Preparation of Structure-Function Integrated Layered CNT/Mg Composites.

Magnesium (Mg)-matrix composites have excellent damping and electromagnetic shielding properties. However, the mismatch between their strength and toughness limits their wide application. The aim of this work is to overcome the strength-toughness mismatch by constructing micro- and nanostructures while maintaining the good functional properties of Mg-matrix composites. Electrophoretic deposition (EPD) was used to spread carbon nanotubes (CNTs) out evenly on a Mg foil matrix. After spark plasma sintering (SPS), the grain organisation was refined, and the interlayer bonding was strengthened by hot rolling deformation. Finally, the microstructure, mechanical properties, damping properties, and electromagnetic shielding properties of the composites were analysed. Compared with the pure Mg laminates, the tensile strength and elongation of the CNT/Mg laminates were increased by 6.4% and 108.4%, respectively, with the significant improvement in toughness resulting from the increase in energy required for crack propagation due to the laminate structure. When the total rolling deflection reaches 80%, the interlayer bond strength of the material is significantly increased, the grain is further refined, and the strength and elongation of the composite material reaches the optimum, with the tensile strength reaching 241.70 MPa and the elongation reaching 6.90%. The interlayer interface and grain refinement also affected the damping Mg and electromagnetic shielding effect of the composites. This work provides an experimental idea for the preparation of high-performance structure-function integrated Mg-based materials.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Influenza and COVID-19 co-infection and vaccine effectiveness against severe cases: a mathematical modeling study.

Background: Influenza A virus have a distinctive ability to exacerbate SARS-CoV-2 infection proven by in vitro studies. Furthermore, clinical evidence suggests that co-infection with COVID-19 and influenza not only increases mortality but also prolongs the hospitalization of patients. COVID-19 is in a small-scale recurrent epidemic, increasing the likelihood of co-epidemic with seasonal influenza. The impact of co-infection with influenza virus and SARS-CoV-2 on the population remains unstudied. Method: Here, we developed an age-specific compartmental model to simulate the co-circulation of COVID-19 and influenza and estimate the number of co-infected patients under different scenarios of prevalent virus type and vaccine coverage. To decrease the risk of the population developing severity, we investigated the minimum coverage required for the COVID-19 vaccine in conjunction with the influenza vaccine, particularly during co-epidemic seasons. Result: Compared to the single epidemic, the transmission of the SARS-CoV-2 exhibits a lower trend and a delayed peak when co-epidemic with influenza. Number of co-infection cases is higher when SARS-CoV-2 co-epidemic with Influenza A virus than that with Influenza B virus. The number of co-infected cases increases as SARS-CoV-2 becomes more transmissible. As the proportion of individuals vaccinated with the COVID-19 vaccine and influenza vaccines increases, the peak number of co-infected severe illnesses and the number of severe illness cases decreases and the peak time is delayed, especially for those >60 years old. Conclusion: To minimize the number of severe illnesses arising from co-infection of influenza and COVID-19, in conjunction vaccinations in the population are important, especially priority for the elderly.

The Association Between the Albumin-Bilirubin Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

The albumin-bilirubin (ALBI) score is considered an effective and convenient scoring system for assessing liver function. We hypothesized that the ALBI score was predictive of contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). We retrospectively observed 5629 patients undergoing elective PCI. Contrast-associated acute kidney injury is defined as a 50% or 0.3 mg/dl increase in baseline serum creatinine levels within 48 h of contrast exposure. The incidence of CA-AKI was 6.2% (n = 350). After adjusting for potential confounding factors, multivariate analysis showed that the ALBI score was an independent predictor of CA-AKI (P = .002). A restricted cubic spline analysis confirmed approximately linear relationships between the ALBI score and risks of CA-AKI. Furthermore, at a median follow-up of 2.8 years, multivariate Cox regression analysis indicated that the ALBI score was an independent risk factor for long-term mortality (P < .001). The ALBI score was closely related to the occurrence of CA-AKI and long-term mortality in patients who underwent elective PCI. This score might be useful for risk stratification in high-risk patient groups to predict CA-AKI.

Cucurbitacin E reduces IL-1ß-induced inflammation and cartilage degeneration by inhibiting the PI3K/Akt pathway in osteoarthritic chondrocytes.

