Search

Abstract Background Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) remains a global health issue. The characterized virulent M. tb H37Rv, avirulent M. tb H37Ra and BCG strains are widely used as reference strains to investigate the mechanism of TB pathogenicity. Here, we attempted to determine metabolomic signatures associated with the Mycobacterial virulence in human macrophages through comparison of metabolite profile in THP-1-derived macrophages following exposure to the M. tb H37Rv, M. tb H37Ra and BCG strains. Results Our findings revealed remarkably changed metabolites in infected macrophages compared to uninfected macrophages. H37Rv infection specifically induced 247 differentially changed metabolites compared to H37Ra or BCG infection. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed H37Rv specifically induces tryptophan metabolism. Moreover, quantitative PCR (qPCR) results showed that indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) which converts the tryptophan to a series of biologically second metabolites were up-regulated in H37Rv-infected macrophages compared to H37Ra- or BCG-infected macrophages, confirming the result of enhanced tryptophan metabolism induced by H37Rv infection. These findings indicated that targeting tryptophan (Trp) metabolism may be a potential therapeutic strategy for pulmonary TB. Conclusions We identified a number of differentially changed metabolites that specifically induced in H37Rv infected macrophages. These signatures may be associated with the Mycobacterial virulence in human macrophages. The present findings provide a better understanding of the host response associated with the virulence of the Mtb strain.

AimTo compare the efficacy and safety of radiotherapy in combination with immunotherapy after achieving disease control from the first-line combination therapy of platinum-based chemotherapy and immunotherapy for advanced lung squamous cell carcinoma (LUSC).MethodsThis study retrospectively evaluated the patients with advanced LUSC treated with the combination of radiotherapy with immunotherapy and chemotherapy (ICRT group, n = 52) or immunotherapy and chemotherapy (ICT group, n = 63) as the first-line treatment from April 2018 to April 2022. Using propensity score matching (PSM), 50 pairs were created, while the confounders and bias were controlled. The objective response rate (ORR), duration of overall response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed in the two groups. The PFS and OS were re-analyzed separately for patients treated with thoracic radiotherapy.ResultsAfter PSM, the median PFS (12.23 vs. 7.43 months; P

Being an important semiconductor material for high power applications, silicon carbide (SiC) faces the problems while used as a gate oxygen layer in traditional Si MOS devices. In view of this, an innovative approach was adopted in the present work to replace the conventional SiO _2 with a high-k material (ZrO _2 ) as the gate oxygen layer to investigate its effect on the electrical characteristics of the devices. In particular ZrO _2 films were deposited on Si and SiC substrates by atomic layer deposition (ALD), and Al was used as the electrode. The atomic force microscopy (AFM) microregion scan revealed a highly flat surface with R _q < 1 nm after the ALD growth of ZrO _2 layer. The sample surface analysis via x-ray photoelectron spectroscopy (XPS) suggested the presence of a small amount of ZrO _x components. According to the electron energy loss spectrum (EELS), the band gap width (E _g ) of this ALD ZrO _2 dielectric was 5.45 eV, which met the requirements for high-quality 4H-SiC-related MOS devices. The electrical properties of the samples were then studied, and the maximum breakdown voltage of the Al/ZrO _2 /SiC/Al MOS structure was obtained to be 23 V, i.e., nearly twice that of the Si substrate. As for the oxide layer, the interface defect density (D _it ) near the conduction band of the Al/ZrO _2 /SiC/Al MOS structure was only 10 ^12 eV ^−1 cm ^−2 orders of magnitude. The N _eff value (the movable charge) of the structure was also controlled at 10 ^12 cm ^−2 . Therefore, the overall performance of the ZrO _2 /SiC structure in terms of electrical properties exceeded that of the ZrO _2 /Si structure and previously reported counterparts. In this respect, the ZrO _2 /SiC MOS capacitor structure has great research potential.

