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Abstract This study aims to explore the application value of the Bayesian Time Structure Sequence (BSTS) model in estimating the acute hemorrhagic conjunctivitis (AHC) epidemics. The reported AHC cases spanning from January 2011 to October 2022 in China were collated. Utilizing R software, the BSTS and Autoregressive Integrated Moving Average (ARIMA) models were constructed using the data from January 2011 to December 2021. The prediction effect of both models was compared using the data from January to October 2022, and finally the AHC incidence from November 2022 to December 2023 was predicted. The results indicated that forecast errors under the BSTS model were lower than those under the ARIMA model. The actual AHC incidence in July 2022 from the ARIMA model deviated from the 95% confidence interval (CI) of the predicted value. However, the observed AHC incidence from the BSTS model fell within the 95% CI of the predicted value. Notably, the BSTS model predicted 26,474 new AHC cases in China from November 2022 to December 2023, exhibiting better prediction performance compared to the ARIMA model. This indicates that the BSTS model possesses a high application value for forecasting the epidemic trends of AHC, making it a valuable tool for disease surveillance and prevention strategies.

Abstract Malignant tumors have increasing morbidity and high mortality, and their occurrence and development is a complicate process. The development of sequencing technologies enabled us to gain a better understanding of the underlying genetic and molecular mechanisms in tumors. In recent years, the spatial transcriptomics sequencing technologies have been developed rapidly and allow the quantification and illustration of gene expression in the spatial context of tissues. Compared with the traditional transcriptomics technologies, spatial transcriptomics technologies not only detect gene expression levels in cells, but also inform the spatial location of genes within tissues, cell composition of biological tissues, and interaction between cells. Here we summarize the development of spatial transcriptomics technologies, spatial transcriptomics tools and its application in cancer research. We also discuss the limitations and challenges of current spatial transcriptomics approaches, as well as future development and prospects.

BackgroundThe low positive rate of blood cultures often leads to downstream consequences. We present a summary of multidisciplinary interventions implemented by a tertiary referral hospital to improve blood culture efficiency and optimize antimicrobial usage.MethodsWe evaluated the knowledge, attitude, and practice (KAP) of healthcare workers in a tertiary care hospital before and after intervention using a questionnaire. A multidisciplinary team was formed to implement the intervention, defining roles, standardizing procedures, continually improving education and feedback, and establishing incentive mechanisms. Regular quality control assessments are conducted on the responsible departments.ResultsFollowing the intervention, the median submission time for blood culture specimens was reduced from 2.2 h to 1.3 h (p

Key Clinical Message Mediastinal monophasic synovial sarcoma is a rare subtype that often lacks specific imaging characteristics, posing diagnostic challenges. This case report describes a mediastinal monophasic synovial sarcoma with vertebral metastasis, emphasizing imaging findings, differential diagnosis, and pathological features, thereby providing crucial support for accurate diagnosis and treatment planning.

Abstract Altered gut microbiome composition has been reported in children with eczema and interventions that restore beneficial bacteria in the gut may improve eczema. This open-label pilot study aimed to investigate the efficacy of a novel infant microbiome formula (SIM03) in young children with eczema. Pre-school Chinese children aged 1–5 years old with eczema received SIM03 twice daily for three months. The novelty of SIM03 consists of both the use of a patented microencapsulation technology to protect the viability of unique Bifidobacterium bifidum and Bifidobacterium breve strains identified through big data analysis of large metagenomic datasets of young Chinese children. Paired stool samples at baseline and following SIM03 were analyzed by metagenomics sequencing. Generalized estimating equation was used to analyze changes in eczema severity, skin biophysical parameters, quality of life and stool microbiome. Twenty children aged 3.0 ± 1.6 years (10 with severe eczema) were recruited. Treatment compliance was ≥ 98%. SCORing Atopic Dermatitis score decreased significantly at two months (P = 0.008) and three months (P

Abstract With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies, cancer immunotherapy has undergone a profound transformation over the past decades. Recently, therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens, including tumor-associated antigens and tumor-specific antigens. The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells. However, the complete realization of these capabilities remains an ongoing pursuit. Therefore, we provide an overview of the current landscape of cancer vaccines in this review. The range of antigen selection, antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design. Furthermore, this review addresses the current status of clinical trials and discusses their strategies, focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment. However, current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges, including tumor immune microenvironment suppression, optimal candidate identification, immune response evaluation, and vaccine manufacturing acceleration. Therefore, the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.

Fish allergy is a significant health concern, with diagnosis and management complicated by diverse fish species and allergens. We conducted a comprehensive RNA-seq analysis of eight fish species to identify allergen profiles, integrating ImmunoCAP sIgE data to explore associations with allergen expression and diagnostic performance. Over 30 putative fish allergens were identified, with varying sequence similarities and expression levels, roughly classifying fish into two groups based on parvalbumin (PV) expression. Higher similarities in allergen expression correlated with stronger sIgE data relationships among fish extracts. High PV expression and conserved PV sequences were linked to elevated sIgE measurements, potentially indicating higher allergenicity. For diagnosis, species-specific extract sIgE remained the best indicator of corresponding fish allergy diagnosis, while incorporating multiple sIgE data enhanced performance. In component-resolved diagnosis (CRD), the current panel with PV alone showed comparable performance to fish extract for PV-high fish allergy, while PV-low fish may require the inclusion of more minor allergens for improved CRD accuracy. This RNA-seq allergen analysis helps reveal fish allergen profiles, classify fish groups, and predict allergenicity, potentially improving CRD design and food management in fish allergy.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo routinely used allergy tests such as a wheat allergen-specific skin prick test (SPT), a blood test for specific immunoglobulin E (sIgE) levels, or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its emerging diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis, and the basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability, and safety of related clinical trials will then be discussed.