BACKGROUND: Osteoarthritis is a degenerative joint disease. Cartilage degeneration is the earliest and most important pathological change in osteoarthritis, and persistent inflammation is one of the driving factors of cartilage degeneration. Cucurbitacin E, an isolated compound in the Cucurbitacin family, has been shown to have anti-inflammatory effects, but its role and mechanism in osteoarthritic chondrocytes are unclear. METHODS: For in vitro experiments, human chondrocytes were stimulated with IL-1ß, and the expression of inflammatory genes was measured by Western blotting and qPCR. The expression of extracellular matrix proteins was evaluated by immunofluorescence staining, Western blotting and saffron staining. Differences in gene expression between cartilage from osteoarthritis patients and normal cartilage were analysed by bioinformatics methods, and the relationship between Cucurbitacin E and its target was analysed by a cellular thermal shift assay, molecular docking analysis and molecular dynamics simulation. For in vivo experiments, knee osteoarthritis was induced by DMM in C57BL/6 mouse knee joints, and the effect of Cucurbitacin E on knee joint degeneration was evaluated. RESULTS: The in vitro experiments confirmed that Cucurbitacin E effectively inhibited the production of the inflammatory cytokine interleukin-1ß(IL-1ß) and cyclooxygenase-2 (COX-2) by IL-1ß-stimulated chondrocytes and alleviates extracellular matrix degradation. The in vivo experiments demonstrated that Cucurbitacin E had a protective effect on the knee cartilage of C57BL/6 mice with medial meniscal instability in the osteoarthritis model. Mechanistically, bioinformatic analysis of the GSE114007 and GSE117999 datasets showed that the PI3K/AKT pathway was highly activated in osteoarthritis. Immunohistochemical analysis of PI3K/Akt signalling pathway proteins in pathological slices of human cartilage showed that the level of p-PI3K in patients with osteoarthritis was higher than that in the normal group. PI3K/Akt were upregulated in IL-1ß-stimulated chondrocytes, and Cucurbitacin E intervention reversed this phenomenon. The cellular thermal shift assay, molecular docking analysis and molecular dynamics experiment showed that Cucurbitacin E had a strong binding affinity for the inhibitory target PI3K. SC79 activated Akt phosphorylation and reversed the effect of Cucurbitacin E on IL-1ß-induced chondrocyte degeneration, demonstrating that Cucurbitacin E inhibits IL-1ß-induced chondrocyte inflammation and degeneration by inhibiting the PI3K/AKT pathway. CONCLUSION: Cucurbitacin E inhibits the activation of the PI3K/AKT pathway, thereby alleviating the progression of OA. In summary, we believe that Cucurbitacin E is a potential drug for the treatment of OA.

A Pilot Study About the Role of PANoptosis-Based Genes in Atherosclerosis Development.

Background: As a chronic inflammatory disease, atherosclerosis (AS) and ischemia events are primarily affected by inflammation in AS. PANoptosis has been implicated in many human systemic disorders, including infection, cancer, neurodegeneration, and inflammation. On the other hand, little is understood about PANoptosis's function in AS. Methods: We used consensus clustering to divide the GSE100927 dataset into two panoptosis-related subgroups. PANoptosis-associated genes were screened by differential analysis and weighted gene co-expression network analysis (WGCNA) and enriched by ClueGO software. Investigating LASSO regression and MCODE to identify AS Diagnostic Markers. Immunoinfiltration analysis and single-cell analysis were used to search for cell types associated with the diagnostic genes. Final validation was performed by polymerase chain reaction (PCR). Results: We classified the GSE100927 dataset into two PANoptosis-related subtypes based on the expression of PANoptosis-related genes (PRGs) using consensus clustering. A total of 36 PANoptosis-associated genes were screened in the differentially expressed genes and WGCNA-related module. 4 hub genes were identified by MCODE and LASSO regression, and 3 AS diagnostic markers (ACP5, CCL3, HMOX1) were screened by external validation set. Immunoinfiltration analysis and single-cell analysis showed that the three diagnostic markers were associated with macrophages, and PCR results demonstrated that ACP5 and HMOX1 could be used as AS diagnostic markers. Conclusion: Our study identified ACP5 and HMOX1 as diagnostic genes for AS that may be associated with PANoptosis. ACP5 and HMOX1 may be involved in the pathogenesis of AS by regulating macrophage PANoptosis.

Temporary impact on medical system and effectiveness of mitigation strategies after COVID-19 policy adjustment in China: a modeling study.

