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ABSTRACTInternal migrants are a challenge for TB control in large Chinese cities and understanding this epidemiology is crucial for designing effective control and prevention strategies. We conducted a prospective genomic epidemiological study of culture-positive TB patients diagnosed between June 1, 2018 and May 31, 2021 in the Longhua District of Shenzhen. Treatment status was obtained from local and national TB registries and all isolates were sequenced. Genomic clusters were defined as strains differing by ≤12 SNPs. Risk factors for clustering were identified with multivariable analysis and then Bayesian models and TransPhylo were used to infer the timing of transmission within clusters. Of the 2277 culture-positive patients, 70.1% (1596/2277) were migrants: 72.1% (1043/1446) of the migrants patients developed TB within two years of arriving in Longhua; 38.8% within 6 months of arriving; and 12.3% (104/843) had TB symptoms when they arrived. Only 15.4% of Longhua strains were in genomic clusters. More than one third (33.6%) of patients were not treated in Shenzhen but were involved in nearly one third of the recent transmission events. Clustering was associated with migrants not treated in Shenzhen, males, and teachers/trainers. TB in Longhua is prinicipally due to reactivation of infections in migrants, but a proportion may have had clinical or incipient TB upon arrival in the district. Patients diagnosed but not treated in Longhua were involved in recent local TB transmission. Controlling TB in Shenzhen will require strategies to comprehensively diagnose and treat active TB in the internal migrant population.

Abstract Background The purpose of this study was to investigate the differences between the clinical characteristics and the factors influencing liver injury in patients with the Omicron subvariant BA.5.2 (Omicron BA.5.2) and the prototype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods Between December 30, 2019 and November 30, 2022, 157 patients infected with the SARS-CoV-2 prototype and 199 patients infected with the Omicron BA.5.2 were included in this case-control, single-center, retrospective study. Differences in clinical characteristics and liver injury between the Omicron BA.5.2 patients and the prototype patients were subsequently analyzed. Results None of the Omicron BA.5.2 patients reached the critical state, and showed relatively milder symptoms including fever, cough, headache, muscle soreness, nausea or vomiting, diarrhea, anorexia and hypoxia. The Omicron BA.5.2 had a lower effect on body temperature (T), white blood cell (WBC) count, hematocrit (HCT), C-reactive protein (CRP) level, D-dimer, finger pulse oxygen saturation (SpO2) and lung lesions. The differences in liver injury between the two groups were related to the severity of the disease, T, blood oxygen levels, albumin (ALB), CRP, and medication usage. Gender, body mass index, and CRP levels influenced liver damage in the Omicron BA.5.2 patients. In particular, CRP was an independent risk factor for liver injury. Because the severity of liver function damage was considerably low, only a small number of Omicron BA.5.2 patients required liver-protective treatment. Conclusion Liver injury is expected in the COVID-19 patients. The Omicron BA.5.2 patients showed milder symptoms of liver injury than the prototype patients. However, dynamic monitoring of liver function is warranted, especially for individuals presenting with elevated levels of CRP.

Abstract Background Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates. Methods This retrospective, propensity-score matched (PSM) case–control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed. Results Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25–2.92; p

Pneumocephalus and empyema in the subarachnoid space secondary to spinal-epidural anesthesia are very rare and have not previously been reported, to our knowledge. Here, we describe the imaging features of an older woman presenting with pneumocephalus plus subarachnoid and intraventricular empyema due to Staphylococcus epidermidis infection after spinal-epidural anesthesia, with the aim of raising awareness regarding this serious complication.