Objective To establish the catalog of maximum surgical blood order schedule(MSBOS) for cesarean sections with different obstetric complications, so as to guide the doctors of clinical and Blood Transfusion Department to prepare blood reasonably. Methods The blood transfusion data during cesarean sections from January to October 2021 in our hospital were collected via medical record information system and blood bank system.The blood recipients were classified according to the main obstetric complications. The incidence of blood transfusion, per capita RBC transfusion units, blood transfusion index (TI) and other indicators were calculated, the literature and the risk of massive hemorrhage were referred, and the actual situation of Obstetrics Department was considered to formulate the obstetric MSBOS of our own. Results 1) The blood recipients during cesarean sections were mainly diagnosed as placental abruption, placental implantation, central placenta previa and severe preeclampsia; the incidence of blood transfusion of them was 17.9%(20/112), 17.7%(15/85), 16.8% (27/161)and 5.2%(9/173), respectively, and TI indexes was 0.9, 1.3, 1.0 and 0.3, respectively. 2) The MSBOS of Obstetrics Department in our hospital had been established, and the blood preparation for obstetric surgery was divided into three categories: T(blood typing)/S(antibody screening), T(blood typing)/S(antibody screening)/C(crossmatch) 2 U, and T/S/C 4 U. Conclusion The establishment of MSBOS in Obstetrics Department of our hospital provides references for preparing blood reasonably.

AIM: To report on the clinical features, surgical outcomes and gene mutation analysis of three ectodermal dysplasia probands with ocular diseases. METHODS: A case-note review of three unrelated probands diagnosing with ectodermal dysplasia with ocular diseases was undertaken. Patient clinical features and the outcomes of surgery were analysed. The suspected pathogenic genes were analysed by whole exome sequencing from patients with ectodermal dysplasia and Sanger sequencing from family members. RESULTS: The ocular clinical features of ectodermal dysplasia with ocular diseases mainly include eyelid ectropion, lagophthalmos and absence of lacrimal punctum. All the probands underwent surgeries of full-thickness free skin flap grafting to correct ectropion. They achieved good recovery, and there were no obvious complications during the follow-up. The gene sequencing results did not show any meaningful genetic mutations. CONCLUSION: Lid ectropion is one of the key clinical traits of ectodermal dysplasia with ocular diseases. Ectropion correction with full-thickness free skin flap grafting is an effective procedure to correct ectropion for ectodermal dysplasia patients with ichthyosis-like tissue. The suspected pathogenic genes of ectodermal dysplasia with ectropion should be further verified or confirmed by large samples of the family.

Copper azide with high density was successfully synthesized by in-situ reaction of nanoporous copper (NPC) precursor with HN3 gaseous. NPC with pore size of about 529 nm has been prepared by electroless plating using polystyrene (PS) as templates. The copper shells thickness of NPC was controlled by adjusting the PS loading amount. The effects of copper shell on the morphology, structure and density of copper azide were investigated. The conversion increased from 87.12% to 95.31% when copper shell thickness decrease from 100 to 50 nm. Meanwhile, the density of copper azide prepared by 529 nm NPC for 24 h was up to 2.38 g/cm3. The hollow structure of this NPC was filled by swelling of copper azide which guaranteed enough filling volume for keeping the same shape as well as improving the charge density. Moreover, HNS-IV explosive was successfully initiated by copper azide with minimum charge thickness of 0.55 mm, showing that copper azide prepared has excellent initiation performance, which has more advantages in the application of miniaturized explosive systems.

