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Few-shot learning is an extremely challenging task in computer vision that has attracted increased research attention in recent years. However, most recent methods do not fully use the task’s information, and few of the seen samples result in large intraclass differences among the same classes. In this paper, we propose a novel task encoding with distribution calibration (TEDC) model for few-shot learning, which uses the relationships among the feature distributions to reduce intraclass differences. In the TEDC model, an integrated feature extraction module (IFEM) is proposed, which extracts the multiangle visual features of an image and fuses them to obtain more representative features. To effectively utilize the task information, a novel task encoding module (TEM) is proposed, which obtains the task features by fusing all the seen samples’ information and uses them to adjust all the samples’ features for more generalizable task-specific representations. We also propose a distribution calibration module (DCM) to reduce the bias between the distribution of the support features and the query features in the same class. Extensive experiments show that our proposed TEDC model achieves an excellent performance and outperforms the state-of-the-art methods on three widely used few-shot classification benchmarks, specifically miniImageNet, tieredImageNet and CUB-200-2011. [ABSTRACT FROM AUTHOR]

Background: Mitral valve prolapse (MVP) is a common cardiovascular disease defined as a late systolic click or mitral valve lobes that move up into the left atrium during ventricular systole, with or without mitral insufficiency. Dachsous catherin‐related 1 (DCHS1) is one of the two known pathogenic genes associated with MVP. However, there is little information about the renal dysfunction caused by MVP and DCHS1 mutations. Methods: We analyzed the genetic etiology in a rare case of 9‐year‐old boy affected by chronic renal failure with MVP. Subsequently, we constructed stable cell lines overexpressing wild‐type DCHS1 or mutant DCHS1 (c.8309G>A, p.R2770Q) to evaluate the influence of the DCHS1 mutation on the proliferation, apoptosis, and autophagy. Results: Complete exome sequencing and pedigree verification revealed a mutation p.R2770Q (c.8309G>A) in exon 21 of the DCHS1 gene carried by the patient, which may affect the DNA binding. No such mutation was detected in his parents, indicating that this was a new mutation. Potential functional impact of sequence variants was predicted using in silico prediction programs including SIFT, Polyphen2, and Condel. This variant was determined to be a pathogenic mutation that has not been reported elsewhere. Subsequently, we used a stable DCHS1 gene‐mutated HK‐2 cell line to analyse proliferation, apoptosis, and autophagy, showed that kidney volume decreased with increasing cell death associated with a reduced proliferation. Conclusions: Our analysis revealed a heterozygous variation of DCHS1 in a child with MVP. Our observations highlight previously unrecognized phenotypes of the currently recognized MVP genotype, including distinct chronic renal failure. [ABSTRACT FROM AUTHOR]

Fused deposition modeling (FDM) technology decreases production time and cost in engineering industry, but with typical low surface quality. In this study, laser polishing was employed to improve surface quality of copper fiber/polylactide acid (Cu/PLA) composite parts fabricated by FDM. Surface roughness, surface morphology, dynamic mechanical analysis (DMA), and tensile properties were studied. The results showed that after laser polishing, the surface roughness was reduced by more than 91% (from 10.52 to 0.87 μm Sa) at the optimized parameters (the laser power of 5 W and the laser beam diameter of 200 μm). Laser polishing can effectively remove surface defects formed during FDM. DMA showed that the storage modulus, loss modulus, and glass transition temperature of Cu/PLA composites were significantly improved, because the Cu fibers and PLA matrix formed a strong interfacial adhesion after treatment. Moreover, the tensile strength and Young's modulus of the Cu/PLA composites sample also improved by laser polishing. The fracture morphologies were observed, and the possible strengthening mechanism was also discussed. [ABSTRACT FROM AUTHOR]

Owing to the layer-by-layer deposition characteristic of fused deposition modeling (FDM) process, parts produced via FDM have typical low surface quality and do not satisfy the requirements for end-use applications. Therefore, it is necessary to improve the surface quality of parts produced via FDM. In this study, laser polishing technology was employed to enhance the surface quality of aluminum fiber/polylactide acid (Al/PLA) composite parts produced via FDM. The surface roughness, surface morphology, dynamic mechanical properties, and tensile properties were investigated. With optimal polishing parameters, the laser polishing process removed the defects formed during the FDM process. The surface roughness was reduced from the initial value of 5.64 μm to 0.32 μm (Ra). The dynamic mechanical analysis (DMA) results showed that there was a remarkable improvement in the storage modulus (E ′), loss modulus (E "), and glass transition temperature of Al/PLA composite specimens after laser polishing. The re-melted and polished surface of the specimens also led to improvement in the tensile strength and Young's modulus. Lastly, the fracture morphologies were observed, and the possible strengthening mechanism was also discussed. These results indicate that laser polishing can be an efficient method for the surface polishing of FDM-printed parts. Unlabelled Image • Laser polished additive manufactured Al/PLA has higher surface quality and many defects are removed. • A maximum reduction in Al/PLA surface roughness of over 93% is achieved at optimized polishing settings. • Laser polishing effectively improves the dynamic mechanical properties and tensile properties of the FMD Al/PLA. • The strengthening mechanism induced by laser polishing is analyzed. [ABSTRACT FROM AUTHOR]

• Pores- and cracks-free TiC/IN625 coatings over AISI 1045 steel were firstly prepared by EHLA. • EHLA TiC/IN625 coatings possessed much more uniform and finer microstructure. • High resistance is attributed to lower surface roughness, smaller dendrite size, smaller grain size, and higher amount of LAGBs. The multi-layer TiC/IN625 coatings were deposited on AISI 1045 steel substrate by conventional laser cladding (CLA) and extreme high-speed laser cladding (EHLA). The surface morphology, microstructure and high-temperature oxidation resistance of the TiC/IN625 coatings were characterized and compared. The results showed that the cladding speed has a significant effect on surface quality. Within the range of the set parameters, the best surface quality is obtained when the cladding speed is 49.8 m/min, where Ra is 11.75 μm and Sa is 13.17 μm. The microstructure of the TiC/IN625 coatings is dominated by dendrites. Smaller dendrites arm spacing and no apparent transition layer are found at the layer-to-layer interface in the EHLA sample. A two-layered oxide structure is formed in the cross-section of all samples. The EHLA sample exhibits a lower mass loss compared to the CLA sample, indicating that EHLA sample can withstand high-temperature oxidation. The improvement of high-temperature oxidation resistance is mainly attributed to the lower surface roughness, smaller dendrite size, smaller grain size, and higher amount of LAGBs. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effects of TNF receptors associated factor 3 (TRAF3) on the signaling pathway and expression of downstream products of nuclear factor kappa B (NF-κB) in the epithelial cells of renal ducts in individuals with polycystic kidney disease (PKD). We observe the TRAF3 genic overexpression of the epithelial cells, which form a tubular branch structure, in polycystic kidneys and to explore the protective effect of TRAF3 on the cystogenesis and progression of PKD. Western blotting analysis was conducted to examine the signaling changes of NF-κB in PKD the epithelial cells and TRAF3 transgenic PKD epithelial cells. Changes in the downstream apoptosis factor and cell proliferation in PKD epithelial cells and TRAF3 transgenic PKD epithelial cells were detected. A three-dimensional matrigel culture experiment was performed to examine abnormal tubulomorphogenesis in vitro. The overexpression of TRAF3 significantly inhibited the signaling pathway of NF-κB in the PKD epithelial cells, downregulated the expression of downstream factors Bcl-2 and Bcl-xl, and significantly decreased cystic epithelial cell proliferation. Additional branch structures were observed in the PKD epithelial cells with a three-dimensional culture compared to wildtype cells. TRAF3 may likely induce apoptosis and resistance to proliferation and may be a new target to inhibit the cyst formation in PKD by regulating the NF-κB signaling pathway Bcl-2 and Bcl-xl activity. © 2017 IUBMB Life, 69(3):170-178, 2017 [ABSTRACT FROM AUTHOR]

