Identification of Six Pathogenic Genes for Tibetan Familial Ventricular Septal Defect by Whole Exome Sequencing.

INTRODUCTION: Ventricular septal defect (VSD) is the most common congenital heart malformation in children. This study aimed to investigate potential pathogenic genes associated with Tibetan familial VSD. METHODS: Whole genomic DNA was extracted from eight Tibetan children with VSD and their healthy parents (a total of 16 individuals). Whole-exome sequencing was performed using the Illumina HiSeq platform. After filtration, detection, and annotation, single nucleotide variations and insertion-deletion markers were examined. Comparative evaluations using the Sorting Intolerant from Tolerant, PolyPhen V2, Mutation Taster, and Combined Annotation Dependent Depletion databases were conducted to predict harmful mutant genes associated with the etiology of Tibetan familial VSD. RESULTS: A total of six missense mutations in genetic disease-causing genes associated with the development of Tibetan familial VSD were identified: activin A receptor type II-like 1 (c.652 C > T: p.R218 W), ATPase cation transporting 13A2 (c.1363 C > T: p.R455 W), endoplasmic reticulum aminopeptidase 1 (c.481 G > A: p.G161 R), MRI1 (c.629 G > A: p.R210Q), tumor necrosis factor receptor-associated protein 1 (c.224 G > A: p.R75H), and FBN2 (c.2260 G > A: p.G754S). The Human Gene Mutation Database confirmed activin A receptor type II-like 1, MRI1, and tumor necrosis factor receptor-associated protein 1 as pathogenic mutations, while FBN2 was classified as a probable pathogenic mutation. CONCLUSIONS: This novel study directly screens genetic variations associated with Tibetan familial VSD using whole-exome sequencing, providing new insights into the pathogenesis of VSD.

The function and mechanisms of action of circular RNAs in Urologic Cancer.

Kidney, bladder, and prostate cancer are the three major tumor types of the urologic system that seriously threaten human health. Circular RNAs (CircRNAs), special non-coding RNAs with a stabile structure and a unique back-splicing loop-forming ability, have received recent scientific attention. CircRNAs are widely distributed within the body, with important biologic functions such as sponges for microRNAs, as RNA binding proteins, and as templates for regulation of transcription and protein translation. The abnormal expression of circRNAs in vivo is significantly associated with the development of urologic tumors. CircRNAs have now emerged as potential biomarkers for the diagnosis and prognosis of urologic tumors, as well as targets for the development of new therapies. Although we have gained a better understanding of circRNA, there are still many questions to be answered. In this review, we summarize the properties of circRNAs and detail their function, focusing on the effects of circRNA on proliferation, metastasis, apoptosis, metabolism, and drug resistance in kidney, bladder, and prostate cancers.

[Improvement in compatibility of hot melt pressure-sensitive adhesive with cinnamon volatile oil and in vitro transdermal property by physical blending].

Hot melt pressure-sensitive adhesive(HMPSA) has broad application potential in the field of traditional Chinese medicine(TCM) plasters due to its high drug loading, weak skin irritation, satisfactory adhesion, etc. compared with rubber plasters.However, the structure of HMPSA is prone to suffer from the damage caused by volatile oils in TCM plasters. In view of this, a kind of HMPSA with a stable structure was prepared by physical blending of DINCH, polypropylene wax and liquid rubber(LIR) in the present study, which is denoted as DPL. The dosage of cinnamon volatile oil(CVO), the model drug, was selected with viscosity, softening point and cohesion as evaluation indexes. The interaction between DPL and HMPSA was investigated by Fourier transform infrared spectroscopy(FT-IR) and differential scanning calorimetry(DSC). The compatibility of HMPSA with CVO and its transdermal ability were studied by in vitro transdermal test, adhesion, scanning electron microscopy( SEM) and rheological evaluation. The results showed that 5% CVO began to damage the structure of HMPSA. The initial adhesion and holding adhesion of DPL-modified HMPSA(DPL-HMPSA) were not significantly changed compared with those of HMPSA, whereas the 180° peel strength was decreased. FI-IR unraveled that DPL formed the n-π conjugated system with styrene-isoprene-styrene block copolymer(SIS), and there was no significant difference in the glass transition temperature according to DSC results, which indicated the good compatibility of DPL with HMPSA. With 5% CVO loaded, the drug content of DPL-HMPSA was 1. 14 times higher than that of HMPSA, and the decrease rate of drug content in DPL-HMPSA was 16% lower than that in HMPSA after 3 months. SEM demonstrated that CVO did not cause obvious structural damage to DPL-HMPSA. Rheological evaluation revealed that the storage modulus and loss factor of DPL-HMPSA were higher than those of HMPSA, and the cohesion was also stronger. The percutaneous penetration rate of cinnamaldehyde in DPL-HMPSA was 2. 25 times that of HMPSA. In conclusion, DPL-HMPSA had more stable structure, better compatibility with CVO, and higher in vitro transdermal efficiency of cinnamaldehyde than before the modification. This study can provide reference for the mitigation of the matrix structure damage caused by volatile oil components in TCM plasters and the enhancement of the content and in vitro transdermal rate of drug.

