A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.

Phenotypic Heterogeneity in Patients with Mutations in the Mitochondrial Complex I Assembly Gene NDUFAF5.

BACKGROUND: Rare mutations in NADH:ubiquinone oxidoreductase complex assembly factor 5 (NDUFAF5) are linked to Leigh syndrome. OBJECTIVE: We aimed to describe clinical characteristics and functional findings in a patient cohort with NDUFAF5 mutations. METHODS: Patients with biallelic NDUFAF5 mutations were recruited from multi-centers in Taiwan. Clinical, laboratory, radiological, and follow-up features were recorded and mitochondrial assays were performed in patients' skin fibroblasts. RESULTS: Nine patients from seven unrelated pedigrees were enrolled, eight homozygous for c.836 T > G (p.Met279Arg) in NDUFAF5 and one compound heterozygous for p.Met279Arg. Onset age had a bimodal distribution. The early-onset group (age <3 years) presented with psychomotor delay, seizure, respiratory failure, and hyponatremia. The late-onset group (age ≥5 years) presented with normal development, but slowly progressive dystonia. Combing 25 previously described patients, the p.Met279Arg variant was exclusively identified in Chinese ancestry. Compared with other groups, patients with late-onset homozygous p.Met279Arg were older at onset (P = 0.008), had less developmental delay (P = 0.01), less hyponatremia (P = 0.01), and better prognosis with preserved ambulatory function into early adulthood (P = 0.01). Bilateral basal ganglia necrosis was a common radiological feature, but brainstem and spinal cord involvement was more common with early-onset patients (P = 0.02). A modifier gene analysis showed higher concomitant mutation burden in early-versus late-onset p.Met279Arg homozygous cases (P = 0.04), consistent with more impaired mitochondrial function in fibroblasts from an early-onset case than a late-onset patient. CONCLUSIONS: The p.Met279Arg variant is a common mutation in our population with phenotypic heterogeneity and divergent prognosis based on age at onset. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical and functional characterization of a novel STUB1 frameshift mutation in autosomal dominant spinocerebellar ataxia type 48 (SCA48).

BACKGROUND: Heterozygous pathogenic variants in STUB1 are implicated in autosomal dominant spinocerebellar ataxia type 48 (SCA48), which is a rare familial ataxia disorder. We investigated the clinical, genetic and functional characteristics of STUB1 mutations identified from a Taiwanese ataxia cohort. METHODS: We performed whole genome sequencing in a genetically undiagnosed family with an autosomal dominant ataxia syndrome. Further Sanger sequencing of all exons and intron-exon boundary junctions of STUB1 in 249 unrelated patients with cerebellar ataxia was performed. The pathogenicity of the identified novel STUB1 variant was investigated. RESULTS: We identified a novel heterozygous frameshift variant, c.832del (p.Glu278fs), in STUB1 in two patients from the same family. This rare mutation is located in the U-box of the carboxyl terminus of the Hsc70-interacting protein (CHIP) protein, which is encoded by STUB1. Further in vitro experiments demonstrated that this novel heterozygous STUB1 frameshift variant impairs the CHIP protein's activity and its interaction with the E2 ubiquitin ligase, UbE2D1, leading to neuronal accumulation of tau and α-synuclein, caspase-3 activation, and promoting cellular apoptosis through a dominant-negative pathogenic effect. The in vivo study revealed the influence of the CHIP expression level on the differentiation and migration of cerebellar granule neuron progenitors during cerebellar development. CONCLUSIONS: Our findings provide clinical, genetic, and a mechanistic insight linking the novel heterozygous STUB1 frameshift mutation at the highly conserved U-box domain of CHIP as the cause of autosomal dominant SCA48. Our results further stress the importance of CHIP activity in neuronal protein homeostasis and cerebellar functions.

[Comparative Analysis of Content of Four Alkaloids in Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea].

