ABSTRACT
Bacterial infections often involve virulence factors that play a crucial role in the pathogenicity of bacteria. Accurate detection of virulence factor genes (VFGs) is essential for precise treatment and prognostic management of hypervirulent bacterial infections. However, there is a lack of rapid and accurate methods for VFG identification from the metagenomic data of clinical samples. Here, we developed a Reads-based Virulence Factors Scanner (RVFScan), an innovative user-friendly online tool that integrates a comprehensive VFG database with similarity matrix-based criteria for VFG prediction and annotation using metagenomic data without the need for assembly. RVFScan demonstrated superior performance compared to previous assembly-based and read-based VFG predictors, achieving a sensitivity of 97%, specificity of 98% and accuracy of 98%. We also conducted a large-scale analysis of 2425 clinical metagenomic datasets to investigate the utility of RVFScan, the species-specific VFG profiles and associations between VFGs and virulence phenotypes for 24 important pathogens were analyzed. By combining genomic comparisons and network analysis, we identified 53 VFGs with significantly higher abundances in hypervirulent Klebsiella pneumoniae (hvKp) than in classical K. pneumoniae. Furthermore, a cohort of 1256 samples suspected of K. pneumoniae infection demonstrated that RVFScan could identify hvKp with a sensitivity of 90%, specificity of 100% and accuracy of 98.73%, with 90% of hvKp samples consistent with clinical diagnosis (Cohen's kappa, 0.94). RVFScan has the potential to detect VFGs in low-biomass and high-complexity clinical samples using metagenomic reads without assembly. This capability facilitates the rapid identification and targeted treatment of hvKp infections and holds promise for application to other hypervirulent pathogens.
Subject(s)
Bacterial Infections , Virulence Factors , Humans , Virulence Factors/genetics , Metagenome , Virulence/genetics , Klebsiella pneumoniae/genetics , Bacterial Infections/geneticsABSTRACT
Prostate specific antigen (PSA) is a widely-used biomarker for the diagnosis, screening, and prognosis of prostate cancer (PCa). It is critical to develop a rapid and convenient method to accurately detect PSA levels, especially when the PSA levels are in the clinical gray area of 4-10 ng/mL. We developed a novel upconversion nanoparticle (UCNP)-based fluorescence lateral flow test strip for qualitatively and quantitatively detecting PSA. The carboxyl group-modified UCNPs (UCNP-COOH) were labeled with anti-PSA antibodies via 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as labeling probes to recognize PSA. The fluorescence intensity of the UCNP-probe was then measured with a laser fluorescence scanner. A total of 1397 serum and 20 fingertip blood samples were collected to validate the UCNP strip. A reliable correlation between the area ratio (TC), reflecting the fluorescence intensity of the test/control line, and the PSA concentration was observed (r = 0.9986). The dose-dependent luminescence enhancement showed good linearity in the PSA concentration range from 0.1 to 100.0 ng/mL with a detection limit of 0.1 ng/mL. Our UCNP POCT strip demonstrated excellent accuracy, anti-interference and stability in the gray zone (4-10 ng/mL) of PSA clinical application and outperformed other PSA test strips. The UCNP strip showed good consistency with the Roche chemiluminescence assay in 1397 serum samples. It also showed good performance for PSA detection using fingertip blood samples. This novel UCNP-based test strip could be a sensitive and reliable POCT assay to detect PSA, facilitating the diagnosis and surveillance of PCa.
Subject(s)
Nanoparticles , Prostatic Neoplasms , Male , Humans , Prostate-Specific Antigen , Luminescence , Prostatic Neoplasms/diagnostic imaging , Immunoassay/methodsABSTRACT
The capacity to identify small amounts of pathogens in real samples is extremely useful. Herein, we proposed a sensitive platform for detecting pathogens using cyclic DNA nanostructure@AuNP tags (CDNA) and a cascade primer exchange reaction (cPER). This platform employs wheat germ agglutinin-modified Fe3O4@Au magnetic nanoparticles (WMRs) to bind the E. coli O157:H7, and then triggers the cPER to generate branched DNA products for CDNA tag hybridization with high stability and amplified SERS signals. It can identify target pathogens as low as 1.91 CFU/mL and discriminate E. coli O157:H7 in complex samples such as water, milk, and serum, demonstrating comparable or greater sensitivity and accuracy than traditional qPCR. Moreover, the developed platform can detect low levels of E. coli O157:H7 in mouse serum, allowing the discrimination of mice with early-stage infection. Thus, this platform holds promise for food analysis and early infection diagnosis.