Extreme high-speed laser cladding (EHLA) was used to develop a pore- and crack-free TiC/IN625 coating. The surface roughness of EHLA could be as low as 6.004 µm. A more uniform dendrite size and composition distribution was obtained by EHLA. The mass gain of EHLA was 57.5% lower than that of the conventional laser cladding sample after hot corrosion in a mixed salt of 75%Na 2 SO 4 + 25% NaCl at 900 ℃ for 60 h. High hot corrosion resistance of EHLA was mainly attributed to the lower surface roughness, smaller dendrite size, smaller grain size, and higher amount of low-angle grain boundaries. • Pores- and cracks-free TiC/IN625 coatings over AISI 1045 steel were firstly prepared by EHLA. • EHLA TiC/IN625 coatings possessed much more uniform and finer microstructure. • The uniformly distributed dendrite sizes and compositions contributed to the formation of a dense oxide film. • Superior hot corrosion behavior of EHLA TiC/IN625 coatings was mainly attributed to the lower surface roughness, smaller dendrite size, smaller grain size, and more low-angle grain boundaries. [ABSTRACT FROM AUTHOR]

• The combined toolbox (Wondfo RDTs plus microscopy) improved the surveillance system sensitivity for malaria in Anhui province. • The improvement was mainly attributed to the excellent ability of RDTs to detect P. falciparum infections. On the other hand, microscopy compensates for some limitations of the use of RDTs in field practice. • Using more than one diagnostic tool to strengthen the surveillance system was effective in the post-elimination stage. Background: In the Anhui Province, China, efforts to interrupt the local malaria transmission were successful, with no endemic cases reported since 2014. Contrastingly, imported malaria cases are still being reported, indicating a disease reintroduction risk after years of elimination. A good surveillance system is key for avoiding the risk, detecting imported cases and possible cases associated with local transmission early. Therefore, rapid diagnostic tests (RDTs) were combined with microscopy to strengthen malaria surveillance in the province. Herein, we aimed to evaluate the efficacy of this surveillance strategy. Methods: We conducted a retrospective study using malaria surveillance data from January 2016 to June 2020. Epidemiological characteristics and diagnostic information were analysed using descriptive and comparative statistics. The diagnostic performance of the combined toolbox (Wondfo RDTs plus microscopy) was evaluated based on its sensitivity, specificity, positive and negative predictive values, and Cohen's kappa coefficient, using real-time polymerase chain reaction as the gold standard. Results: The combined toolbox displayed a higher overall sensitivity for malaria cases than that of microscopy alone (93.74% vs 89.37%; p adj <0.05), which could detect 94.65%, 88.16%, 95.00%, and 100.00% of Plasmodium falciparum, P. ovale, P. vivax , and P. malariae infections, respectively. In clinical practice, Wondfo RDTs ability to detect P. falciparum infections was better than that of microscopy (97.55% vs 89.67%, p adj < 0.05). In contrast, microscopy displayed a higher specificity than that of Wondfo RDTs (81.82% vs 63.28%, p adj <0.05). Moreover, the consistency between microscopy and the gold standard results was also better than that of RDTs (Kappa value:0.669 vs 0.596). Conclusions: The combination of microscopy and RDTs is an effective strategy for malaria surveillance because it possibly detected more P. falciparum infections due to the introduction of RDTs. In contrast, microscopy is complementary to some limitations related to the use of RDTs in field practice. Thus, monitoring malaria cases in non-endemic areas may require employing more than one diagnostic tool in surveillance strategies. Moreover, further understanding of the advantages and disadvantages of different detection methods is necessary for applying optimum combinations in field settings. [ABSTRACT FROM AUTHOR]

Recently, research on the circadian rhythm of hypertension has gained popularity. However, few bibliometric analyses have been conducted in this field. In this study, CiteSpace 6.1. R6, VOSviewer 1.6.18, R language (version 4.2.3), R package Bibliometrix (4.1.2), and Microsoft Excel 365 were used to conduct the data mining and knowledge visualization analysis. A total of 1,560 papers from 1,825 institutions in 77 countries were included. Research on the role of circadian rhythms in hypertension is increasing annually. Overall, Chronobiology International published the most literature and Hypertension received the most citations. Ramon Hermida from the Universidade de Vigo in Spain published the most papers and had the most citations. The United States of America and Japan have been the most productive countries. The University of Ferrara, Universidade de Vigo, and the University of California system produced the most publications. Amongst authors, Hermida had the most and longest literature bursts. Keywords such as “chronic kidney disease,” “oxidative stress,” and “gene expression” have been breakout keywords since 2014. This study revealed the dynamic evolution of research on circadian rhythms in hypertension and provides a knowledge base for researchers. [ABSTRACT FROM AUTHOR]

Using extreme high‐speed laser cladding technology, Ni60 coatings are laser cladded onto stainless‐steel, 20# steel, and 45# steel substrates. The effect of substrate material properties on the cracking behavior, microstructure, and tribological properties of the Ni60 coating is systematically studied. The results show that as the difference of the coefficient of thermal expansion between the substrate and cladding material decreases, the tendency for crack generation in the cladding layer is reduced. In addition, the difference of the thermal physical properties of the substrate has an important effect on the temperature gradient during the cooling process of the coating, and then affects the growth rate of the grain in the coating and the overall mechanical properties of the coating. Finer grain size, fewer macroscopic coating cracks, and the evenly distributed hard phase in the Ni60 coating on the 20# steel substrate lead to better wear resistance. [ABSTRACT FROM AUTHOR]