Abstract Background Pathogenic viruses can be transmitted by female Aedes aegypti (Ae. aegypti) mosquitoes during blood-meal acquisition from vertebrates. Silencing of mosquito- and midgut-specific microRNA (miRNA) 1174 (miR-1174) impairs blood intake and increases mortality. Determining the identity of the proteins and metabolites that respond to miR-1174 depletion will increase our understanding of the molecular mechanisms of this miRNA in controlling blood-feeding and nutrient metabolism of mosquitoes. Methods Antisense oligonucleotides (antagomirs [Ant]) Ant-1174 and Ant-Ct were injected into female Ae. aegypti mosquitoes at 12–20 h posteclosion, and depletion of miR-1174 was confirmed by reverse transcription quantitative real-time PCR (RT-qPCR). Ant-1174-injected and control mosquitoes were collected before the blood meal at 72 h post-injection for tandem mass tag-based proteomic analysis and liquid chromatography-tandom mass spectrometry non-target metabolomic analysis to identify differentially expressed proteins and metabolites, respectively. RNA interference (RNAi) using double-stranded RNA (dsRNA) injection was applied to investigate the biological roles of these differentially expressed genes. The RNAi effect was verified by RT-qPCR and western blotting assays. Triglyceride content and ATP levels were measured using the appropriate assay kits, following the manufacturers’ instructions. Statistical analyses were conducted with GraphPad7 software using the Student’s t-test. Results Upon depletion of mosquito- and midgut-specific miR-1174, a total of 383 differentially expressed proteins (DEPs) were identified, among which 258 were upregulated and 125 were downregulated. Functional analysis of these DEPs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggested that miR-1174 plays important regulatory roles in amino acid metabolism, nucleotide metabolism, fatty acid metabolism and sugar metabolism pathways. A total of 292 differential metabolites were identified, of which 141 were upregulated and 151 were downregulated. Integrative analysis showed that the associated differential proteins and metabolites were mainly enriched in a variety of metabolic pathways, including glycolysis, citrate cycle, oxidative phosphorylation and amino acid metabolism. Specifically, the gene of one upregulated protein in miR-1174-depleted mosquitoes, purine nucleoside phosphorylase (PNP; AAEL002269), was associated with the purine, pyrimidine and niacin-nicotinamide metabolism pathways. PNP knockdown seriously inhibited blood digestion and ovary development and increased adult mortality. Mechanically, PNP depletion led to a significant downregulation of the vitellogenin gene (Vg); in addition, some important genes in the ecdysone signaling and insulin-like peptide signaling pathways related to ovary development were affected. Conclusions This study demonstrates differential accumulation of proteins and metabolites in miR-1174-depleted Ae. aegypti mosquitoes using proteomic and metabolomic techniques. The results provide functional evidence for the role of the upregulated gene PNP in gut physiological activities. Our findings highlight key molecular changes in miR-1174-depleted Ae. aegypti mosquitoes and thus provide a basis and novel insights for increased understanding of the molecular mechanism involved in a lineage-specific miRNA in mosquito vectors. Graphical Abstract

Background: The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern in fish allergic subjects from two distinct populations in Asia. Methods: One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients’ sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80 °C were evaluated by SDS-PAGE and mass spectrometry. Results: Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens. Conclusions: Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients’ allergic manifestations.

Objective To explore the influencing factors of herpes zoster neuralgia in order to provide reference for the diagnosis and the treatment of this disease. Methods We retrospectively analyzed 89 cases of craniofacial herpes zoster and 168 cases of non-craniofacial herpes zoster hospitalized in the First Affiliated Hospital of Wannan Medical College from January, 2019 to December, 2019. The demographic and clinical characteristics were compared between these two groups. Pearson analysis was used to determine the correlation between NLR and pain score and severity score of the skin lesions. Logistic regression was used to analyze the risk factors for herpes zoster neuralgia. Results There were no significant differences in age, gender, pain score and severity of skin lesions between the two groups when admitted to hospital. Patients with craniofacial herpes zoster had a higher rate of pustules, blood blister and necrosis than that with non-craniofacial herpes zoster (25.84% vs. 15.48%, χ2=4.05, P=0.044). Moreover, the NLR were higher in patients with craniofacial herpes zoster than that with non-craniofacial herpes zoster (4.11±1.62 vs. 2.35±1.51, t=6.27, P

As a public infrastructure service, remote sensing data provided by smart cities will go deep into the safety field and realize the comprehensive improvement of urban management and services. However, it is challenging to detect criminal individuals with abnormal features from massive sensing data and identify groups composed of criminal individuals with similar behavioral characteristics. To address this issue, we study two research aspects: pickpocketing individual detection and pickpocketing group identification. First, we propose an IForest-FD pickpocketing individual detection algorithm. The IForest algorithm filters the abnormal individuals of each feature extracted from ticketing and geographic information data. Through the filtered results, the factorization machines (FM) and deep neural network (DNN) (FD) algorithm learns the combination relationship between low-order and high-order features to improve the accuracy of identifying pickpockets composed of factorization machines and deep neural networks. Second, we propose a community relationship strength (CRS)-Louvain pickpocketing group identification algorithm. Based on crowdsensing, we measure the similarity of temporal, spatial, social and identity features among pickpocketing individuals. We then use the weighted combination similarity as an edge weight to construct the pickpocketing association graph. Furthermore, the CRS-Louvain algorithm improves the modularity of the Louvain algorithm to overcome the limitation that small-scale communities cannot be identified. The experimental results indicate that the IForest-FD algorithm has better detection results in Precision, Recall and F1score than similar algorithms. In addition, the normalized mutual information results of the group division effect obtained by the CRS-Louvain pickpocketing group identification algorithm are better than those of other representative methods.

Abstract Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole‐brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate‐induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high‐gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.

Abstract Background Astigmatic mites contain potent allergens that can trigger IgE‐mediated immune responses, leading to allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. In house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, group 1 allergens (Der p 1 and Der f 1), characterized as papain‐like cysteine proteases, have been defined as the major allergens that have high prevalence and potency. Previous studies of mite group 1 allergens mainly focused on identification, comparison of sequence and structure, as well as the investigation of cross‐reactivity. To achieve a comprehensive view of mite group 1 allergens, we performed a comparative genomic analysis of all the cysteine proteases in six astigmatic mite species to elucidate the evolutionary relationships of group 1 allergens. Methods Based on the high‐quality and annotated genomes, all the cysteine proteases in six astigmatic mite species were identified by sequence homology search. The phylogenetic relationships, gene synteny and expression levels were revealed by bioinformatic tools. The allergenicity of recombinant cysteine proteases was evaluated by enzyme‐linked immunosorbent assay. Results Tandem duplication was revealed as the major feature of cysteine protease gene evolution in astigmatic mites. The high IgE‐binding capacity and the significant expression level of the cysteine protease DP_007902.01 suggested its potential as a novel group 1 allergen of D. pteronyssinus. In addition, gene decay events were identified in the skin‐burrowing parasitic mite Sarcoptes scabiei. Conclusion This comprehensive analysis provided insights into the evolution of cysteine proteases, as well as the component‐resolved diagnosis of mite allergies.

