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Abstract Purpose Prior research had indicated a relationship between fibrinogen and stroke-associated pneumonia (SAP), yet the nature of this relationship had not been thoroughly investigated. Therefore, this study was designed to elucidate the prognostic value of fibrinogen levels in forecasting the occurrence of SAP among patients with acute ischemic stroke (AIS). Patients and methods In this retrospective cross-sectional analysis, we included 1092 patients who had experienced AIS and were admitted to our facility within 72 h of the onset of their symptoms. Based on the SAP diagnostic criteria, patients were classified into two groups: SAP and non-SAP. The correlation between serum fibrinogen concentration and SAP was examined using univariate analysis. Curve fitting and multivariable logistic regression model were utilized for statistical evaluation. Results Out of the ischemic stroke patients included in the study, SAP was identified in 112 (10.26%) patients. A direct correlation was observed between fibrinogen levels and the incidence of SAP. An increase in fibrinogen levels corresponded with a heightened incidence of SAP. Multivariable logistic regression revealed a significant positive association between fibrinogen levels and SAP incidence (OR = 1.53, 95% confidence interval [CI]: 1.18, 1.99)). Conclusion A linear relationship between serum fibrinogen levels and the incidence of SAP in ischemic stroke patients was shown. The serum fibrinogen levels were positively and linearly correlated to SAP risk.

The importance of decellularized extracellular matrix (dECM) as a natural biomaterial in tissue engineering and regenerative medicine is rapidly growing. The core objective of the decellularization process is to eliminate cellular components while maximizing the preservation of the ECM’s primary structure and components. Establishing a rapid, effective, and minimally destructive decellularization technique is essential for obtaining high-quality dECM to construct regenerative organs. This study focused on human umbilical cord tissue, designing different reagent combinations for decellularization protocols while maintaining a consistent processing time. The impact of these protocols on the decellularization efficiency of human umbilical cord tissue was evaluated. The results suggested that the composite decellularization strategy utilizing trypsin/EDTA + Triton X-100 + sodium deoxycholate was the optimal approach in this study for preparing decellularized human umbilical cord dECM. After 5 h of decellularization treatment, most cellular components were eliminated, confirmed through dsDNA quantitative detection, hematoxylin and eosin (HE) staining, and DAPI staining. Meanwhile, Masson staining, periodic acid-silver methenamine (PASM) staining, periodic acid-Schiff (PAS) staining, and immunofluorescent tissue section staining results revealed that the decellularized scaffold retained extracellular matrix components, including collagen and glycosaminoglycans (GAGs). Compared to native umbilical cord tissue, electron microscopy results demonstrated that the microstructure of the extracellular matrix was well preserved after decellularization. Furthermore, Fourier-transform infrared spectroscopy (FTIR) findings indicated that the decellularization process successfully retained the main functional group structures of extracellular matrix (ECM) components. The quantitative analysis of collagen, elastin, and GAG content validated the advantages of this decellularization process in preserving and purifying ECM components. Additionally, it was confirmed that this decellularized matrix exhibited no cytotoxicity in vitro. This study achieved short-term decellularization preparation for umbilical cord tissue through a combined decellularization strategy.

Abstract The slow-developing neurological disorder Alzheimer’s disease (AD) has no recognized etiology. A bioinformatics investigation verified copper metabolism indicators for AD development. GEO contributed AD-related datasets GSE1297 and GSE5281. Differential expression analysis and WGCNA confirmed biomarker candidate genes. Each immune cell type in AD and control samples was scored using single sample gene set enrichment analysis. Receiver Operating Characteristic (ROC) analysis, short Time-series Expression Miner (STEM) grouping, and expression analysis between control and AD samples discovered copper metabolism indicators that impacted AD progression. We test clinical samples and cellular function to ensure study correctness. Biomarker-targeting miRNAs and lncRNAs were predicted by starBase. Trust website anticipated biomarker-targeting transcription factors. In the end, Cytoscape constructed the TF/miRNA-mRNA and lncRNA-miRNA networks. The DGIdb database predicted biomarker-targeted drugs. We identified 57 differentially expressed copper metabolism-related genes (DE-CMRGs). Next, fourteen copper metabolism indicators impacting AD progression were identified: CCK, ATP6V1E1, SYT1, LDHA, PAM, HPRT1, SCG5, ATP6V1D, GOT1, NFKBIA, SPHK1, MITF, BRCA1, and CD38. A TF/miRNA-mRNA regulation network was then established with two miRNAs (hsa-miR-34a-5p and 34c-5p), six TFs (NFKB1, RELA, MYC, HIF1A, JUN, and SP1), and four biomarkers. The DGIdb database contained 171 drugs targeting ten copper metabolism-relevant biomarkers (BRCA1, MITF, NFKBIA, CD38, CCK2, HPRT1, SPHK1, LDHA, SCG5, and SYT1). Copper metabolism biomarkers CCK, ATP6V1E1, SYT1, LDHA, PAM, HPRT1, SCG5, ATP6V1D, GOT1, NFKBIA, SPHK1, MITF, BRCA1, and CD38 alter AD progression, laying the groundwork for disease pathophysiology and novel AD diagnostic and treatment.