Although fused deposition modeling (FDM) has gradually become one of the popular additive manufacturing technologies in different industries, high surface roughness has always been an inevitable disadvantage of FDM parts. Laser polishing represents a recent and novel application of laser surface irradiation that can be used for precise, post-process smoothing of the rough surfaces commonly encountered on FDM parts. The influence of laser polishing on surface modification and mechanical properties of aluminum/Polylactic Acid (Al/PLA) composites has been investigated. Laser scanning speed was varied to evaluate its effect on the surface quality and mechanical properties of the experimental samples. The results indicated that laser polishing could enable reductions in surface roughness of over 86.6% (from 23.27 μm to 3.11 μm Sa). The tensile strength of specimen also increased from 41.01 MPa to 51.31 MPa with increasement of 25.1%. The dynamic mechanical analysis (DMA) results showed that there was a remarkable improvement in the storage modulus and glass transition temperature of Al/PLA composite specimens after laser polishing, which suggested that the laser polishing treatment could play a role in decreasing the porosity inside the FDM parts and improve interfacial adhesion between the PLA matrix and Al fibers. Moreover, the fracture morphologies were observed to investigate the possible strengthening mechanism. These results demonstrate how laser polishing can simultaneously smooth and modify the surface characteristics of a FDM part surface. Image 1 • Laser polished additive manufactured Al/PLA has higher surface quality and many defects are removed. • A maximum reduction in Al/PLA surface roughness is achieved at optimized polishing settings (laser scan speed of 100 mm/s). • Laser polishing effectively improves the dynamic mechanical properties and tensile properties of the FMD Al/PLA. • After laser polishing treated, Al/PLA composite specimens had a higher storage modulus and glass transition temperature. • The strengthening mechanism induced by laser polishing is analyzed. [ABSTRACT FROM AUTHOR]

Extreme-high-speed laser cladding (EHLA), as a novel surface treatment technique, has attracted great attention because of its high cladding rate and good performance of cladding coatings. However, when depositing coatings with high cracking susceptibility, such as Ni60 coatings, cracks are difficult to avoid. Therefore, an extreme-high-speed laser-induction hybrid cladding technology (EH-LIHC) was innovatively proposed in this study. The effects of different preheating temperatures on the surface morphology, internal defects, microstructure, and mechanical properties of Ni60 coatings that were deposited by EHLA and EH-LIHC were analyzed. The results show that the roughness of the coating deposited by EHLA is 26.228 μm. However, the surface roughness of the coating deposited by EH-LIHC at 400 ℃ decreases to 14.316 μm. Simultaneously, the pores- and cracks-free Ni60 coating was deposited at 400 ℃. The coating dilution rate obviously increases as the preheating temperature rises. When the preheating temperature rises, the size of the grains and precipitates also increases. However, although Fe elemental diffusion is increased, there is no significant effect on the properties of the coating. The hardness of the coating fluctuates between 700 and 900 HV, nearly three times that of the substrate. As the preheating temperature rises, the coating's wear mechanism shifts from abrasive to abrasive and adhesive wear, and eventually back to abrasive wear. The improvement of wear resistance of the Ni60 coating deposited at 400 ℃ was mainly attributed to its high hardness and uniform and dense microstructure. The proposed EH-LIHC technique provides a promising method for the efficient deposit of crack-free coatings with good properties. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Delayed intestinal perforation has various manifestations. For peritonitis with delayed treatment and multi‐bacterial peritonitis, we should be alert to the occurrence of this rare complication. Abdominal CT examination and imaging results judgment based on clinical conditions are particularly important for diagnosis. Delayed intestinal perforation of peritoneal dialysis catheter is a rare but serious complication. We reported a 49‐year‐old patient who had been hospitalized twice within 3 months due to poor drainage of the peritoneal dialysis catheter. During the first hospitalization, peritoneal dialysis‐related peritonitis was diagnosed, and a variety of bacterial infections were cultivated. However, at that time, the actual peritoneal dialysis catheter‐related intestinal perforation was missed, and he was discharged after anti‐infection treatment until a clinical cure was met. After more than 2 months of normal peritoneal dialysis after returning home, the patient again had poor drainage of the peritoneal dialysis catheter, accompanied by the outflow of yellowish‐brown sediment. It was found that the peritoneal dialysis catheter had evidence of intestinal perforation. After the removal of the catheter and intestinal repair, he recovered and was discharged from the hospital and received long‐term hemodialysis treatment. In the case of delayed intestinal perforation, peritoneal dialysis was maintained normally for more than 2 months, which was an unprecedented situation in previous case reports. In addition, we should be alert to the occurrence of this rare complication, especially when we find the occurrence of polybacterial Peritonitis. Abdominal CT examination and imaging results judgment based on clinical conditions are particularly important for diagnosis. [ABSTRACT FROM AUTHOR]

Background: End-stage renal disease (ESRD) is a condition that is characterized by the loss of kidney function. ESRD patients suffer from various endothelial dysfunctions, inflammation, and immune system defects. Lysine malonylation (Kmal) is a recently discovered post-translational modification (PTM). Although Kmal has the ability to regulate a wide range of biological processes in various organisms, its specific role in ESRD is limited. Methods: In this study, the affinity enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques have been used to create the first global proteome and malonyl proteome (malonylome) profiles of peripheral blood mononuclear cells (PBMCs) from twenty patients with ESRD and eighty-one controls. Results: On analysis, 793 differentially expressed proteins (DEPs) and 12 differentially malonylated proteins (DMPs) with 16 Kmal sites were identified. The Rap1 signaling pathway and platelet activation pathway were found to be important in the development of chronic kidney disease (CKD), as were DMPs TLN1 and ACTB, as well as one malonylated site. One conserved Kmal motif was also discovered. Conclusions: These findings provided the first report on the Kmal profile in ESRD, which could be useful in understanding the potential role of lysine malonylation modification in the development of ESRD. [ABSTRACT FROM AUTHOR]

Objective: We aimed to reveal a spatial proteomic and immune signature of kidney function regions in lupus nephritis (LN). Material and methods: The laser capture microdissection (LCM) was used to isolate the glomerulus, tubules, and interstitial of the kidney from paraffin samples. The data-independent acquisition (DIA) method was used to collect proteomics data. The bioinformatic analysis was performed. Results: A total of 49,658 peptides and 4056 proteins were quantitated. Our results first showed that a high proportion of activated NK cells, naive B cells, and neutrophils in the glomerulus, activated NK cells in interstitial, and resting NK cells were accumulated in tubules in LN. The immune-related function analysis of differential expression proteins in different regions indicated that the glomerulus and interstitial were major sites of immune disturbance and regulation connected with immune response activation. Furthermore, we identified 7, 8, and 9 hub genes in LN's glomerulus, renal interstitial, and tubules. These hub genes were significantly correlated with the infiltration of immune cell subsets. We screened out ALB, CTSB, LCN2, A2M, CDC42, VIM, LTF, and CD14, which show higher performance as candidate biomarkers after correlation analysis with clinical indexes. The function within three regions of the kidney was analyzed. The differential expression proteins (DEGs) between interstitial and glomerulus were significantly enriched in the immune-related biological processes, and myeloid leukocyte-mediated immunity and cellular response to hormone stimulus. The DEGs between tubules and glomerulus were significantly enriched in cell activation and leukocyte-mediated immunity. While the DEGs between tubules and interstitial were enriched in response to lipid, antigen processing, and presentation of peptide antigen response to oxygen-containing compound, the results indicated a different function within kidney regions. Conclusions: Collectively, we revealed spatial proteomics and immune signature of LN kidney regions by combined using LCM and DIA. [ABSTRACT FROM AUTHOR]