Subject(s)
Escherichia coli O157 , Nanoparticles , Animals , Mice , DNA, Complementary , DNA , Escherichia coli O157/genetics , Food MicrobiologyABSTRACT
Multidrug-resistant (MDR) bacteria are important public health problems. Antibiotic susceptibility testing (AST) currently uses time-consuming culture-based procedures, which cause treatment delays and increased mortality. We developed a machine learning model using Acinetobacter baumannii as an example to explore a fast AST approach using metagenomic next-generation sequencing (mNGS) data. The key genetic characteristics associated with antimicrobial resistance (AMR) were selected through a least absolute shrinkage and selection operator (LASSO) regression model based on 1,942 A. baumannii genomes. The mNGS-AST prediction model was accordingly established, validated, and optimized using read simulation sequences of clinical isolates. Clinical specimens were collected to evaluate the performance of the model retrospectively and prospectively. We identified 20, 31, 24, and 3 AMR signatures of A. baumannii for imipenem, ceftazidime, cefepime, and ciprofloxacin, respectively. Four mNGS-AST models had a positive predictive value (PPV) greater than 0.97 for 230 retrospective samples, with negative predictive values (NPVs) of 100% (imipenem), 86.67% (ceftazidime), 86.67% (cefepime), and 90.91% (ciprofloxacin). Our method classified antibacterial phenotypes with an accuracy of 97.65% for imipenem, 96.57% for ceftazidime, 97.64% for cefepime, and 98.36% for ciprofloxacin. The average reporting time of mNGS-based AST was 19.1 h, in contrast to the 63.3 h for culture-based AST, thus yielding a significant reduction of 44.3 h. mNGS-AST prediction results coincided 100% with the phenotypic AST results when testing 50 prospective samples. The mNGS-based model could be used as a rapid genotypic AST approach to identify A. baumannii and predict resistance and susceptibility to antibacterials and could be applicable to other pathogens and facilitate rational antimicrobial usage.
Subject(s)
Acinetobacter baumannii , Anti-Infective Agents , Retrospective Studies , Cefepime , Ceftazidime , Prospective Studies , Anti-Bacterial Agents/pharmacology , Imipenem , Ciprofloxacin , Drug Resistance, Multiple, Bacterial/genetics , High-Throughput Nucleotide Sequencing , Microbial Sensitivity TestsABSTRACT
Silaspiranes bearing a spiro-silicon center are promising ring frameworks for the synthesis of novel spirocyclic molecules possessing unique properties. Development of efficient methods towards these ring structures has therefore attracted considerable attentions of synthetic chemists. This minireview highlights the representative advances in the field, and is categorized into four parts according to the ring formation strategies: cyclization, annulation, ring expansion and cycloaddition.
ABSTRACT
An asymmetric [3+2] cycloaddition of quinone esters with 2,3-dihydrofuran has been realized via a newly developed Cu(II)/SPDO complex. It provides straightforward access to 2,3,3a,8a-tetrahydrofuro[2,3-b]benzofurans (TFB) with high enantioselectivity (up to 97.5:2.5 er) and diastereoselectivity (all >20:1 dr). The resulting adducts contain two adjacent stereocenters and a continuously functionalized benzene ring. Additionally, this transformation could be easily performed on a gram scale, allowing for expedient synthesis of natural dihydroaflatoxin D2 and aflatoxin B2.