Background: As China amends its "zero COVID" strategy, a sudden increase in the number of infections may overwhelm medical resources and its impact has not been quantified. Specific mitigation strategies are needed to minimize disruption to the healthcare system and to prepare for the next possible epidemic in advance. Method: We develop a stochastic compartmental model to project the burden on the medical system (that is, the number of fever clinic visits and admission beds) of China after adjustment to COVID-19 policy, which considers the epidemiological characteristics of the Omicron variant, age composition of the population, and vaccine effectiveness against infection and severe COVD-19. We also estimate the effect of four-dose vaccinations (heterologous and homologous), antipyretic drug supply, non-pharmacological interventions (NPIs), and triage treatment on mitigating the domestic infection peak. Result: As to the impact on the medical system, this epidemic is projected to result in 398.02 million fever clinic visits and 16.58 million hospitalizations, and the disruption period on the healthcare system is 18 and 30 days, respectively. Antipyretic drug supply and booster vaccination could reduce the burden on emergency visits and hospitalization, respectively, while neither of them could not reduce to the current capacity. The synergy of several different strategies suggests that increasing the heterologous booster vaccination rate for older adult to over 90% is a key measure to alleviate the bed burden for respiratory diseases on the basis of expanded healthcare resource allocation. Conclusion: The Omicron epidemic followed the adjustment to COVID-19 policy overloading many local health systems across the country at the end of 2022. The combined effect of vaccination, antipyretic drug supply, triage treatment, and PHSMs could prevent overwhelming medical resources.

Apolipoprotein C-III itself stimulates the Syk/cPLA2-induced inflammasome activation of macrophage to boost anti-tumor activity of CD8+ T cell.

Increased prevalence of cancer in obese individuals is involved with dyslipidemia- induced chronic inflammation and immune suppression. Although apolipoprotein C-III (ApoC3)-transgenic mice (ApoC3TG mice) or poloxamer 407 (P407)-treated mice had hyperlipidemia, CD8+ T cells with upregulated antitumor activities were observed in ApoC3TG mice, and decreased CD8+ T cell activities were observed in P407-treated mice. Increased ApoC3 expression in hepatocellular carcinoma was associated with increased infiltration of CD8+ T cells and predicted survival. Recombinant ApoC3 had no direct effects on CD8+ T cells. The upregulation of CD8+ T cells in ApoC3TG mice was due to cross-talk with context cells, as indicated by metabolic changes and RNA sequencing results. In contrast to dendritic cells, the macrophages of ApoC3TG mice (macrophagesTG) displayed an activated phenotype and increased IL-1ß, TNF-α, and IL-6 production. Coculture with macrophagesTG increased CD8+ T cell function, and the adoptive transfer of macrophagesTG suppressed tumor progression in vivo. Furthermore, spleen tyrosine kinase (Syk) activation induced by TLR2/TLR4 cross-linking after ApoC3 ligation promoted cellular phospholipase A2 (cPLA2) activation, which in turn activated NADPH oxidase 2 (NOX2) to promote an alternative mode of inflammasome activation. Meanwhile, mitochondrial ROS produced by increased oxidative phosphorylation of free fatty acids facilitated the classical inflammasome activation, which exerted an auxiliary effect on inflammasome activation of macrophagesTG. Collectively, the increased antitumor activity of CD8+ T cells was mediated by the ApoC3-stimulated inflammasome activation of macrophages, and the mimetic ApoC3 peptides that can bind TLR2/4 could be a future strategy to target liver cancer.

Interaction between N6-methyladenosine modification and the tumor microenvironment in colorectal cancer.

The incidence and mortality of colorectal cancer (CRC) are rapidly increasing worldwide. Recently, there has been significant attention given to N6-methyladenosine (m6A), the most common mRNA modification, especially for its effects on CRC development. It is important to note that the progression of CRC would be greatly hindered without the tumor microenvironment (TME). The interaction between CRC cells and their surroundings can activate and influence complex signaling mechanisms of epigenetic changes to affect the survival of tumor cells with a malignant phenotype. Additionally, the TME is influenced by m6A regulatory factors, impacting the progression and prognosis of CRC. In this review, we describe the interactions and specific mechanisms between m6A modification and the metabolic, hypoxia, inflammatory, and immune microenvironments of CRC. Furthermore, we summarize the therapeutic role that m6A modification can play in the CRC microenvironment, and discuss the current status, limitations, and potential future directions in this field. This review aims to provide new insights into the molecular targets and theoretical foundations for the treatment of CRC.

Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII).

BACKGROUND: Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps. METHODS: A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry. RESULTS: Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L- T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RII­immunized mice. CONCLUSIONS: PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities.

Predictive Value of Systemic Inflammation Score for Contrast-Associated Acute Kidney Injury and Adverse Outcomes Among Patients Undergoing Elective Percutaneous Coronary Intervention.

Purpose: Prior research has demonstrated a key role of systemic inflammatory state in the pathogenesis and progression of contrast-associated acute kidney injury (CA-AKI). Recently, the systemic inflammation score (SIS) has been introduced to evaluate the inflammatory status, utilizing the lymphocyte-to-monocyte ratio (LMR) and albumin. The primary objective of this study was to determine whether the SIS can predict CA-AKI and long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: A total of 5726 patients who underwent elective PCI were included from January 2012 to December 2018. The primary outcome was CA-AKI, defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl or ≥50% than baseline SCr within 48 h after the PCI procedure. The secondary outcome was long-term mortality. All patients were classified into low- and high-SIS groups. Results: During hospitalization, 349 (6.1%) patients developed CA-AKI. Multivariate logistic regression analysis showed that patients in the high SIS group had a 1.47-fold higher risk of developing CA-AKI than those in the low SIS group [odds ratio (OR): 1.50, 95% confidence interval (CI): 1.12-2.01, P =0.006]. Furthermore, the SIS showed the greatest prediction performance for CA-AKI compared with other inflammatory hematological ratios. In the multivariate Cox regression analysis, the high SIS group was found to be closely associated with long-term mortality [hazard ratio (HR): 1.58, 95% CI: 1.26-1.97, P <0.001, vs low SIS group]. The Kaplan-Meier curve analysis also demonstrated a difference in long-term mortality between the two groups (Log rank test, P <0.001). Conclusion: The SIS was closely associated with CA-AKI and long-term mortality in patients after elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI and improving the prognosis of patients undergoing PCI.

Study on the Properties of Carbon Nanotube (CNTs) Reinforced AlSi10Mg Composites Fabricated by Powder Metallurgy.

The objective of this study is to prepare CNT/AlSi10Mg composites using mechanical ball milling combined with SPS. The study investigates the influence of ball-milling time and CNT content on the mechanical and corrosion resistance of the composite. This is performed to address the challenge of CNTs dispersion and to understand how CNTs impact the mechanical and corrosion resistance of the composites. The morphology of the composites was characterized using scanning electron microscopy (SEM) transmission electron microscopy (TEM) and Raman spectroscopy, and the mechanics and corrosion resistance of the composite materials were tested. The results demonstrate that the uniform dispersion of CNTs can significantly enhance both the mechanical properties and corrosion resistance of the material. Specifically, when the ball-milling time was 8 h, CNTs were uniformly dispersed in the Al matrix. The CNT/AlSi10Mg composite shows the best interfacial bonding when the mass fraction of CNTs is 0.8 wt.%, with a tensile strength of -256 MPa. This is 69% higher than the original matrix material without the addition of CNTs. Moreover, the composite exhibited the best corrosion resistance.

Effects of ß-Si3N4 Seeds on Microstructure and Performance of Si3N4 Ceramics in Semiconductor Package.

Among the various ceramic substrate materials, Si3N4 ceramics have demonstrated high thermal conductivity, good thermal shock resistance, and excellent corrosion resistance. As a result, they are well-suited for semiconductor substrates in high-power and harsh conditions encountered in automobiles, high-speed rail, aerospace, and wind power. In this work, Si3N4 ceramics with various ratios of α-Si3N4 and ß-Si3N4 in raw powder form were prepared by spark plasma sintering (SPS) at 1650 °C for 30 min under 30 MPa. When the content of ß-Si3N4 was lower than 20%, with the increase in ß-Si3N4 content, the ceramic grain size changed gradually from 1.5 µm to 1 µm and finally resulted in 2 µm mixed grains. However, As the content of ß-Si3N4 seed crystal increased from 20% to 50%, with the increase in ß-Si3N4 content, the ceramic grain size changed gradually from 1 µm and 2 µm to 1.5 µm. Therefore, when the content of ß-Si3N4 in the raw powder is 20%, the sintered ceramics exhibited a double-peak structure distribution and the best overall performance with a density of 97.5%, fracture toughness of 12.1 MPa·m1/2, and a Vickers hardness of 14.5 GPa. The results of this study are expected to provide a new way of studying the fracture toughness of silicon nitride ceramic substrates.