The coupled model between trapezoidal cavity and its clamped flexible wall is developed using classical modal coupling theory. Based on the coupled model, the resonance frequencies of coupled system are obtained and compared with the corresponding uncoupled one. Meanwhile, the reason for the variation of resonance frequencies of coupled system modes is analyzed in detail. Then, the response of coupled system is investigated using the acoustic potential energy in the cavity and panel vibration kinetic energy when it is excited by an incident plane wave outside of the cavity. Coupling coefficient between trapezoidal cavity and its clamped flexible wall is proposed to assess the modal matching degree between them. It is shown that the coupling selection is not satisfied except in the axis direction which is parallel to the inclined wall. In addition, a rectangular cavity with a clamped flexible wall is also considered and compared with that of the trapezoidal one. [ABSTRACT FROM AUTHOR]

Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics. The present results revealed that the BCR/TCR CDR3 clones were expressed at very low frequencies, and the composition of clone types in patients with IgAN was skewed; the majority of clones were unique, and only 12 BCR and 228 TCR CDR3 clones were public ones, of which 16 were expressed at a significantly higher frequency in patients with IgAN (P<0.001). There were also certain conserved amino acid residues between unique clones or groups, and the residues GMDV, EQY and EQF were recurring only in the IgAN group. In addition, some VDJ gene recombinations indicated great variation between groups, including 4 high‑frequency VDJ gene recombinations in the IgAN patients (P<0.001). Immune repertoires provide novel information, and conserved BCR/TCR CDR3 clones and VDJ gene recombinations with great variation may be potential therapeutic targets for IgAN patients. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine the frequency of virulence genes in high biofilm formation bla KPC-2 producing Klebsiella pneumoniae strains collected over a period of two years. A total of 43 non-repetitive high biofilm bla KPC-2 producing isolates were screened from 429 strains. The MIC of carbapenems (imipenem and meropenem) ranged from 4 to 32 μg/ml. The OD595 value of the biofilm ranged from 0.56 to 2.56. The K1, K2, K5, K20, K54, K57 genotypes, MLST and virulence factors, including entB, ybtS, mrkD, fimH, rmpA, allS, iutA, kfu, wcaG, aerobaction, fecIRA, shiF, magA and pagO gene, were determined by PCR. The results showed that, among the 43 isolates, 5 of 43 were K1 type, 25 of 43 were K2 type, 4 strains and 2 strains were K5 and K57 respectively. The MLST results showed that 23/43 strains were ST11, followed by ST433(4/43), ST107(4/43), ST690(4/43), ST304(2/43), ST2058(1/43), ST1(1/43), ST146(1/43), ST914(1/43), ST2636(1/43), ST2637(1/43). As to the virulence factors, all 43 strains carried entB, ybtS and mrkD gene, followed by fimH (38/43), rmpA (14/43), allS (34/43), iutA (27/43), kfu (25/43), wcaG (21/43), aerobaction (16/43), fecIRA (15/43), shiF (10/43), magA (5/43) and pagO (5/43). This study demonstrated that high frequency of virulence factors emerging in high biofim bla KPC-2 producing strains. It also suggested that we should continue to focus on the toxicity variation and it's high time to enhance clinical awareness to the infections causing by Klebsiella pneumoniae . [ABSTRACT FROM AUTHOR]

Objective: This study aims to provide a new perspective of determining the pathophysiology of chronic hepatitis B (CHB) development by analyzing the gene regulatory network in CHB patients using single-cell ATAC sequencing. Background: Hepatitis B virus (HBV)-related liver disease induces liver damage by hepatic immune and inflammatory responses. The exact mechanism is unknown. As such, there is an urgent need to address this problem and study the relationship between aberrant peripheral blood mononuclear cell (PBMC) immune response and progression of liver disease. Method: The sequencing of the chromatin accessibility of 8016 cells from the whole venous blood of normal control (NC) individuals and CHB patients was performed through assay for transposase-accessible chromatin in single-cell sequencing (ScATAC-seq). Unsupervised clustering and annotation analyses were performed by Signac (version 1.7.0) and Seurat clustering to identify different cell types. Then, TF motif enrichment analysis and differentially expressed peak analysis were performed to identify cell-type-specific candidate open chromatins related to CHB. Result: We identified 12 leukocytic clusters corresponding to five cell types. The specific cell types associated with CHB were found to be located in B-0 and T-3. We have drawn the regulatory network of the hepatitis B signal pathway composed of genes linked to the differentially expressed peaks of these two CHB disease-specific cell types. Further, we profoundly explored the potential mechanisms of B-0-associated TF motif IRF2 and T-3-associated TF motif FOXC2 in the occurrence of CHB. Conclusion: We have drawn a systematic and distinguishing gene regulatory network of CHB-related PBMCs. Key Points • Peripheral blood mononuclear cells were robustly clustered based on their types without using antibodies. • We draw a systematic and distinctive gene regulatory network of CHB-related PBMC through ScATAC-seq. [ABSTRACT FROM AUTHOR]

Background: Roxadustat is a new oral anti-renal anemia medication that works by stabilizing hypoxia-inducible factor (HIF) which can activate the expression of more than 100 genes in addition to genes related to anemia. However, the more potential molecular targets of roxadustat are not completely clear. Therefore, it is essential to further reveal its molecular targets to guide its clinical applications. Methods: We performed label-free quantification and LC-MS/MS to study the proteomic alterations in serum exosome of renal anemia patients before and after roxadustat therapy. Results were validated by PRM. Results: A total of 30 proteins were significantly changed after treatment with roxadustat. Among these proteins, 18 proteins were up-regulated (and 12 were down-regulated). The results are statistically significant (P < 0.05). Then, we validated the result by PRM, the results confirmed that TFRC, HSPA8, ITGB3, COL1A2, and YWHAZ were markedly upregulated, while ITIH2 and CFH were significantly downregulated upon treatment with roxadustat. Conclusions: TFRC and HSPA8 could be an important target of the action of roxadustat, and roxadustat may increase cardiovascular risk through its influence on platelet activation. Our results provide a theoretical basis for its wider clinical application and preventing expected side effects. [ABSTRACT FROM AUTHOR]

Background: Research on spatiotemporal gene landscape can provide insights into the spatial characteristics of human kidney development and facilitate kidney organoid cultivation. Here, we profiled the spatiotemporal gene programs of the human embryonic kidneys at 9 and 18 post-conception weeks (PCW) by integrating the application of microarray-based spatial transcriptomics and single-cell transcriptomics. Results: We mapped transcriptomic signatures of scRNA-seq cell types upon the 9 and 18 PCW kidney sections based on cell-type deconvolution and multimodal intersection analyses, depicting a spatial landscape of developing cell subpopulations. We established the gene characteristics in the medullary regions and revealed a strong mitochondrial oxidative phosphorylation and glycolysis activity in the deeper medullary region. We also built a regulatory network centered on GDNF-ETV4 for nephrogenic niche development based on the weighted gene co-expression network analysis and highlighted the key roles of Wnt, FGF, and JAG1-Notch2 signaling in maintaining renal branching morphogenesis. Conclusions: Our findings obtained by this spatiotemporal gene program are expected to improve the current understanding of kidney development. [ABSTRACT FROM AUTHOR]