ABSTRACT
BACKGROUND: Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies. METHODS: In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14-15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken. FINDINGS: Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41-7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October-December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline vs 1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 [100%] of 65 at baseline to 58 [92·1%] of 63 at second follow-up among symptomatic individuals, and 437 [100%] of 437 at baseline to 329 [90·9%] of 362 at second follow-up among asymptomatic individuals). INTERPRETATION: 6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic. FUNDING: Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/epidemiology , COVID-19/prevention & control , Child , Child, Preschool , China/epidemiology , Coronavirus Nucleocapsid Proteins/immunology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Immunity, Herd/immunology , Immunity, Humoral , Infant , Infant, Newborn , Longitudinal Studies , Male , Mass Vaccination/organization & administration , Middle Aged , Seroepidemiologic Studies , Young AdultABSTRACT
MoSe2 , as a typical 2D material, possesses tremendous potential in Na-ion batteries (SIBs) owing to larger interlayer distance, more favorable band gap structure, and higher theoretical specific capacity than other analogs. Nevertheless, the low intrinsic electronic conductivity and irreversible conversion of discharged products of Mo/Na2 Se to MoSe2 seriously hamper its electrochemical performance. Herein, through a facile hydrothermal method combined with calcination process, Sn-doped MoSe2 nanosheets grown on graphene substrate in the vertical direction are fabricated. Benefiting from the improved electronic conductivity contributed by the abundant defects and expanded interlamellar spacing of MoSe2 originated from Sn doping, combined with a smart strategy of raising discharge cut-off voltage to 0.2 V during the actual performance testing for SIBs, the as-fabricated anode material delivers superior Na-ions storage performance in terms of electrons/ions transfer, reversible sodium storage as well as cycle stability. An ultra-stable reversible specific capacity of 268.5 mAh g-1 at 1 A g-1 can be maintained after 1600 cycles. Moreover, the great sodium storage property in the SIB full-cell system of the as-obtained nanocomposite illustrates practical potential. Density functional theory calculation and in situ/ex situ measurements are employed to further reveal the storage mechanism and process of Na-ions.
ABSTRACT
BACKGROUND: The prevalence of syphilis is very high in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), and effective interventions are needed to educate HIV-positive individuals about behavioral and biological risk factors. Therefore, we developed a standard case management process and conducted a randomized controlled study to investigate the impact on risky sexual behaviors and syphilis in HIV-positive MSM. METHODS: Men who have sex with men (n = 220) were enrolled and randomized to the case management intervention group and the control group between May 2016 and January 2017. The control group received routine HIV-related care. In addition to routine HIV-related care, those in the intervention group regularly received extended services from a well-trained case manager. Epidemiological information was collected during the baseline face-to-face interviews by a trained investigator. Serological tests for syphilis and assessments of risky sexual behaviors were performed at baseline and 6 and 12 months after the initiation of treatment. RESULTS: The syphilis incidence rates in the intervention and control groups were 11.3 per 100 person-years and 20.6 per 100 person-years, respectively. The multivariable-adjusted hazard ratio (95% confidence inter) for syphilis in case management group was 0.34 (0.14-0.87). The percentages of participants who resumed risky sexual behaviors in both groups were significantly reduced (P < 0.05) but did not significantly differ between the 2 groups. CONCLUSIONS: A case management intervention reduced the incidence of syphilis in HIV-positive MSM. We should further increase the content of case management on the basis of providing routine HIV-related care to those people.
Subject(s)
HIV Infections , Sexual and Gender Minorities , Syphilis , Case Management , China/epidemiology , HIV Infections/complications , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Prevalence , Risk Factors , Sexual Behavior , Syphilis/epidemiology , Syphilis/prevention & controlABSTRACT
BACKGROUND: Breast leiomyoma is a rare benign mesenchymal tumor, accounting for less than 1% of all breast neoplasms. Cases of breast atypical leiomyoma is even more rarely reported and its diagnostic criteria together with its clinical courses is not cleared defined. CASE PRESENTATION: We described two patients with breast leiomyomas. One has unilateral benign breast leiomyoma, the other one has bilateral breast leiomyomas. For the bilateral case, the left-side tumor was diagnosed as benign leiomyoma while the right-side tumor was diagnosed as atypical leiomyoma. The morphological features that lead to the diagnosis of atypical leiomyoma are its invasive growth pattern, mild nuclear atypia, and mitotic figures up to 3mitoses/10HPF. CONCLUSIONS: Atypical breast leiomyoma appears to behave like benign leiomyoma without recurrence in our study with nine-year follow-up. Due to the limited experience, cases presented as atypical intraparenchymal breast leiomyoma should be closely followed.