BackgroundHepatocellular carcinoma (HCC) is highly aggressive, with delayed diagnosis, poor prognosis, and a lack of comprehensive and accurate prognostic models to assist clinicians. This study aimed to construct an HCC prognosis-related gene signature (HPRGS) and explore its clinical application value.MethodsTCGA-LIHC cohort was used for training, and the LIRI-JP cohort and HCC cDNA microarray were used for validation. Machine learning algorithms constructed a prognostic gene label for HCC. Kaplan–Meier (K-M), ROC curve, multiple analyses, algorithms, and online databases were used to analyze differences between high- and low-risk populations. A nomogram was constructed to facilitate clinical application.ResultsWe identified 119 differential genes based on transcriptome sequencing data from five independent HCC cohorts, and 53 of these genes were associated with overall survival (OS). Using 101 machine learning algorithms, the 10 most prognostic genes were selected. We constructed an HCC HPRGS with four genes (SOCS2, LCAT, ECT2, and TMEM106C). Good predictive performance of the HPRGS was confirmed by ROC, C-index, and K-M curves. Mutation analysis showed significant differences between the low- and high-risk patients. The low-risk group had a higher response to transcatheter arterial chemoembolization (TACE) and immunotherapy. Treatment response of high- and low-risk groups to small-molecule drugs was predicted. Linifanib was a potential drug for high-risk populations. Multivariate analysis confirmed that HPRGS were independent prognostic factors in TCGA-LIHC. A nomogram provided a clinical practice reference.ConclusionWe constructed an HPRGS for HCC, which can accurately predict OS and guide the treatment decisions for patients with HCC.

Abstract Background In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet’s-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China. Case presentation Here, we report a rare case of Behcet’s-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet’s-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control. Conclusions In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations.

AbstractThe GRAS transcription factor (TF) is a plant-specific regulator that plays a critical role in plant growth, development and response to various abiotic stresses. While the functions of many GRAS TFs have been extensively studied in numerous model plants with fully sequenced genomes, the GRAS TFs in white clover (Trifolium repens L.) remain elusive despite the sequencing of its genome. To bridge this knowledge gap, homologs of GRAS TFs from Arabidopsis were employed and subjected to a genome-wide blast against white clover proteins. This analysis identified and characterized 102 putative GRAS genes, designated as TrGRAS, based on the presence of GRAS domains in positive blast hits. Concurrently, an exploration of their gene structures, classification, evolutionary relationships and conservative motifs provided insights into the distinctive features of TrGRAS in white clover. Furthermore, gene duplication analysis revealed an expansion of TrGRAS genes in the PAT1 and LISCL subfamilies, indicating functional diversity within the white clover genome. Lastly, RNA-seq and quantitative reverse transcription-PCR (qRT-PCR) experiments confirmed their higher expression during the early or intermittent responses to cold stress, suggesting their potential and crucial roles in determining the cold tolerances of white clover. The analysis of TrGRAS genes, coupled with expression studies, contributes to the functional characterization of TrGRAS genes in white clover. This knowledge is pivotal for informing genetic improvement strategies in future breeding efforts aimed at enhancing cold tolerance in white clover.

Abstract α-Enolase (ENO1) is a crucial molecular target for tumor therapy and has emerged as a research hotspot in recent decades. Here, we aimed to explore the role of ENO1 in bladder cancer (BLCA) and then construct a signature to predict the prognosis and treatment response of BLCA. Firstly, we found ENO1 was highly expressed in BLCA tissues, as verified by IHC, and was associated with poor prognosis. The analysis of the tumor immune microenvironment by bulk RNA-seq and scRNA-seq showed that ENO1 was associated with CD8+ T-cell exhaustion. Additionally, the results in vitro showed that ENO1 could promote the proliferation and invasion of BLCA cells. Then, the analysis of epithelial cells (ECs) revealed that ENO1 might promote BLCA progression by metabolism, the cell cycle and some carcinogenic pathways. A total of 249 hub genes were obtained from differentially expressed genes between ENO1-related ECs, and we used LASSO analysis to construct a novel signature that not only accurately predicted the prognosis of BLCA patients but also predicted the response to treatment for BLCA. Finally, we constructed a nomogram to better guide clinical application. In conclusion, through multi-omics analysis, we found that ENO1 was overexpressed in bladder cancer and associated with poor prognosis, CD8+ T-cell exhaustion and epithelial heterogeneity. Moreover, the prognosis and treatment of patients can be well predicted by constructing an epithelial-related prognostic signature.

AbstractHuman papillomavirus (HPV) is the infectious etiological agent for diseases such as cervical cancer. Developing HPV vaccines is of great significance for cancer prevention. During the development of polyvalent HPV vaccines, such as 9-valent and 15-valent HPV vaccines, specifical identification of different HPV antigen is very important. The homemade HPV31 L1 VLPs was used as an immunogen to generate HPV 31 monoclonal antibodies (mAbs) through hybridoma cell culture. We generated several mAbs through hybridoma cell culture and selected two specific neutralizing antibodies, 19B2 and 19C4, which were further analyzed and characterized for binding activity, neutralizing activity, and specificity by enzyme-linked immunosorbent assays (ELISA). It is shown that both 19B2 and 19C4 could specifically recognize HPV31 L1 virus-like particles (VLPs). These two specific mAbs were further used to assemble a HPV31 antigen ELISA test kit. The assembled kit with high detection performance could be widely applied for the quantitative detection of HPV31 antigen during vaccine production as well as in the preliminary analysis of HPV31 infection.