OBJECTIVE: To establish an assay method for simultaneous determination of peimine, peiminine, peimissine and hupehenine and to make a comparative analysis of the content of four alkaloids in Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea for the first time. METHODS: A Unitary C18 column(250 mm x 4.6 mm, 5 µm) was chosen with acetonitrile-water (containing 0.05% diethylamine) as mobile phase in a gradient program. The column temperature was 35 degrees C and the flow-rate was 1.0 mL/min. RESULTS: There was high content of peiminine and the content of peimissine was inferior to peiminine in Fritillaria hupehensis. Relatively speaking, peimine and hupehenine were much lower than the other two ingredients. Fritillaria ebeiensis var. purpurea also contained high levels of peiminine, the minimum content of peimine and equivalent content of peimissine comparing with Fritillaria hupehensis. In addition, it didn't contain hupehenine in Fritillaria ebeiensis var. purpurea. CONCLUSION: This method is simple and fast, and it has good separation, reproducibility and reliable results. Also, it can be used as basis for the quality evaluation of Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea.

Autocrine CCL3 and CCL4 induced by the oncoprotein LMP1 promote Epstein-Barr virus-triggered B cell proliferation.

Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were detected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokine in vivo. This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies.

Effect of nitrate addition on reductive transformation of pentachlorophenol in paddy soil in relation to iron(III) reduction.

Reductive dechlorination is a crucial pathway for anaerobic biodegradation of highly chlorinated organic contaminants. Under an anoxic environment, reductive dechlorination of organic contaminants can be affected by many redox processes such as nitrate reduction and iron reduction. In the present study, batch incubation experiments were conducted to investigate the effect of nitrate addition on reductive dechlorination of PCP in paddy soil with consideration of iron transformation. Study results demonstrate that low concentrations (0, 0.5 and 1 mM) of nitrate addition can enhance the reductive dechlorination of PCP and Fe(III) reduction, while high concentrations (5, 10, 20 and 30 mM) of nitrate addition caused the contrary. Significant positive correlations between PCP degradation rates and the formation rates of dissolved Fe(II) (pearson correlation coefficients r = 0.965) and HCl-extractable Fe(II) (r = 0.921) suggested that Fe(III) reduction may enhance PCP dechlorination. Furthermore, consistent variation trends of PCP degradation and the abundances of the genus Comamonas, capable of Fe(III) reduction coupled to reductive dechlorination, and of the genus Dehalobacter indicated the occurrence of microbial community variation induced by nitrate addition as a response to PCP dechlorination.

Controlling factors of heavy metal(loid) accumulation in rice: Main and interactive effects.

Identifying the key determinants of heavy metal(loid) accumulation in rice and quantifying their contributions are critical for precise prediction of heavy metal(loid) concentrations in rice and the formulation of effective pollution control strategies. The accumulation of heavy metal(loid)s in rice can be influenced by both natural and anthropogenic factors, which may interact with each other. However, distinguishing the independent roles (main effects) from interactive effects and quantifying their impacts separately pose challenges. To address this knowledge gap, we employed TreeExplainer-based SHAP and random forest algorithms in this study to quantitatively estimate the primary influencing factors and their main and interactive effects on heavy metal(loid)s in rice. Our findings reveal that soil cadmium (SCd) and rice cultivation time (C_TIME) were the primary contributors to rice cadmium (RCd) and rice arsenic (RAs), respectively. Soil lead (SPb) and sampling distances from roads significantly contributed to rice lead (RPb). Additionally, we identified significant interactive effects of SCd and C_TIME, C_TIME and RCd, and RCd and rice variety on RCd, RAs, and RPb, respectively, emphasizing their significance. These insights are pivotal in improving the accuracy of heavy metal(loid) concentration predictions in rice and offering theoretical guidance for the formulation of pollution control measures.

[Genetic evolution analysis of matrix protein 2 gene of avian influenza H5N1 viruses from boundary of Yunnan province].