Abstract Background Epidemiological studies have demonstrated a wide, unexplained disparity in the prevalence of juvenile idiopathic arthritis (JIA) subtypes depending on geographical location, ethnicity and other factors. Enthesitis-related arthritis (ERA) is more prevalent in Southeast Asia. Axial involvement in ERA patients is increasingly recognised to occur early in the disease course. Inflammation in the sacroiliac joint (SIJ) observed on MRI seems highly predictive of subsequent structural radiographic progression. The resulting structural damage can have significant impacts on both functional status and spinal mobility. This study aimed to evaluate the clinical characteristics of ERA in a tertiary centre in Hong Kong. The primary objective of the study was to provide a comprehensive description of the clinical course and radiological findings of the SIJ among ERA patients. Method Paediatric patients diagnosed with JIA attending the paediatric rheumatology clinic from January 1990 to December 2020 were recruited from our registry based at the Prince of Wales Hospital. Results In our cohort, 101 children were included. The median age of diagnosis was 11 years, interquartile range (IQR) 8-15 years. The median follow-up duration was 7 years (IQR 2–11.5 years). ERA was the most prevalent subtype (40%), followed by oligoarticular JIA (17%). Axial involvement was frequently reported in our cohort of ERA patients. 78% demonstrated radiological evidence of sacroiliitis. Among those, 81% had bilateral involvement. The median duration from disease onset to confirmation of radiological sacroiliitis was 17 months (IQR 4-62 months). Among the ERA patients, 73% had structural changes of the SIJ. Alarmingly, 70% of these patients had already developed radiological structural changes when sacroiliitis was first detected on imaging (IQR 0-12 months). Erosion was the most common finding (73%), followed by sclerosis (63%), joint space narrowing (23%), ankylosis (7%) and fatty change (3%). The duration from symptom onset to diagnosis was significantly longer in ERA patients with SIJ structural changes (9 vs 2 months, p = 0.009), comparing with those without. Conclusion We found that a high proportion of ERA patients had sacroiliitis and a significant number of them had radiological structural changes during early disease. Our findings illustrate the importance of prompt diagnosis and early treatment in these children.

ABSTRACT The first few years of life is a key period for the development of the gut microbiome. However, our current understanding of this topic is largely biased toward Western populations. In this study, we characterized the development and determinants of the gut microbiome in a prospective cohort of 112 term Chinese children by sequencing 713 stool samples collected at nine time points from birth to 3 years of age using 16S rRNA gene sequencing. We revealed alterations in the composition and alpha and beta diversities of the gut microbiota across the first 3 years of life. We identified mode of delivery, feeding mode, and intrapartum antibiotics as the major determinants of the early-life gut microbiome, the effects of all of which persisted up to 12 months. Importantly, by conducting a nested case–control study, we showed that alterations in the infant gut microbiota precede the development of eczema. Interestingly, we identified a depletion of Bacteroides and an enrichment of Clostridium sensu stricto 1 in the gut microbiome of infants with eczema at 1 year old. The same patterns were also observed in C-section-born infants within the same time frames, suggesting a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema. Our study has revealed important associations between the gut microbiome and eczema in infancy and has established the basis for potential prevention/treatment of eczema via modulation of the gut microbiota. IMPORTANCE Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera Clostridium sensu stricto 1 and Finegoldia in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of Bacteroides from 1 to 6 months of age and an enrichment of Clostridium sensu stricto 1 at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.

Asthma is a chronic inflammatory disease characterized by airway hypersensitivity and remodeling. The current treatments provide only short-term benefits and may have undesirable side effects; thus, alternative or supplementary therapy is needed. Because intracellular calcium (Ca2+) signaling plays an essential role in regulating the contractility and remodeling of airway smooth muscle cells, the targeting of Ca2+ signaling is a potential therapeutic strategy for asthma. Houttuynia cordata is a traditional Chinese herb that is used to treat asthma due to its anti-allergic and anti-inflammatory properties. We hypothesized that H. cordata might modulate intracellular Ca2+ signaling and could help relieve asthmatic airway remodeling. We found that the mRNA and protein levels of inositol trisphosphate receptors (IP3Rs) were elevated in interleukin-stimulated primary human bronchial smooth muscle cells and a house dust mite–sensitized model of asthma. The upregulation of IP3R expression enhanced intracellular Ca2+ release upon stimulation and contributed to airway remodeling in asthma. Intriguingly, pretreatment with H. cordata essential oil rectified the disruption of Ca2+ signaling, mitigated asthma development, and prevented airway narrowing. Furthermore, our analysis suggested that houttuynin/2-undecanone could be the bioactive component in H. cordata essential oil because we found similar IP3R suppression in response to the commercially available derivative sodium houttuyfonate. An in silico analysis showed that houttuynin, which downregulates IP3R expression, binds to the IP3 binding domain of IP3R and may mediate a direct inhibitory effect. In summary, our findings suggest that H. cordata is a potential alternative treatment choice that may reduce asthma severity by targeting the dysregulation of Ca2+ signaling.

Background: Given the life-threatening nature of food allergy (FA), it is important to assess the level of knowledge among families with food-allergic patients and their ability to cope with anaphylaxis. This study constructed a FA knowledge questionnaire (FAKQ) and confidence in FA management skills (CIFAMS) questionnaire to assess understanding and attitudes toward FA management in food-allergic families. Methods: Items from literature review and expert panel showing ≥80% content validity index and semantic equivalence were selected for translation into Chinese. These questionnaires underwent feasibility pilot testing followed by cross-sectional validation to assess their psychometric properties of internal consistency, test–retest reliability, and construct validity with a FA quality-of-life questionnaire and discriminant validity. Exploratory factor analysis was performed to confirm their factor structure. Results: A total of 155 subjects (104 patients and 51 parents) completed a 20-item FAKQ and 10-item CIFAMS. Both tools showed acceptable internal consistency in baseline and retest groups. FAKQ and CIFAMS correlated for all subjects (P = .002) and for adults (P = .002), and similarly between CIFAMS and parent-reported FA independent measure (P = .005). Total score of FAKQ was sensitive to within-group differences of patients hospitalized for FA (P < .001). FAKQ and CIFAMS items were factored into 4 and 2 domains, respectively. Subjects scored the lowest on FAKQ items about signs of allergic reaction and CIFAMS items on epinephrine autoinjector use. Conclusion: FAKQ and CIFAMS developed by our group are valid and reliable in assessing knowledge and confidence in FA management in patients and parents. These tools are crucial for formulating education programs and advocacy campaigns for FA.