BackgroundCarotid atherosclerosis (CAS) is a complication of atherosclerosis (AS). PAN-optosome is an inflammatory programmed cell death pathway event regulated by the PAN-optosome complex. CAS’s PAN-optosome-related genes (PORGs) have yet to be studied. Hence, screening the PAN-optosome-related diagnostic genes for treating CAS was vital.MethodsWe introduced transcriptome data to screen out differentially expressed genes (DEGs) in CAS. Subsequently, WGCNA analysis was utilized to mine module genes about PANoptosis score. We performed differential expression analysis (CAS samples vs. standard samples) to obtain CAS-related differentially expressed genes at the single-cell level. Venn diagram was executed to identify PAN-optosome-related differential genes (POR-DEGs) associated with CAS. Further, LASSO regression and RF algorithm were implemented to were executed to build a diagnostic model. We additionally performed immune infiltration and gene set enrichment analysis (GSEA) based on diagnostic genes. We verified the accuracy of the model genes by single-cell nuclear sequencing and RT-qPCR validation of clinical samples, as well as in vitro cellular experiments.ResultsWe identified 785 DEGs associated with CAS. Then, 4296 module genes about PANoptosis score were obtained. We obtained the 7365 and 1631 CAS-related DEGs at the single-cell level, respectively. 67 POR-DEGs were retained Venn diagram. Subsequently, 4 PAN-optosome-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) were identified via machine learning. Cellular function tests on four genes showed that these genes have essential roles in maintaining arterial cell viability and resisting cellular senescence.ConclusionWe obtained four PANoptosis-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) associated with CAS, laying a theoretical foundation for treating CAS.

BackgroundHyaluronan-mediated motility receptor (HMMR) is overexpressed in multiple carcinomas and influences the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear.MethodsThe “limma” and “GSVA” packages in R were used to perform differential expression analysis and to assess the activity of signalling pathways, respectively. InferCNV was used to infer copy number variation (CNV) for each hepatocyte and “CellChat” was used to analyse intercellular communication networks. Recursive partitioning analysis (RPA) was used to re-stage HCC patients. The IC50 values of various drugs were evaluated using the “pRRophetic” package. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm HMMR expression in an HCC tissue microarray. Flow cytometry (FCM) and cloning, Edu and wound healing assays were used to explore the capacity of HMMR to regulate HCC tumour.ResultsMultiple cohort studies and qRT-PCR demonstrated that HMMR was overexpressed in HCC tissue compared with normal tissue. In addition, HMMR had excellent diagnostic performance. HMMR knockdown inhibited the proliferation and migration of HCC cells in vitro. Moreover, high HMMR expression was associated with “G2M checkpoint” and “E2F targets” in bulk RNA and scRNA-seq, and FCM confirmed that HMMR could regulate the cell cycle. In addition, HMMR was involved in the regulation of the tumour immune microenvironment via immune cell infiltration and intercellular interactions. Furthermore, HMMR was positively associated with genomic heterogeneity with patients with high HMMR expression potentially benefitting more from immunotherapy. Moreover, HMMR was associated with poor prognosis in patients with HCC and the re-staging by recursive partitioning analysis (RPA) gave a good prognosis prediction value and could guide chemotherapy and targeted therapy.ConclusionThe results of the present study show that HMMR could play a role in the diagnosis, prognosis, and treatments of patients with HCC based on bulk RNA-seq and scRAN-seq analyses and is a promising molecular marker for HCC.

Abstract Background Small-cell lung cancer (SCLC) is a highly aggressive and lethal malignancy that accounts for 10–15% of lung cancers, and it is generally divided into limited and extensive stage. The standard of care for patients with newly diagnosed extensive-stage SCLC (ES-SCLC) is still platinum-based chemotherapy and as maintenance therapy scheme. Although most parts of patients experience a significant tumor response to first-line therapy, the disease recurs invariably. Anlotinib hydrochloride, a novel oral multitarget tyrosine kinase inhibitor, has significant inhibitory activity against angiogenesis-related kinases, such as VEGFR, FGFR, PDGFR, and c-Kit kinase associated with tumor cell proliferation. Fluzoparib is a type of inhibitor of poly ADP ribose polymerase (PARP, including PARPl, PARP2 and PARP3). Previous studies have shown that Fluzoparib has a strong inhibitory effect on PARP1 activity at the molecular and cellular levels. Methods This is a multi-center, prospective, single-arm phase II clinical study. A total of 50 ES-SCLC patients who experienced disease progression after first-line standard platinum-based chemotherapy with/without immune checkpoint inhibitors scheme, or within 6 months after the completion of treatment will be recruited. Those who had prior treatment with any PARP inhibitor or antiangiogenic agent includes anlotinib, bevacizumab, sorafenib, and thalidomide are excluded. Eligible patients will receive oral anlotinib 8 mg once daily and oral fluzoparib 150 mg twice daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). Discussion The addition of fluzoparib to anlotinib is expected to increase the clinical benefit in ES-SCLC patients after platinum-based chemotherapy. Trial registration This study protocol was prospectively registered on June 17, 2021. ClinicalTrials.gov Identifier: NCT04933175 .

Organ and tissue dysfunction represents a clinically significant condition. By integrating cell biology with materials science, tissue engineering enables the reconstruction and restoration of damaged tissues or organs, offering a noninvasive repair approach. In our study, we replicated the cellular growth environment by utilizing a human umbilical cord-derived decellularized extracellular matrix (dECM) as a modifying agent for the polyethylene terephthalate (PET) polymeric fiber scaffold. This allowed us to create a dECM-coated polyester fiber-based scaffold, PET-dECM, tailored for liver tissue engineering purposes. We effectively produced a decellularized human umbilical cord-derived ECM through a combined decellularization process involving trypsin/EDTA, TritonX-100, and sodium deoxycholate. The application of the dECM coating onto the PET material was accomplished through several steps, such as ester hydrolysis, EDC/NHS-activated crosslinking, and dECM conjugation. The biological performance of the PET-dECM was validated using RG cell culture assays. Notably, the dECM coating significantly improved PET’s hydrophilicity and biocompatibility, thereby aiding cell adhesion, proliferation, and functional differentiation (p < 0.05). It was further found that the hepatocyte function of HepaRG was significantly enhanced on the PET-dECM, which may be attributed to the dECM’s ability to facilitate the restoration of cell polarity. The PET-dECM holds promise as an effective hepatocyte culture carrier and could potentially find application in liver tissue engineering.