Compact generation of a two-photon multipath Dicke state from a single χ(2) nonlinear photonic crystal.

Multipartite quantum entanglement is a powerful resource for enriching the functionality of quantum computation and quantum communication. In this Letter, we propose a new method to generate a two-photon multipath Dicke state with concurrent spontaneous parametric downconversion processes from a single periodically poled nonlinear photonic crystal. We design the poling structure to produce a three-path Dicke state where three quasi-phase-matching conditions are fulfilled simultaneously by a hybrid one- and two-dimensionally poled nonlinear photonic crystal. We use genuine multipartite entanglement concurrence to quantify the entanglement of the Dicke state. Using a more complicated poling configuration like multiple-periodically poled two-dimensional nonlinear photonic crystal, we can also produce four-path, five-path, or multipath Dicke states by a single crystal. The multiple-periodically poled two-dimensional nonlinear photonic crystal provides a new method, to the best of our knowledge, for the integrated generation of multipartite quantum light sources.

Birth Outcomes of Pregnant Women Infected with COVID-19 in Highland Areas of China from 2020 to 2022: A Retrospective Analysis.

Purpose: To explore the effect of coronavirus disease 2019 (COVID-19) infection on neonates in plateau regions. Methods: Cases of newborns born to pregnant women infected with COVID-19 who received prenatal care or treatment at the Women and Children's Hospital of the Tibet Autonomous Region and the Lhasa People's Hospital between January 2020 and December 2022 (infected group) and newborns born to healthy pregnant women (non-infected group) who were included by age, underlying disease and length of hospital stay were retrospectively collected. According to the inclusion and exclusion criteria, 381 patients in the infected group and 314 patients in the non-infected group were included in the study. Results: The results of multivariate analysis showed that admission to the neonatal intensive care unit (OR = 3.342, 95% CI = 1.564-6.764), shortness of breath (OR = 2.853, 95% CI = 1.789-3.154), irregular breathing (OR = 2.465, 95% CI = 1.879-4.112) and neonatal jaundice (OR = 2.324, 95% CI = 1.989-2.445) were the factors influencing the low Apgar scores of neonates in the infected group (all P < 0.05). Conclusion: Neonates born to pregnant women infected with COVID-19 had lower Apgar scores and higher incidences of complications, such as shortness of breath, groaning, irregular breathing and neonatal jaundice, than newborns born to pregnant women not infected with COVID-19.

Attachment of Acidithiobacillus ferrooxidans onto different solid substrates and fitting through Langmuir and Freundlich equations.

Attachments of Acidithiobacillus ferrooxidans ATCC 23270 onto elemental sulfur, quartz and complex chalcopyrite were investigated by analysis of its extracellular polymeric substances as well as applying Langmuir and Freundlich equations. The two equations fitted the adsorption equilibrium data with significant correlation coefficient over 0.9. This indicated that bacterial attachment is complicated and involves Langmuir and Freundlich characterizations. Sulfur-grown cells showed the highest affinity for the three solid substrates. The investigated complex chalcopyrite possessed a higher maximum adsorption capacity for A. ferrooxidans than elemental sulfur or quartz. The Freundlich fitting parameters suggested that quartz had a weaker adsorption capacity and smaller adsorption areas than elemental sulfur or the complex chalcopyrite. It is not the content of total carbohydrates or proteins in EPS but their ratios that determine the affinity differences between cells and substrates.

