830) of anti-CD30 CAR-T treatment combined with PD-1 inhibitor in r/r CD30+ lymphoma was conducted. After a lymphocyte-depleting chemotherapy with fludarabine and cyclophosphamide, 4 patients in cohort 1 and 3 patients in cohort 2 received 106/kg and 107/kg CAR-T cells, respectively, and 5 patients in cohort 3 received 107/kg CAR-T cells combined with anti-PD-1 antibody. The safety and the efficacy of CAR-T cell therapy were analyzed. Cytokine release syndrome (CRS) was observed in 4 of 12 patients, and only 1 patient (patient 9) experienced grade 3 CRS and was treated with glucocorticoid and tocilizumab. No CAR-T-related encephalopathy syndrome was observed. Only two patients in cohorts 2 and 3 experienced obviously high plasma levels of IL-6 and ferritin after CD30 CAR-T cell infusion. The overall response rate (ORR) was 91.7% (11/12), with 6 patients achieving complete remission (CR) (50%). In cohorts 1 and 2, 6 patients got a response (85.7%), with 2 patients achieving CR (28.6%). In cohort 3, 100% ORR and 80% CR were obtained in 5 patients without ≥3 grade CRS. With a median follow-up of 21.5 months (range: 3-50 months), the progression-free survival and the overall survival rates were 45 and 70%, respectively. Of the 11 patients who got a response after CAR-T therapy, 7 patients (63.6%) maintained their response until the end of follow-up. Three patients died last because of disease progression. Taken together, the combination of anti-PD-1 antibody showed an enhancement effect on CD30 CAR-T therapy in r/r CD30+ lymphoma patients with minimal toxicities.

The aim of this study was to determine the global genetic diversity and transmission dynamics of coxsackievirus B4 (CVB4) and to propose future directions for disease surveillance. Next-generation sequencing was performed to obtain the complete genome sequence of CVB4, and the genetic diversity and transmission dynamics of CVB4 worldwide were analyzed using bioinformatics methods such as phylogenetic analysis, evolutionary dynamics, and phylogeographic analysis. Forty complete genomes of CVB4 were identified from asymptomatic infected individuals and hand, foot, and mouth disease (HFMD) patients. Frequent recombination between CVB4 and EV-B multiple serotypes in the 3Dpol region was found and formed 12 recombinant patterns (A-L). Among these, the CVB4 isolated from asymptomatic infected persons and HFMD patients belonged to lineages H and I, respectively. Transmission dynamics analysis based on the VP1 region revealed that CVB4 epidemics in countries outside China were dominated by the D genotype, whereas the E genotype was dominant in China, and both genotypes evolved at a rate of > 6.50 × 10−3 substitutions/site/year. CVB4 spreads through the population unseen, with the risk of disease outbreaks persisting as susceptible individuals accumulate. Our findings add to publicly available CVB4 genomic sequence data and deepen our understanding of CVB4 molecular epidemiology.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from the Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cutoff points of continuous variables; univariate and multivariate Cox analyses were used for variable selection, and the Kaplan–Meier curve was used to analyze the value of variables on prognosis. The C-index, Brier Score, and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio, and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in the derivation and validation cohorts by using a bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous non-Hodgkin lymphoma, and the prognosis of DLBCL patients is widely affected by multivariables. Clinical-factors-based prognostic systems stratify the prognosis of DLBCL with certain limitations, and the value of ferritin on the prognosis of DLBCL is unclear. In this study, 225 cases were retrieved from 4 centers of Huaihai Lymphoma Working Group (HHLWG) as the derivation cohort, and 66 cases were from the other 6 centers of HHLWG as external validation cohort. X-Tile program divided ferritin into three groups when applying 175.00 and 391.90 μg/L as the optimal cutoff points. Based on multivariable analysis, ferritin appeared to be a stronger predictor. A total of three variables (ferritin, age, and lactate dehydrogenase) were included for the development of the nomogram. The C-indexes were 0.73 and 0.70 in the derivation and validation cohort, and the calibration curve showed the consistency between the nomogram prediction and the actual observation. In conclusion, Ferritin-based nomogram enhanced the prognostic value of IPI in DLBCL.

Introduction Threatened miscarriages is a common complication of first-trimester pregnancy. Due to the beneficial effects, there are increasing clinical studies on Yunkang oral liquid(YKOL). However, the efficacy and safety of YKOL are still unknown. The aim of this systematic review was to assess the efficacy and safety of YKOL in the treatment of threatened miscarriage during the first-trimester pregnancy (TMFP). Methods This protocol will be prepared according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. The systematic review will include all randomized controlled trials (RCTs) studies published until April 2021. Electronic sources including CNKI, WF, VIP, CBM, MEDLINE(PubMed), Embase, Cochrane Library, and Web of Science will be searched for potentially eligible studies. The international clinical trial registration platform and the Chinese clinical trial registration platform of controlled trials will be searched from their inception until April 1st, 2021. According to the inclusion and exclusion criteria, screening literature, extraction data will be conducted by two researchers independently. Statistical analysis will use RevMan 5.3.5 software. The strength of evidence from the studies will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods. Results This study will provide evidence for YKOL combined with conventional therapy for TMFP. Conclusion The efficacy and safety of YKOL combined with conventional therapy for TMFP will be assessed. Systematic review registration INPLASY202140105 (https://www.doi.org/10.37766/inplasy2021.4.0105).