OBJECTIVE: To elucidate the variation in characterizations and genetic evolution of the matrix protein 2 or ion channel protein(M2) genes of avian influenza subtype H5N1 viruses in the boundary region of Yunnan province from 2008 to 2012. METHODS: A total of swab samples were collected from foreign poultry such as the junction between Yunnan and Vietnam, Laos,myanmar and wild birds in boundary region of Yunnan province from 2008 to 2012 and screened by H5N1 subtype-specific multiplex RT-PCR. The M genes of H5N1 virus from the positive samples were amplified by RT-PCR and cloned into pMD18-T vectors for sequencing. The alignment and phylogenetic analysis of M2 genes were performed with sequences of the known reference strains. RESULTS: A total of 71 positive samples were found out of 1240 samples and the positive rate was 5.72%. A total of 14 different M2 sequences were obtained from 30 positive samples and were divided into 3 distinct clades or sub-clades(1.2.1, 1.2.2 and 2) by phylogenetic analysis, 5, 7 and 2, respectively. The M2 genes and Hemagglutinin(HA) genes of H5N1 viruses from the boundary region of Yunnan province had showed different relationship of genetic evolution. The substitution or mutation of key amino acids sites had been found among the domains of epitope, adamantane-resistance, and poultry or human original viral strains. CONCLUSION: The M2 genes of H5N1 subtype viruses in boundary region of Yunnan province from 2008 to 2012 showed genetic divergence and the virus of clade 1.2.2 had become dominant epidemic strain in this region.

Clinical study on prevention of atopic dermatitis by oral administration of probiotics in infants.

Introduction: This study aimed to investigate the preventive effects of oral administration of probiotics on the incidence and severity of atopic dermatitis (AD) in infants. Material and methods: A total of 396 full-term infants were enrolled in this study. Of these, 132 newborns without a family history of AD were assigned to group A, and the other 264 newborns were randomly divided into groups B and C. Infants in groups A and B were solely breastfed, while probiotics were administered to those in group C as well as breastfeeding. The information of all subjects was recorded, and the incidence of AD was followed up. The levels of serum IgE and IL-4 were measured at the age of 3 years. Results: The incidence of AD in infants in group B was higher than that in group A at 3 months, 4-6 months, and 7-36 months after birth, together with increased symptom scores. For infants in group C, the incidence of AD at 4-6 months and 7-36 months after birth and the SCORAD scores at 0-3 months and 4-6 months after birth were lower than those in group B. The levels of IgE and IL-4 in group B were higher than those in groups A and C at 36 months old. Conclusions: Adding probiotics could favor the establishment of the intestinal microecological balance in the neonatal period, thereby reducing the incidence of AD, decreasing the levels of serum immune indexes and alleviating the severity of the disease.

Knockdown of FGFR3 inhibits the proliferation, migration and invasion of intrahepatic cholangiocarcinoma.

The FGF/FGFR signaling axis deregulation of the fibroblast growth factor receptor (FGFR) family is closely related to tumorigenesis, tumor progression and drug resistance to anticancer therapy. And fibroblast growth factor receptor 3 (FGFR3) is one member of this family. In this study, we aimed to investigate the effect of siRNA-induced knockdown of FGFR3 on the biological behaviors of intrahepatic cholangiocarcinoma (ICC). The expression levels of FGFR3 were determined in three intrahepatic cholangiocarcinoma cell lines RBE, HUCCT1 and HCCC9810 cell lines by Western blot. FGFR3 expression in RBE cell line was knocked down by siRNA. Our study found that knockdown of FGFR3 inhibited the migration, invasion and proliferation of ICC cells using Wound healing assay, Transwell migration and invasion assays and Cell proliferation assay. And significantly down-regulated the protein expression levels of MMP2, cyclinD1, and NCadherin, but had no significant effect on MMP9, cyclinD3, vimentin, E-cadherin protein. In addition, we found that ERK/c-Myc presumably is its signaling pathway by bioinformatics analysis and Western blot verification. To sum up, knockdown of FGFR3 inhibited the migration, invasion and proliferation of ICC cells. It demonstrated that FGFR3 probably becomes a therapeutic target for ICC and increases the proportion of potentially curable intrahepatic cholangiocarcinoma patients treated with FGFR inhibitors.

