The number of patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 is still increasing. In the case of COVID-19 and tuberculosis (TB), the presence of one disease affects ...the infectious status of the other. Meanwhile, coinfection may result in complications that make treatment more difficult. However, the molecular mechanisms underpinning the interaction between TB and COVID-19 are unclear. Accordingly, transcriptome analysis was used to detect the shared pathways and molecular biomarkers in TB and COVID-19, allowing us to determine the complex relationship between COVID-19 and TB. Two RNA-seq datasets (GSE114192 and GSE163151) from the Gene Expression Omnibus were used to find concerted differentially expressed genes (DEGs) between TB and COVID-19 to identify the common pathogenic mechanisms. A total of 124 common DEGs were detected and used to find shared pathways and drug targets. Several enterprising bioinformatics tools were applied to perform pathway analysis, enrichment analysis and networks analysis. Protein-protein interaction analysis and machine learning was used to identify hub genes (GAS6, OAS3 and PDCD1LG2) and datasets GSE171110, GSE54992 and GSE79362 were used for verification. The mechanism of protein-drug interactions may have reference value in the treatment of coinfection of COVID-19 and TB.
•Liver metastasis, ALB, LDH, MLR, and pre-treatment plasma EBV-DNA were independent prognostic indicators for ICI outcomes.•A nomogram using these 5 factors can estimate anti-PD-1-response in RM-NPC ...patients.•The nomogram performed well in a training and in a validation cohort.•The nomogram could provide new insights into anti-PD-1 monotherapy in RM-NPC.
About 17.7–34.0 % of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) responded well to anti–PD-1 monotherapy. We sought to establish a nomogram to estimate the progression-free survival (PFS) of RM-NPC patients receiving subsequent-line anti-PD-1 monotherapy.
This cohort study investigated consecutive RM-NPC patients undergoing anti-PD-1 monotherapy. A nomogram was developed in the training cohort (n = 161), using a Cox multivariate model with backward stepwise inclusion, and was validated in the validation cohort (n = 69). Its predictive accuracy was assessed using a concordance index (C-index) and calibration curve. The primary endpoint was PFS. Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), and overall survival (OS).
Liver metastasis, albumin, lactate dehydrogenase, monocyte-to-lymphocyte ratio, and plasma Epstein–Barr virus DNA were used to develop a nomogram that could separate patients into favourable- and unfavourable-prognosis groups. The C-index in the training and validation cohort were 0.70 and 0.68, respectively, which was confirmed by calibration curves. Median PFS (mPFS) was lower for the unfavourable-prognosis than for the favourable-prognosis group (1.80 vs 4.93; hazard ratio 2.49 95 % confidence interval: 1.78–3.49; p < 0.001), across all subgroups. OS exhibited the same pattern. The ORR and DCR were markedly lower in the unfavourable-prognosis than in the favourable-prognosis group. All results were confirmed in the validation cohort.
Our model is a reliable prognostic indicator of PFS in RM-NPC patients undergoing anti-PD-1 monotherapy, allowing robust estimation of the immunotherapy benefit an individual might derive.
Cognitive impairment caused by diabetes has been gradually recognized. Generally, nicotinic acetylcholine receptors (nAChRs) play an important role in the pathogenesis in dementia disorders including ...Alzheimer's disease (AD). However, the expression of nAChRs in the brains of type 2 diabetes mellitus (T2DM) is unexplored. This study explored the alterations of nAChRs in the postmortem brains of patients with T2DM and brains of
mice. Morris water maze test was used to appraise the ability of spatial learning and memory; Western blotting and RT-qPCR were performed to determine the expressions of target protein and mRNA, respectively; TUNEL was used to detect the apoptosis of neurons. We found that the protein levels of nAChR α7 and α4 subunits were significantly decreased and the apoptosis rates in neurons elevated in the hippocampus of T2DM patients and
mice as comparison to controls. Furthermore, the
mice exhibited the impaired cognition, the elevated level of pro-apoptotic protein and the reduced level of anti-apoptotic and synaptic proteins. This study shows the lowered level of nAChR α7 and α4 subunits and the elevated apoptosis in the hippocampus of T2DM patients and
mice, which might help explain the impaired cognition in T2DM.
•The confined thermal-erosion was used to synthesize a highly accessible Mn single-atom catalyst.•The catalyst possesses ultrahigh BET area (1419 m2 g−1) and superior half-wave potential ...(0.863 V).•The catalyst shows outstanding stability and high power density exceeding the Pt/C.•The high ORR activity is attributed to the formation of defective single Mn-N3 sites.