Abstract Purpose Anti‐CD19 chimeric antigen receptor T (CAR‐T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti‐CD19 and anti‐CD20 CAR‐T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity. Methods Totally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti‐CD19 and anti‐CD20 CAR‐T cells. Treatment response, toxicity, and persistence were monitored continuously. Results Of the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%‐94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%‐74.3%) had a complete response (CR). Peak levels of anti‐CD19 and anti‐CD20 CAR cells were associated with response (P = .007 and .002). Grade 3‐4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression‐free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level. Conclusions Coadministration of anti‐CD19 and CD20 CAR‐T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at www.clinicaltrials.gov as NCT03207178.

This paper proposes a new hybrid evaluation method including Improved Analytic Hierarchy Process (IAHP), Entropy Method (EM), and Grey Comprehensive Evaluation Method (GCEM) to assess the transfer efficiency between rail transit and public bicycles. In particular, the IAHP method that replaces the nine-scale approach with three-scale approach to naturally meet the consistency requirements is applied to qualitatively calculate the weights of evaluation indices, the EM method is utilized to calculate the weights of evaluation indices with relatively high degrees of quantification, and the GCEM method is used to calculate the transfer efficiency between rail transit and public bicycles. In addition, a three-level evaluation-index system including target level, criteria level and index level is established. A numerical example is also provided to verify the feasibility of the proposed hybrid evaluation method and explore the reasons for low transfer efficiency between rail transit and public bicycles.

ABSTRACTCoronavirus disease 2019 (COVID-19) has become a pandemic with increasing numbers of cases worldwide. SARS-CoV-2, the causative virus of COVID-19, is mainly transmitted through respiratory droplets or through direct and indirect contact with an infected person. The possibility of potential faecal-oral transmission was investigated in this study. We collected 258 faecal specimens from nine provinces in China and detected the nucleic acid of SARS-CoV-2 using real-time RT–PCR. Vero cells were used to isolate the virus from SARS-CoV-2 nucleic acid positive samples, after which sequencing of Spike gene in eight samples was performed. In all, 93 of 258 (36%) stool samples were positive for SARS-CoV-2 RNA. The positive rates of critical, severe, moderate, and mild patients were 54.4%, 56.1%, 30.8%, and 33.3%, respectively. The content of nucleic acid increased within 2 weeks after the onset of the disease. From the perspective of clinical typing, the nucleic acid can be detected in the faeces of critical patients within two weeks and until four to five weeks in the faeces of severe and mild patients. SARS-CoV-2 was isolated from stool specimens of two severe patients. Four non-synonymous mutations in Spike gene were newly detected in three stool samples. A small number of patients had strong faecal detoxification ability. The live virus in faeces could be an important source of contamination, which may lead to infection and further spread in areas with poor sanitary conditions. The findings of this study have public health significance and they should be considered when formulating disease control strategies.

ABSTRACTEV-A120 is a recently identified serotype of the enterovirus A species. Only one full-length genomic sequence is currently available in GenBank, and very few studies have been conducted on EV-A120 globally. Thus, additional information and research on EV-A120 are needed to explore its genetic characteristics, phylogeny, and relationship with enteroviral disease. In this study, we report the phylogenetic characteristics of a EV-A120 strain (Q0082/XZ/CHN/2000) from Tibet, China. The amino acid sequence similarity and nucleotide sequence similarity of the full-length genomic sequence of this EV-A120 strain and the EV-A120 prototype strain were 96.3% and 79.9%, respectively, showing an evolutionary trend. Recombination analysis found intraspecies recombination in the 5′ -UTR, 2B, 2C, and 3D regions. Serum neutralization testing of the EV-A120 (Q0082) strain was also carried out. Low serum-positive rates and geometric mean titres (GMTs) indicated that the extent of EV-A120 transmission and exposure in the population was very limited compared with that in the outbreaks of EV-A71 and CV-A16 in China since 2008. The EV-A120 strain (Q0082) is non-temperature sensitive, indicating its potential to spread in the population. In summary, this study reports the full-length genomic sequence of EV-A120 and provides important information for its global molecular epidemiology.