Abstract Biomarkers play important roles in the diagnosis and differential diagnosis of Parkinson’s disease (PD). Thus, we carried out a systematic review and meta-analysis evaluating the diagnostic utility of cerebrospinal fluid (CSF) biomarkers to distinguish PD from atypical parkinsonian syndromes (APSs) and controls. Data for PD and APS and controls were extracted from 123 studies that reported the concentration of CSF biomarkers. Comparisons were presented using pooled Hedges’ g. Sources of heterogeneity were evaluated using meta-regression, and subgroup and sensitivity analyses. We found that compared with controls, PD patients had lower levels of amyloid beta 1-42, phosphorylated tau, total tau, total α-synuclein, Zn, DJ-1, and YKL-40, and higher levels of oligomeric and phosphorylated α-synuclein. Moreover, lower CSF levels of neurofilament light chain, t-tau, YKL-40, and C-reactive protein were found in PD patients compared to those with multiple system atrophy. PD patients also had lower levels of NFL and higher levels of Aβ42 compared with patients with progressive supranuclear palsy. Reduced levels of p-tau and t-tau and higher Aβ42 levels were found in PD patients compared with patients with dementia with Lewy bodies. Finally, reduced NFL levels were found in patients with PD compared with patients with cortical basal degeneration. Therefore, we believe that the combinations of t-α-syn, Aβ42, and NFL could be promising biomarkers for the differential diagnosis of PD and APSs.

Abstract A solid‐state electrolyte (SSE), which is a solid ionic conductor and electron‐insulating material, is known to play a crucial role in adapting a lithium metal anode to a high‐capacity cathode in a solid‐state battery. Among the various SSEs, the single Li‐ion conductor has advantages in terms of enhancing the ion conductivity, eliminating interfacial side reactions, and broadening the electrochemical window. Covalent organic frameworks (COFs) are optimal platforms for achieving single Li‐ion conduction behavior because of well‐ordered one‐dimensional channels and precise chemical modification features. Herein, we study in depth three types of Li‐carboxylate COFs (denoted LiOOC‐COFn, n = 1, 2, and 3) as single Li‐ion conducting SSEs. Benefiting from well‐ordered directional ion channels, the single Li‐ion conductor LiOOC‐COF3 shows an exceptional ion conductivity of 1.36 × 10−5 S cm−1 at room temperature and a high transference number of 0.91. Moreover, it shows excellent electrochemical performance with long‐term cycling, high‐capacity output, and no dendrites in the quasi‐solid‐state organic battery, with the organic small molecule cyclohexanehexone (C6O6) as the cathode and the Li metal as the anode, and enables effectively avoiding dissolution of the organic electrode by the liquid electrolyte.

Abstract Background Could nutritional status serve as prognostic factors for coronavirus disease 2019 (COVID-19)? The present study evaluated the clinical and nutritional characteristics of COVID-19 patients and explored the relationship between risk for malnutrition at admission and in-hospital mortality. Methods A retrospective, observational study was conducted in two hospitals in Hubei, China. Confirmed cases of COVID-19 were typed as mild/moderate, severe, or critically ill. Clinical data and in-hospital death were collected. The risk for malnutrition was assessed using the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the Controlling Nutritional Status (CONUT) via objective parameters at admission. Results Two hundred ninety-five patients were enrolled, including 66 severe patients and 41 critically ill patients. Twenty-five deaths were observed, making 8.47% in the whole population and 37.88% in the critically ill subgroup. Patients had significant differences in nutrition-related parameters and inflammatory biomarkers among three types of disease severity. Patients with lower GNRI and PNI, as well as higher CONUT scores, had a higher risk of in-hospital mortality. The receiver operating characteristic curves demonstrated the good prognostic implication of GNRI and CONUT score. The multivariate logistic regression showed that baseline nutritional status, assessed by GNRI, PNI, or CONUT score, was a prognostic indicator for in-hospital mortality. Conclusions Despite variant screening tools, poor nutritional status was associated with in-hospital death in patients infected with COVID-19. This study highlighted the importance of nutritional screening at admission and the new insight of nutritional monitoring or therapy.

Abstract Background Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. Methods In this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein–protein interaction (PPI) network for mRNAs interacting with these lncRNAs. Results We identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. Conclusions Our research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.