Enterobacter sp. E1 increased arsenic uptake in Pteris vittata by promoting plant growth and dissolving Fe-bound arsenic.

Microbes affect arsenic accumulation in the arsenic-hyperaccumulator Pteris vittata, but the associated molecular mechanism remains uncertain. Here, we investigated the effect of Enterobacter sp. E1 on arsenic accumulation by P. vittata. Strain E1 presented capacities of arsenate [As(V)] and Fe(III) reduction during cultivation. In the pot experiment with P. vittata, the biomass, arsenic content, and chlorophyll content of P. vittata significantly increased by 30.03%, 74.9%, and 112.1%, respectively. Strikingly, the water-soluble plus exchangeable arsenic (WE-As) significantly increased by 52.05%, while Fe-bound arsenic (Fe-As) decreased by 29.64% in the potted soil treated with strain E1. The possible role of activation of arsenic by strain E1 was subsequently investigated by exposing As(V)-absorbed ferrihydrite to the bacterial culture. Speciation analyses of As showed that strain E1 significantly increased soluble levels of As and Fe and that more As(V) was reduced to arsenite. Additionally, increased microbial diversity and soil enzymatic activities in soils indicated that strain E1 posed few ecological risks. These results indicate that strain E1 effectively increased As accumulation in P. vittata mainly by promoting plant growth and dissolving soil arsenic. Our findings suggest that As(V) and Fe(III)-reducer E1 could be used to enhance the phytoremediation of P. vittata in arsenic-contaminated soils.

NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2 Genetic Variations are Associated with Ventricular Septal Defect in the Chinese Tibetan Population Through Whole-Exome Sequencing.

Background: Ventricular septal defect (VSD) is the most common congenital cardiac abnormality in children and the second most common in adults. This study aimed to explore the potentially causative genes in VSD patients in the Chinese Tibetan population, and to provide a theoretical basis for the genetic mechanism of VSD. Methods: Peripheral venous blood was collected from 20 VSD subjects, and whole-genome DNA was extracted. High-throughput sequencing was performed on qualified DNA samples using whole-exome sequencing (WES) technology. After filtering, detecting, and annotating qualified data, single nucleotide variations (SNVs) and insertion-deletion (InDel) markers were analyzed, and data processing software such as GATK, SIFT, Polyphen, and MutationTaster were used for comparative evaluation and prediction of pathogenic deleterious variants associated with VSD. Results: A total of 4793 variant loci, including 4168 SNVs, 557 InDels and 68 unknown loci and 2566 variant genes were obtained from 20 VSD subjects through bioinformatics analysis. According to the screening of the prediction software and database, the occurrence of VSD was predicted to be associated with five inherited pathogenic gene mutations, all of which were missense mutations, including NOTCH2 (c.1396C >A:p.Gln466Lys), ATIC (c.235C >T:p.Arg79Cys), MRI1 (c.629G >A:p.Arg210Gln), SLC6A13 (c.1138G >A:p.Gly380Arg), ATP13A2 (c.1363C >T:p.Arg455Trp). Conclusion: This study demonstrated that NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2 gene variants were potentially associated with VSD in Chinese Tibetan population.

Exercise therapy for adolescent idiopathic scoliosis rehabilitation: a bibliometric analysis (1999-2023).

Background: Among the conservative treatments for rehabilitation of adolescent idiopathic scoliosis (AIS), exercise therapy has attracted a large number of studies as its advantages of good clinical effect, high operability, high compliance, few side effects and low cost. We conduct a bibliometric analysis of previous research to identify prevalent areas of study and inform research for the future directions in this paper. Methods: Relevant publications and reviews were collected using the Science Citation Index Expanded from the Web of Science Core Collection. Information from the included studies was analyzed systematically using VOSviewer and Citespace software to identify patterns regarding publications, keywords, authors, citations, countries, institutions and journals. Results: A total of 172 articles published from 1999 to 2023 were identified. Over the last decade, the number of publications has gradually increased, reaching a peak of 21 publications in 2021. China, North America and Western European countries and institutions are leading the way as far as the quantity of publications and the total number of citations are concerned. The current areas of focus are the efficacy of exercise therapy in relation to enhancing the quality of life of adolescents during rehabilitation. Conclusions: This is the first bibliometric analysis that provides a comprehensive review of the research trends and advances in exercise therapy for the rehabilitation of AIS. The study identifies latest research frontiers and hot directions, providing a valuable reference for scholars in the field of exercise therapy.