Preterm children show developmental cognitive and language deficits that can be subtle and sometimes undetectable until later in life. Studies of brain development in children who are born preterm have largely focused on vascular and gross anatomical characteristics rather than pathophysiological processes that may contribute to these developmental deficits. Neural encoding of speech as reflected in EEG recordings is predictive of future language development and could provide insights into those pathophysiological processes. We recorded EEG from 45 preterm (≤ 34 weeks of gestation) and 45 term (≥ 38 weeks) Chinese-learning infants 0–12 months of (corrected) age during natural sleep. Each child listened to three speech stimuli that differed in lexically meaningful pitch (2 native and 1 non-native speech categories). EEG measures associated with synchronization and gross power of the frequency following response (FFR) were examined. ANCOVAs revealed no main effect of stimulus nativeness but main effects of age, consistent with earlier studies. A main effect of prematurity also emerged, with synchronization measures showing stronger group differences than power. By detailing differences in FFR measures related to synchronization and power, this study brings us closer to identifying the pathophysiological pathway to often subtle language problems experienced by preterm children.

COCH (coagulation factor C homology) is one of the most frequently mutated genes of autosomal dominant non-syndromic hearing loss. Variants in COCH could cause DFNA9, which is characterized by late-onset hearing loss with variable degrees of vestibular dysfunction. In this study, we report a Chinese family with a novel COCH variant (c.1687delA) causing p.D544Vfs*3 in the cochlin. Comprehensive audiometric tests and vestibular function assessments were taken to acquire the phenotypic profile of the subjects. Next-generation sequencing was conducted and segregation analysis was carried out using Sanger sequencing. The proband presented mild vestibular symptoms and normal functional assessment results in almost every test, while the variant co-segregated with hearing impairment in the pedigree. The variant was located beyond the vWFA2 domain, which was predicted to affect the post-translational cleavage of the cochlin via molecular modeling analysis. Notably, in the overexpressing study, by transient transfecting the HEK 293T cells, we found that the p.D544Vfs*3 variant increased the formation of multimeric cochlin. Our result enriched the spectrum of DFNA9-linked pathological COCH variants and suggested that variants, causative of cochlin multimerization, could be related to DFNA9 with sensorineural hearing loss rather than serious vestibular symptoms.

Cardiac masses commonly involve primary tumors, metastatic diseases, and nonbacterial thrombotic and infective endocarditis. myxomas are the most common primary tumors, accounting for 75%. Hemolymphangiomas are a group of congenital vascular and lymphatic malformations that originate from the mesenchyme, with an incidence rate of 0.12%–0.28% per year. Hemolymphangiomas have been found in the rectum, small intestine, spleen, liver, chest wall, and mediastinum but have not yet been reported in the ventricular outflow tract in the heart. Herein, we report a case of a hemolymphangioma tumor in the right ventricular outflow tract (RVOT). The tumor was successfully resected, and the patient was followed up for 18 months and did not exhibit tumor recurrence.

BackgroundVirtual reality (VR) technology has been widely used in rehabilitation training because of its immersive, interactive, and imaginative features. A comprehensive bibliometric review is required to help researchers focus on future directions based on the new definitions of VR technologies in rehabilitation, which reveal new situations and requirements. ObjectiveHerein, we aimed to summarize effective research methods for and potential innovative approaches to VR rehabilitation by evaluating publications from various countries to encourage research on efficient strategies to improve VR rehabilitation. MethodsThe SCIE (Science Citation Index Expanded) database was searched on January 20, 2022, for publications related to the application of VR technology in rehabilitation research. We found 1617 papers, and we created a clustered network, using the 46,116 references cited in the papers. CiteSpace V (Drexel University) and VOSviewer (Leiden University) were used to identify countries, institutions, journals, keywords, cocited references, and research hot spots. ResultsA total of 63 countries and 1921 institutes have contributed publications. The United States of America has taken the leading position in this field; it has the highest number of publications; the highest h-index; and the largest collaborative network, which includes other countries. The reference clusters of SCIE papers were divided into the following nine categories: kinematics, neurorehabilitation, brain injury, exergames, aging, motor rehabilitation, mobility, cerebral palsy, and exercise intensity. The research frontiers were represented by the following keywords: video games (2017-2021), and young adults (2018-2021). ConclusionsOur study comprehensively assesses the current research state of VR rehabilitation and analyzes the current research hot spots and future trends in the field, with the aims of providing resources for more intensive investigation and encouraging more researchers to further develop VR rehabilitation.

Transportation is the forerunner of economic and social development. Therefore, the high-quality development of comprehensive transportation is of great significance to ensure overall economic and social progress and the smooth implementation of major national strategies. The essence of high-quality development in transportation is to realize the optimal allocation of transportation resources. This study handles two aspects. First, the factors that reflect the quality of comprehensive transportation development are defined and analyzed, and an evaluation system is proposed to build China’s comprehensive transportation development quality with transportation efficiency as the core is proposed, taking into account transportation infrastructure and transportation scale. Second, the static comprehensive evaluation value is calculated by the entropy weight method, and then the incentive control model is constructed by introducing incentive factors to achieve a dynamic comprehensive evaluation of comprehensive transportation development. The research results not only propose new indicators but also evaluate different modes of transportation within the same dimension. The results show that the quality of comprehensive transportation development in China is generally on the rise, but there are obvious regional differences. The proposed model is derived from evaluation cases in transportation-related fields and has not yet been applied in the transportation field. It can help understand the development status of the industry and assist in policy formulation.

Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.

Background A quadrivalent split influenza vaccine IIV4-W against both influenza A and B viruses is urgently needed. Methods To evaluate the safety and immunogenicity of IIV4-W in people aged 3–60 years, 2400 participants recruited in a double-blind phase III trial and were randomly assigned to the IIV4-W, TIV1 and TIV2 groups. The immunogenicity indicators were measured at 28 days postvaccination and for 180 days for safety follow-up. Results Adverse events (AEs) occurred in 162 (20.28%), 116 (14.55%) and 123 (15.41%) participants in the IIV4-W, TIV1 and TIV2 groups, respectively. All these AEs were mild and self-limiting, and no serious AEs related to the vaccines were observed. IIV4-W elicited a non-inferior immune response for matched strains (the lower limit of 95% CI for GMT ratio >0.67, for SCR and SPR difference >-10%) and superior immune response for the additional B strains (the lower limit of 95% CI for GMT ratio >1.5, for SCR difference >10%) versus TIVs. The lower limit of the 95% confidence interval of the GMT increase fold, the seroconversion rate and the seroprotection rate exceeded 2.5, 40% and 70% for the four strains in IIV4-W respectively. Conclusions IIV4-W was noninferior to the TIV-matched strains and was superior to the additional B strain. IIV4-W was safe in the participants and elicited high antibody titers.