A novel C19orf12 frameshift mutation in a MPAN pedigree impairs mitochondrial function and connectivity leading to neurodegeneration.

BACKGROUND: Mitochondrial membrane protein‒associated neurodegeneration (MPAN) is a rare genetic disease characterized by progressive neurodegeneration with brain iron accumulations combined with neuronal α-synuclein and tau aggregations. Mutations in C19orf12 have been associated with both autosomal recessive and autosomal dominant inheritance patterns of MPAN. METHODS: We present clinical features and functional evidence from a Taiwanese family with autosomal dominant MPAN caused by a novel heterozygous frameshift and nonsense mutation in C19orf12, c273_274 insA (p.P92Tfs*9). To verify the pathogenicity of the identified variant, we examined the mitochondrial function, morphology, protein aggregation, neuronal apoptosis, and RNA interactome in p.P92Tfs*9 mutant knock-in SH-SY5Y cells created with CRISPR-Cas9 technology. RESULTS: Clinically, the patients with the C19orf12 p.P92Tfs*9 mutation presented with generalized dystonia, retrocollis, cerebellar ataxia, and cognitive decline, starting in their mid-20s. The identified novel frameshift mutation is located in the evolutionarily conserved region of the last exon of C19orf12. In vitro studies revealed that the p.P92Tfs*9 variant is associated with impaired mitochondrial function, reduced ATP production, aberrant mitochondria interconnectivity and ultrastructure. Increased neuronal α-synuclein and tau aggregations, and apoptosis were observed under conditions of mitochondrial stress. Transcriptomic analysis revealed that the expression of genes in clusters related to mitochondrial fission, lipid metabolism, and iron homeostasis pathways was altered in the C19orf12 p.P92Tfs*9 mutant cells compared to control cells. CONCLUSION: Our findings provide clinical, genetic, and mechanistic insight revealing a novel heterozygous C19orf12 frameshift mutation to be a cause of autosomal dominant MPAN, further strengthening the importance of mitochondrial dysfunction in the pathogenesis of MPAN.

Sedimentary loadings and ecological significance of polycyclic aromatic hydrocarbons in a typical mariculture zone of South China.

Two sediment cores were collected from Hailing Bay located in a typical mariculture zone of Guangdong Province, South China, and analyzed for polycyclic aromatic hydrocarbons (PAHs). The concentrations of the sum of 27 PAHs ranged from 62 to 1200 ng g(-1) dry wt, and sediment in the study area was considered to be moderately polluted by PAHs. Source diagnostics based on PAH composition and principal component analysis suggested that PAHs in the study area were mainly derived from petroleum combustion, with discharge of PAHs from fishing boats as an important source. Ecological risk assessment results indicate that PAHs in sediment of the present study currently have minimal adverse effect on the mariculture environment. Comparison of sedimentary inventory of PAHs in the fish harbor of the study area with those in the Pearl River Estuary and the coastal Bohai Bay indicate that the sediment has become an important reservoir of PAHs.

EIF5A2 promotes proliferation and invasion of intrahepatic cholangiocarcinoma cells.

PURPOSE: Intrahepatic cholangiocarcinoma (ICC) can invade and metastasize. EIF5A2 is involved in the invasive metastatic process of several digestive malignancies. However, its role in ICC is yet to be elucidated. METHODS: Immunohistochemistry (IHC) and Western blot (WB) were used to detect the level of EIF5A2 in the tumor specimens of ICC patients and evaluate the correlation between its expression and clinicopathological characteristics. The significance of EIF5A2 in the prognosis of ICC patients was further evaluated by Kaplan-Meier and Cox regression analysis. In addition, CCK-8, EdU, Transwell invasion, and scratch assays were utilized to detect tumor cell proliferation, invasion, and metastasis. Furthermore, the role of EIF5A2 in ICC cells was evaluated after modification of EIF5A2 expression. RESULTS: The level of EIF5A2 protein was significantly higher in ICC than in adjacent tissues. This high expression in the tumor samples was significantly associated with malignant phenotypes, such as lymph node metastasis (LNM), microvascular or bile duct invasion, and poor differentiation. ICC patients with high expression of EIF5A2 had short overall survival and a high cumulative recurrence rate. The multifactorial analysis showed that EIF5A2 is an independent prognostic marker. Furthermore, high levels of EIF5A2 may activate the PI3K/AKT/mTOR signaling pathway and upregulate Cyclin D1, Cyclin D3, MMP2, and MMP9 to promote ICC cell proliferation, migration, and invasion. CONCLUSION: The current study found that EIF5A2 promotes ICC progression and is a prognostic biomarker and candidate therapeutic target for ICC patients.

