ABSTRACT
Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon "Dianmu" from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak. Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections.
Subject(s)
Burkholderia pseudomallei , Disease Outbreaks , Genetic Variation , Melioidosis , Multilocus Sequence Typing , Phylogeny , Melioidosis/epidemiology , Melioidosis/microbiology , Humans , Burkholderia pseudomallei/genetics , Burkholderia pseudomallei/classification , Evolution, Molecular , China/epidemiology , Whole Genome Sequencing , GenotypeABSTRACT
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Memory T Cells , Reinfection , SARS-CoV-2 , Humans , Adolescent , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Male , Reinfection/immunology , Reinfection/virology , Female , Memory T Cells/immunology , Prospective Studies , Immunoglobulin G/blood , Immunoglobulin G/immunology , Antibody Formation , Spike Glycoprotein, Coronavirus/immunology , Immunologic Memory , Child , T-Lymphocytes/immunologyABSTRACT
In a clinical isolate of Burkholderia pseudomallei from Hainan, the association between the emergence of ceftazidime resistance and a novel PenA P174L allele was identified for the first time, providing an understanding of one mechanism by which ceftazidime resistance arises in B. pseudomallei.
Subject(s)
Anti-Bacterial Agents , Burkholderia pseudomallei , Ceftazidime , Drug Resistance, Bacterial , Melioidosis , Microbial Sensitivity Tests , Point Mutation , Burkholderia pseudomallei/genetics , Burkholderia pseudomallei/drug effects , Ceftazidime/pharmacology , Humans , China , Anti-Bacterial Agents/pharmacology , Melioidosis/microbiology , Melioidosis/drug therapy , Drug Resistance, Bacterial/genetics , Bacterial Proteins/genetics , AllelesABSTRACT
Burkholderia semiarida was previously identified solely as a plant pathogen within the Burkholderia cepacia complex. We present a case in China involving recurrent pneumonia attributed to B. semiarida infection. Of note, the infection manifested in an immunocompetent patient with no associated primary diseases and endured for >3 years.
Subject(s)
Burkholderia Infections , Burkholderia , Recurrence , Humans , Burkholderia Infections/diagnosis , Burkholderia Infections/microbiology , Burkholderia Infections/drug therapy , China , Burkholderia/isolation & purification , Burkholderia/genetics , Male , Immunocompetence , Anti-Bacterial Agents/therapeutic use , Middle Aged , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/drug therapyABSTRACT
A miniaturized photoacoustic spectroscopy-based gas sensor is proposed for the purpose of detecting sub-ppm-level carbonyl sulfide (OCS) using a tunable mid-infrared interband cascade laser (ICL) and a Helmholtz photoacoustic cell. The tuning characteristics of the tunable ICL with a center wavelength of 4823.3â¯nm were investigated to achieve the optimal driving parameters. A Helmholtz photoacoustic cell with a volume of â¼2.45â¯mL was designed and optimized to miniaturize the measurement system. By optimizing the modulation parameters and signal processing, the system was verified to have a good linear response to OCS concentration. With a lock-in amplifier integration time of 10â¯s, the 1σ noise standard deviation in differential mode was 0.84â¯mV and a minimum detection limit (MDL) of 409.2 ppbV was achieved at atmospheric pressure and room temperature.
ABSTRACT
Biofuel production from lignocellulose feedstocks is sustainable and environmentally friendly. However, the lignocellulosic pretreatment could produce fermentation inhibitors causing multiple stresses and low yield. Therefore, the engineering construction of highly resistant microorganisms is greatly significant. In this study, a composite functional chimeric cellulosome equipped with laccase, versatile peroxidase, and lytic polysaccharide monooxygenase was riveted on the surface of Saccharomyces cerevisiae to construct a novel yeast strain YI/LVP for synergistic lignin degradation and cellulosic ethanol production. The assembly of cellulosome was assayed by immunofluorescence microscopy and flow cytometry. During the whole process of fermentation, the maximum ethanol concentration and cellulose conversion of engineering strain YI/LVP reached 8.68 g/L and 83.41%, respectively. The results proved the availability of artificial chimeric cellulosome containing lignin-degradation enzymes for cellulosic ethanol production. The purpose of the study was to improve the inhibitor tolerance and fermentation performance of S. cerevisiae through the construction and optimization of a synergistic lignin-degrading enzyme system based on cellulosome.