[Display omitted] • Relatively dense multilayer AA6061 alloys were manufactured by AFSD. • The AFSD AA6061 alloy exhibited refinement microstructure with absent of β″ strengthening phases. • The microstructural evolution of AFSD AA6061 alloy before and after heat treatment was investigated. • The electrochemical corrosion behavior and mechanism of AFSD AA6061 alloy were studied. Multilayer AA6061 aluminum alloy components were successfully fabricated by additive friction stir deposition (AFSD). The effect of heat treatment on the microstructure and electrochemical corrosion behavior of the AA6061-T6 aluminum alloy components was studied. The average grain size in AFSD samples was 2.67 μm, where 89.7 % of grains were smaller than 5 μm. Abnormal grain growth was observed in the heat-treated AFSD (AFSD-HT) sample, and the average grain size of AFSD-HT sample was 592 μm. In the base material (BM) sample, apart from the β″ strengthening phases, hard-brittle Al 5 FeSi intermetallic compounds (IMCs) aggregated along the boundaries of the coarser grains. Due to the high temperature generated during the process of AFSD, β″ phases dissolved into the matrix. After heat treatment, a larger amount of fine needle-like β″ phases were re-precipitated in the AFSD-HT sample. Al 5 FeSi IMCs accelerated the corrosion of the Al matrix. Fine β″ phases significantly inhibited the corrosion expansion to Al matrix and improved the corrosion resistance of AA6061 alloys. [ABSTRACT FROM AUTHOR]

Hongwei Wu and Fanna Liu contributed equally to this work Correction to: Cell & Bioscience (2022) 12:80 https://doi.org/10.1186/s13578-022-00801-x In the original version [[1]] of this article, in the result section, we have cited the Additional file 1: Fig. (d) The proportion of each scRNA-seq cell subpopulation arising from each ST spot in the 9 and 18 PCW kidneys. [Extracted from the article]

Background Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. Methods We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. Results We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. Conclusions We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of systemic lupus erythematosus (SLE) is complicated. This study explores the expression of circular RNAs (circRNAs), which are closed non-coding RNAs in which the 5′ and 3′ ends are covalently linked and which work by sponging microRNAs. CircRNAs were extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients to identify novel circRNA species that might be used for SLE diagnosis. Methods: Microarray was applied to screening circRNAs changes in PBMCs obtained from SLE patients (n = 10) and healthy participants (n = 10), paired for age and sex. We then verified the selected circRNAs in PBMCs using quantitative reverse transcription-polymerase chain reaction amplification (qRT-PCR) in another cohort, including ten paired SLE patients and healthy participants. The correlation between the differential circRNAs and clinical pathology of SLE were analyzed. Results: 182 up-regulated and 563 significantly down-regulated circRNAs in PBMCs of patients with SLE were identified. Besides, the qRT-PCR results were consistent with the microarray results. The correlation analysis revealed that has_circRNA_100236, has_circRNA_102489, and has_circRNA_101413 were correlated with positive anti-dsDNA, thrombocytopenia, and positive IgG, respectively. Lastly, their miRNAs targets and the binding sites were predicted. Conclusion: We identified some dysregulated circRNAs in PBMCs from SLE patients, and these circRNAs may be developed as the novel biomarkers for the diagnosis of SLE. [ABSTRACT FROM AUTHOR]

Background: Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. Methods: In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. Results: Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. Conclusions: Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN. [ABSTRACT FROM AUTHOR]

Refractory high-entropy alloys (RHEAs) are a new category of high-temperature materials that are high-entropy alloys with refractory metal elements as the major components. SLM technique provides distinct benefits in preparing refractory metals with high melting points. The effects of laser power and scanning speed on the surface morphology and internal defects of VNbMoTaW RHEAs samples were examined using numerical and experimental methods. A DEM-CFD model was created to simulate the process of SLM producing a single-layer, single-track model. The simulation findings show that the melt pool's channel width is 62.31 μm at a scanning speed of 300 mm/s and a laser power of 150 W. The channel width grows to 96.92 μm when the laser power rises to 450 W. When the laser power is increased, the channel becomes flatter. To prepare the VNbMoTaW samples, the process parameters with the highest quality in the numerical simulation were chosen. At a scanning speed of 300 mm/s and a laser power of 450 W, the measured channel width of the high-entropy alloy samples is approximately 104.13 m. Similarly to the numerical simulation results, the channel width of the models generated at the same scanning speed increases as the laser power increases. At low laser power, it was discovered that many unmelted powder particles were dispersed on the surface of the samples. The primary defects found in the samples were pores and fractures. The interlayer non-melting cracks on the sample cross-section vanish at elevated laser power. Whereas the quality of samples created at low scanning speeds is higher at the same laser power, the quality of samples declines as the scanning speed of the laser increases. • The forming process of VNbMoTaW RHEAs by SLM was firstly simulated numerically. • Process parameters such as laser power and scanning speed affected the RHEAs surface morphology. • The experimental results were in good agreement with the simulation rules. • Pores and cracks are the main defects in the RHEAs alloys and cannot be completely avoided. [ABSTRACT FROM AUTHOR]

The prevalence of ferroptosis in diabetic kidney tubules has been documented, yet the underlying mechanism remains elusive. The aim of this study was to ascertain the pivotal gene linked to ferroptosis and establish a novel target for the prevention and management of diabetic kidney disease (DKD). Transcriptomics data (GSE184836) from DKD mice (C57BLKS/J) were retrieved from the GEO database and intersected with ferroptosis-related genes from FerrDb. Then, differentially expressed genes associated with ferroptosis in the glomeruli and tubules were screened. Gene ontology analysis and protein-protein interaction network construction were used to identify key genes. Western blotting and real-time quantitative polymerase chain reaction were employed to validate the expression in the same model. Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) expression in patients and mice with DKD was assessed using immunohistochemistry staining. ARNTL knockdown in C57BLKS/J mice was established and plasma malonaldehyde, superoxide dismutase, and renal pathology were analyzed. The efficacy of ARNTL knockdown was evaluated using proteomics analysis. Mitochondrial morphology was observed using transmission electron microscopy. ARNTL was screened by bioinformatics analysis and its overexpression verified in patients and mice with DKD. ARNTL knockdown reduced oxidative stress in plasma. Kidney proteomics revealed that ferroptosis was inhibited. The reduction of the classic alteration in mitochondrial morphology associated with ferroptosis was also observed. Gene set enrichment analysis demonstrated that the downregulation of the TGFβ pathway coincided with a decrease in collagen protein and TGFβ1 levels. The ferroptosis-associated gene ARNTL is a potential target for treating DKD. • Significantly increased expression of ferroptosis related gene ARNTL is found in the tubules of obese DKD mice, which may be related to iron metabolism. • ARNTL inhibition alleviates oxidative stress and ferroptosis in DKD. • TGFβ signaling pathway is downregulated after ARNTL knockdown. [ABSTRACT FROM AUTHOR]