Evaluation of Transplacental Antibody Transfer in SARS-CoV-2-Immunized Pregnant Women.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy could result in adverse perinatal outcome. Clinical data on the assessment of the immune response in vaccinated pregnant women and subsequent transplacental antibody transfer are quite limited. OBJECTIVE: To assess maternal and neonatal neutralizing antibody levels against both wildtype and Delta (B.1.617.2) variants after maternal mRNA vaccination. STUDY DESIGN: This cohort study was conducted 29 pregnant women who were vaccinated at least one dose of Moderna (mRNA-1273) vaccine. Both neutralizing antibody (wildtype and Delta variant) and S1 receptor binding domain IgG antibody levels were evaluated in maternal and cord blood on the day of delivery. RESULTS: Superiority of antibody level was significant in fully vaccinated women compared with the one-dose group (maternal sera, median, 97.46%; cord sera, median, 97.37% versus maternal sera, median, 4.01%; cord sera, median, 1.44%). No difference in antibody level was noted in relation to interval of second immunization to delivery in the two-dose group (95.99% in 0-2 weeks, 97.45% in 2-4 weeks, 97.48% in 4-8 weeks, 97.72% in 8-10 weeks). The most pronounced reduction was observed for the Delta variant. The wildtype neutralizing antibody level of full-vaccinated women was not influenced by the pertussis vaccination. CONCLUSION: The data underscore the importance of full vaccination in pregnancy and support the recommendation of COVID-19 immunization for pregnant women. The lower level of vaccine-induced neutralizing antibodies for the Delta variant indicates insufficient protection for mother and newborn and highlights the need for development of effective vaccine strategies.

Bioavailability of antimony and arsenic in a flowering cabbage-soil system: Controlling factors and interactive effect.

Soil contamination with antimony (Sb) and arsenic (As) has become a well-recognized environmental and human health issue. Consumption of vegetables, especially leafy vegetables, is one of the most important sources of Sb and As exposure in humans. Accordingly, it is necessary to understand the behaviors of Sb and As in the vegetable-soil system. Moreover, although Sb and As are often assumed to have similar biogeochemical behavior, identified differences in the controlling factors affecting mobility and bioavailability of Sb and As in soils need further investigation. In this study, 112 pairs of soil and flowering cabbage samples were collected from typical farmland protection areas and vegetable-producing regions across the Pearl River Delta (PRD), South China. The contamination levels of Sb and As in soils and harvested cabbages across the PRD were investigated. The main factors affecting the mobility and bioavailability of Sb and As in the cabbage-soil system were disentangled using a random forest model. The contamination levels of Sb in the cabbages and soils of the PRD were generally low, but the soils were moderately polluted by As. Increased concentrations of Fe oxides could decrease Sb accumulation in cabbages but increased the mobilization of As in soils to some extent. In contrast, Al oxides contributed strongly to the mobilization of Sb and the immobilization of As. Moreover, an increased sand content promoted the mobility of Sb and As, whereas increased silt and clay contents showed inhibitory effects. The interactions of As and Sb with Fe oxides decreased the mobility of Sb but moderately increased the mobility of As in soils. Overall, the behaviors of Sb and As in the cabbage-soil system under the effect of several important environmental factors showed some differences indicating that these differences should be considered in the remediation of co-contaminated soils.