Subject(s)
Breast Neoplasms , Leiomyoma , Uterine Neoplasms , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Cell Proliferation , Female , Humans , Leiomyoma/diagnostic imaging , Leiomyoma/surgery , Uterine Neoplasms/pathologyABSTRACT
BACKGROUND: We aimed to describe the epidemiological, virological, and serological features of coronavirus disease 2019 (COVID-19) cases in people living with human immunodeficiency virus (HIV; PLWH). METHODS: This population-based cohort study identified all COVID-19 cases among all PLWH in Wuhan, China, by 16 April 2020. The epidemiological, virological, and serological features were analyzed based on the demographic data, temporal profile of nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the disease, and SARS-CoV-2-specific immunoglobin (Ig) M and G after recovery. RESULTS: From 1 January to 16 April 2020, 35 of 6001 PLWH experienced COVID-19, with a cumulative incidence of COVID-19 of 0.58% (95% confidence interval [CI], .42-.81%). Among the COVID-19 cases, 15 (42.86) had severe illness, with 2 deaths. The incidence, case-severity, and case-fatality rates of COVID-19 in PLWH were comparable to those in the entire population in Wuhan. There were 197 PLWH who had discontinued combination antiretroviral therapy (cART), 4 of whom experienced COVID-19. Risk factors for COVID-19 were ageâ ≥50 years old and cART discontinuation. The median duration of SARS-CoV-2 viral shedding among confirmed COVID-19 cases in PLWH was 30 days (interquartile range, 20-46). Cases with high HIV viral loads (≥20 copies/mL) had lower IgM and IgG levels than those with low HIV viral loads (<20 copies/ml; median signal value divided by the cutoff value [S/CO] for IgM, 0.03 vs 0.11, respectively [Pâ <â .001]; median S/CO for IgG, 10.16 vs 17.04, respectively [Pâ =â .069]). CONCLUSIONS: Efforts are needed to maintain the persistent supply of antiretroviral treatment to elderly PLWH aged 50 years or above during the COVID-19 epidemic. The coinfection of HIV and SARS-CoV-2 might change the progression and prognosis of COVID-19 patients in PLWH.
Subject(s)
COVID-19 , HIV Infections , Aged , Cohort Studies , HIV , HIV Infections/complications , HIV Infections/epidemiology , Humans , Middle Aged , SARS-CoV-2ABSTRACT
Efficient heat removal and recovery are two conflicting processes that are difficult to achieve simultaneously. Here, in this work, we pave a new way to achieve this through the use of a smart thermogalvanic hydrogel film, in which the ions and water undergo two separate thermodynamic cycles: thermogalvanic reaction and water-to-vapor phase transition. When the hydrogel is attached to a heat source, it can achieve efficient evaporative cooling while simultaneously converting a portion of the waste heat into electricity. Moreover, the hydrogel can absorb water from the surrounding air to regenerate its water content later on. This reversibility can be finely designed. As an applicative demonstration, the hydrogel film with a thickness of 2 mm was attached to a cell phone battery while operating. It successfully decreased the temperature of the battery by 20 °C and retrieved electricity of 5 µW at the discharging rate of 2.2 C.
ABSTRACT
Tuberculosis (TB) is a complex infectious disease caused by the pathogen Mycobacterium tuberculosis (Mtb) which has coexisted with humanity since the Neolithic. Recent research indicated that SIRT3 plays a pivotal role in promoting the antimycobacterial response of mitochondria and autophagy during Mtb infection. A case-control study comprised 900 TB patients and 1534 healthy controls who were retrospectively enrolled to assess the association between Sirt3 gene polymorphisms and TB susceptibility. In total, five single-nucleotide polymorphisms (SNPs) (rs511744, rs3782118, rs7104764, rs536715 and rs28365927) were selected through database 1000 Genomes Project and offline software Haploview V4.2 and genotyped by a customized 2 × 48-Plex SNPscan™ Kit. Our results suggested that the minor allele genotypes (A carriers) of rs3782118 confers the decreased risk of TB susceptibility (pBonferroni = 0.032), and a similar but more significant effect was observed under the dominant model analysis (OR 0.787, 95% CI 0.666-0.931, pBonferroni = 0.026). Haplotype analysis showed that haplotype AGAAG (rs511744/rs3782118/rs7104764/rs536715/rs28365927) was associated with an increased risk of TB (p = 0.023, OR 1.159, 95% CI 1.019-1.317). In stratification analysis, we found that rs3782118 was associated with decreased risk of TB in female subgroup under the dominant model analysis (pBonferroni = 0.016, OR 0.678, 95% CI 0.523-0.878). Moreover, functional annotations for three loci (rs7930823, rs3782116 and rs3782115) which are strongly linked to rs3782118 indicated that they may be responsible for the changes in some motifs. In conclusion, our study suggested that the SNP rs3782118 was associated with a lower susceptibility to TB, especially under the dominant model analysis and that the haplotype AGAAG (containing the major allele G of rs3782118) was associated with an increased risk of TB. Further independent cohort studies are necessary to validate the protective effect of Sirt3 genetic variants on the risk of TB.