While metal additive manufacturing has seen significant growth in recent years, the surfaces produced often need post-processing to improve surface finish, mitigate residual stresses, and remove surface-connected porosity. Laser polishing, by means of remelting a thin layer of the surface, is one post-processing method being investigated for surface finish improvements and other surface enhancements. In this work, the surface morphology and microstructure of laser powder bed fused (L-PBF) stainless-steel 316 L (316 L) before and after laser polishing are characterized by optical microscopy (OM), scanning electron microscopy (SEM), electron back-scatter diffraction (EBSD), and transmission electron microscopy (TEM). In addition, the cross-sectional microhardness of the samples is measured and reported. Additionally, the as-built and laser-polished sample's tensile properties are characterized using uniaxial tension tests. The results indicate that the surface roughness of as-built 316 L (Sa = 4.84 μm) can be substantially reduced through laser polishing (Sa = 0.65 μm). After laser polishing, the average grain diameter is reduced and the proportion of low angle grain boundaries (2°~5°) is increased in the L-PBF 316 L. The maximum sub-surface hardness reaches 262 HV, and both the tensile strength and ductility of 316 L are increased after laser polishing. This enhancement is attributed to thermal cycling stresses, grain refinement, the elimination of surface defects, and dislocation strengthening after laser polishing. [ABSTRACT FROM AUTHOR]

• This study examined the effects of lateral unsaturated flow on shallow landslides triggering in situations of rising water level at the uphill/downhill boundary. • Lateral unsaturated flow is important for slope stability assessment of loamy hillslopes but can be ignored for sandy hillslopes. • The effect of lateral unsaturated flow highly depends on slope angle and the rising rate of uphill boundary water level. • Intensive rainfall may weaken the role of lateral unsaturated flow in activating slope failure. Lateral unsaturated flow was found to contribute little to rainfall-induced shallow landslides, but it can be important when the landslides are triggered under conditions of varying boundary water level. By considering a hillslope with an impermeable bedrock and rising water level at the uphill/downhill boundary, this study explored how lateral unsaturated flow would affect slope stability. Three different Hillslope-Storage Boussinesq models that differ in their treatment of the unsaturated flow were coupled with the same infinite slope stability model to predict and compare the safety factor and instability time. Specific to the situations considered, this study discovered that, despite the inclusion of lateral unsaturated flow effect, the hillslope remains stable when water level at the downhill boundary rises. Under the condition of increasing uphill boundary water level, the consideration of lateral unsaturated flow leads to earlier slope failure for loamy hillslopes with a moderate slope. Also, the lateral unsaturated flow may not induce slope failure for mildly sloping loamy hillslopes and plays an ignorable role when landslides occur fast in very steep hillslopes. By contrast, the lateral unsaturated flow does not affect much the failure of sandy hillslopes. Moreover, when water level at the uphill boundary increases faster, the lateral unsaturated flow exerts a greater influence on initiating slope failure. Further examination shows that intensive rainfall may weaken the effect of lateral unsaturated flow on shallow landslides triggering under the condition of rising uphill boundary water level. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the molecular mechanism of miR‐182 in kidney fibrosis in polycystic kidney disease (PKD). We measured the expression of miR‐182 in kidney tissue of autosomal dominant PKD. Additionally, we investigated the relationship between miR‐182 and fibrotic protein by transfecting miR‐182 mimics and miR‐182 inhibitor into polycystic kidney cyst‐lined epithelial cells, respectively. Furthermore, we observed the interaction between transforming growth factor β1 (TGF‐β1) and miR‐182 and fibrinogen factors of cyst‐lined epithelial cells after TGF‐β1 intervention, and measured the expression of Smad2 and Smad3 protein. Results are presented as follows: (a) MiR‐182 was positively correlated with fibrosis of cyst‐lined epithelial cells; (b) TGF‐β1 could induce fibrosis of cyst‐lined epithelial cells; (c) the expression of miR‐182 had a remarkably impact on the fibrosis induced by TGF‐β1, but had little effect on the expression of TGF‐β1; (d) the expression of Smad3 protein in TGF‐β1 induce‐cyst‐lined epithelial cells was increased. TGF‐β1 and miR‐182 promoting the fibrosis of polycystic kidney cyst‐lined epithelial cells may be mediated by the TGF‐β1/Smad3 signaling pathway, of which Smad3 was an important regulator. [ABSTRACT FROM AUTHOR]

It is common for diabetic kidney disease (DKD) to be complicated by abnormal blood glucose, blood lipids, and blood pressure rhythms. Thus, it is essential to examine diagnostic and treatment plans from the perspective of circadian disruption. This brief review discusses the clinical relevance of circadian rhythms in DKD and how the core clock gene encoding brain and muscle arnt-like protein 1 (BMAL1) functions owing to the importance of circadian rhythm disruption processes, including the excretion of urinary protein and irregular blood pressure, which occur in DKD. Exploring Bmal1 and its potential mechanisms and signaling pathways in DKD following contact with Sirt1 and NF-κB is novel and important. Finally, potential pharmacological and behavioral intervention strategies for DKD circadian rhythm disturbance are outlined. This review aids in unveiling novel, potential molecular targets for DKD based on circadian rhythms. [Display omitted] • DKD has abnormality in albuminuria and hypertension rhythm. • Bmal1 deficiency in the renal correlates with low blood pressure and BMAL1 has obesity paradox. • BMAL1 probably modulates BMAL1/SIRT1/NF-κB pathway to reduce kidney injury in DKD. • Targeted therapeutic approaches for DKD rhythm disorders encompass pharmacological intervention and small-molecule targets. • Regulating daily eating pattern, enhancing sleep quality, and scheduling exercise are also critical. [ABSTRACT FROM AUTHOR]

• A risk prediction for IDH in HD-patients can be an important tool for clinical work. • LightGBM model plays as an interpretable and best-performing model for the task. • IDH-A and IDH-B model can usefully complement each other for risk prediction. Intradialytic hypotension (IDH) is closely associated with adverse clinical outcomes in HD-patients. An IDH predictor model is important for IDH risk screening and clinical decision-making. In this study, we used Machine learning (ML) to develop IDH model for risk prediction in HD patients. 62,227 dialysis sessions were randomly partitioned into training data (70%), test data (20%), and validation data (10%). IDH-A model based on twenty-seven variables was constructed for risk prediction for the next HD treatment. IDH-B model based on ten variables from 64,870 dialysis sessions was developed for risk assessment before each HD treatment. Light Gradient Boosting Machine (LightGBM), Linear Discriminant Analysis, support vector machines, XGBoost, TabNet, and multilayer perceptron were used to develop the predictor model. In IDH-A model, we identified the LightGBM method as the best-performing and interpretable model with C- statistics of 0.82 in Fall30Nadir90 definitions, which was higher than those obtained using the other models (P <0.01). In other IDH standards of Nadir90, Nadir100, Fall20, Fall30, and Fall20Nadir90, the LightGBM method had a performance with C- statistics ranged 0.77 to 0.89. As a complementary application, the LightGBM model in IDH-B model achieved C- statistics of 0.68 in Fall30Nadir90 definitions and 0.69 to 0.78 in the other five IDH standards, which were also higher than the other methods, respectively. Use ML, we identified the LightGBM method as the good-performing and interpretable model. We identified the top variables as the high-risk factors for IDH incident in HD-patient. IDH-A and IDH-B model can usefully complement each other for risk prediction and further facilitate timely intervention through applied into different clinical setting. [Display omitted] [ABSTRACT FROM AUTHOR]

