Research progress on the mechanism of action and clinical application of remote ischemic post-conditioning for acute ischemic stroke.

Remote ischemic post-conditioning (RIPostC) can reduce cerebral ischemia reperfusion injury (IRI) by inducing endogenous protective effects, the distal limb ischemia post-treatment and in situ ischemia post-treatment were classified according to the site of intervention. And in the process of clinical application distal limb ischemia post-treatment is more widely used and more conducive to clinical translation. Therefore, in this paper, we review the mechanism of action and clinical application of RIPostC in cerebral ischemia, hoping to provide reference help for future experimental directions and clinical translation.

The predictive value of GLIM criteria on clinical outcomes and responses to nutritional support in patients with neurocritical illnesses.

Neurocritically ill patients frequently exhibit coma, gastroparesis, and intense catabolism, leading to an increased risk of malnutrition. The Global Leadership Initiative on Malnutrition (GLIM) criteria for the diagnosis of malnutrition was created to achieve a consistent malnutrition diagnosis across diverse populations. This study aimed to validate the concurrent and predictive validity of GLIM criteria in patients with neurocritical illnesses. A total of 135 participants were followed from admission to the neurocritical unit (NCU) until discharge. Comparing GLIM criteria to the Subjective Global Assessment (SGA), sensitivity was 0.95 and specificity was 0.69. Predictive validity of GLIM criteria was assessed using a composite adverse clinical outcome, comprising mortality and various major complications. Adjusted hazard ratios for moderate and severe malnutrition were 2.86 (95% CI 1.45-5.67) and 3.88 (95% CI 1.51-9.94), respectively. Changes in indicators of nutritional status, including skeletal muscle mass and abdominal fat mass, within 7 days of admission were obtained for 61 participants to validate the predictive capability of the GLIM criteria for the patients' response of standardized nutritional support. The GLIM criteria have a statistically significant predictive validity on changes in rectus femoris muscle thickness and midarm muscle circumference. In conclusion, the GLIM criteria demonstrate high sensitivity for diagnosing malnutrition in neurocritically ill patients and exhibit good predictive validity.

Clinical efficacy and identification of factors confer resistance to afatinib (tyrosine kinase inhibitor) in EGFR-overexpressing esophageal squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal squamous cell carcinoma (ESCC) patients, but anti-EGFR treatments offer limited survival benefits. Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC. This proof-of-concept, phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients (n = 41) with EGFR overexpression (NCT03940976). The study met its primary endpoint, with a confirmed objective response rate (ORR) of 39% in 38 efficacy-evaluable patients and a median overall survival of 7.8 months, with a manageable toxicity profile. Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2 (NTRK2) was negatively associated with afatinib sensitivity and might serve as a predictive biomarker, irrespective of EGFR expression. Notably, knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment. Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

Formation of chlorophyll-anionic polysaccharide complex coacervates to improve chlorophyll color stability: Thermodynamic and kinetic stability studies.

Chlorophyll (Chl) is the predominant pigment in green plants that can act as a food color and possesses various functional activities. However, its instability and rapid degradation on heating compromise the sensory qualities of its products. This study aimed to enhance the heat resistance of Chl by forming complex coacervates with two negatively charged polysaccharides, sodium alginate (SA) and K-carrageenan (KC). Dynamic light scattering and scanning electron microscopy analyses confirmed the formation of coacervates between Chl and the polysaccharides, whereas Fourier-transform infrared spectroscopy revealed that hydrogen bonding and electrostatic attraction were the primary forces behind complex formation. Electron spin resonance and thermodynamic studies further revealed that these complexes bolstered the thermal stability of Chl, with a maximum improvement of 70.38 % in t1/2 and a reduction of 50.72 % in the degradation rate constant. In addition, the antioxidant capacity of Chl was enhanced up to 35 %. Therefore, this study offers a novel approach to Chl preservation and suggests a viable alternative to artificial pigments in food products.

Mussel inspired 3D elastomer enabled rapid calvarial bone regeneration through recruiting more osteoprogenitors from the dura mater.