Subject(s)
Asian People/genetics , Polymorphism, Single Nucleotide , Sirtuin 3/genetics , Tuberculosis/genetics , Adult , Asian People/ethnology , Case-Control Studies , China/ethnology , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Haplotypes , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Clinically diagnosed pulmonary tuberculosis (PTB) patients lack microbiological evidence of Mycobacterium tuberculosis, and misdiagnosis or delayed diagnosis often occurs as a consequence. We investigated the potential of long noncoding RNAs (lncRNAs) and corresponding predictive models to diagnose these patients. We enrolled 1,764 subjects, including clinically diagnosed PTB patients, microbiologically confirmed PTB cases, non-TB disease controls, and healthy controls, in three cohorts (screening, selection, and validation). Candidate lncRNAs differentially expressed in blood samples of the PTB and healthy control groups were identified by microarray and reverse transcription-quantitative PCR (qRT-PCR) in the screening cohort. Logistic regression models were developed using lncRNAs and/or electronic health records (EHRs) from clinically diagnosed PTB patients and non-TB disease controls in the selection cohort. These models were evaluated by area under the concentration-time curve (AUC) and decision curve analyses, and the optimal model was presented as a Web-based nomogram, which was evaluated in the validation cohort. Three differentially expressed lncRNAs (ENST00000497872, n333737, and n335265) were identified. The optimal model (i.e., nomogram) incorporated these three lncRNAs and six EHRs (age, hemoglobin, weight loss, low-grade fever, calcification detected by computed tomography [CT calcification], and interferon gamma release assay for tuberculosis [TB-IGRA]). The nomogram showed an AUC of 0.89, a sensitivity of 0.86, and a specificity of 0.82 in differentiating clinically diagnosed PTB cases from non-TB disease controls of the validation cohort, which demonstrated better discrimination and clinical net benefit than the EHR model. The nomogram also had a discriminative power (AUC, 0.90; sensitivity, 0.85; specificity, 0.81) in identifying microbiologically confirmed PTB patients. lncRNAs and the user-friendly nomogram could facilitate the early identification of PTB cases among suspected patients with negative M. tuberculosis microbiological evidence.
Subject(s)
Mycobacterium tuberculosis , RNA, Long Noncoding , Tuberculosis, Pulmonary , Tuberculosis , Humans , Interferon-gamma Release Tests , Mycobacterium tuberculosis/genetics , RNA, Long Noncoding/genetics , Tuberculosis, Pulmonary/diagnosisABSTRACT
Adsorption is one of the most preferred techniques in the advanced treatment of dyeing wastewater. Magnetic porous materials with good adsorption performance, excellent reusability, and a green synthesis route are highly desirable adsorbents in commerce. In this study, we synthesized a magnetic ß-cyclodextrin polymer (MNP-CM-CDP) containing many macro- and ultramicropores in aqueous phase. CO2 adsorption-desorption isotherms and a dye adsorption method provided Langmuir specific surface areas for the MNP-CM-CDP of 114.4â¯m2â¯g-1 and 153â¯m2â¯g-1, respectively. Model pollutants (BPA, MB, BO2, RhB, Cr(III), Pb(II), Zn(II), and Cu(II)) were rapidly and efficiently removed from the aqueous solution by the MNP-CM-CDP. In addition, the polymer could be easily separated from the solution under an external magnetic field. The adsorption of the contaminants was dependent on pH, while the effects of ionic strength and humic acid were slight in the concentration range studied. The polymer could be easily regenerated at room temperature and retained good adsorption performance. Moreover, the MNP-CM-CDP showed good feasibility for the removal of pollutants from actual dyeing wastewater samples.