Acute and chronic liver failure are clinically significant conditions, and the artificial liver support system (ALSS) is emerging as a novel and effective approach for the clinical management of liver failure. Within this framework, scaffold materials occupy a pivotal position as integral components of the bioreactor. Elevating the performance capabilities of these scaffolds not only augments the therapeutic efficacy of the artificial liver but also lays the groundwork for refining and selecting large-scale hepatocyte culture models. In this study, we introduced a novel hepatocyte scaffold material designated as PET-COL, crafted by coating polyethylene terephthalate (PET) with collagen. This involved a sequence of modifications, including alkaline hydrolysis, EDC/NHS activation and crosslinking, as well as collagen conjugation. The physicochemical attributes of the scaffold were thoroughly characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), second harmonic generation (SHG), water contact angle measurements, and high-performance liquid chromatography–mass spectrometry (HPLC-MS). Furthermore, an investigation into the material’s biological properties was conducted that encompassed SEM (HepaRG growth), fluorescence staining (assessment of cell viability), staining by trypan blue (HepaRG counting), CCK-8 (proliferation of cells), biochemical testing, and immunosorbent assay. Our findings revealed that collagen was covalently bonded to the PET surface, leading to a substantial enhancement in the material’s hydrophilicity (p < 0.001). The quantity of collagen coating was determined to be precisely 33.30 μg per scaffold. Human liver progenitor HepaRG cells thrived on the PET-COL material. Compared with the untreated group, cell viability, albumin secretion, urea synthesis, and the expression levels of CYP3A4 and CPS1 increased significantly (p < 0.001), demonstrating remarkable biological vitality. The PET-COL scaffold, as developed in this study, holds immense potential for application in bioartificial livers.

Plant polysaccharides, one of the main sources of natural polysaccharides, has significant antitumor activity and are potentially exploitable in the field of food and medicine. This paper systematically summarizes the anti-tumor mechanism and structure-activity relationships of plant polysaccharides, focusing on three perspectives: Inhibition of tumor cell growth, enhancement of immune regulation, and inhibition of tumor cell invasion and metastasis. The functional-structural relationships of plant polysaccharides are further dissected based on their molecular weight, glycosidic bond types and monosaccharide composition, modified modifications and advanced structures. In this paper, the antitumor activity and structure-bioactivity relationships of plant polysaccharides are systematically summarized to provide a reference for discovering its new breakthroughs and further development.

The rapid development of unmanned aerial vehicles (UAVs) provides a new application mode for gas remote sensing. Compared with fixed observation and vehicle-mounted platforms, a Fourier transform infrared spectrometer (FTIR) integrated in the UAV can monitor chemical gases across a large area, can collect data from multiple angles in three-dimensional space, and can operate in contaminated or hazardous environments. The unmanned helicopter has a larger payload and longer endurance than the rotary-wing drone, which relaxes the weight, size and power consumption limitations of the spectrometer. A FTIR remote sensing system integrated in an unmanned helicopter was developed. In order to solve the data acquisition and analysis problem caused by vibration and attitude instability of the unmanned helicopter, a dual-channel parallel oscillating mirror was designed to improve the stability of the interferometer module, and a robust principal component analysis algorithm based on kernel function was used to separate background spectrum and gas features. The flight experiment of sulfur hexafluoride gas detection was carried out. The results show that the system operates stably and can collect and identify the target spectrum in real time under the motion and hovering modes of an unmanned helicopter, which has broad application prospects.

In the current study, a novel intrinsic functionalization approach based on composite feeding additive for silkworms to produce silk fibers (SFs) with enhanced mechanical properties has been successfully developed. Effect of single feeding additive by either nano hydroxyapatite (Nano-HA) or collagen, and composite feeding by both additives on the silkworm larvae growth and cocooning, crystalline structure, molecular conformationas as well as mechanical properties of SFs have been systematically investigated. Experimental results demonstrated that feeding additive strategy could greatly facilitate the growth and cocooning of the silkworms. Surface and cross-section morphology observation suggested the additive has been absorbed into silkworm body and eventually embedded in SFs. Meanwhile, the basic structure of SFs still kept integrity after feeding additive from X-ray diffraction (XRD) analysis. Furthermore, fourier transform infrared (FTIR) spectrum demonstrated that random coil/α-helix and β-sheet content of SFs by feeding additive presented an increase and decrease change than natural SFs. More importantly, mechanical properties of SFs exhibited an obvious enhancement by composite additive than single additive feeding due to the nanoconfined crystallite toughening and polymer physical blending mechanism. Inspired by this approach, the composite additive feeding may open a novel and green strategy to fabricate SFs with enhanced mechanical properties.

Fabricating crack-free 7075 aluminium alloy by laser powder bed fusion (LPBF) is currently a hot research topic. In this work, pre-alloyed 7075Al + Er powder was prepared, and crack-free samples were printed by LPBF by adjusting the process parameters. Furthermore, the influence of process parameters and the mechanism of crack inhibition by Er were discussed. Er can generate Al3Er coherent with the Al matrix, which has the grain refinement effect, shortens the length of columnar crystals from 106 μm to 84 μm and is conducive to the dispersion and further solidification of the liquid film in the paste solidification stage. Al3Er also reduces the texture strength and makes the thermal stress more uniform. The final measured tensile strength of the printed sample was 338 MPa, and the elongation was 15.9%, which was 32% and 74.7% higher than those of the 7075Al samples without Er addition, respectively. In this work, the effect of rare earth element Er on the improvement of the printability and crack suppression of 7075 aluminium alloy by laser powder bed fusion was discussed, which provides experimental support for crack-free additive manufacturing and application of high-strength aluminium alloys.