The metabolism and homeostasis of the skeletal system have historically been considered to be associated with the endocrine system. However, this view has been expanded with the recognition of several neural pathways playing important roles in the regulation of bone metabolism via central relays. In particular, bone metabolism and homeostasis have been reported to be precisely modulated by the central neural signaling. Initiated by the finding of leptin, the axis of neural regulation on bone expands rapidly. The semaphorin–plexin system plays an important role in the cross‐talk between osteoclasts and osteoblasts; a complex system has also been identified and includes neuropeptide Y and cannabinoids. These findings facilitate our understanding of the central neuropeptides and neural factors in the modulation of bone metabolism and homeostasis, and these neuronal pathways also represent an area of research scenario that identifies the novel regulation between brain and bone. These regulatory mechanisms correlate with other homeostatic networks and demonstrate a more intricate and synergetic bone biology than previously envisioned. As such, this review summarizes the current knowledge of the neural regulation of bone metabolism and homeostasis, as well as its role in skeletal diseases and discusses the emerging challenges presented in this field. This review summarizes the current knowledge of the neural regulation of bone metabolism and homeostasis, as well as its role in skeletal diseases and discusses the emerging challenges presented in this field. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to further explore the pathogenesis of idiopathic membranous nephropathy (IMN), gene-sequencing was used to analyze the differentially expressed circRNAs in exosomes of patients with IMN, which may lay the foundation for the research of circRNAs as a new class of exosome-based IMN diagnosis biomarkers.Material and Methods: Ten patients with IMN and ten normal controls were recruited as experimental subjects in our study. The exosomes were extracted from the collected serum and urine. Then, pure circRNAs were extracted from the exosomes with a series of enzymatic reactions. Afterwards, the significantly differentially expressed circRNAs were chosen by the method of gene-sequencing.Results: Compared with normal controls, the circRNAs were reduced in the exosomes from serum of patients with IMN, which mostly originated from intron gene regions. Meanwhile, a total of 89 circRNAs were significantly differentially expressed, which were also mostly derived from intron gene regions, including 49 up-regulated and 40 down-regulated genes. However, the species were increased in the exosomes from the urine of patients with IMN compared to normal controls, and they mainly originated from exon gene regions. Simultaneously, 60 circRNAs were significantly differentially expressed, which primarily belonged to intron gene regions, including 54 up-regulated and 6 down-regulated regions.Conclusions: The significant differential and specific expression of circRNAs in the exosomes from patients with IMN were observed. For example, MUC3A, which originated from chr7:100550808|100551062, could be considered a potential diagnostic biomarker of IMN. Furthermore, these figures may be used as a reference or supplement in the research of the pathogenesis of IMN. [ABSTRACT FROM AUTHOR]

Introduction: To analyze the microRNA expression of tumor necrosi factor α (TNF-α) stimulated mesenchymal stem cells (MSCs) and exosomes from their culture supernatant.Material and Methods: TNF-α (20 ng/ml) was used to stimulate MSCs, which were then regarded as TNF-α cells (TC), while unstimulated cells were the normal control cells (NCC). MSCs and their culture supernatant were harvested after 48 h. Subsequently, exosomes were isolated from culture supernatants with ExoQuick-TC and were divided into two groups, TNF-α exosomes (TE) and normal control exosomes (NCE). Then, the microRNAs were measured by high-throughput sequencing and the results were differentially analyzed. Finally, the correlation of the target genes corresponding to differently expressed microRNAs was analyzed by gene ontology (GO) and KEGG pathway analysis.Results: High-throughput sequencing showed that the cellular compartment (TC vs. NCC) had 280 microRNAs. miR-146a-5p was a uniquely up-regulated microRNA (p < 0.001) and the most significantly down-regulated microRNA among the 279 microRNAs included was miR-150-5p (p < 0.001). There were 180 differentially expressed microRNAs in the exosome compartment (TE vs. NCE), where miR-146-5p (p < 0.001) was one of 176 upregulated microRNAs and miR-203b-5p (p < 0.001) was one of 4 downregulated microRNAs. Coincidentally, bioinformatics analysis showed that IRAK1 was a critical target gene of miR-146-5p related to the Toll-like receptor (TLR) signaling pathway.Conclusions: In contrast with the control group, there were significantly differentially expressed microRNAs in both MSCs and exosomes. Interestingly, miR-146a-5p was up-regulated in both comparative groups, and its target gene IRAK1 plays a crucial part in the TLR signaling pathway. These investigations demonstrate a new direction for subsequent inflammation mechanistic studies. [ABSTRACT FROM AUTHOR]

• Spinal astrocytes in Stress-induced gastric mucosal damage in rat. • Astrocytic toxin L-a-aminoadipate (L-AA) prevented the stress-induced gastric damage. • Astrocytes contributed to the stress-induced gastric damage via CX43. Rat restraint water-immersion stress (RWIS) is a compound stress of high intensity and is widely used to study the pathological mechanisms of stress gastric ulcers. The spinal cord, as a part of the central nervous system, plays a dominant role in the gastrointestinal tract, but whether the spinal cord is involved in rat restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of spinal astrocytic glial fibrillary acidic protein (GFAP), neuronal c-Fos, connexin 43 (Cx43), and p-ERK1/2 during RWIS by immunohistochemistry and Western blotting. In addition, we intrathecally injected the astrocytic toxin L-a-aminoadipate (L-AA), gap junction blocker carbenoxolone (CBX), and ERK1/2 signaling pathway inhibitor PD98059 to explore the role of astrocytes in the spinal cord in RWIS-induced gastric mucosal damage and its possible mechanism in rats. The results showed that the expression of GFAP, c-Fos, Cx43, and p-ERK1/2 was significantly elevated in the spinal cord after RWIS. Intrathecal injection of both the astrocyte toxin L-AA and the gap junction blocker CBX significantly attenuated RWIS-induced gastric mucosal damage and decreased the activation of astrocytes and neurons induced in the spinal cord. Meanwhile, the ERK1/2 signaling pathway inhibitor PD98059 significantly inhibited gastric mucosal damage, gastric motility and RWIS-induced activation of spinal cord neurons and astrocytes. These results suggest that spinal astrocytes may regulate the RWIS-induced activation of neurons via CX43 gap junctions and play a critical role in RWIS-induced gastric mucosa damage through the ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]

Shape-memory epoxy resins were synthesized using plant oils and cellulose nanocrystals (CNCs). Epoxidized soybean homopolymers (PESBMA) were grafted from CNCs using surface-initiated atom transfer radical polymerization (SI-ATRP). The polymer grafted CNCs were combined with P(ESBMA- co -SBMA) copolymer and cured using anhydride to prepare epoxy resins. Controlling weight fractions of CNCs and ratios of epoxide to anhydride provided tunability over mechanical and thermal properties. The grafted polymer nanocomposites were also compared to simple blends to confirm better properties of the grafted system. Thermo- and chemo-responsive shape memory properties were obtained for these materials. [ABSTRACT FROM AUTHOR]