Subject(s)
Environmental Pollutants , Metals, Heavy , Wastewater , Water Pollutants, Chemical , Adsorption , Cellulose , Cyclodextrins , Magnetic Phenomena , PolymersABSTRACT
BACKGROUND: Antituberculosis drug-induced liver injury (ATDILI) is increasing globally and, hence, it is crucial to predict its risk in the clinical management of antituberculosis therapy. As a major antioxidant, superoxide dismutase (SOD) is mainly responsible for providing defence against oxidative stress, which is involved in ATDILI. The present study aimed to investigate the associations between polymorphisms in SOD genes, including Cu/ZnSOD (SOD1), mitochondrial manganese SOD (MnSOD or SOD2) and extracellular SOD (SOD3), as well as the susceptibility to ATDILI in a Chinese Han population. METHODS: In total, 1060 Chinese Han subjects highly suspected to have tuberculosis (TB) were prospectively enrolled from West China Hospital of Sichuan University. Overall, 746 subjects comprising 118 ATDILI and 628 ATD-tolerant TB patients were eligible and were genotyped for seven single-nucleotide polymorphisms in three SOD genes (SOD1: rs4816407 and rs1041740; SOD2: rs4880; SOD3: rs699473, rs2536512, rs2855262 and rs8192290). RESULTS: Logistic regression analysis showed that none of the seven genetic variants in the three SOD genes were significantly associated with susceptibility to ATDILI in the Chinese Han population after Bonferroni correction, except for a potential association for the SOD2 rs4880 A>G (G allele, p = 0.190, odds ratio = 1.53, 95% confidence interval = 1.05-2.23; GG genotype, p = 0.155). CONCLUSIONS: The promising application of single-nucleotide polymorphisms in the SOD1, SOD2 and SOD3 genes as genetic markers for ATDILI is challenged, and further studies are needed with larger sample sizes and different ethnicities, especially for SOD2 rs4880.
Subject(s)
Antitubercular Agents/adverse effects , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Superoxide Dismutase/genetics , Adult , Alleles , Chemical and Drug Induced Liver Injury/diagnosis , China/epidemiology , Ethnicity/genetics , Female , Genotype , Haplotypes , Humans , Linkage Disequilibrium , Male , Middle Aged , Multigene Family , Phenotype , Quantitative Trait LociABSTRACT
The development of high-efficiency electrocatalysts with low costs for the oxygen evolution reaction (OER) is essential, but remains challenging. Herein, a new synthetic process is proposed to prepare Ni3 S4 particles embedded in N,P-codoped honeycomb porous carbon aerogels (Ni3 S4 /N,P-HPC) through a hydrogel approach. The preparation of Ni3 S4 /N,P-HPC begins with the sol-gel polymerization of tripolyphosphate, chitosan, and guanidine polymer that contains metal-binding sites, allowing for the uniform incorporation of Ni ions into the gel matrix, freeze-drying, and subsequent carbonization under an inert atmosphere. This synthesis resolves difficulties in synthesizing the pure Ni3 S4 phase caused by the instability of Ni3 S4 at high temperature, while affording good control of the porous structure and N,P-doping of carbon aerogels. The synergy between the structural advantages of N,P-carbon aerogels (such as easily accessible active sites, high specific surface area, and excellent electron transport) and the intrinsic electrochemical properties of Ni3 S4 result in the outstanding OER performance of Ni3 S4 /N,P-HPC, with overpotentials as low as 0.37â V at 10â mA cm-2 . The work outlined herein offers a simple and effective method for the development of carbon-based electrocatalysts for renewable energy conversion.
ABSTRACT
BACKGROUND: Little knowledge about the biological functions of RP11-37B2.1, a newly defined long noncoding RNA (lncRNA) molecule, is currently available. Previous studies have shown rs160441, located in the RP11-37B2.1 gene, is significantly associated with tuberculosis (TB) in a Ghanaian and the Gambian populations. METHODS: We investigated the influence of single-nucleotide polymorphisms (SNPs) within lncRNA RP11-37B2.1 on the risk of TB and the possible correlation with adverse drug reactions (ADRs) from TB treatment in a Western Chinese population. Four SNPs within lncRNA RP11-37B2.1 were genotyped in 554 TB cases and 561 healthy subjects using the improved multiplex ligation detection reaction method, and the patients were followed up monthly to monitor the development of ADRs. RESULTS: No significant association between the SNPs of lncRNA RP11-37B2.1 and TB susceptibility was observed (all P > 0.05). Surprisingly, significant association was observed between two SNPs (rs218916 and rs160441) and thrombocytopenia development during anti-TB therapy under the dominant model (P = 0.003 and 0.014, respectively). CONCLUSIONS: Our findings firstly exhibit that rs218916 and rs160441 within lncRNA RP11-37B2.1 significantly associate with the occurrence of thrombocytopenia and suggest RP11-37B2.1 genetic variants are potential biosignatures for thrombocytopenia during anti-TB treatment.