Abstract Background Sexual and Reproductive Health (SRH) targets have been included as part of the United Nations Sustainable Development Goals and indictors are important to monitor progress towards these targets. SRH indicators are recommended for setting norms and measuring progress globally. However, given the diverse political, socioeconomic and cultural contexts in different countries, and lack of global agreement on broad indicators, it is important to select appropriate indicators for specific countries. Based on internationally recommended indicators and data availability in China, this paper selected four indictors to reflect SRH in China and interpreted these indictors by analyzing the underlying factors. Methods We employed secondary data analysis and key informant interviews. Secondary data were obtained from the China Health Statistical Yearbook (2005–2017), China Statistical Yearbook (2005–2017), and the sub-national estimates of the Global Burden Diseases Study 2016. We interviewed 36 key informants at national and sub-national levels. Results The four selected SRH indicators are contraceptive prevalence rate (CPR), adolescent birth rate, abortion rate, and availability of school sex education. CPR of married women has remained above 75% over the last three decades, indicating a high level of access to family planning (FP) services; however, unmarried but sexually active women have significant unmet needs for FP services. Although adolescent birth rates in China remain low, the abortion rate, abortion numbers, and the ratio of abortions to births increased from 2014 to 2016 while FP policy was relaxed. This suggests that abortion among unmarried women is a significant contributor to overall figures. Qualitative analysis of the availability of school sex education, reveals an absence of policy due to conservative attitudes of key stakeholders. Conclusion Since SRH challenges vary significantly between contexts, indicators for measuring progress towards SRH targets should be selected based on country context. The CPR and abortion rate are currently available and important indicators to monitor the most basic part of SRH in China, but require modification to ensure they reflect universal access to quality reproductive healthcare by all reproductive age women, regardless of their marriage status. Policy and indicators on sex education need to be carefully developed to fit the context in China.

Abstract Background Chlorops oryzae is an important pest of rice crops. There have been frequent outbreaks of this pest in recent years and it has become the main rice pest in some regions. To elucidate the molecular mechanism of frequent C. oryzae outbreaks, we estimated the genetic diversity and genetic differentiation of 20 geographical populations based on a dataset of ISSR markers and COI sequences. Results ISSR data revealed a high level of genetic diversity among the 20 populations as measured by Shannon’s information index (I), Nei’s gene diversity (H), and the percentage of polymorphic bands (PPB). The mean coefficient of gene differentiation (Gst) was 0.0997, which indicates that only 9.97% genetic variation is between populations. The estimated gene flow (Nm) value was 4.5165, indicating a high level of gene flow and low, or medium, genetic differentiation among some populations. The results of a Mantel test revealed no significant correlation between genetic and geographic distance among populations, which means there is no evidence of significant genetic isolation by distance. An UPGMA (unweighted pair-group method with arithmetic averages) dendrogram based on genetic identity, did not indicate any major geographic structure for the 20 populations examined. mtDNA COI data indicates low nucleotide (0.0007) and haplotype diversity (0.36) in all populations. Fst values suggest that the 20 populations have low, or medium, levels of genetic differentiation. And the topology of a Neighbor-Joining tree suggests that there are no independent groups among the populations examined. Conclusions Our results suggest that C. oryzae populations have high genetic diversity at the species level. There is evidence of frequent gene flow and low, or medium, levels of genetic differentiation among some populations. There is no significant correlation between genetic and geographic distance among C. oryzae populations, and therefore no significant isolation by distance. All results are consistent with frequent gene exchange between populations, which could increase the genetic diversity, and hence, adaptability of C. oryzae, thereby promoting frequent outbreaks of this pest. Such knowledge may provide a scientific basis for predicting future outbreaks.