Corrigendum: Nitazoxanide, an antiprotozoal drug, reduces bone loss in ovariectomized mice by inhibition of RANKL-induced osteoclastogenesis.

[This corrects the article DOI: 10.3389/fphar.2021.781640.].

The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation.

Transporter associated with antigen processing 1(TAP1) serves as a protein to transport antigenic peptides from the surface of the endoplasmic reticulum to the lumen of the endoplasmic reticulum when the antigens are presented by major histocompatibility complex type I (MHC-I), which has been identified to play a critical role in antigen presentation in innate immunity. In tumors, the role of TAP1 seems to remain controversial. On the one hand, given the role of TAP1 in antigen presentation, it is indicated that high TAP1 expression corresponds to the emergence of more neoantigens epitopes that facilitate the recognition for phagocytes, T cells and other cells. On the other hand, the genetic ablation of transporter associated with antigen processing (TAP) results in the presentation of new class I-restricted epitopes encoded in house-keeping products. Opposite result has been revealed by studies in other tumors suggest, which implies a more complex function of TAP1. Therefore, it's significant to clarify the role of TAP1 in clear cell renal cell carcinoma (ccRCC). In this study, we found the elevated expression levels in mRNA and protein of TAP1 in ccRCC tissues, which indicated a relatively worse prognosis. Transwell assay and Scratch assay in vitro demonstrated the promotive role of TAP1 in ccRCC migration as well as a significant role in metastasis. And the increased expression of TAP1 resulted in more immune cells infiltrated in cancer tissues. TAP1 was also demonstrated to be related to immune regulator genes, as gene set enrichment analysis (GSEA) indicated its significant role in immune regulation. The results of CancerSEA indicated the positive association of the high-level TAP1 expression with epithelial-mesenchymal transition (EMT) and the inverse association with Cell Cycle. The effective drugs were also predicted based on TAP1 expression, of which the high level was indeed associated with resistance to multiple drugs, but some effective drugs still identified based on high TAP1 expression. According to the analysis of various databases, the role of TAP1 in ccRCC was explored, especially in relationship of TAP1 with tumor microenvironment. These results indicate that TAP1 can serve as a potential target for treatment of ccRCC.

Nitazoxanide, an Antiprotozoal Drug, Reduces Bone Loss in Ovariectomized Mice by Inhibition of RANKL-Induced Osteoclastogenesis.

Nitazoxanide (NTZ) is an FDA-approved anti-parasitic drug with broad-spectrum anti-infective, anti-inflammatory, and antineoplastic potential. However, its regulatory effects on osteoclastogenesis and the underlying mechanisms remain unclear. The present study found that NTZ potently inhibited osteoclast formation at the early stage of receptor activator of NF-κB ligand-induced osteoclastogenesis in a concentration-dependent manner at a non-growth inhibitory concentration. NTZ suppressed actin ring formation and decreased osteoclast marker gene expression, including TRAP, MMP9, and cathepsin K. NTZ significantly impaired the bone resorption activity of osteoclasts. In vivo, ovariectomized mice were treated with 50, 100 and 200 mg/kg/d NTZ for 3 months. NTZ (100 mg/kg/d) administration markedly reduced ovariectomy-induced bone loss by suppressing osteoclast activity. Mechanistically, osteoclastogenesis blockade elicited by NTZ resulted from inhibition of STAT3 phosphorylation, and reduction of the Ca2+ fluorescence intensity and NFATc1 expression. NTZ weakened the binding between STAT3 and the NFATc1 promoter region. Furthermore, enforced NFATc1 expression partly rescued the impaired osteoclast differentiation in NTZ-treated RAW264.7 cells. In summary, NTZ could inhibit osteoclastogenesis and bone loss through modulation of the receptor activator of NF-κB ligand-induced STAT3-NFATc1 signaling pathway, which might be a potential alternative treatment regimen against bone destruction-related diseases including osteoporosis.