Currently, the successful healing of critical-sized calvarial bone defects remains a considerable challenge. The immune response plays a key role in regulating bone regeneration after material grafting. Previous studies mainly focused on the relationship between macrophages and bone marrow mesenchymal stem cells (BMSCs), while dural cells were recently found to play a vital role in the calvarial bone healing. In this study, a series of 3D elastomers with different proportions of polycaprolactone (PCL) and poly(glycerol sebacate) (PGS) were fabricated, which were further supplemented with polydopamine (PDA) coating. The physicochemical properties of the PCL/PGS and PCL/PGS/PDA grafts were measured, and then they were implanted as filling materials for 8 mm calvarial bone defects. The results showed that a matched and effective PDA interface formed on a well-proportioned elastomer, which effectively modulated the polarization of M2 macrophages and promoted the recruitment of dural cells to achieve full-thickness bone repair through both intramembranous and endochondral ossification. Single-cell RNA sequencing analysis revealed the predominance of dural cells during bone healing and their close relationship with macrophages. The findings illustrated that the crosstalk between dural cells and macrophages determined the vertical full-thickness bone repair for the first time, which may be the new target for designing bone grafts for calvarial bone healing.

Research on coronavirus disease 2019 and the kidney: A bibliometric analysis.

Background: In addition to damage to the lungs, coronavirus disease 2019 (COVID-19) can damage multiple organs, including the kidney. Our purpose was to analyze the research hotspots and trends in COVID-19 and kidney diseases using bibliometrics to help clarify the development direction of this field. Methods: We selected and extracted all relevant publications related to COVID-19 and the kidney from the Web of Science from December 1, 2019, to July 24, 2022. VOSviewer, RStudio, CiteSpace, and other software were used to visualize keywords, publishing trends, authors and their countries, and institutions in this field and perform the statistical analysis. Results: A total of 645 articles published in 220 journals were included in this study. The United States and China contributed the most publications and were most active in international cooperation. In addition to COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), acute kidney injury (AKI), kidney transplant and mortality were the three keywords with the highest frequencies. In the initial stage of the COVID-19 outbreak, research focused on the clinical symptoms of COVID-19 and other macrocharacteristics, while in a later stage, the associations between SARS-CoV-2 infection and CKD and AKI, as well as the prognosis of patients with kidney disease or those who underwent kidney transplantation, gained more attention. The immune response and vaccines were also recent research hotspots. Conclusions: This bibliometric analysis provides a comprehensive overview of research on COVID-19 and kidney disease, which has received continuous, global attention. AKI, CKD, kidney transplantation, immune response and vaccines are among the hotspots in this field.

Highly efficient degradation of tetracycline in groundwater by nanoscale zero-valent iron-copper bimetallic biochar: active [H] attack and direct electron transfer mechanism.

Development of carbon materials with high activity was important for rapid degradation of emerging pollutants. In this paper, a novel nanoscale zero-valent iron-copper bimetallic biochar (nZVIC-BC) was synthesized by carbothermal reduction of waste pine wood and copper-iron layered double hydroxides (LDHs). Characterization and analysis of its structural, elemental, crystalline, and compositional aspects using XRD, FT-IR, SEM, and TEM confirmed the successful preparation of nZVIC-BC and the high dispersion of Fe-Cu nanoparticles in an ordered carbon matrix. The experimental results showed that the catalytic activity of nZVIC-BC (Kobs of 0.0219 min-1) in the degradation of tetracycline (TC) in anoxic water environment was much higher than that of Fe-BC and Cu-BC; the effective degradation rate reached 85%. It was worth noting that the negative effects of Ca2+, Mg2+, and H2PO4- on TC degradation at ionic strengths greater than 15 mg/L were due to competition for active sites. Good stability and reusability were demonstrated in five consecutive cycle tests for low leaching of iron and copper. Combined with free radical quenching experiments and XPS analyses, the degradation of TC under air conditions was only 62%, with hydroxyl radicals (·OH) playing a dominant role. The synergistic interaction between Fe2+/Fe3+ and Cu0/Cu+/Cu2+ under nitrogen atmosphere enhances the redox cycling process; π-π adsorption, electron transfer processes, and active [H] were crucial for the degradation of TC; and possible degradation pathways of TC were deduced by LC-MS, which identified seven major aromatic degradation by-products. This study will provide new ideas and materials for the treatment of TC.