Porcine epidemic diarrhea virus (PEDV) infection causes lethal watery diarrhea and high mortality in neonatal piglets, leading to huge economic losses in the global swine industry. Currently, the existing commercial vaccines cannot fully control PEDV, so it is urgent to develop effective antiviral agents to complement vaccine therapy. In the present study, we investigated the antiviral effect of Hypericum japonicum extract (HJ) against PEDV in vivo and in vitro. In in vitro assays, HJ could directly inactivate PEDV strains; moreover, it inhibited the proliferation of PEDV strains in Vero or IPI-FX cells at its non-cytotoxic concentrations. Time of addition assays revealed that HJ mainly inhibited PEDV at the later stages of the viral life cycle. In in vivo, compared with the model group, HJ could reduce the viral titers in the intestines of infected piglets, and improve their intestinal pathological, indicating that HJ could protect the newborn piglets from highly pathogenic PEDV variant infection. Furthermore, this effect may be related to the fact that HJ can not only directly inhibit viruses, but also regulate the structure of intestinal microbiota. In conclusion, our results indicate that Hypericum japonicum could inhibit PEDV replication in vitro and in vivo and might possess the potential to develop as the anti-PEDV drug.

Background: Endothelial cells in the tumor microenvironment play an important role in the development of kidney renal clear cell carcinoma (KIRC). We wanted to further identify the function of endothelial cells in KIRC patients by integrating single-cell and bulk RNA sequencing data.Methods: Online databases provide the original data of this study. An endothelial-related prognostic index (ERPI) was constructed and validated by R version 3.6.3 and relative packages.Results: The ERPI consisted of three genes (CCND1, MALL, and VWF). Patients with high ERPI scores were significantly correlated with worse prognosis than those with low ERPI scores in the TCGA training group, TCGA test group, and GSE29609 group. A positive correlation was identified between the ERPI score and poor clinical features. The results of functional analysis indicated that ERPI was significantly associated with immune-related activities. We suggested that patients with high ERPI scores were more likely to benefit from immunotherapy based on the results of immune checkpoints, tumor microenvironment, stemness index, and TCIA, while patients with low ERPI scores were sensitive to gemcitabine, docetaxel, paclitaxel, axitinib, pazopanib, sorafenib, and temsirolimus according to the results of the “pRRophetic” algorithm. Therefore, this ERPI may help doctors choose the optimal treatment for patients with KIRC.Conclusion: By integrating single-cell and bulk RNA sequencing data from KIRC patients, we successfully identified the key genes from the perspective of endothelial cells in the tumor microenvironment and constructed ERPIs that had positive implications in precision medicine.

Objective To investigate the clinical and genetic characteristics of hemolytic disease of the newborn(HDN) induced by anti-M complicated with pyruvate kinase deficiency (PKD) disease. Methods The clinical data of a pregnant woman with unexplained adverse pregnancy outcome in the third trimester were retrospectively analyzed, and neonate anemia status and blood transfusion were followed up. With informed consent, peripheral blood of the neonate and her parents were collected for serological tests and disease-related gene target sequence capture and sequencing. The clinical and genetic characteristics of HDN induced by anti-M or PKD were reviewed. Results The neonate presented severe anemia, hepatosplenomegalism, hyperbilirubinemia at birth, and was confirmed MN combined with ABO neonatal hemolysis by serological tests. The neonate recovered by receiving blood exchange and phototherapy treatments, but he needed to receive blood transfusion each month because of hemolytic anemia. Genetic analysis showed that the neonate had compound heterozygous mutations (c. 1096C>T; c. 941T>C) of PKLR gene inherited from her parents. Conclusion The clinical manifestations of PKD are similar to that of HDN caused by anti-M in the early stage of the disease. Clinicians should exclude the metabolic diseases of red blood cells when diagnosing severe HDN caused by anti-M.