BackgroundThe pathogenesis of Alzheimer’s disease (AD) is complex and multi-factorial. Increasing evidence has shown the important role of immune infiltration in AD. Thus the current study was designed to identify immune infiltration-related genes and to explore their diagnostic value in AD.MethodsThe expression data of AD patients were downloaded from the GEO database. The limma R package identified differentially expressed genes (DEGs) between AD and controls. The CIBERSORT algorithm identified differentially infiltrated immune cells (DIICs) between AD and controls. DIIC-correlated DEGs were obtained by Pearson correlation analysis. WGCNA was employed to identify DIIC-related modules. Next, LASSO, RFE, and RF machine learning methods were applied to screen robust DIIC-related gene signatures in AD, followed by the construction and validation of a diagnostic nomogram. Detection of the expression of related genes in the peripheral blood of Alzheimer’s disease and healthy volunteers by RT-PCR. In addition, the CTD database predicted chemicals targeting DIIC-related gene signatures in the treatment of AD.ResultsNK cells, M0 macrophages, activated myeloid dendritic cells, resting mast cells, CD8+ T cells, resting memory CD4+ T cells, gamma delta T cells, and M2 macrophages were differentially infiltrated between AD and controls. Pearson analysis identified a total of 277 DIIC-correlated DEGs between AD and controls. Thereafter, 177 DIIC-related genes were further obtained by WGCNA analysis. By LASSO, RFE and RF algorithms, CMTM2, DDIT4, LDHB, NDUFA1, NDUFB2, NDUFS5, RPL17, RPL21, RPL26 and NDUFAF2 were identified as robust gene signature in AD. The results of RT-PCR detection of peripheral blood samples from Alzheimer’s disease and healthy volunteers showed that the expression trend of ten genes screened was consistent with the detection results; among them, the expression levels of CMTM2, DDIT4, LDHB, NDUFS5, and RPL21 are significantly different among groups. Thus, a diagnostic nomogram based on a DIIC-related signature was constructed and validated. Moreover, candidate chemicals targeting those biomarkers in the treatment of AD, such as 4-hydroxy-2-nonenal, rosiglitazone, and resveratrol, were identified in the CTD database.ConclusionFor the first time, we identified 10 immune infiltration-related biomarkers in AD, which may be helpful for the diagnosis of AD and provide guidance in the treatment of AD.

In this paper, we focus on the numerical solution of the second kind of Volterra integral equation with a highly oscillatory Fourier kernel. Based on the calculation of the modified moments, we propose four collocation methods to solve the equations: direct linear interpolation, direct higher order interpolation, direct Hermite interpolation and piecewise Hermite interpolation. These four methods are simple to construct and can quickly compute highly oscillatory integrals involving Fourier functions. We present the corresponding error analysis and it is easy to see that, in some cases, our proposed method has a fast convergence rate in solving such equations. In some cases, our proposed methods have significant advantages over the existing methods. Some numerical experiments demonstrating the efficiency of the four methods are also presented.

Interconnect development for the new technology node requires coordinated efforts of multiple module teams working to co-optimize patterning and metallization solutions to meet performance and yield, and reliability targets. This paper presents the results of interconnect patterning optimization to improve overlay and process window control using a novel methodology, Design-for-Inspection™ (DFI). Using design-assisted voltage contrast measurement techniques, the method enables in-line test and monitoring of process induced overlay and CD variation of back-end-of line (BEOL) features built with litho-etch-litho-etch (LELE) patterning. While only some of the features of multi-color patterning scheme are chosen to be aligned directly, other combination of metal line and via colors may have uncontrolled misalignment risking open or short failures. The paper shows how the complete metrology coverage of multi-color combinations between dual patterned via and dual patterned metal lines helps driving the improvement of overlay and process margins in 14nm technology. The optimized process margin for via opens enables higher yields and better reliability.

BackgroundExosome is an important component of the tumor immune microenvironment and plays critical role in cancer pathogenesis. The exosome transcriptome of gastric cancer (GC) response to paclitaxel chemotherapy has not been investigated in the past.MethodsceRNA microarrays were performed in exosomes from six advanced GC patients before and after paclitaxel treatment. Bioinformatics tools were used to identify differential expressing genes and construct competing endogenous RNA (ceRNA) networks. The importance of hub genes in the ceRNA network was confirmed by survival analysis and functional analysis.ResultsA total of 213 differential mRNAs, 370 lncRNAs, and 376 circRNAs were identified, and hub genes in ceRNA networks were screened. The differential genes were associated with GO terms SNAP complex, gap junction, protein transporter activity, cytokine receptor, and KEGG pathways synaptic vesicle cycle, propanoate metabolism, Epstein–Barr virus infection, heparin, and steroid biosynthesis, and beta-alanine metabolism. ULK2, CYP2R1, BTLA, and miR-105-5p are prognostic genes for overall survival. Paclitaxel may target ULK2 which is involved in mitosis and cell cycle. miR-105-5p may target ULK2 3’UTR.ConclusionThe work for the first time identified exosomal RNA biomarkers and constructed a ceRNA network in GC response to paclitaxel, revealed novel molecular mechanisms of GC, and provided new candidates for GC diagnosis and treatment.

Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. And then BJP-2 was identified by SEC-MALLS-RI, GC-MS, methylation and NMR for the following characteristics: molecular weight of 6.42 × 104 Da, monosaccharide composition of glucuronic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), xylose (Xyl), glucuronic acid (GlcA), glucose (Glc), fucose (Fuc) and mannose (Man) with the percentage of 39.78, 31.93, 16.86, 6.43, 1.86, 1.28, 1.02, 0.61, and 0.23%, as well as the main chain of → 5)-α-L-Araf (1 → 4)-β-D-Gal(1 → , T-α-L-Araf (1 → 4)-β-D-Gal(1 → , and → 4)-α-L-6MeGalAp(1 → . The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. The analysis by MTT and flow cytometry showed that BJP-2 suppressed cell proliferation by inducing apoptosis in a concentration-dependent manner. Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent.