Phycocyanin-phlorotannin complexes improve the structure and functional properties of yogurt.

Adding natural bioactive ingredients to yogurt can improve the nutritional and physiological benefits. In this study, we used ultrasonic-assisted phlorotannin from Ascophyllum nodosum (A. nodosum) modified phycocyanin (PC) to form a complex (UPP) to produce a fortified fermented yogurt. The effects of PC and UPP on the structure, stability, and function of fermented yogurt within 7 days were assessed using physicochemical properties, texture analysis, rheological testing, 16S rDNA sequencing analysis, and lipidomics analysis. Molecular docking indicated that PC might bind to phlorotannin via ARG-77, ARG-84, LEU-120, ALA-81, CYS-82, and ASP-85 sites.When the mass ratio of the complex is 1:1, the ability of UPP1:1 to remove DPPH· scavenging ability in an acid environment increased by about 50 %. UPP1:1 with more acid stability changed the microstructure of the yogurt, enhanced the stability of the yogurt, improved the antioxidant properties, and inhibited the growth of harmful bacteria within 7 days. This work encouraged the extraction and use of phlorotannin from edible brown algae and offered a straightforward method for making yogurt supplemented with PC.

Exploring the common mechanism of vascular dementia and inflammatory bowel disease: a bioinformatics-based study.

Objective: Emerging evidence has shown that gut diseases can regulate the development and function of the immune, metabolic, and nervous systems through dynamic bidirectional communication on the brain-gut axis. However, the specific mechanism of intestinal diseases and vascular dementia (VD) remains unclear. We designed this study especially, to further clarify the connection between VD and inflammatory bowel disease (IBD) from bioinformatics analyses. Methods: We downloaded Gene expression profiles for VD (GSE122063) and IBD (GSE47908, GSE179285) from the Gene Expression Omnibus (GEO) database. Then individual Gene Set Enrichment Analysis (GSEA) was used to confirm the connection between the two diseases respectively. The common differentially expressed genes (coDEGs) were identified, and the STRING database together with Cytoscape software were used to construct protein-protein interaction (PPI) network and core functional modules. We identified the hub genes by using the Cytohubba plugin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to identify pathways of coDEGs and hub genes. Subsequently, receiver operating characteristic (ROC) analysis was used to identify the diagnostic ability of these hub genes, and a training dataset was used to verify the expression levels of the hub genes. An alternative single-sample gene set enrichment (ssGSEA) algorithm was used to analyze immune cell infiltration between coDEGs and immune cells. Finally, the correlation between hub genes and immune cells was analyzed. Results: We screened 167 coDEGs. The main articles of coDEGs enrichment analysis focused on immune function. 8 shared hub genes were identified, including PTPRC, ITGB2, CYBB, IL1B, TLR2, CASP1, IL10RA, and BTK. The functional categories of hub genes enrichment analysis were mainly involved in the regulation of immune function and neuroinflammatory response. Compared to the healthy controls, abnormal infiltration of immune cells was found in VD and IBD. We also found the correlation between 8 shared hub genes and immune cells. Conclusions: This study suggests that IBD may be a new risk factor for VD. The 8 hub genes may predict the IBD complicated with VD. Immune-related coDEGS may be related to their association, which requires further research to prove.

Global burden of non-communicable diseases attributable to kidney dysfunction with projection into 2040.

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and Sociodemographic Index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION: NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.

Precision Phenotypic Profiling and Capture of Circulating Tumor Cells via a Vertical Laminar Flow-Stacked Microfluidic Chip.

The heterogeneity of circulating tumor cells has a significant impact on the diagnosis, treatment, and monitoring of cancer. Research on the subtypes of circulating tumor cells can bring better treatment outcomes for cancer patients. Here, we proposed a microfluidic chip for the magnetic capture of subtypes of circulating tumor cells from the whole blood and phenotypic profiling by stacking laminar flow vertically. Circulating tumor cells were sorted and captured by the three-dimensional regulation of both magnetic fields in the vertical direction and flow fields in the lateral direction. Using EpCAM-magnetic beads, we achieved sorting and sectional capture of target cells in whole blood and analyzed the surface expression levels of the captured cells, confirming the functionality of the microfluidic chip in sorting and capturing subtypes of circulating tumor cells. This microfluidic chip can also aid in the subsequent subtype analysis of other rare cells.