Subject(s)
Cellulosomes , Ethanol , Fermentation , Lignin , Saccharomyces cerevisiae , Ethanol/metabolism , Lignin/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/enzymology , Cellulosomes/metabolism , Cellulosomes/genetics , Cellulose/metabolism , Laccase/metabolism , Laccase/geneticsABSTRACT
In Lepidoptera (butterflies and moths), the genomic region around the gene cortex is a 'hotspot' locus, repeatedly used to generate intraspecific melanic wing color polymorphisms across 100-million-years of evolution. However, the identity of the effector gene regulating melanic wing color within this locus remains unknown. Here, we show that none of the four candidate protein-coding genes within this locus, including cortex, serve as major effectors. Instead, a micro-RNA (miRNA), mir-193, serves as the major effector across three deeply diverged lineages of butterflies, and its function is conserved in Drosophila. In Lepidoptera, mir-193 is derived from a gigantic long non-coding RNA, ivory, and it functions by directly repressing multiple pigmentation genes. We show that a miRNA can drive repeated instances of adaptive evolution in animals.
ABSTRACT
The introduction of cantilever-based fiber-optic microphones (FOMs) has proven to be effective in acoustic sensing. Further improvements in cantilevers face two key constraints: the challenge of achieving minimal sizes with sufficient reflective area and the trade-off between sensitivity and response bandwidth. Herein, we present a geometry optimization framework for a cantilever-based FOM that addresses this issue. Employing drumstick-shaped cantilevers housed within a Fabry-Perot (F-P) interferometric structure, we showcase a heightened sensitivity of 302.8 mV/Pa at 1 kHz and a minimum detectable acoustic pressure (MDP) of 2.35 µPa/H z. Notably, these metrics outperform those of the original rectangular cantilever with identical dimensions. Furthermore, our proposed cantilever effectively mitigates the reduction in resonance frequencies, thereby improving the response bandwidth. This geometry optimization framework offers considerable design flexibility and scalability, making it especially suitable for high-performance acoustic sensing applications.
ABSTRACT
We report a high-quality genome draft assembly of the dark-branded bushbrown, Mycalesis mineus, a member of the Satyrinae subfamily of nymphalid butterflies. This species is emerging as a promising model organism for investigating the evolution and development of phenotypic plasticity. Using 45.99â Gb of long-read data (N50 = 11.11â kb), we assembled a genome size of 497.4â Mb for M. mineus. The assembly is highly contiguous and nearly complete (96.8% of Benchmarking Universal Single-Copy Orthologs lepidopteran genes were complete and single copy). The genome comprises 38.71% of repetitive elements and includes 20,967 predicted protein-coding genes. The assembled genome was super-scaffolded into 28 pseudo-chromosomes using a closely related species, Bicyclus anynana, with a chromosomal-level genome as a template. This valuable genomic tool will advance both ongoing and future research focused on this model organism.