A water quality parameter retrieval scheme based on the UAV push-broom hyperspectral images was designed and validated for assessing the ecological health of Zhang Wei Xin River in Dezhou distinct, China. First, a UAV carrying a push-broom hyperspectral imager that is lightweight and has a small size was used to acquire high spatial and hyperspectral resolution images. Then, the mosaicked reflectance data of the whole river were produced by a seamless image mosaicking method with high geometrical accuracy and spectral fidelity. Next, the in-field measurements of different parameters and the corresponding spectral reflectance from the mosaicked images at the sampling points were used to build the water quality parameter retrieval models for total phosphorus (TP), chlorophyll a (Chla), and total suspended solids (TSS). To validate the model, the retrieval results of the testing sampling points were compared with the measured parameters. The coefficients of determination R2 of TP, Chla, and TSS were 0.886, 0.918, and 0.968, respectively. The retrieved TP, Chla, and TSS maps showed that the water pollution of Zhang Wei Xin River is serious, the total phosphorus exceeds the standard, and the water body is in a state of eutrophication. The UAV-based hyperspectral remote sensing technique provides a cost-effective method for inland water monitoring at a local scale with high accuracy.

Hyperspectral (HS) imaging has achieved breakthroughs in many applications, such as remote sensing and object recognition. However, the spatial resolution of HS images is still insufficient due to the limitations of sensor technology and cost. In this article, we propose an HS image superresolution method that combines low-resolution (LR) HS images and high-resolution (HR) panchromatic (PAN) images. To exploit the spectral signatures in the LR-HS images while introducing details from the HR-PAN images during the image fusion procedure, an image matting model is used to fuse the original LR-HS images and the HR-PAN images. Specifically, to preserve the spectral components during the fusion procedure, two different alpha channels in the image matting model are generated based on the HS and PAN image structure tensors, which suppress spectral distortion and improve the quality of the reconstructed HR-HS image. Experimental results based on public datasets demonstrate the advantage of our proposed method in both preserving spectral information and enhancing HS image spatial resolution.

For fuel cells, to produce high-quality and low-platinum catalyst is a pressing technical problem. In this study, graphene cathode catalysts with controllable platinum content were decorated by pyrolyzing chloroplatinic acid under various process parameters to obtain a high catalytic activity and durability. The results show that platinum particles generated by pyrolyzing chloroplatinic acid are uniformly loaded on graphene without agglomeration. The average particle size of platinum particles is about 2.12 nm. The oxygen reduction reaction catalytic activity of catalyst samples first increases, then decreases with increasing platinum loading in cyclic voltammetry and LSV. Compared with the commercial Pt/C (20 wt% Pt) catalyst, the initial potential and the current density retention rate of the catalyst decorated with 8% platinum are 55 mV and 23.7% higher, respectively. From i-t curves, it was found that the stability of the catalyst prepared in this paper was improved compared with the commercial Pt/C catalyst. The catalysts prepared in the present research exhibits superior catalytic activity and stability.

In order to improve the efficiency of a central heating system’s control system, this paper puts forward the application scheme of a frequency converter in central heating electrical automation control. In the central heating electrical automation control system, the frequency converter plays an important role. It can regulate and control the relevant equipment, realize the electrical automation of the heating system under the action of the frequency converter AC motor, and effectively adjust the performance and speed, so as to achieve the purpose of energy saving. The experimental results show that the temperature control strategy using a frequency converter automatic compensation method reduces the energy waste caused by manual regulation to a certain extent. When the speed of a water pump motor decreases to 4/5 of the original, the power consumption will decrease to about 52% of the original and save about 48% of the power; When the speed drops by 3/5, the power consumption is about 22% of the original, saving about 78% of the power. Conclusion. This technology can fully realize the demand of electrical automatic control of the heating system, greatly improve the stability and safety of the heating system, have good energy-saving effect, and greatly save energy consumption. The frequency converter has a remarkable effect in ensuring heating quality and improving heating efficiency in the heating industry.

The purpose of this study was to establish a collagen determination method based on an isotope-labeled collagen peptide as an internal reference via high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS), and using the established method to evaluate the degradation process of collagen-based implants in vivo. The specific peptide (GPAGPQGPR) of bovine type I collagen was identified with an Orbitrap mass spectrometer. Then, the quantification method based on the peptide detection with HPLC-MS/MS was established and validated, and then further used to analyze the degradation trend of the collagen sponge and acellular matrix (ACM) in vivo at 2, 4, 6, 8, 12, 16, and 18 weeks after implantation. The results indicate that the relative standard deviation (RSD) of the detection precision and repeatability of the peptide-based HPLC-MS/MS quantification method were 3.55% and 0.63%, respectively. The limitations of quantification and detection were 2.05 × 10−3 μg/mL and 1.12 × 10−3 μg/mL, respectively. The collagen sponge and ACM were completely degraded at 10 weeks and 18 weeks, respectively. Conclusion: A specific peptide (GPAGPQGPR) of bovine type I collagen was identified with an Orbitrap mass spectrometer, and a standardized HPLC-MS/MS-based internal reference method for the quantification of bovine type I collagen was established. The method can be used for the analysis of the degradation of collagen-based implants in vivo.