[Clinical application of prospective electrocardiogram-gated 320-detector computed tomography coronary angiography].

OBJECTIVE: to compare the success rate, radiation dose, image quality and diagnosis of prospective electrocardiogram(ECG)-gated 320-detector computed tomography coronary angiography (CTCA) versus retrospective ECG-gated CTCA. METHODS: patients suspected coronary artery disease were divided into two groups which underwent 320-detector CTCA with prospective ECG-gated and retrospective ECG-gated scanning (n = 240 each, HR < 65 bpm). Curved-planar reconstruction (CPR), maximum intensity projection (MIP) and volume rendering (VR) were performed to demonstrate the coronary arteries. The image quality was defined as excellent, good and poor by motion and stair-step artifacts. Effective radiation exposure dose was estimated from the dose-length product. Effective radiation dose, image quality and diagnosis were evaluated. RESULTS: the success rate of examination was 100% in prospective ECG-gated group and retrospective ECG-gated group. The mean effective radiation dose of prospective ECG-gated CTCA [(3.3 ± 1.3) mSv] was significantly lower than that of retrospective ECG-gated CTCA [(13.0 ± 1.6) mSv, P < 0.01]. Segments of diagnostic image quality (95.42%, 3435/3600) and non-diagnostic coronary segments (4.58%, 165/3600) in prospective ECG-gated group were similar as those of retrospective ECG-gated group (95.81%, 3449/3600 and 4.19%, 151/3600, all P > 0.05). Compared with CAG, the sensitivity, specificity, false positive and false negative value in prospective ECG-gated group (93.22%, 99.21%, 91.64%, 99.05%) and retrospective ECG-gated group (94.55%, 98.80%, 95.86%, 98.54%) were not significantly different. CONCLUSION: though the effective radiation dose is significantly lower, the success rate, image quality and diagnosis of prospective ECG-gated 320-detector CTCA is comparable with that of retrospective ECG-gated 320-detector CTCA on patients with stable heart rates less than 65 bpm.

[The preparation and identification on monoclonal antibody to platelet-derived growth factor receptor].

OBJECTIVE: Through genetic engineering to produce the fusion protein of glutathione S-transferase (GST) linked to amino-terminal end of platelet-derived growth factor receptor (PDGFR), and to prepare the bioactive monoclonal antibody. METHODS: With taking GST-PDGFR-N fusion protein as immunogen, the anti-PDGFR monoclonal antibody was produced by using the hybridoma technique, of which then the antigen binding characteristic was identified by indirect enzyme-linked immunosorbent assay (ELISA), Western blot and immunohistochemistry methods. RESULTS: Two cell strains of hybridoma were obtained and named as 3B12F5 and 3C6H7C11 which secreted the anti-PDGFR monoclonal antibody, of which the class and subtype identification demonstrated both strains to produce all type of IgG1. The indirect ELISA result showed that the titers of ascites fluid which two hybridoma induced were 1 : 102400 and 1 : 25600. Western blot demonstrated that the two antibodies could recognize specifically the immunogen on PDGFR and U251 cell line. The cell immunohistochemistry proved that the antibody could recognize the expressed PDGFR antigens of neurogliocytoma U251 and bladder carcinoma BIU87 cell lines. CONCLUSION: We prepare successfully the PDGFR monoclonal antibody and provide a useful tool for researching on the PDGFR expression and clinical detection.

Identification of Factors for the Preoperative Prediction of Tumour Subtype and Prognosis in Patients with T1 Lung Adenocarcinoma.

Aims. Identification of factors that can predict the subtypes of lung adenocarcinoma preoperatively is important for selecting the appropriate surgical procedure and for predicting postoperative survival. Methods. We retrospectively evaluated 87 patients with lung adenocarcinomas ≤30 mm. Results. Preoperative radiological findings, serum CEA level, serum microRNA-183 (miR-183) level, and tumour size differed significantly between patients with adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) and those with invasive adenocarcinoma (IAC). Receiver operating characteristic curves and univariate analysis revealed that patients who were older than 57 years or had a pure solid nodule or a tumour with mixed ground-glass opacity (mGGO), a tumour >11 mm, a serum CEA level >2.12 ng/mL, or a serum miR-183 level >1.233 (2-ΔΔCt) were more likely to be diagnosed with IAC than with AIS or MIA. The combination of all five factors had an area under the curve of 0.946, with a sensitivity of 89.13% and a specificity of 95.12%. Moreover, patients with a cut-off value >0.499 for the five-factor combination had poor overall survival. Conclusions. The five-factor combination enables clinicians to distinguish AIS or MIA from IAC, thereby aiding in selecting the appropriate treatment, and to predict the prognosis of lung adenocarcinoma patients.