Abstract Gold nanoparticles (GNPs) are one of the most widely used nanomaterials in various fields. Especially, the unique chemical and physical properties make them as the promising candidates in drug target identification, unfortunately, little is known about their application in parasites. In this paper, GNPs were employed as new solid support to identify drug targets of natural bioactive compound arctigenin (ARG) against fish monogenean parasite Gyrodactylus kobayashi. Before target identification, GNPs with ARG on the surface showed the ability to enter the live parasites even the nucleus or mitochondria, which made the bound compounds capable of contacting directly with target proteins located anywhere of the parasites. At the same time, chemically modified compound remained the anthelminthic efficacy against G. kobayashii. The above results both provide assurance on the reliability of using GNPs for drug target-binding specificity. Subsequently, by interrogating the cellular proteome in parasite lysate, myosin-2 and UNC-89 were identified as the potential direct target proteins of ARG in G. kobayashii. Moreover, results of RNA-seq transcriptomics and iTRAQ proteomics indicated that myosin-2 expressions were down-regulated after ARG bath treatment both in transcript and protein levels, but for UNC-89, only in mRNA level. Myosin-2 is an important structural muscle protein expressed in helminth tegument and its identification as our target will enable further inhibitor optimization towards future drug discovery. Furthermore, our findings demonstrate the power of GNPs to be readily applied to other parasite drugs of unknown targets, facilitating more broadly therapeutic drug design in any pathogen or disease model.

Aqueous zinc-ion batteries offer the greatest promise as an alternative technology for low-cost and high-safety energy storage. However, the development of high-performance cathode materials and their compatibility with aqueous electrolytes are major obstacles to their practical applications. Herein, we report the synthesis of orthorhombic V2O5·nH2O nanorods as cathodes for aqueous zinc batteries. As a result, the electrode delivers a reversible capacity as high as 320 mAh g−1 at 1.0 A g−1 and long-term cycling stability in a wide window of 0.2 to 1.8 V using a mild ZnSO4 aqueous electrolyte. The superior performance can be attributed to the improved stability of materials, inhibited electrolyte decomposition and facilitated charge transfer kinetics of such materials for aqueous zinc storage. Furthermore, a full cell using microsized Zn powder as an anode within capacity-balancing design exhibits high capacity and stable cycling performance, proving the feasibility of these materials for practical application.

Abstract Objectives To evaluate the pharmacokinetic changes in lamotrigine (LTG) from prepregnancy to postpartum and to assess the impact of therapeutic drug monitoring (TDM) on seizure management during pregnancy in a Chinese population. Methods A series of women who were on LTG monotherapy before conception or during pregnancy were included in this retrospective study. The clinical characteristics of the mothers and fetuses were collected. The apparent clearance (AC) and the ratio to target concentration (RTC) were calculated for each trimester or for each month. RTCs were compared between patients with and without an increase in the frequency of seizures. A receiver operating characteristic curve to determine the RTC threshold, which predicts increased seizure frequency best, was drawn. Results A total of 12 patients and their 12 pregnancies were reviewed retrospectively. AC increased by 82.5% during the first trimester (p = 0.0343), 203.2% during the second trimester (p = 0.0010), and 197.0% during the third trimester (p = 0.0061) compared with the prepregnancy level. The value returned to the prepregnancy level after delivery. Seven patients who had adequate baseline information were included to examine the association between serum LTG concentration and seizure frequency. The RTC values of patients with and without an increased frequency of seizures were significantly different (p = 0.0164), and increased seizure frequency was associated with a lower RTC. An RTC

Supramolecular host-guest interaction and sensing between cationic pillar[5]arenes (CP5) and L-carnitine were developed by the competitive host-guest recognition for the first time. The fluorescence sensing platform was constructed by CP5 functionalized Au nanoparticles (CP5@Au-NPs) as receptor and probe (rhodamine 123, R123), which shown high sensitivity and selectivity for L-carnitine detection. Due to the negative charge and molecular size properties of L-carnitine, it can be highly captured by the CP5 via electrostatic interactions and hydrophobic interactions. The host-guest mechanism between PP5 and L-carnitine was studied by 1H NMR and molecular docking, indicating that more affinity binding force of CP5 with L-carnitine. Therefore, a selective and sensitive fluorescent method was developed. It has a linear response of 0.1⁻2.0 and 2.0⁻25.0 μM and a detection limit of 0.067 μM (S/N = 3). The fluorescent sensing platform was also used to detect L-carnitine in human serum and milk samples, which provided potential applications for the detection of drugs abuse and had path for guarding a serious food safety issues.