Drought stress is one of the major abiotic stress factors that affect plant growth and crop productivity. Tartary buckwheat is a nutritionally balanced and flavonoid-rich pseudocereal crop and also has strong adaptability to different adverse environments including drought. However, little is known about its drought tolerance mechanism. In this study, we performed comparative physiological and transcriptomic analyses of two contrasting drought-resistant Tartary buckwheat genotypes under nature drought treatment in the reproductive stage. Under drought stress, the drought-tolerant genotype XZSN had significantly higher contents of relative water, proline, and soluble sugar, as well as lower relative electrolyte leakage in the leaves than the drought-susceptible LK3. A total of 5,058 (2,165 upregulated and 2,893 downregulated) and 5,182 (2,358 upregulated and 2,824 downregulated) potential drought-responsive genes were identified in XZSN and LK3 by transcriptome sequencing analysis, respectively. Among the potential drought-responsive genes of XZSN, 1,206 and 1,274 genes were identified to be potential positive and negative contributors for XZSN having higher drought resistance ability than LK3. Furthermore, 851 out of 1,206 positive drought-resistant genes were further identified to be the core drought-resistant genes of XZSN based on WGCNA analysis, and most of them were induced earlier and quicker by drought stress than those in LK3. Functional annotation of the 851 core drought-resistant genes found that a large number of stress-responsive genes were involved in TFs, abscisic acid (ABA) biosynthesis, signal transduction and response, non-ABA signal molecule biosynthesis, water holding, oxygen species scavenging, osmotic adjustment, cell damage prevention, and so on. Transcriptional regulatory network analyses identified the potential regulators of these drought-resistant functional genes and found that the HD-ZIP and MYB TFs might be the key downstream TFs of drought resistance in Tartary buckwheat. Taken together, these results indicated that the XZSN genotype was more drought-tolerant than the LK3 genotype as evidenced by triggering the rapid and dramatic transcriptional reprogramming of drought-resistant genes to reduce water loss, prevent cell damage, and so on. This research expands our current understanding of the drought tolerance mechanisms of Tartary buckwheat and provides important information for its further drought resistance research and variety breeding.

Objective Transfer RNA-derived small RNAs (tsRNAs) are a novel type of non-coding RNA with various regulatory functions. They are associated with oxidative stress in various diseases, but their potential functions in radiation-induced lung injury (RILI) remain uncertain. Methods To explore the role of tsRNAs in RILI, we used X-rays to irradiate human bronchial epithelial cells and examined the expression profile of altered tsRNAs by RNA sequencing and bioinformatics analysis. Sequencing results were verified by qRT-PCR. tsRNA functions were explored using several methods, including CCK-8, reactive oxygen species (ROS) assays, cell transfection, and western blotting. Results Eighty-six differentially expressed tRNA-derived fragments (tRFs) were identified: 64 were upregulated, and 22 were downregulated. Among them, the regulation of tRF-Gly-GCC, associated with oxidative stress, may be mediated by the inhibition of cell proliferation, promotion of ROS production, and apoptosis in the occurrence and development of RILI. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the underlying molecular mechanism may involve the PI3K/AKT and the FOXO1 signaling pathways. Conclusion Our findings provide new insights into the molecular mechanisms underpinning RILI, advancing the clinical prevention and treatment of this disease.

Lightweight ciphers are often used as the underlying encryption algorithm in resource-constrained devices. Their cryptographic security is a mandatory goal for ensuring the security of data transmission. Differential cryptanalysis is one of the most fundamental methods applicable primarily to block ciphers, and the resistance against this type of cryptanalysis is a necessary design criterion. ANU-II is an ultra-lightweight block cipher proposed in 2017, whose design offers many advantages such as the use of fewer hardware resources (logic gates), low power consumption and fast encryption for Internet of Things devices. The designers of ANU-II claimed its resistance against differential cryptanalysis and postulated that the design is safe enough for Internet of Things devices. However, as addressed in this article, the security claims made by designers appear not to be well grounded. Using mixed-integer linear programming–like techniques, we identify one-round differential characteristic that holds with probability 1, which is then efficiently employed in mounting the key recovery attack on full-round ANU-II with only 2 2 chosen plaintexts and 2 62.4 full-round encryptions. The result shows that the designers’ security evaluation of ANU-II against differential cryptanalysis is incorrect and the design rationale is flawed. To remedy this weakness, we provide an improved variant of ANU-II, which has much better resistance to differential cryptanalysis without affecting the hardware and/or software implementation cost.

Introduction: Deep learning technology has been widely used in genetic research because of its characteristics of computability, statistical analysis, and predictability. Herein, we aimed to summarize standardized knowledge and potentially innovative approaches for deep learning applications of genetics by evaluating publications to encourage more research.Methods: The Science Citation Index Expanded TM (SCIE) database was searched for deep learning applications for genomics-related publications. Original articles and reviews were considered. In this study, we derived a clustered network from 69,806 references that were cited by the 1,754 related manuscripts identified. We used CiteSpace and VOSviewer to identify countries, institutions, journals, co-cited references, keywords, subject evolution, path, current characteristics, and emerging topics.Results: We assessed the rapidly increasing publications concerned about deep learning applications of genomics approaches and identified 1,754 articles that published reports focusing on this subject. Among these, a total of 101 countries and 2,487 institutes contributed publications, The United States of America had the most publications (728/1754) and the highest h-index, and the US has been in close collaborations with China and Germany. The reference clusters of SCI articles were clustered into seven categories: deep learning, logic regression, variant prioritization, random forests, scRNA-seq (single-cell RNA-seq), genomic regulation, and recombination. The keywords representing the research frontiers by year were prediction (2016–2021), sequence (2017–2021), mutation (2017–2021), and cancer (2019–2021).Conclusion: Here, we summarized the current literature related to the status of deep learning for genetics applications and analyzed the current research characteristics and future trajectories in this field. This work aims to provide resources for possible further intensive exploration and encourages more researchers to overcome the research of deep learning applications in genetics.