Switchable Regioselective C-H Activation/Annulation of Acrylamides with Alkynes for the Synthesis of 2-Pyridones.

A catalyst-based switchable regioselective C-H activation/annulation of acrylamides with propargyl carbonates has been developed, delivering C5 or C6 alkenyl substituted 2-pyridones. This robust protocol proceeds with a broad substrate scope and good functional group tolerance under redox-neutral reaction conditions. More significantly, this reaction is highly effective with previously challenging unsymmetrical alkynes, including unbiased alkyl-alkyl substituted alkynes, with perfect and switchable regioselectivity. Additionally, mechanistic studies and DFT calculations were performed to shed light on the switchable regioselectivity.

Sequential Dearomatization/Rearrangement of Quinazoline-Derived Azomethine Imines for the Synthesis of Nitrogen-Rich Three-Dimensional Cage-Like Molecules.

A sequential dearomatization/rearrangement reaction between quinazoline-derived azomethine imines and crotonate sulfonium salts has been developed to provide a series of three-dimensional cage-like molecules. The reaction involves two dearomatizations, two cyclizations, and two C-C bond and three C-N bond formations in one step. The new transformation has a broad substrate scope, does not require any added reagents, and proceeds under room temperature in a short time. A mechanistic rationale for the sequential dearomatization/rearrangement is also presented. Furthermore, the synthetic compounds are evaluated for their glucose control effect. Compounds 3aa and 3aj were found to be hyperglycemic, which might be lead compounds for treating hypoglycemia.

Genome assemblies of 11 bamboo species highlight diversification induced by dynamic subgenome dominance.

Polyploidy (genome duplication) is a pivotal force in evolution. However, the interactions between parental genomes in a polyploid nucleus, frequently involving subgenome dominance, are poorly understood. Here we showcase analyses of a bamboo system (Poaceae: Bambusoideae) comprising a series of lineages from diploid (herbaceous) to tetraploid and hexaploid (woody), with 11 chromosome-level de novo genome assemblies and 476 transcriptome samples. We find that woody bamboo subgenomes exhibit stunning karyotype stability, with parallel subgenome dominance in the two tetraploid clades and a gradual shift of dominance in the hexaploid clade. Allopolyploidization and subgenome dominance have shaped the evolution of tree-like lignified culms, rapid growth and synchronous flowering characteristic of woody bamboos as large grasses. Our work provides insights into genome dominance in a remarkable polyploid system, including its dependence on genomic context and its ability to switch which subgenomes are dominant over evolutionary time.

Single-cell transcriptome analysis upon ECM-remodeling meningioma cells.

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.

Single-Cell Proteomics by Barcoded Phage-Displayed Screening via an Integrated Microfluidic Chip.

Recent advancements in the profiling of proteomes at the single-cell level necessitate the development of quantitative and versatile platforms, particularly for analyzing rare cells like circulating tumor cells (CTCs). In this chapter, we present an integrated microfluidic chip that utilizes magnetic nanoparticles to capture single tumor cells with exceptional efficiency. This chip enables on-chip incubation and facilitates in situ analysis of cell-surface protein expression. By combining phage-based barcoding with next-generation sequencing technology, we successfully monitored changes in the expression of multiple surface markers induced by CTC adherence. This innovative platform holds significant potential for comprehensive screening of multiple surface antigens simultaneously in rare cells, offering single-cell resolution. Consequently, it will contribute valuable insights into biological heterogeneity and human disease.

Combined Use of Endoscopic Techniques and Virtual Surgical Planning for Intraoral Approach for Hemi-mandibular Resection and Reconstruction.