Field validation of anaerobic degradation pathways for dichlorodiphenyltrichloroethane (DDT) and 13 metabolites in marine sediment cores from China.

Although the production and use of dichlorodiphenyltrichloroethane (DDT), a legacy component of persistent organic pollutants, have been highly restricted worldwide, the environmental fate of DDT has remained a great concern as it is not only ubiquitous and bioaccumulative but can also be degraded to a series of metabolites that may be more hazardous ecologically. The present study, taking advantage of the abundant levels of DDT and its metabolites in a subtropical coastal region of China, investigated into the degradation pathways of DDT in natural coastal sediment. Sediment profiles indicated that degradation of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (p,p'-DDT) to 1,1-dichloro-2,2-bis-(p-chlorophenyl)ethane (p,p'-DDD) mainly occurred in sediment of the top 20 cm layer. 1,1-dichloro-2,2-bis-(p-chlorophenyl)ethylene (p,p'-DDE), aerobically transformed from p,p'-DDT prior to sedimentation, was likely to degrade to 1-chloro-2,2-bis-(p-chlorophenyl)ethylene (p,p'-DDMU) which was further converted to 2,2-bis(p-chlorophenyl)ethylene (p,p'-DDNU). In addition, p,p'-DDNU could be transformed to 2,2-bis(p-chlorophenyl)ethane (p,p'-DDNS) and other high-order metabolites. On the other hand, the conversions of p,p'-DDD to p,p'-DDMU and 1-chloro-2,2-bis-(p-chlorophenyl)ethane (p,p'-DDMS) to p,p'-DDNU were deemed slow in anaerobic sediment. Therefore, the present study confirmed all the degradation pathways involving reductive dechlorination and p,p'-DDE being a more important precursor for p,p'-DDMU than p,p'-DDD in anaerobic sediment, as proposed previously. On the other hand, the present study suggested that p,p'-DDMU instead of p,p'-DDMS was more likely the precursor for formation of high-order metabolites. Based on the current assessments, use of (DDD+DDE)/DDTs to indicate whether there is fresh DDT input may lead to large uncertainties if the concentrations of high-order metabolites are not negligible. Similarly, ecological risk assessment associated with DDT should be conducted with consideration of high-order DDT metabolites.

Rheological Properties of Graphene/Polyethylene Composite Modified Asphalt Binder.

Aiming to improve the comprehensive road performance of asphalt binders, especially the high-temperature performance, a novel asphalt binder was prepared by compounding high-quality and low-cost polyethylene (PE) with graphene (GNPs) using a high-speed shearing machine. The rheological properties and interaction mechanism of PE/GNPs composite modified asphalt were investigated using temperature sweep (TeS), multiple stress creep recovery (MSCR), linear amplitude sweep (LAS) and Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscopy (FESEM). The experimental results demonstrated that GNPs and PE can synergistically improve the high-temperature performance of asphalt binders and enhance the rutting resistance of pavements; the pre-blended PE/GNPs masterbatch has good medium-temperature fatigue and low-temperature cracking resistance. Meanwhile, PE/GNPs dispersed uniformly in the asphalt matrix, and the microstructure and dispersion of premixed PE/GNPs masterbatch facilitated the asphalt modification. No new absorption peaks appeared in the FT-IR spectra of the composite modified asphalt, indicating that asphalt binders were physically modified with GNPs and PE. These findings may cast light on the feasibility of polyethylene/graphene composite for asphalt modification.

Clinical Evaluation of a Self-Testing Kit for Vaginal Infection Diagnosis.