Collagen and fibronectin (FN) are important components in the extracellular matrix (ECM). Collagen-FN binding belongs to protein-protein interaction and plays a key role in regulating cell behaviors. In this study, FN-binding peptides were isolated from gelatin (degraded collagen) using affinity chromatography, and the amino acid sequences were determined using HPLC-MS. The results indicated that all FN-binding peptides contained GPAG or GPPG. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and dual-polarization interferometry (DPI) were used to analyze the effects of hydroxylation polypeptide on FN binding activity. DPI analysis indicated that peptides with molecular weight (MW) between 2 kDa and 30 kDa showed higher FN-binding activity, indicating MW range played an important role in the interaction between FN and peptides. Finally, two peptides with similar sequences except for hydroxylation of prolines were synthesized. The FN-binding properties of the synthesized peptides were determined by MALDI-TOF MS. For peptide, GAPGADGP*AGAPGTP*GPQGIAGQR, hydroxylation of P8 and P15 is necessary for FN-binding. For peptide, GPPGPMGPPGLAGPPGESGR, the FN-binding process is independent of proline hydroxylation. Thus, FN-binding properties are proline-hydroxylation dependent.

Aims. To explore the effects of Biejiaxiaozheng pills on carbon tetrachloride-induced hepatic fibrosis in rats through the NF-κB/Nrf2 pathway and to explore the possible antifibrotic mechanisms of the drug. Material and Method. A rat model of hepatic fibrosis was established via CCl4 induction. Liver function and antioxidant indices were detected using commercial kits. Hematoxylin-eosin and Masson staining were used to detect pathological changes in hepatic tissues. ELISA was used to measure plasma TNF-α, IL-β, and IL-6 levels. RT-PCR was used to measure changes in TNF-α, IL-β, and IL-6 levels in hepatic tissues. Changes in p65, P-p65, Nrf2, and HO-1 protein expression were detected using western blotting. Results. In rats with hepatic fibrosis, Biejiaxiaozheng pills effectively improved liver function, alleviated fibrosis in hepatic tissues, and significantly reduced collagen accumulation. The pills significantly downregulated inflammatory cytokine expression in hepatic tissues by suppressing p65 phosphorylation and reduced plasma inflammatory cytokine levels to some extent. The pills upregulated Nrf2 and HO-1 expression in hepatic tissues, enhanced antioxidant potential, and upregulated plasma antioxidant levels. Conclusion. Biejiaxiaozheng pills improved hepatic fibrosis symptoms and lesions in rats, likely by inhibiting the NF-κB pathway and promoting the Nrf2 pathway.

Friction stir brazing (FSB) using a pinless tool together with a braze was developed to extend bond area over friction stir lap welding. When using a large pinless tool of Ø40 mm to clad 10 mm thick 5083Al plate to 16Mn steel by FSB with Zn braze, the thermomechanical effect was sufficient to achieve wetting on Al side by dissolving Al into molten Zn, but joint could not be formed due to poor wettability on steel side. To enhance mechanical disruption of oxide film on the steel, multilayer FSB (ML-FSB) process was proposed by adding a thin (3 mm thickness) and soft aluminum sheet as interlayer. The first FSB pass created bonding between the thin interlayer and steel substrate with 4.7 μm thick FeAl3 without Zn residue, having 55 MPa shear strength. The second FSB pass created bonding between the thin interlayer and thick 5083Al clad with a diffusion zone with a little Zn, having 50 MPa shear strength. This work provided a new way to fabricate “thick clad” layered composite with “strong substrate”, and suggested that mechanical route for strong substrate and metallurgical route (eutectic reaction) for Al for removing oxide film should be preferential and available in FSB. Keywords: Friction stir brazing (FSB), Multilayer friction stir brazing (ML-FSB), Thick clad, Strong substrate, Interlayer

In this study, we investigated the structure–absorption relationship of common surface modifiers of chitosan (CTS), polyvinyl acetate (PVA), and titanium dioxide (TiO2) with α-quartz surface using molecular dynamics simulation. And the orientations and combinations derived from structures between modified α-quartz and ZSM-5 crystallites were also investigated. The results show that PVA is a non-linear organic macromolecule with a large amount of hydroxyl groups on its surface, which easily adhere to the surface of the substrate and agglomerate. CTS is a straight-chain structure containing a large number of hydroxyl and amino groups, which easily accumulate and spread on the surface of the substrate. TiO2 not only forms hydrogen bonds and complexes with the substrate but also interacts with each other to form a dense modifier layer. We observed that a large number of stable Ti–O–Si chemical bonds formed between the modified layer of inorganic small-molecule TiO2 and the surface of α-quartz, which compacted and stabilized the attached ZSM-5 film. Moreover, the orientation angle of the ZSM-5 nanocrystalline nucleus on the modified α-quartz was computed, which confirmed that the b-axis orientation of the ZSM-5 nanocrystalline nucleus was the highest on the surface of the substrate modified by TiO2. We discussed the influence of the modified temperature of modifiers in the constructed materials, and we have observed the adsorption state differences of TiO2 at different modified temperatures. We also discussed the catalytic properties of the materials prepared by the corresponding methods in conversion of methanol-to-aromatics (MTA) reaction. These results agree with our previous experimental data. By employing molecular dynamics simulation, we have obtained more precise conclusive information of the b-oriented growth of ZSM-5 crystallites, which highly depends on the surface modifiers.