Carbon-supported single Mn atoms catalysts are seen as one of the most promising substitutes for the conventional Pt-based catalysts owing to weaker Fenton reaction, higher stability and lower cost. We here report a confined thermal-erosion strategy for converting Mn-based MOF materials (Mn-ZIF-8) into a pore-rich graphene structure (4 ∼ 5 layers) with highly accessible defect-hosted Mn-N3 sites and ultrahigh specific surface area (1419 m2 g−1) via high-temperature full-gasification of graphitic C3N4, which can serve as an efficient single Mn atoms catalyst for oxygen reduction reaction (ORR). The catalyst shows superior ORR catalytic activity with a half-wave potential of 0.863 V (vs. RHE), high cycling stability and four-electron selectivity for the ORR. Theoretical calculations indicate that the promoted ORR activity of the Mn-SAC catalyst may be mostly attributed to the defective Mn-N3 sites with a lower free energy barrier and a higher intrinsic activity compared to in-plane Mn-N4 sites. The Zn-air battery assembled with this catalyst represents a maximum power density (226 mW cm−2) and superior energy density of 857 Wh kgZn-1, far exceeding the air battery performance using the Pt/C catalyst. Our findings can provide new design methods and in-depth insights for defect-hosted active single-metal-atoms ORR catalysts.
Wh
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•J-1063 suppressed ECM deposition in HSCs, preventing the progress of HSCs transdifferentiation.•J-1063 exerted its anti-hepatic fibrosis activity by inhibiting the activation of ...TGF-β/Smad signaling pathway.•J-1063 prevented fibrotic inflammation by inhibiting the activation of NLRP3 inflammasome.•J-1063 inhibited the infiltration of macrophages and neutrophils in TAA-induced liver fibrosis.
In the present study, we completed the synthesis of a pyrazole derivative J-1063 and evaluated the kinase inhibitory activity of J-1063 activin receptor-like kinase 5 (ALK5) and p38α mitogen-activated protein (MAP) in the enzymatic assay. We evaluated anti-fibrotic effects of J-1063 on TGF-β-induced hepatic stellate cells activation and TAA induced mice liver fibrosis. J-1063 showed much prior anti-fibrotic effects than those with LY2157299. Our data revealed that J-1063 exerted anti-fibrotic activity by inhibiting TGF-βR1 (ALK5), which is likely related to the inhibition of TGF-β--Smad signaling and NLRP3 inflammasome activation. The results suggest that J-1063 might be potential candidates for further anti-liver fibrosis drug development.
Strictly anaerobic bacteria are important to both human health and industrial usage. These bacteria are sensitive to oxygen, therefore, it is preferable to manipulate these microbes in an anaerobic ...chamber. However, commercial anaerobic chambers (CACs) are expensive, making them less accessible to scientists with a limited budget, especially to those in developing countries. The high price of commercial chambers has hindered, at least partially, the progress of research on anaerobes in developing countries. In the research presented here, we developed an inexpensive and reliable anaerobic chamber and successfully achieved routine maintenance of eleven strictly anaerobic bacterial strains. Furthermore, genetic manipulation examples have been set for both Clostridioidesdifficile 630 and Clostridiumbeijerinckii NCIMB 8052 strains to validate that the chamber could applied to advanced genetic engineering of strictly anaerobes. C. difficile and C. beijerinckii were both genetically manipulated in this chamber, showing it’s utility for the genetic engineering of anaerobes. Most importantly, the anaerobic chamber was 76% - 88% less expensive than a CACs and has similar functionality with regards to the cultivation and manipulation of strictly anaerobic bacteria. The anaerobic chamber described in this study will promote the research of anaerobes in developing counties and scientists who have limited research budgets.
•The characteristics of an inexpensive and reliable anaerobic chamber were described.•The anaerobic chamber was 76% - 88% less expensive than a commercial available chamber.•Anaerobes were maintained and genetically manipulated using this anaerobic chamber.•The anaerobic chamber could promote research on anaerobes in developing counties.