Subject(s)
Butterflies , Animals , Butterflies/genetics , Molecular Sequence Annotation , Genomics , Repetitive Sequences, Nucleic Acid , Genome Size , ChromosomesABSTRACT
Latent thermal energy storage (LTES) devices can efficiently store renewable energy in thermal form and guarantee a stable-temperature thermal energy supply. The gravity-driven motion melting (GDMM) process improves the overall melting rate for packaged phase-change material (PCM) by constructing an enhanced flow field in the liquid phase. However, due to the complex mechanisms involved in fluid-solid coupling and liquid-solid phase transition, numerical simulation studies that demonstrate physical details are necessary. In this study, a simplified numerical model based on the Eulerian method is proposed. We aimed to introduce a fluid deformation yield stress equation to the "solid phase" based on the Bingham fluid assumption. As a result, fluid-solid coupling and liquid-solid phase transition processes become continuously solvable. The proposed model is validated by the referenced experimental measurements. The enhanced performance of liquid-phase convection and the macroscopic settling of the "solid phase" are numerically analyzed. The results indicate that the enhanced liquid-phase fluidity allows for a stronger heat transfer process than natural convection for the pure liquid phase. The gravity-driven pressure difference is directly proportional to the vertical melting rate, which indicates the feasibility of controlling the pressure difference to improve the melting rate.
ABSTRACT
The integration of fluorine atoms into biologically active organic compounds has proved to be a vital technique in small molecule drugs. This technique can substantially enhance crucial properties, including metabolic stability, lipophilicity, and bioavailability, often with a mere addition of a single fluorine atom or a trifluoromethyl group. Over the past few decades, this concept has also been applied in nucleic acid chemistry. A commonly employed 2'-OH substitution is the introduction of a 2'-deoxy-2'-fluoro (2'-F) group. The strong electronegativity of fluorine prompts the modified siRNA to readily adopt a C3'-endo conformation, resulting in significant advantages in terms of binding affinity. To enrich the toolbox of chemical modification of oligonucleotides, the replacement of the 2'-OH with the 2'-O-trifluoromethyl group has been developed in RNA analog synthesis. Oligodeoxynucleotides containing the 2'-O-trifluoromethyl group can greatly increase the thermal stability of DNA/RNA duplexes depending on the position and amount of the modification. Moreover, 2'-O-trifluoromethylated oligodeoxynucleotide also exhibited a slightly higher resistance to snake venom phosphodiesterase than the unmodified oligodeoxynucleotide. The 2'-O-trifluoromethylated oligonucleotides can emerge as a label to study RNA structure and function as well, or to develop DNA/RNA-based diagnostics. Hence, it is necessary to report an effective method for the synthesis, deprotection, purification, and characterization of oligonucleotides bearing a 2'-O-trifluoromethyl group. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 6-N-benzoyl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl adenosine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 2: Preparation of 4-N-acetyl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl cytidine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 3: Preparation of 2-N-isobutyryl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl guanine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 4: Preparation of 5'-O-dimethoxytrityl-2'-O-2-trifluoromethyl uridine 3'-(2-cyanoethyl N,N-diisopropyl) phosphoramidite Basic Protocol 5: Solid-phase synthesis of 2'-O-trifluoromethylated RNA analogs Basic Protocol 6: Deprotection and purification of 2'-O-trifluoromethyl-RNAs.
Subject(s)
Nucleotides , Organophosphorus Compounds , RNA , RNA/chemistry , Fluorine , Oligonucleotides/chemistry , Oligodeoxyribonucleotides/chemistry , DNAABSTRACT
Although small interfering RNA (siRNA) is a key player among gene inhibition therapeutics, there are many obstacles to the development of siRNA drugs due to inherent properties of oligonucleotides, including the unsatisfactory stability of unmodified siRNA, poor pharmacokinetic distribution, and the toxicity induced by off-target effects. To maximize treatment potency, chemical modification of siRNA has undoubtedly been the most successful strategy by far. Widely applied modifications include phosphorothioate linkages, 2'-O-methyl modifications, and 2'-fluoro modifications, among others. To extend the family of chemical modifications for oligonucleotides, 2'-O-cyanoethylated RNA analogs were developed through the replacement of the 2'-hydroxyl group with a 2'-O-cyanoethyl group (-OCH2 CH2 CN). This modification can provide several advantages over unmodified RNA, such as increased stability, improved binding affinity to complementary DNA or RNA strands, and resistance to degradation by cellular nucleases. The 2'-O-cyanoethyl-modified RNAs not only are applied in RNA silencing machinery but also act as research tools for studying RNA structure and function or for developing RNA-based diagnostics. Therefore, the efficient synthesis, deprotection, purification, and characterization of 2'-O-cyanoethylated RNAs deserves more attention. This protocol describes the chemical synthesis of 2'-O-cyanoethylated nucleotides and the solid-phase synthesis, deprotection, and purification of 2'-O-cyanoethylated RNAs. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 6-N-dimethylformamidyl-5'-O-dimethoxytrityl-2'-O-cyanoethyl adenosine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 2: Preparation of 4-N-acetyl-5'-O-dimethoxytrityl-2'-O-cyanoethyl cytidine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 3: Preparation of 2-N-dimethylformamidyl-5'-O-dimethoxytrityl-2'-O-cyanoethyl guanine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 4: Preparation of 5'-O-dimethoxytrityl-2'-O-2-cyanoethyl uridine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 5: Solid-phase synthesis of 2'-O-cyanoethylated RNA analogs Basic Protocol 6: Deprotection and purification of synthesized 2'-O-cyanoethyl-RNAs.