Subject(s)
Antitubercular Agents/adverse effects , Polymorphism, Single Nucleotide , RNA, Long Noncoding/genetics , Tuberculosis/drug therapy , Tuberculosis/genetics , Adult , Anemia/chemically induced , Anemia/genetics , Asian People/genetics , Case-Control Studies , China , Female , Genetic Predisposition to Disease , Humans , Isoniazid/adverse effects , Leukopenia/chemically induced , Leukopenia/genetics , Male , Middle Aged , Prospective Studies , Rifampin/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/geneticsABSTRACT
BACKGROUND: We investigated the relationship between hepatitis B virus (HBV)-related pathogenesis and single nucleotide polymorphisms (SNPs) in interleukin-21 (IL-21)-JAK-STAT signaling pathway genes. METHODS: We used the high-resolution melting (HRM) method to genotype five SNPs (IL-21 rs2221903, IL-21 rs4833837, IL-21 receptor (IL-21R) rs2285452, JAK3 rs3008, and STAT3 rs1053023) in 546 HBV-infected patients and 353 healthy Chinese subjects. The HBV-infected patients were further divided into subgroups based on the HBV-related pathologies: chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC), and HBV-related hepatocellular carcinoma (HCC). RESULTS: There were no significant differences in the genotype and allele distributions of the five SNPs between the HBV-infected patients and healthy subjects. The genotype and allele frequencies were similar in the two groups for IL-21 rs2221903 (A>G, P = 0.83 and 0.67), rs4833837 (A>G, P = 0.80 and 0.49), IL-21R rs2285452 (G>A, P = 0.25 and 0.68), STAT3 rs1053023 (A>G, P = 1.00 and 0.96), and JAK3 rs3008 (C>T, P = 0.32 and 0.54). However, patients with the IL-21R rs2285452 AA genotype were more susceptible to HBV-related HCC than those with the IL-21R rs2285452 GA/GG genotype (P = 0.03, OR = 3.27, 95% CI = 1.16-9.20). The serological marker model of "HBsAg+, HBeAg+, HBcAb+" was predominant among patients with HBV infection. However, there was no association between the genotype's distribution of the five SNPs and the serological marker models (P > 0.05). CONCLUSIONS: These findings demonstrate that the IL-21R rs2285452 AA genotype increases the risk of HBV-related HCC in Chinese patients.
Subject(s)
Carcinoma, Hepatocellular/genetics , Hepatitis B, Chronic/genetics , Interleukin-21 Receptor alpha Subunit/genetics , Liver Neoplasms/genetics , Polymorphism, Single Nucleotide , Adult , Asian People/genetics , Carcinoma, Hepatocellular/virology , Case-Control Studies , Female , Gene Frequency , Hepatitis B Antigens/blood , Hepatitis B Antigens/genetics , Hepatitis B, Chronic/complications , Humans , Liver Cirrhosis/genetics , Liver Cirrhosis/virology , Liver Neoplasms/virology , Male , Middle AgedABSTRACT
BACKGROUND: Delirium, which is one of the most disturbing postoperative complications in elderly patients, shows high morbidity in patients undergoing lung cancer surgery. Dexmedetomidine (DEX) is considered a potential prophylactic agent for preventing patients' delirium after lung cancer surgery. SUBJECTS AND METHODS: Medical records of lung cancer patients over 65 years old with radical pulmonary resection at Henan Provincial People's Hospital from January 2015 to December 2017, China, were evaluated. Patients, care-providers, and investigators were all blinded to group assignment. DEX was administered in the preoperative and intraoperative periods. The incidence of delirium was calculated based on the Intensive Care Delirium Screening Checklist (ICDSC). Scores of ≥4 and 1-3 points represent the diagnoses of delirium and a pre-delirious state, respectively. RESULTS: During postoperative day 1 (POD 1) to POD 7, delirium occurs in both groups. During postoperative POD 1 to POD 7, the incidence of delirium is lower in the DEX group than that in the control group. Furthermore, there are more mild delirium patients but fewer moderate and severe delirium patients in the DEX group compared with the control group. Finally, patients in the DEX group have a shorter duration of delirium, lower numeric pain rating scale during movement and better sleep quality. CONCLUSION: Preoperative and intraoperative application of DEX can reduce the incidence and intensity of delirium after pulmonary resection in elderly patients with lung cancer.