In this study, two Al-Cr-Ti ternary alloy coatings (denoted as AlCr and AlCrTi0.5) were fabricated on a Ti-4Al-2V alloy substrate by using a pulsed laser cladding method. Specific microstructure ...characteristics of those coatings were thoroughly revealed by using various characterization methods, with their hardnesses and wear rates measured by a Vickers indenter and a tribological tester. The results reveal that both AlCr and AlCrTi0.5 coatings are comprised of a body-centered cubic phase (β-Ti phase with average grain sizes of 12.6 ± 9.1 μm and 14.6 ± 10.0 μm, respectively), which is related to non-equilibrium solidification and sluggish diffusion of alloying elements during the laser processing. Heat-affected zones of both the laser-cladded specimens are mainly composed of submicron martensitic laths (α′-Ti). Average microhardness values of the AlCr and the AlCrTi0.5 coatings are measured to be 526 ± 37 HV and 510 ± 24 HV, respectively, approximately two times higher than the substrate (270 ± 8 HV). Their wear rates are almost the same, ~2.2 × 10−4 mm3 N−1 m−1, only ~1/3 of that of the substrate. Based on dedicated microstructure analyses, the greatly enhanced performance of the laser-cladded coatings could be attributed to joint strengthening from strong solid solution and lattice distortion, as well as Al/Cr-induced phase structure differences from the substrate.
•Two Al-Cr-Ti ternary alloy coatings (denoted as AlCr and AlCrTi0.5) were laser-clad on Ti-4Al-2V alloy.•Both the coatings are comprised of a single solid-solution phase as a result of non-equilibrium solidification.•Hardness and wear resistance of the Al-Cr-Ti coatings are greatly improved compared to the substrate.•Such superior properties can be jointly attributed to strong solid solution and lattice distortion, as well as phase changes.
The Mn-N5 active moiety with inhomogeneous charge distribution will effectively promote the overall ORR process due to the considerably higher selectivity of the catalyst for the four-electron ...reaction path.
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Designing single-atom catalysts for oxygen reduction reaction (ORR) are fashionable but challenging to boost the zinc-air battery performance. Significantly enhanced ORR activity by manganese (Mn) single-atom catalysts can be achieved by accurately regulating the coordination number of isolated Mn atoms. Theoretical calculations indicate that the single Mn-N5 sites possess lower free energy barrier and higher oxygen adsorption performance than single Mn-N4 sites to accelerate the ORR kinetics. Target to it, here we synthesize an atomically dispersed Mn-N5 catalyst by precisely axial coordination of pyridinic-N doped into two-dimensional (2D) porous nanocarbon sheets (∼3.56 nm thickness), which reveals outstanding catalytic activity and ultrahigh stability for the ORR in zinc-air battery owing to the inhomogeneous charge distribution of Mn-N5 sites compared to the conventional single-site Mn-N4 catalyst and Pt/C. This work gives a new strategy for in situ regulating the electronic structure of metal single-atoms and further promoting the overall ORR performance in energy systems.
Recently, the
DAOA gene locus on chromosome 13q32–q34 has been implicated in the etiology of schizophrenia. We genotyped three single-nucleotide polymorphisms (SNPs: rs778294, rs779293 and rs3918342) ...in this region in 126 Chinese family trios. In this study, we have identified statistically significant transmission disequilibrium in two markers rs778293 (
P
=
0.01) and rs3918342 (
P
=
0.02), and a highly significant under-transmission between haplotype
CAT (
P
=
0.0005) and schizophrenia. The results provide further evidence to support that
DAOA gene locus is involved in conferring susceptibility to schizophrenia.
A novel actinomycete strain, designated YIM 002(T), was isolated from a desert soil sample in Gansu Province, north-west China. This actinomycete isolate formed well-differentiated aerial and ...substrate mycelia. In the early stages of growth, the substrate mycelia fragmented into short or elongated rods. Chemotaxonomically, it contained ll-2,6-diaminopimelic acid in the cell wall. The cell-wall sugars contained ribose and glucose. Phospholipids present were phosphatidylinositol mannosides, phosphatidylinositol and diphosphatidylglycerol. MK-9(H(4)) was the predominant menaquinone. The major fatty acids were anteiso C(15 : 0) (35.92 %), anteiso C(17 : 0) (15.84 %), iso C(15 : 0) (10.40 %), iso C(16 : 0) (7.07 %) and C(17 : 1)omega8c (9.37 %). The G+C content of the DNA was 70 mol%. Phylogenetic analysis and signature nucleotide data based on 16S rRNA gene sequences showed that strain YIM 002(T) is distinct from all recognized genera of the family Nocardioidaceae in the suborder Propionibacterineae. On the basis of the phenotypic and genotypic characteristics, it is proposed that isolate YIM 002(T) be classified as a novel species in a new genus, Jiangella gansuensis gen. nov., sp. nov. The type strain is YIM 002(T) (=DSM 44835(T)=CCTCC AA 204001(T)=KCTC 19044(T)).
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