[Distribution and resistance trends of pathogens from urinary tract infections and impact on management].

OBJECTIVE: To assess the bacterial profile and pattern of antibiotic resistance of urinary tract infections (UTIs) pathogens and to determine its clinical impact on management. METHODS: Midstream urine samples were submitted for culture from 1998 to 2002, and 798 isolates were obtained for antimicrobial susceptibility testing including amikacin (AMK), ampicillin (AMP), cefzolin (CFZ), cefuroxime (CXM), ceftriaxone (CRO), ceftaxime (CTX), ceftazidime (CAZ), nalidixoc acid (NAL), ciprofloxacin (CIP), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NIT) for Gram-negative bacteria and oxcillin (OXA), ampicillin (AMP), cefzolin (CFZ), ciprofloxacin (CIP), gentamicin (Gen), vancomycin (VAN), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NIT) for Gram-positive cocci. beta-lactamases and ESBLs were tested when needed. RESULTS: Enterobacteriaceae was the most frequently isolated pathogen. Among all the isolates, Escherichia coli accounted for 66.0%, followed by Enterococcus (6.5%), Klebsiella spp. (6.0%), Staphylococcus (5.4%). High resistance rates to CIP (56.0%), SXT (67.0%) and AMP (78.9%) were observed among the E. coli. CIP-resistant E. coli strains are being isolated with increasing frequency. From 1998 to 2002 the incidence of CIP-resistant increased steadily from 46.6% to 59.4%. A higher resistance rate to NAL was apparent. In contrast, NIT displayed a resistance rate of 8.9%, and AMK 4.9%. The ESBLs positive rate was 12.9% among the E. coli and 33.3% among the Klebsiella spp. respectively. A high resistance rate to CIP was also observed among the Staphylococcus (38.1%), Enterococcus (61.5%) and Streptococcus (85.0%), and the beta-lactamases positive rate was 95.2% among the Staphylococcus, but a lower resistance rate to NIT among Staphylococcus (2.4%) and Enterococcus (11.5%). CONCLUSIONS: Resistance rates among common uropathogens continue to evolve and appear to be increasing to many commonly used agents especially to quinolones. Continued surveillance of resistance rates among uropathogens is needed to ensure appropriate recommendations for the treatment of the infections. Currently, the most appropriate agent for the empirical management of UTIs seems to be nitrofurantoin.

Plasmid-mediated degradation of 4-chloronitrobenzene by newly isolated Pseudomonas putida strain ZWL73.

A strain of Pseudomonas putida ZWL73 was isolated from soil contaminated with chloronitrobenzenes and identified by 16S rDNA sequencing. This bacterium released chloride and ammonia into the medium when grown on 4-chloronitrobenzene (4CNB) as the sole source of carbon, nitrogen and energy. A plasmid designated pZWL73 of approximately 100 kb in this strain was found to be responsible for 4CNB degradation. This was based on the fact that the plasmid-cured strains showed 4CNB- phenotype and the 4CNB+ phenotype could be conjugally transferred. The cell-free extracts of strain ZWL73 exhibited chloronitrobenzene nitroreductase and 2-amino-5-chlorophenol 1, 6-dioxygenase (2A5CPDO) activities, but neither activity was found from that of the plasmid-cured strain. We have also cloned a 4.9-kb EcoRI fragment exhibiting 2A5CPDO activity. Sequencing results revealed beta-subunit (cnbCa) and alpha subunit (cnbCb) of a meta-cleavage dioxygenase, which were subsequently expressed in E. coli with 2A5CPDO activity. The phylogenetic analysis suggested that 2A5CPDO may form a new subgroup in class III meta-cleavage dioxygenase with its close homologs.