Abstract Introduction LncRNA CCAT1 promotes inflammatory responses, which contribute to tuberculosis. Therefore, CCAT1 may participate in tuberculosis. Therefore, we analyzed the involvement of CCAT1 in tuberculosis. Methods Plasma samples were donated by a total of 200 patients with newly developed tuberculosis (N‐TB), 102 patients with recurrent tuberculosis (R‐TB), and 102 healthy controls on the day of admission. Plasma samples were also collected from N‐TB and R‐TB patients every month after the initiation of treatment for a total of 6 months. CCAT1 expression in these samples was detected by quantitative reverse transcription polymerase chain reaction. Levels of IFN‐γ, IL‐1β, iNOS, TNF‐α, and IL‐10 in plasma were determined by enzyme‐linked immunosorbent assay. N‐TB and R‐TB patients were monitored for 2 months to analyze their survival. Results On the day of admission, the highest levels of CCAT1, IFN‐γ, IL‐1β, iNOS, and TNF‐α were detected in N‐TB patients, followed by R‐TB patients and controls, while the lowest levels of plasma IL‐10 were detected in N‐TB patients, followed by R‐TB patients and controls. Across R‐TB and N‐TB patients, CCAT1 was inversely correlated with IL‐10 but not closely correlated with other inflammatory factors. During the treatment, plasma CCAT1 levels decreased in both N‐TB and R‐TB patients. High CCAT1 levels were closely correlated with high mortality rates of both N‐TB and R‐TB patients. Conclusion CCAT1 is overexpressed in tuberculosis patients and predicts their survival. Its function in tuberculosis may be related to IL‐10.

Orthoptera species are characterised by their expansive genomes. However, crickets, the third largest group of this order, have notably smaller genomes than grasshoppers or katydids. The evolutionary drivers behind these differences in genome size (GS) remain largely uncharted. In our study involving 56 cricket species, we assessed GS using flow cytometry and assembled 43 novel mitochondrial genomes for phylogenetic analysis. Model fitting indicated that GS generally conformed to an Ornstein‐Uhlenbeck adaptive evolutionary model, displaying a 5.1‐fold range of variation in GS, from 0.82 pg in Myrmecophilus quadrispina Perkins to 4.68 pg in Ornebius formosanus Shiraki. Remarkably, despite such variations, no significant trends in genome contraction or expansion were detected, suggesting an adaptive stabilisation. We found strong evidence that expansions of repeat elements, particularly transposable elements (TEs), are key drivers of the large GS in crickets. Across the 56 cricket species analysed, TE content exhibited substantial variability, spanning from a mere 3.63% to a pronounced 31.22%. Clades exhibiting significant GS or TE variations, such as mole crickets (Gryllotalpidae), ant‐loving crickets (Myrmecophilidae) and scaly crickets (Mogoplistidae), are often observed at basal phylogenetic nodes and exhibit distinct ecological niches and morphological divergences. This implies that cricket genomes undergo early mutations and stabilise throughout evolution. Our findings shed light on common patterns and uncover lineage‐specific differences in content and evolution of TEs in crickets. We anticipate that our study will provide a foundation for future comparative research on the insect TE repertoire. [ABSTRACT FROM AUTHOR]

Altered glycan levels in serum have been associated with increased risk of cancer. In this study, we have developed and validated a HPLC-based method to analyze monosaccharide composition (D-mannose, Glucosamine, Galactosamine, Glucuronic acid, D-glucose, D-galactose, D-xylose, L-fucose) in human serum, with L-rhamnose, being used as internal standard. Monosaccharides obtained from hydrolyzed serum samples were derivatized by 1-Phenyl-3-methyl-5-pyrazolone. A ZORBAX XDB-C18 column(150×4.6mm) was used for chromatographic separation with 100 mM ammonium acetate buffer (NH4Ac-HAc, PH=5.5, solvent A), acetonitrile (ACN, solvent B) as a mobile phase. The calibration standard curves for the eight monosaccharides showed good linearity over the range of 2.5-500μg/mL with R2 > 0.995. The relative standard deviation values for intra-day and inter-day precision were ≤ 5.49%. Recovery was 69.01-108.96%. We observed that this column exhibited high specificity and selectivity to separate monosaccharides from serum. This method was then applied to quantitatively analyze the serum monosaccharide levels in 30 patients with endometrial cancer and 30 matched healthy controls. Statistical analysis indicated that the serum monosaccharide levels were significantly higher in patients compared with healthy controls (P value< 0.0001). Overall, we report here a simple, reliable, low-cost, and reproducible HPLC method for the separation and quantification monosaccharides in the human serum, which has potential value to serve as a screening marker for endometrial cancer.