We report an atom-efficient approach to the preparation of sustainable polyesters and their corresponding thermosetting resins (RESINs) from renewable plant oils. Specifically, a diol monomer, oleic acid diethanol amide (OADEA), was derived from high oleic soybean oil (HOSBO) via a powerful amidation reaction. A series of OADEA-derived polyesters were prepared by condensation polymerization of this diol monomer with four different diacids. These polyesters were then epoxidized and cured using anhydrides with the aid of organocatalytic amines, yielding HOSBO-derived RESINs. Both thermal and mechanical properties of RESINs were dictated by the main-chain structures. The curing formulations and conditions were tested extensively to obtain the optimal mechanical properties of thermosetting resins, ranging from plastic to elastomeric properties. Both polyesters and RESINs were fully degradable under basic conditions. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is the most prevalent urological cancer in men. T cells serve a central role in the cancer's immunological microenvironment. In the present study, we applied multiplex PCR and Illumina next-generation sequencing to study the clonal diversity of the T-cell receptor (TCR) repertoire in cancer tissues and paracancer tissues from patients with PC. It was found that the TCR repertoire in the PC samples had a notably more skewed clonotype composition, with a greater number of highly expanded clones (HECs) compared with the prostate paracancer samples. The amino acid sequences ATSRVAGETQY (1.008 vs. 0.002%), ATSRTGRWETQY (3.985 vs. 0.007%), ATSDSSDYEQY (12.464 vs. 0.027%), ATSDFRGQPQETQY (2.205 vs. 0.06%), ASSQQDEAF (1.109 vs. 0.002%) and ARPTRTEETQY (1.263 vs. 0.002%) were found to vary markedly between cancer and paracancer tissues, respectively. In conclusion, the present study identified PC-specific HECs, which are critical to improving understanding of the TCR repertoire in PC. This may accelerate the screening process for potential new autoantigens and provide information for generating more effective T cell-targeted diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

The refractory high-entropy alloys possess both high melting points and excellent high-temperature properties. As a result, they are expected to become a new generation of high-temperature materials. Along these lines, in this work, selective laser melting (SLM) was used to prepare WMoTaNbV and TiC/WMoTaNbV-based alloys, while the influence of the SLM process parameters on the surface morphology, internal defects distribution and microstructure of the alloy was thoroughly analyzed. On top of that, the long-term high-temperature oxidation behavior of the two alloys at 600°C was studied. The extracted results showed that the process parameters had a serious impact on the surface quality and internal defects of the refractory high-entropy alloys. By optimizing the process parameters, the final surface roughness value of the WMoTaNbV-based alloy was 9.148 μm (Sa). On the contrary, the surface roughness value of the TiC/WMoTaNbV compound was 14.218 μm (Sa). It is also interesting to notice that the incorporation of TiC could significantly reduce the number of cracks within the TiC/WMoTaNbV alloy. Moreover, the WMoTaNbV-based alloy was mainly composed of dendritic structures, while the TiC/WMoTaNbV-based alloy consisted of cellular structures. The main oxidation products of the WMoTaNbV-based alloy were the Ta 16 W 18 O 94 and Nb 14 W 3 O 47 ternary oxidation products. After the TiC particles were added, the Ti-containing oxidation products such as TiO 2 , Ti 2 Nb 10 O 29. etc. within the TiC/WMoTaNbV-based alloy increased significantly, preventing thus effectively the alloy from being seriously oxidized. The cellular structures, carbides and TiO 2 phase are helpful in improving the oxidation resistance of the TiC/WMoTaNbV-based alloy. • The TiC could significantly reduce the number of cracks within the TiC/WMoTaNbV alloy. • The oxidation resistance of the TiC/WMoTaNbV was improved. • The cellular structures, carbides and TiO 2 phase were helpful in improving the oxidation resistance of the TiC/WMoTaNbV alloy. [ABSTRACT FROM AUTHOR]

Abstract: Mutations in PKHD1 (polycystic kidney and hepatic disease gene 1) gene cause the autosomal recessive polycystic kidney disease (ARPKD). Fibrocystin/polyductin (FPC), encoded by PKHD1, is a membrane-associated receptor-like protein. Although it is widely accepted that cystogenesis is mostly due to aberrant cell proliferation and apoptosis, it is still unclear how apoptosis is regulated. The aim of this study is to analyze the relationship among apoptosis, phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor κB (NF-κB) in FPC knockdown kidney cells. We show that PKHD1-silenced HEK293 cells demonstrate a higher PI3K/Akt activity. Selective inhibition of PI3K/Akt using LY294002 or wortmannin in these cells increases serum starvation-induced HEK293 cell apoptosis with a concomitant decrease in cell proliferation and higher caspase-3 activity. PI3K/Akt inhibition also leads to increased NF-κB activity in these cells. We conclude that the PI3K/Akt pathway is involved in apoptotic function in PKHD1-silenced cells, and PI3K/Akt inhibition correlates with upregulation of NF-κB activity. These observations provide a potential platform for determining FPC function and therapeutic investigation of ARPKD. [Copyright &y& Elsevier]

Abstract: Mutations in PKHD1 (polycystic kidney and hepatic disease gene 1) gene cause the autosomal recessive polycystic kidney disease (ARPKD). It is widely accepted that cystogenesis is owing to aberrant cell proliferation and apoptosis, increased fluid secretion, and extracellular matrix abnormality. Fibrocystin/polyductin (FPC), the encoded protein product by PKHD1, is a single transmembrane protein and believed to be a novel receptor-like molecule. FPC has been located mainly on the plasma membrane and cilium/basal body. However, its biological functions remain poorly understood. To investigate the roles of FPC in the pathogenesis of ARPKD, we searched for FPC-interacting proteins by yeast two-hybrid assay, and found a novel partner, prosaposin. Prosaposin is a glycoprotein with multiple functions. With GST pull-down assay and co-immunoprecipitation, we confirmed the interaction between FPC and prosaposin. In order to study the effects of FPC–prosaposin interaction on cell proliferation and apoptosis, we have made stable cell lines in which FPC was overexpressed or knocked down alone or in combination with prosaposin overexpression. By MTT assay, we found that FPC knockdown and prosaposin overexpression increased cell proliferation, respectively, while overexpression of FPC C-tail did the opposite. With apoptosis assay, we found that overexpression of FPC C-tail promoted cell apoptosis. However, overexpression of prosaposin significantly enhanced cell survival in FPC knockdown cells. All these findings indicated that FPC and prosaposin may play significant roles in regulation of cell proliferation and apoptosis. Taken together, we have disclosed a novel signaling pathway of FPC, which may be important for the pathogenesis of ARPKD. [ABSTRACT FROM AUTHOR]

Abstract: Potassium dihydrogen phosphate (KDP) crystal presents a host of problems to engineers and opticians. Moreover, because of its anisotropic character, a particular crystal orientation and plane wave transmission are required while the machining process is performed. In this study, by applying the principle of the maximized shearing deformed specific energy and the different shearing elastic modulus along different crystal planes and orientations, a theoretical model to calculate the shear angles when cutting KDP crystal was established. Based on this model, the shear angles’ variation regularity under different cutting conditions was obtained. Additionally, the variation regularities of cutting forces and roughness on different crystal planes were discussed. The results indicate that on different crystal planes the average cutting force and roughness as well as their variation amplitude are different. In addition, the calculated results show that rake angle plays an important role on suppression and minimizing material anisotropic character. Furthermore, the ultra-precision turning and milling experiments were conducted, and the theoretical model matched the experiments well within normal operating conditions. [Copyright &y& Elsevier]