Vaginitis is a common disorder among women of varying ages that arises from a change in the normal pH balance of vaginal bacteria or an infection. Characteristic symptoms of itching, irritation, and odor cause considerable discomfort and increase the risk of contracting other sexually transmitted infections. Because of the sensitive and personal nature of the condition, some women may be reluctant to seek treatment. This behavior not only fails to solve the problem but may also delay medical treatment and result in additional medical complications. The pH changes associated with vaginitis and vaginosis, which are characterized by the presence or absence of inflammation, respectively, are well known but can vary. For example, bacterial vaginosis and trichomoniasis infection will raise vaginal pH above 4.5, while vulvovaginal candidiasis does not result in any measurable change to pH. Nonetheless, diagnostic tools relying on pH measurement are a valuable approach from which additional testing and treatment may be launched. Here, we focused on the use of a vaginal self-test tool and tested 50 patients, including pregnant women. When used according to the instructions, the Hygeia Touch Self-Testing Kit for Vaginal Infection demonstrated over 88% accuracy compared to a clinical diagnostic workup, with a sensitivity of 87% and a specificity of 89% in the patients where the swab was correctly interpreted. This study demonstrated an effective self-test method with high acceptability among women that provided them with greater autonomy regarding health management.

Health-related quality of life and its related factors in coronary heart disease patients: results from the Henan Rural Cohort study.

The aims were to identify the possible influencing factors of health-related quality of life (HRQoL) and its domain-specific scores in patients with coronary heart disease (CHD). A total of 1247 patients with CHD from the Henan Rural Cohort Study (n = 39,259) were included in this study. The Chinese version of the European Quality of Life Five Dimension Five level scale (EQ-5D-5L) and Visual Analogue Scale (VAS) were used to evaluate HRQoL in patients with CHD. Tobit regression, generalized linear models and binary logistic regression were applied to determine the potential factors influencing the EQ-5D utility, as well as each domain, and the VAS. CHD patients had lower per capita monthly actual income, and higher rates of diabetes mellitus, stroke, anxiety and poor sleep quality, which significantly decreased EQ-5D index and VAS scores. In addition, sex, older age, education, not having a spouse, ever drinking alcohol, a high-fat diet, physical activity, hypertension and depression affected the various domain-specific EQ-5D scores in CHD patients. CHD patients in rural areas have a lower HRQoL. Factors associated with the EQ-5D index, including each domain, and the VAS need attention. CHD patients in rural areas need to be managed systematically.

Genotype-Phenotype Analysis and Mutation Spectrum in a Cohort of Chinese Patients With Congenital Nystagmus.

Purpose: Congenital nystagmus (CN) is a genetically and clinically heterogeneous ocular disorder that manifests as involuntary, periodic oscillations of the eyes. To date, only FRMD7 and GPR143 have been reported to be responsible for causing CN. Here, we aimed to identify the disease-causing mutations and describe the clinical features in the affected members in our study. Methods: All the subjects underwent a detailed ophthalmic examination. Direct sequencing of all coding exons and splice site regions in FRMD7 and GPR143 and a mutation assessment were performed in each patient. Results: We found 14 mutations in 14/37 (37.8%) probands, including nine mutations in the FRMD7 gene and five mutations in the GPR143 gene, seven of which are novel, including c.284G>A(R95K), c.964C>T(P322S), c.284+10T>G, c.901T>C (Y301H), and c.2014_2023delTCACCCATGG(S672Pfs*12) in FRMD7, and c.250+1G>C, and c.485G>A (W162*) in GPR143. The mutation detection rate was 87.5% (7/8) of familial vs. 24.1% (7/29) of sporadic cases. Ten mutations in 24 (41.7%) non-syndromic subjects and 4 mutations in 13(30.8%) syndromic subjects were detected. A total of 77.8% (7/9) of mutations in FRMD7 were concentrated within the FERM and FA domains, while all mutations in GPR143 were located in exons 1, 2, 4 and 6. We observed that visual acuity tended to be worse in the GPR143 group than in the FRMD7 group, and no obvious difference in other clinical manifestations was found through comparisons in different groups of patients. Conclusions: This study identified 14 mutations (seven novel and seven known) in eight familial and 29 sporadic patients with congenital nystagmus, expanding the mutational spectrum and validating FRMD7 and GPR143 as mutation hotspots. These findings also revealed a significant difference in the screening rate between different groups of participants, providing new insights for the strategy of genetic screening and early clinical diagnosis of CN.