Subject(s)
Nucleotides , Solid-Phase Synthesis Techniques , RNA, Small Interfering/genetics , Oligonucleotides , ABO Blood-Group SystemABSTRACT
IMPORTANCE: This study focused on the development of a reaction system using rhPCR to amplify a specific gene, ORF2, of B. pseudomallei and to identify the P174L mutation associated with increased drug resistance to ceftazidime (CAZ). The system incorporated universal primer probes and a simple temperature cycle reaction. The amplified products were then analyzed using lateral flow strip assay (LFSA) for strain identification and mutation interpretation. The developed system provides a reliable basis for diagnosing melioidosis and selecting appropriate drugs. Its potential impact is particularly significant in resource-limited settings where access to advanced diagnostic techniques is limited. This platform stands out for its simplicity, convenience, sensitivity, specificity, and portability. It shows promise as a point-of-care testing method for detecting single nucleotide polymorphism in genes associated with other diseases. By leveraging the advantages of this platform, researchers and healthcare professionals can potentially expand its use beyond melioidosis and apply it to the rapid detection of genetic variations in other disease-related genes.
Subject(s)
Burkholderia pseudomallei , Melioidosis , Humans , Burkholderia pseudomallei/genetics , Ceftazidime/pharmacology , Melioidosis/diagnosis , Hydrolysis , Mutation , RibonucleasesSubject(s)
COVID-19 , SARS-CoV-2 , Humans , Reinfection , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.
Subject(s)
Bartonella , Coinfection , Leptospira , Animals , Bartonella/genetics , China/epidemiology , Phylogeny , Rodentia/microbiology , Shrews/microbiologyABSTRACT
PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Osteoporosis , Female , Humans , Breast Neoplasms/drug therapy , Bone Density , Docetaxel/adverse effects , Epirubicin/adverse effects , Calcium , East Asian People , Cyclophosphamide/adverse effects , Vitamin D , Vitamins , Osteoporosis/chemically induced , Osteoporosis/epidemiology , Osteoporosis/prevention & control , Antineoplastic Agents/adverse effectsABSTRACT
Transducer components are crucial in optimizing the sensitivity of microphones. Cantilever structure is commonly used as a structural optimization technique. Here, we present a novel Fabry-Perot (F-P) interferometric fiber-optic microphone (FOM) using a hollow cantilever structure. The proposed hollow cantilever aims to reduce the effective mass and spring constant of the cantilever, thereby enhancing the sensitivity of the FOM. Experimental results demonstrate that the proposed structure outperforms the original cantilever design in terms of sensitivity. The sensitivity and minimum detectable acoustic pressure level (MDP) can reach 91.40 mV/Pa and 6.20 µPa/Hz at 1.7 kHz, respectively. Notably, the hollow cantilever provides an optimization framework for highly sensitive FOMs.