Background: The study aimed to describe our experience in using endoscopic procedures to aid hemi-mandibular reconstruction with bone flaps through transoral approach. Methods: Five patients with huge benign mandibular tumors underwent transoral mandibulectomy and hemi-mandibular reconstruction, using endoscopy. Facial symmetry, occlusion, bone healing, and mandibular similarity were all evaluated postoperatively. The paired-samples t test was used to compare quantitative data, and a P value less than 0.05 was considered a significant difference. Results: All five patients who received transoral mandibular surgery recovered in terms of TMJ functionality, facial symmetry, and aesthetic results. Endoscopy monitored and ensured that bone flaps were correctly connected and fixed. The accuracy of endoscopy-guided mandibular reconstruction was confirmed by quantitative examination for four cases, which revealed no statistically significant variations between postoperative CT analysis and preoperative virtual surgical planning data. Conclusions: Endoscopy-assisted virtual surgery may resolve concerns with transoral hemi-mandibular reconstruction and broaden indications for mini-invasive mandibular reconstruction. However, only patients with benign mandibular tumors were included in our study, so surgeons should be very cautious if applying this technique to malignant lesions or bony tumors invading soft tissues.

Prognostic and predictive value of angiogenesis-associated serum proteins for immunotherapy in esophageal cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved patient survival in multiple cancers. However, therapy response in esophageal cancer is limited to subgroups of patients and clinically useful predictive biomarkers are lacking. METHODS: We collected a series of plasma samples from 91 patients with esophageal cancer before and after ICI treatment. The Olink Immuno-Oncology panel (92 proteins) with proximity extension assays was used to detect the dynamic changes in plasma and potential biomarkers associated with treatment outcomes. We screened all survival-related proteins and established a risk score model to better predict the prognosis and treatment response in patients with esophageal cancer immunotherapy. RESULTS: We found that 47 out of 92 quantified proteins had significant changes in plasma levels during ICI treatment (p<0.050), and these changed proteins were involved in immune-related reactions, such as intercellular adhesion and T-cell activation. Notably, the baseline levels of three angiogenesis-related proteins (IL-8, TIE2, and HGF) were significantly associated with the survival outcomes of patients treated with ICIs (p<0.050). According to these prognostic proteins, we established an angiogenesis-related risk score, which could be a superior biomarker for ICI response prediction. In addition, antiangiogenic therapy combined with ICIs significantly improved overall survival compared with ICI monotherapy (p=0.044). CONCLUSIONS: An angiogenesis-related risk score based on three proteins (IL-8, TIE2, and HGF) could predict ICI response and prognosis in patients with esophageal cancer, which warrants verification in the future. Our study highlights the potential application of combining ICIs and antiangiogenic therapy and supports Olink plasma protein sequencing as a liquid biopsy method for biomarker exploration.

Comprehensive bioinformation analysis of homeodomain-leucine zipper gene family and expression pattern of HD-Zip I under abiotic stress in Salix suchowensis.

BACKGROUND: Homeodomain-leucine zipper (HD-Zip) transcription factors are plant-specific and play important roles in plant defense against environmental stresses. Identification and functional studies have been carried out in model plants such as rice, Arabidopsis thaliana, and poplar, but comprehensive analysis on the HD-Zip family of Salix suchowensis have not been reported. RESULTS: A total of 55 HD-Zip genes were identified in the willow genome, unevenly distributed on 18 chromosomes except for chromosome 19. And segmental duplication events containing SsHD-Zip were detected on all chromosomes except chromosomes 13 and 19. The SsHD-Zip were classified into 4 subfamilies subfamilies (I-IV) according to the evolutionary analysis, and members of each subfamily shared similar domain structure and gene structure. The combination of GO annotation and promoter analysis showed that SsHD-Zip genes responded to multiple abiotic stresses. Furthermore, the results of qPCR analysis showed that the SsHD-Zip I gene exhibited different degrees of expression under salt stress, PEG treatment and heat treatment. Moreover, there was a synergistic effect between SsHD-Zip I genes under stress conditions based on coregulatory networks analysis. CONCLUSIONS: In this study, HD-Zip transcription factors were systematically identified and analyzed at the whole genome level. These results preliminarily clarified the structural characteristics and related functions of willow HD-Zip family members, and it was found that SsHox34, SsHox36 and SsHox51 genes were significantly involved in the response to various stresses. Together, these findings laid the foundation for further research on the resistance functions of willow HD-Zip genes.