A dissection of plant defense pathways was initiated through gene expression profiling of the responses of a single Arabidopsis thaliana genotype to isogenic Pseudomonas syringae strains expressing one of four different cloned avirulence (avr) genes. Differences in the expression profiles elicited by different resistance (R)-avr interactions were observed. A role for poly(ADP-ribosyl)ation in plant defense responses was suggested initially by the upregulated expression of genes encoding NUDT7 and poly(ADP-ribose) glycohydrolase in multiple R-avr interactions. Gene knockout plant lines were tested for 20 candidate genes identified by the expression profiling, and Arabidopsis NUDT7 mutants allowed less growth of virulent P. syringae (as previously reported) but also exhibited a reduced hypersensitive-response phenotype. Inhibitors of poly(ADP-ribose) polymerase (PARP) disrupted FLS2-mediated basal defense responses such as callose deposition. EIN2 (ethylene response) and IXR1 and IXR2 (cellulose synthase) mutants impacted the FLS2-mediated responses that occur during PARP inhibition, whereas no impacts were observed for NPR1, PAD4, or NDR1 mutants. In the expression profiling work, false-positive selection and grouping of genes was reduced by requiring simultaneous satisfaction of statistical significance criteria for each of three separate analysis methods, and by clustering genes based on statistical confidence values for each gene rather than on average fold-change of transcript abundance.

We report the results of a genome-wide analysis of transcription in Arabidopsis thaliana after treatment with Pseudomonas syringae pathovar tomato. Our time course RNA-Seq experiment uses over 500 million read pairs to provide a detailed characterization of the response to infection in both susceptible and resistant hosts. The set of observed differentially expressed genes is consistent with previous studies, confirming and extending existing findings about genes likely to play an important role in the defense response to Pseudomonas syringae. The high coverage of the Arabidopsis transcriptome resulted in the discovery of a surprisingly large number of alternative splicing (AS) events--more than 44% of multi-exon genes showed evidence for novel AS in at least one of the probed conditions. This demonstrates that the Arabidopsis transcriptome annotation is still highly incomplete, and that AS events are more abundant than expected. To further refine our predictions, we identified genes with statistically significant changes in the ratios of alternative isoforms between treatments. This set includes several genes previously known to be alternatively spliced or expressed during the defense response, and it may serve as a pool of candidate genes for regulated alternative splicing with possible biological relevance for the defense response against invasive pathogens.

Achieving a balance between luminescence and stability poses challenges for covalent organic frameworks (COF). Herein, two types of COF materials, namely, CN-COF and CC-COF, are synthesized using Schiff-base and Knoevenagel condensation reactions, respectively. FTIR, solid-state 13C NMR, PXRD, HRXPS, SEM, and TEM techniques are used to characterize the structure and micromorphology of COF materials. The microporous structure of CN-COF exhibits a well-defined cube-shaped with an average length of ∼100 nm. CC-COF has good dispersion and uniform morphology, which is very similar to nanorods, with an average length of ∼450 nm and an average width of ∼80 nm. Density functional theory calculations are employed to gain further insights into the relationship between the composition, linkage, and fluorescent properties. 1,4-Phenyldiacetonitrile and 1,3,6,8-tetrakis-(4-formylphenyl)-pyrene serve as the precursors of the donor (D)-acceptor (A) type CC-COF framework, thereby enhancing the luminescent performance of COF materials. The results indicate that the D-A-type CC-COF in tetrahydrofuran exhibits higher luminescent intensity compared to CN-COF. It is noteworthy that the fluorescence signal of the D-A-type CC-COF is quenched upon the gradual addition of 2,4,6-trinitrophenol to the suspension. The findings of this study offer valuable insights for the rational design of linkages to develop stable, porous, and highly luminescent COF materials. [ABSTRACT FROM AUTHOR]

Abstract Background The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. Methods These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. Results Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. Conclusions This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide. Graphical Abstract