ABSTRACT Despite distinct nasopharyngeal microbiome (NPM) profiles between asthmatics and healthy subjects, little is known about the NPM dynamics and its relation to childhood asthma exacerbation (AE). We investigated NPM changes by longitudinally collecting 135 flocked nasopharyngeal swabs (FNPSs) from 33 school-age asthmatic children at six time points (2 to 4-week intervals) from September to December 2017 in Hong Kong. Subjects were categorized into AE and stable asthma (AS) groups according to whether they experienced any exacerbation during follow-up. One-off FNPSs from nine nonasthmatic children were included as controls. Microbiota profiles were analyzed using 16S rRNA gene sequencing. All 144 NPMs were classified into six microbiome profile groups (MPGs), each dominated by Moraxella, Corynebacterium 1, Dolosigranulum, Staphylococcus, Streptococcus, or Anoxybacillus. The microbial diversity and compositions of NPM in exacerbation samples were different from both baseline samples and those from healthy controls. Moraxella and Dolosigranulum-dominated NPM exhibited high temporal stability revealed by MPG transition analysis. NPM diversity decreased whereas microbial composition remained similar over time. The relative abundances of Moraxella increased while Corynebacterium 1, Anoxybacillus, and Pseudomonas decreased longitudinally. However, these temporal patterns did not differ between AE and AS groups, suggesting that short-term dynamic patterns were not sufficient to predict AE occurrence. Asthmatic NPM underwent Moraxella expansion during AE and presented a high microbiome resilience (recovery potential) after AE resolution. Microbial pathways involved in methane, ketone bodies, and vitamin B3 metabolisms were enhanced during AE and primarily contributed by Moraxella. IMPORTANCE Evidence on the dynamic changes of NPM in asthmatic patients remains limited. Here, we present that asthmatic NPMs deviating from a healthy status still showed resilience after disturbance. Our data imply from a longitudinal perspective that Moraxella increase is closely related to AE occurrence. The finding of functional dysbiosis (imbalance) during AE offers a plausible explanation for the known association between nasopharyngeal Moraxella expansion and increased AE risk. This work serves as a basis for future long-term prospective studies leveraging multiomics approaches to elucidate the temporal association between NPM and pediatric AE.

Abstract Background Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear. Results Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity. Conclusions In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.

Abstract Background Endoscopic submucosal dissection (ESD) has been accepted as a standard treatment for early gastric cardiac cancer (EGCC). Here, we investigate the clinical outcomes of the EGCC patients who underwent ESD in different indications. Methods From January 2011 to October 2019, we enrolled 502 EGCC lesions from 495 patients which were resected by ESD at our center. We retrospectively analyzed the short-term and long-term clinical outcomes among different indication groups. Results The number of the patients in the absolute indication (AI), expanded indication (EI) and beyond the expanded indication (BEI) groups was 265, 137 and 93, respectively. The en bloc resection rate was 100%, 100% and 98.9% (P = 0.185). The complete resection rate was 99.3%, 98.5% and 74.5%, respectively (P

Eczema is a common inflammatory skin disorder during infancy. Evidence has shown that skin-microbiome fluctuations may precede eczema development, but their predictive value for eczema phenotypes remains unknown. We aimed to investigate the early-life evolution of the skin microbiome and its temporal associations with different pairs of eczema phenotypes (transient versus persistent, atopic versus non-atopic) in Chinese children. We followed 119 term Chinese infants from birth to 24 months old within a Hong Kong birth cohort. The skin microbes at the left antecubital fossa were serially sampled by flocked swabs at 1, 6, and 12 months for bacterial 16S rRNA gene sequencing. The atopic sensitization at 12 months was strongly associated with eczema persisting to 24 months (odds ratio 4.95, 95% confidence interval 1.29–19.01). Compared with those with non-atopic eczema, the children with atopic eczema had reduced alpha diversity at 12 months (p < 0.001) and transiently higher abundance of the genus Janibacter at 6 months (p < 0.001). Our findings suggest that atopic sensitization at 12 months may predict persistent eczema by 24 months, and atopic eczema at 12 months is associated with unique skin microbiome profiles at 6 and 12 months. Non-invasive skin-microbiome profiling may have predictive value for atopic eczema.

Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum–curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt–CUR@PSPPN) to facilitate intracellular release and synergistic anti-cancer effects. Pt–CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both in vivo and in vitro. In addition, Pt–CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt–CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.

Microbiome mediates early life immune deviation in asthma development. Recurrent wheeze (RW) in pre-school years is a risk factor for asthma diagnosis in school-age children. Dysbiosis exists in asthmatic airways, while its origin in pre-school years and relationship to RW is not clearly defined. This study investigated metagenomics of nasopharyngeal microbiome in pre-school children with RW. We applied whole-genome shotgun sequencing and human rhinovirus (HRV) detection on nasopharyngeal samples collected from three groups of pre-school children: (i) RW group: 16 children at-risk for asthma who were hospitalized for RW, (ii) inpatient control (IC): 18 subjects admitted for upper respiratory infection, and (iii) community control (CC): 36 children without respiratory syndromes. Sequence reads were analyzed by MetaPhlAn2 and HUMAnN2 algorithm for taxonomic and functional identification. Linear discriminant analysis effect size (LEfSe) analysis was used to identify discriminative features. We identified that Moraxella catarrhalis and Dolosigranulum pigrum were predominant species in nasopharynx. RW had lower alpha diversity (Shannon diversity index) than CC (0.48 vs. 1.07; Padj = 0.039), characterized by predominant Proteobacteria. LEfSe analysis revealed D. pigrum was the only discriminative species across groups (LDA = 5.57, P = 0.002), with its relative abundance in RW, IC, and CC being 9.6, 14.2, and 37.3%, respectively (P < 0.05). LEfSe identified five (ribo)nucleotides biosynthesis pathways to be group discriminating. Adjusting for HRV status, pre-school children with RW have lower nasopharyngeal biodiversity, which is associated with Proteobacteria predominance and lower abundance of D. pigrum. Along with discriminative pathways found in RW and CC, these microbial biomarkers help to understand RW pathogenesis.