A nation-wide case surveillance was conducted in China since 1995 for the objective of identifying acute flaccid paralysis (AFP) in children so that potential wild polioviruses and vaccine-derived poliovirus (VDPV) could be identified on time. Two outbreaks associated with type I circulating VDPVs, eight native independent type I ambiguous VDPVs (aVDPV), and one imported aVDPV were identified during the AFP case surveillance in China from 1995 to 2019. The VP1 coding region of the Chinese type I VDPVs differed from the polio vaccine strain by 1.00%–3.75% (9–34 substitutions in 906 nucleotides). Most of the Chinese type I VDPV strains shared 4 amino acid substitutions in the neutralizing antigenic (NAg) sites: 3 located at the BC loop, which formed the NAg site 1, and another at NAg site 3a. All of the Chinese type I VDPVs identified during the AFP case surveillance were young VDPVs, which indicated a limited viral replication resulted from the administration of the initiating oral polio vaccine (OPV) dose. VDPVs can emerge and spread in isolated communities with immunity gaps and the circulation ceases following a mass immunization with OPV. As such, high-quality surveillance permitted very early detection and response and it played a key role in stalling the widespread circulation of the emergent cVDPV strains in China.

Abstract Background The quality of the family environment—in particular, the kind of parenting children receive in their early years—plays a critical role in influencing children’s growth and development. To facilitate the development and delivery of appropriate parenting and family interventions for Chinese parents, this study explores the prevalence of the difficulties that may arise in the course of child-rearing, the associated sociodemographic factors and parents’ help-seeking behavior. Methods A cross-sectional self-reporting survey was conducted with a sample of 2229 parents of children between 6 and 35 months of age. Using a stratified random-digit design, parents from 15 Chinese cities were surveyed to determine their child-rearing difficulties, support-seeking behavior and their preferences for service delivery. The sociodemographic factors that influenced major child-rearing difficulties were analyzed using bivariate and logistic analyses. Results The majority (87.5%) of Chinese parents of children aged 6–35 months reported experiencing child-rearing difficulties. Nearly one third (31.5%) of parents reported experiencing major difficulties. Feeding and sleep problems were most often reported. Regression analysis revealed that major child-rearing difficulties most often involved male children (OR = 1.35, 95% CI 1.11–1.64), single-child households (OR = 1.38, 95% CI 1.07–1.77), and households with financial problems (OR = 1.40, 95% CI 1.06–1.85). Just over one third of parents (33.44%) sought professional support, while 21.37% had attended a parenting course in the past year. Prefer ways of sourcing parental support included professional online platform (69.24%), self-help books (43.70%), face-to-face consultation (24.99%), and attending lectures (36.57%). Conclusions Child-rearing difficulties are common among parents of children between 6 and 35 months of age in Chinese cities. The family with boys, single-child, financial problems, and father not joining in child-rearing may face the high risk to major child-rearing difficulties. The national initiative to provide more guidance and support for child-rearing difficulties is worthwhile, as is the development of online parenting programs.

Early response could be obtained in most patients with relapsed or refractory B cell lymphoblastic leukemia (R/R B-ALL) treated with chimeric antigen receptor T-cell (CAR-T) therapy, but relapse occurs in some patients. There is no consensus on treatment strategy post CAR-T cell therapy. In this retrospective study of humanized CD19-targeted CAR-T cell (hCART19s) therapy for R/R B-ALL, we analyzed the patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or received a second hCART19s infusion, and summarized their efficacy and safety. We retrospectively studied 28 R/R B-ALL patients treated with hCART19s in the Affiliated Hospital of Xuzhou Medical University from 2016 to 2020. After the first hCART19s infusion, 10 patients received allo-HSCT (CART+HSCT group), 7 patients received a second hCART19s infusion (CART2 group), and 11 patients did not receive HSCT or a second hCART19s infusion (CART1 group). The safety, efficacy, and long-term survival were analyzed. Of the 28 patients who received hCART19s treatment, 1 patient could not be evaluated for efficacy, and 25 (92.6%) achieved complete remission (CR) with 20 (74.7%) achieving minimal residual disease (MRD) negativity. Seven (25%) patients experienced grade 3-4 CRS, and one died from grade 5 CRS. No patient experienced ≥3 grade ICANS. The incidence of second CR is higher in the CART+HSCT group compared to the CART2 group (100% vs. 42.9%, p=0.015). The median follow-up time was 1,240 days (range: 709–1,770). Significantly longer overall survival (OS) and leukemia-free survival (LFS) were achieved in the CART+HSCT group (median OS and LFS: not reached, p=0.006 and 0.001, respectively) compared to the CART2 group (median OS: 482; median LFS: 189) and the CART1 group (median OS: 236; median LFS: 35). In the CART+HSCT group, the incidence of acute graft-versus-host disease (aGVHD) was 30% (3/10), and transplantation-related mortality was 30% (3/10). No chronic GVHD occurred. Multivariate analysis results showed that blasts ≥ 20% in the bone marrow and MRD ≥ 65.6% are independent factors for inferior OS and LFS, respectively, while receiving allo-HSCT is an independent factor associated with both longer OS and LFS. In conclusion, early allo-HSCT after CAR-T therapy can achieve long-term efficacy, and the adverse events are controllable.