This paper proposes a systematic image mosaicking methodology to produce hyperspectral image for environment monitoring using an emerging UAV-based push-broom hyperspectral imager. The suitability of alternative methods in each step is assessed by experiments of an urban scape, a river course and a forest study area. First, the hyperspectral image strips were acquired by sequentially stitching the UAV images acquired by push-broom scanning along each flight line. Next, direct geo-referencing was applied to each image strip to get initial geo-rectified result. Then, with ground control points, the curved surface spline function was used to transform the initial geo-rectified image strips to improve their geometrical accuracy. To further remove the displacement between pairs of image strips, an improved phase correlation (IPC) and a SIFT and RANSAC-based method (SR) were used in image registration. Finally, the weighted average and the best stitching image fusion method were used to remove the spectral differences between image strips and get the seamless mosaic. Experiment results showed that as the GCPs‘ number increases, the mosaicked image‘s geometrical accuracy increases. In image registration, there exists obvious edge information that can be accurately extracted from the urban scape and river course area; comparative results can be achieved by the IPC method with less time cost. However, for the ground objects with complex texture like forest, the edges extracted from the image is prone to be inaccurate and result in the failure of the IPC method, and only the SR method can get a good result. In image fusion, the best stitching fusion method can get seamless results for all three study areas. Whereas, the weighted average fusion method was only useful in eliminating the stitching line for the river course and forest areas but failed for the urban scape area due to the spectral heterogeneity of different ground objects. For different environment monitoring applications, the proposed methodology provides a practical solution to seamlessly mosaic UAV-based push-broom hyperspectral images with high geometrical accuracy and spectral fidelity.

Dissimilar joining of molybdenum (Mo) to titanium (Ti) is of great significance to the design and fabrication of high-temperature facilities. However, few reports were found about fusion joining of these two metals. The objective of this paper is to assess the feasibility of laser beam welding (LBW) of 2 mm-thick molybdenum and titanium. The effects of laser beam offset on the laser dissimilar joint of pure molybdenum to pure titanium were analyzed in terms of microstructure, chemical composition, microhardness, and tensile behavior. The results showed that the weld appearance improved with the increase of the offset. The fusion zone was strengthened because of the solid solution of these two elements. The mechanical properties of samples increased firstly and then decreased with the increasing of offset. When the laser beam irradiated on the titanium plate and the center of the laser spot was 0.5 mm away from the Mo/Ti interface, the joint performed the highest tensile strength, which was about 70% that of titanium base metal. LBW was demonstrated to be a promising method to join dissimilar Mo/Ti joint.

Since the cost of Ophiocordyceps sinensis, an important fungal drug used in Chinese medicine, has increased dramatically, and the counterfeits may have adverse health effects, a rapid and precise marker using the peptide mass spectrometry identification system could significantly enhance the regulatory capacity. In this study, we determined the marker peptides in the digested mixtures of fungal proteins in wild O. sinensis fruiting bodies and various commercially available mycelium fermented powders using ultra-performance liquid chromatography/Orbitrap Fusion mass spectrometry coupled with chemometrics. The results indicated the following marker peptides: TLLEAIDSIEPPK (m/z 713.39) was identified in the wild O. sinensis fruiting body, AVLSDAITLVR (m/z 579.34) was detected in the fermented O. sinensis mycelium powder, FAELLEK (m/z 849.47) was found in the fermented Ophiocordyceps mycelium powder, LESVVTSFTK (m/z 555.80) was discovered in the artificial Ophiocordyceps mycelium powder, and VPSSAVLR (m/z 414.75) was observed in O. mortierella mycelium powder. In order to verify the specificity and applicability of the method, the five marker peptides were synthesized and tested on all samples. All in all, to the best of our knowledge, this is the first time that mass spectrometry has been employed to detect the marker peptides of O.sinensis and its related products.

Background: Hyaluronan-mediated motility receptor (HMMR) is overexpressed in multiple carcinomas and influences the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Methods: The "limma" and "GSVA" packages in R were used to perform differential expression analysis and to assess the activity of signalling pathways, respectively. InferCNV was used to infer copy number variation (CNV) for each hepatocyte and "CellChat" was used to analyse intercellular communication networks. Recursive partitioning analysis (RPA) was used to re-stage HCC patients. The IC50 values of various drugs were evaluated using the "pRRophetic" package. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm HMMR expression in an HCC tissue microarray. Flow cytometry (FCM) and cloning, Edu and wound healing assays were used to explore the capacity of HMMR to regulate HCC tumour. Results: Multiple cohort studies and qRT-PCR demonstrated that HMMR was overexpressed in HCC tissue compared with normal tissue. In addition, HMMR had excellent diagnostic performance. HMMR knockdown inhibited the proliferation and migration of HCC cells in vitro. Moreover, high HMMR expression was associated with "G2M checkpoint" and "E2F targets" in bulk RNA and scRNA-seq, and FCM confirmed that HMMR could regulate the cell cycle. In addition, HMMR was involved in the regulation of the tumour immune microenvironment via immune cell infiltration and intercellular interactions. Furthermore, HMMR was positively associated with genomic heterogeneity with patients with high HMMR expression potentially benefitting more from immunotherapy. Moreover, HMMR was associated with poor prognosis in patients with HCC and the re-staging by recursive partitioning analysis (RPA) gave a good prognosis prediction value and could guide chemotherapy and targeted therapy. Conclusion: The results of the present study show that HMMR could play a role in the diagnosis, prognosis, and treatments of patients with HCC based on bulk RNA-seq and scRAN-seq analyses and is a promising molecular marker for HCC. [ABSTRACT FROM AUTHOR]

In order to achieve data analysis of thermal energy loss for electrical automation management, the author proposes a Broyden Fletcher Goldfarb Shanno (BFGS) trust region algorithm based thermal energy loss calculation method for the integrated energy system of electricity and gas, the BFGS trust region algorithm is utilized to obtain the thermal energy loss distribution of natural gas system, which is not highly dependent on the initial value, this solves the problem of non-convergence in power flow calculation when using the Newton method for calculation. The experimental results show that the relative errors of natural gas system node pressure, pipe-line flow and power system node voltage and phase angle calculated by Newton's method and BFGS trust region algorithm are within 1 · 10-4, within the allowable range, which verifies the correctness of the calculation results of the method described by the author. It has been proven that the BFGS trust region algorithm can achieve data analysis of thermal energy loss for electrical automation management. [ABSTRACT FROM AUTHOR]