Background. Deep brain stimulation of the subthalamic nuclei (STN-DBS) is a standard treatment option for advanced Parkinson’s disease (PD) patients. Delirium following DBS electrode implantation is common, by several studies, and cognitive impairment is a risk factor for developing postoperative delirium (POD). This prospective observational study was conducted to identify whether preoperative baseline cognitive status has an association with POD in PD patients undergoing DBS surgery. Methods. Preoperatively, neuropsychiatric and neuropsychological assessments of the patients were performed including clinical dementia rating (CDR) score, instrumental activities of daily living (IADL) score, mini-mental state exam (MMSE) score, Montreal cognitive assessment (MoCA) score, Hamilton anxiety (HAMA) and Hamilton depression (HAMD) scores, and numerical cancellation test. POD was identified by the confusion assessment method (CAM) twice per day on postoperative day 1 until discharge. Results. Twenty-seven (21.6%) of 125 patients developed POD. Among the variables screened, age, CDR score, MMSE score, and HAMA score were indicated to be independent influence factors of POD. The cutoff score, AUC, sensitivity, and specificity of age, CDR score, MMSE score, and HAMA score associated with POD was 58.5, 0.751, 92.6%, 52.0%; 0.5, 0.848, 77.8%, 91.8%; 27.5, 0.827, 88.9%, 62.2%; and 12.5, 0.706, 85.2%, 54.1%, respectively. Conclusions. We observed age, CDR score, MMSE score, and HAMA score were independent influence factors of POD in PD patients who received DBS. It is necessary to assess the cognitive status of PD patients before surgery to identify high-risk patients.

Since our country put forward the rural revitalization strategy, we have attached great importance to the construction and development of urban and rural areas. In recent years, we have continuously enhanced the driving force of development and further promoted rural reform. However, in the construction of rural cultural industry, how to purify environmental pollution is a key and difficult point. Through the comprehensive analysis of the role and effect of biomaterials in environmental pollution purification, this study compares the comprehensive role of different materials in environmental purification, compares the trend of environmental pollution in the development of rural industries in recent years, and analyzes the coupling degree of environmental pollution purification in different technological environments. Through the analysis, we can draw a conclusion that under the action of nanomaterials and biomaterials, some water pollution, air pollution, construction waste pollution, and noise pollution in industrial development have achieved good results and impact. Through continuous practice and research, it can be seen that biotechnology and materials can play a relatively good role in the environmental pollution control. And this treatment technology has the advantages of low cost, high efficiency, and no secondary pollution. It also plays an important role in the treatment of pollutants and the development of new energy. It conforms to the concept of sustainable development and environmental construction in the modern society and provides more reference data and research value for the future research and development prospects of nanomaterials and biomaterials in industrial development and environmental governance.

Chiral phosphoric acids (CPAs) have received considerable attention due to their high activity for enantioselective transformations. However, the role of various chiral skeletons of CPAs in regulating the mechanism and enantioselectivity of asymmetric transfer hydrogenation has remained unclear. Density functional theory (DFT) calculations are performed to elucidate the role of chiral skeletons on the acidity, mechanism, enantioselectivity, and kinetic stabilities of transition states (TSs) in Asymmetric Transfer Hydrogen (ATH) reaction catalyzed by five CPAs. We found that the acidity of CPAs is strongly dependent on the chiral skeleton. The origin of enantioselectivity of ATH reaction arises from the differential noncovalent interactions between TSs and CPAs. Moreover, the shape and size of the catalyst pocket depending on chiral skeletons play key roles in the stability of TSs and the enantioselectivity of ATH. This study might facilitate to design and computationally screening of CPAs and guide the strategic choice of CPA skeletons to reduce the experimental workload.

A density functional theory (DFT) study is reported to examine the asymmetric transfer hydrogenation (ATH) of imines catalyzed by an indium metal-organic framework (In-MOF) derived from a chiral phosphoric acid (CPA). It is revealed that the imine and reducing agent (i.e., thiazoline) are simultaneously adsorbed on the CPA through H-bonding to form an intermediate, subsequently, a proton is transferred from thiazoline to imine. The transition state TS-R and TS-S are stabilized on the CPA via H-bonding. Compared to the TS-S, the TS-R has shorter H-bonding distances and longer C-H···π distances, it is more stable and experiences less steric hindrance. Consequently, the TS-R exhibits a lower activation barrier affording to the (R)-enantiomer within 68.1% ee in toluene. Imines with substituted groups such as −NO2, −F, and −OCH3 are used to investigate the substitution effects on the ATH. In the presence of an electron-withdrawing group like −NO2, the electrophilicity of imine is enhanced and the activation barrier is decreased. The non-covalent interactions and activation-strain model (ASM) analysis reveal that the structural distortions and the differential noncovalent interactions of TSs in a rigid In-MOF provide the inherent driving force for enantioselectivity. For −OCH3 substituted imine, the TS-S has the strongest steric hindrance, leading to the highest enantioselectivity. When the solvent is changed from toluene to dichloromethane, acetonitrile, and dimethylsulfoxide with increasing polarity, the activation energies of transition state increase whereas their difference decreases. This implies the reaction is slowed down and the enantioselectivity becomes lower in a solvent of smaller polarity. Among the four solvents, toluene turns out to be the best for the ATH. The calculated results in this study are in fairly good agreement with experimental observations. This study provides a mechanistic understanding of the reaction mechanism, as well as substitution and solvent effects on the activity and enantioselectivity of the ATH. The microscopic insights are useful for the development of new chiral MOFs toward important asymmetric reactions.

Abstract Background Shigella spp., facultative anaerobic bacilli of the family Enterobacteriaceae, are one of the most common causes of diarrheal diseases in human worldwide which have become a significant public health burden. So, we aimed to analyze the antimicrobial phenotypes and to elucidate the molecular mechanisms underlying resistance to cephalosporins and fluoroquinolones in Shigella isolates from patients with diarrhea in Shanxi Province. Results During 2006–2016, we isolated a total of 474 Shigella strains (including 337 S. flexneri and 137 S. sonnei). The isolates showed high rates of resistance to traditional antimicrobials, and 26, 18.1 and 3.0% of them exhibited resistance to cephalosporins, fluoroquinolones and co-resistance to cephalosporins and fluoroquinolones, respectively. Notably, 91.1% of these isolates, including 22 isolates that showed an ACTSuT profile, exhibited multidrug resistance (MDR). The resistance rates to cephalosporins in S. sonnei isolates were higher than those in S. flexneri. Conversely, the resistance rates to fluoroquinolones were considerably higher in S. flexneri isolates. Among the 123 cephalosporins-resistant isolates, the most common extended-spectrum beta-lactamase gene was bla TEM-1, followed by bla CTX-M, bla OXA-1, and bla SHV-12. Six subtypes of bla CTX-M were identified, bla CTX-M-14 (n = 36) and bla CTX-M-55 (n = 26) were found to be dominant. Of all the 86 isolates with resistance to fluoroquinolones and having at least one mutation (Ser83Leu, His211Tyr, or Asp87Gly) in the the quinolone resistance-determining regions of gyrA, 79 also had mutation of parC (Ser80Ile), whereas 7 contained plasmid-mediated quinolone resistance genes including qnrA, qnrB, qnrS, and aac(60)-Ib-cr. Furthermore, pulsed-field gel electrophoresis analysis (PFGE) showed a considerable genetic diversity in S. flexneri isolates. However, the S. sonnei isolates had a high genetic similarity. Conclusions Coexistence of diverse resistance genes causing the emergence and transmission of MDR might render the treatment of shigellosis difficult. Therefore, continuous surveillance might be needed to understand the actual disease burden and provide guidance for shigellosis.

In this study, coaxial dielectric barrier discharge (DBD) plasma, in conjunction with a metal oxide catalyst, was used to degrade naphthalene. The characteristics of plasma discharge were studied by measuring voltage and current waveforms and the Lissajous figure. The effects of different parameters of the process on naphthalene decomposition in air were investigated. XRD, BET, and SEM data were used to investigate the nature, specific surface area, and surface morphology of the catalyst. The results show that the mineralization of naphthalene reached 82.2% when the initial naphthalene concentration was 21 ppm and the total gas flow rate was 1 L/min in the DBD reactor filled with Al2O3. The mineralization of naphthalene first increased and then became stable with the increase in treatment time and discharge power. The TiO2 catalyst has more apparent advantages than the two other studied catalysts in terms of the removal efficiency and mineralization of naphthalene due to this catalyst’s large specific surface area, porous structure, and photocatalytic properties. In addition, the introduction of a small amount of water vapor can promote the mineralization and CO2 selectivity of naphthalene. With further increases in the water vapor, Fe2O3 has a negative effect on the naphthalene oxidation due to its small pore size. The TiO2 catalyst can overcome the adverse effects of water molecule attachment due to its photocatalytic properties.

Background: The selection of the maintenance of general anesthesia may affect the development of postoperative delirium (POD), notably for Parkinson’s disease (PD) patients, due to their lower cognitive reserve. The present study was designed to compare the potential impact of propofol vs. sevoflurane based general anesthesia maintenance methods on the development of POD in PD patients following deep brain stimulation (DBS) surgery. Methods: A total of 125 PD patients who were scheduled to undergo DBS surgery were randomly divided into the propofol (n = 63) and the sevoflurane groups (n = 62). The patients in the two groups randomly received propofol- or sevoflurane-based general anesthesia. The Confusion Assessment Method (CAM) was employed by an investigator who was blinded to the anesthesia regimen and was administered twice per day from postoperative day 1 until discharge. Results: The incidence of POD was 22.22% (14/63) with propofol anesthesia and 20.97% (13/62) with sevoflurane anesthesia (p = 0.865). In addition, no difference was noted in the duration and severity of delirium between the propofol and sevoflurane groups. Conclusions: In the present study, propofol- and sevoflurane-based general anesthesia exhibited comparable results with regard to the POD incidence in PD patients undergoing deep brain stimulation surgery.

Aims: Early gastric cardiac cancer (EGCC) has a low risk of lymph node metastasis with the potential for endoscopic therapy. We aimed to evaluate the short- and long-term outcomes of endoscopic submucosal dissection (ESD)-resected EGCCs in a large cohort of Chinese patients and compare endoscopic and clinicopathologic features between EGCC and early gastric non-cardiac cancer (EGNC). Methods: We retrospectively studied 512 EGCCs in 499 consecutive patients and 621 EGNCs in 555 consecutive patients between January 2011 and March 2018 at our center. We investigated clinicopathological characteristics of EGCC tumors, ESD treatment results, adverse events, and postresection patient survival. Results: Compared with EGNC patients, EGCC patients were significantly older (average age: 66 years versus 62 years, p

Abstract Introduction Major depressive disorder (MDD) is a mental disorder caused by the combination of genetic, environmental, and psychological factors. Over the years, a number of genes potentially associated with MDD have been identified. However, in many cases, the role of these genes and their relationship in the etiology and development of MDD remains unclear. Under such situation, a systems biology approach focusing on the function correlation and interaction of the candidate genes in the context of MDD will provide useful information on exploring the molecular mechanisms underlying the disease. Methods We collected genes potentially related to MDD by screening the human genetic studies deposited in PubMed (https://www.ncbi.nlm.nih.gov/pubmed). The main biological themes within the genes were explored by function and pathway enrichment analysis. Then, the interaction of genes was analyzed in the context of protein–protein interaction network and a MDD‐specific network was built by Steiner minimal tree algorithm. Results We collected 255 candidate genes reported to be associated with MDD from available publications. Functional analysis revealed that biological processes and biochemical pathways related to neuronal development, endocrine, cell growth and/or survivals, and immunology were enriched in these genes. The pathways could be largely grouped into three modules involved in biological procedures related to nervous system, the immune system, and the endocrine system, respectively. From the MDD‐specific network, 35 novel genes potentially associated with the disease were identified. Conclusion By means of network‐ and pathway‐based methods, we explored the molecular mechanism underlying the pathogenesis of MDD at a systems biology level. Results from our work could provide valuable clues for understanding the molecular features of MDD.

In the present study, the therapeutic effects of 5-androstenediol on radiation-induced myeloid suppression and tissue damage in mice and the possible mechanism were explored. The mice were subjected to whole-body irradiation, and 5-androstenediol was administered subcutaneously at different times and doses. The evaluation of the survival rate showed that the administration of 5-androstenediol every three days post-irradiation was the most effective in decreasing the death of the mice. Additionally, 5-androstenediol dose-dependently reduced the death caused by 9 Gy radiation. The pharmacological mechanism was investigated by blood analysis, western blot analysis, immunofluorescence and immunohistochemistry. 5-Androstenediol significantly ameliorated myeloid suppression, as demonstrated by elevated levels of total white blood cells, including neutrophils and platelets, in the peripheral blood. By H&E staining, we found that radiation-induced myeloid suppression in the bone marrow and spleen, as well as tissue damage in the lung and colon, was significantly ameliorated by treatment with 5-androstenediol. Immunohistochemistry showed elevated phosphorylation of p65 in the bone marrow and spleen, indicating the activation of NF-κB signaling. Moreover, 5-androstenediol markedly hampered the radiation-induced activation of caspase-1 and GSDMD in the colon by decreasing the interaction between AIM2 and ASC. Taken together, our results suggest that, by promoting NF-κB signaling and inhibiting inflammasome-mediated pyroptosis, 5-androstenediol can be used as a radioprotective drug.