Real-time assessment of COVID-19 epidemic in Guangdong Province, China using mathematical models.

China government has relaxed the response measures of COVID-19 in early December 2022. In this report, we assessed the number of infections, the number of severe cases based on the current epidemic trend (October 22, 2022 to November 30, 2022) using a transmission dynamics model, called modified susceptible-exposed-infectious-removed (SEIR) to provide valuable information to ensure the medical operation of the healthcare system under the new situation. Our model showed that the present outbreak in Guangdong Province peaked during December 21, 2022 to December 25, 2022 with about 14.98 million new infections (95% CI: 14.23-15.73 million). The cumulative number of infections will reach about 70% of the province's population from December 24, 2022 to December 26, 2022. The number of existing severe cases is expected to peak during January 1, 2023 to January 5, 2023 with a peak number of approximately 101.45 thousand (95% CI: 96.38-106.52 thousand). In addition, the epidemic in Guangzhou which is the capital city of Guangdong Province is expected to have peaked around December 22, 2022 to December 23, 2022 with the number of new infections at the peak being about 2.45 million (95% CI: 2.33-2.57 million). The cumulative number of infected people will reach about 70% of the city's population from December 24, 2022 to December 25, 2022 and the number of existing severe cases is expected to peak around January 4, 2023 to January 6, 2023 with the number of existing severe cases at the peak being about 6.32 thousand (95% CI: 6.00-6.64 thousand). Predicted results enable the government to prepare medically and plan for potential risks in advance.

Deficiency of angiopoietin-like 4 enhances CD8+ T cell bioactivity via metabolic reprogramming for impairing tumour progression.

Angiopoietin-like 4 (ANGPTL4) is a secreted metabolism-modulating glycoprotein involved in the progression of tumours, cardiovascular diseases, metabolic syndrome and infectious diseases. In this study, more CD8+ T cells were activated to be effector T cells in ANGPTL4-/- mice. Impaired growth of tumours implanted in 3LL, B16BL6 or MC38 cells and reduced metastasis by B16F10 cells were observed in ANGPTL4-/- mice. Bone marrow (BM) transplantation experiments displayed that deficiency of ANGPTL4 in either host or BM cells promoted CD8+ T cell activation. However, ANGPTL4 deficiency in CD8+ T cells themselves showed more efficient anti-tumour activities. Recombinant ANGPTL4 protein promoted tumour growth in vivo with the less CD8+ T cell infiltration and it directly downregulated CD8+ T cell activation ex vivo. Transcriptome sequencing and metabolism analysis identified that ANGPTL4-/- CD8+ T cells increased glycolysis and decreased oxidative phosphorylation, which was dependent on the PKCζ-LKB1-AMPK-mTOR signalling axis. Reverse correlation of elevated ANGPTL4 levels in sera and tumour tissues with activated CD8+ T cells in the peripheral blood was displayed in patients with colorectal cancer. These results demonstrated that ANGPTL4 decreased immune surveillance in tumour progression by playing an immune-modulatory role on CD8+ T cells via metabolic reprogramming. Efficient blockade of ANGPTL4 expression in tumour patients would generate an effective anti-tumour effect mediated by CD8+ T cells.

Liver Transcriptome Analysis of the Black Porgy (Acanthopagrus schlegelii) under Acute Low-Temperature Stress.

High nutritional value and the development of efficient biotechnological methods of controlled production have made black porgy (Acanthopagrus schlegelii) an economically important fish in Chinese aquaculture in recent years. However, aquaculture production of the species faces multiple issues associated with reduced growth rate, low reproduction ability, and high mortality during production, which are associated with the species' limited tolerance to low temperatures. To date, comprehensive information on the genetic-based mechanisms of cold tolerance and adaptation to low temperature in the species are still unavailable. In this study, the HiSeq™2500 (Illumina) sequencing platform was used to analyze the transcriptomic profile of the liver tissue in the black porgy subjected to different extents of cold shock, including a control temperature group (AS, T = 15 °C), an intermediate temperature group (AL1, T = 10 °C), and an acute low-temperature stress group (AL2, T = 5 °C). For this purpose, three standardized cDNA libraries of AS, AL1, and AL2 were established. We obtained 43,258,908, 48,239,072, and 38,983,833 clean reads from the AS group, AL1 group, and AL2 group, respectively. After pairwise comparison, 70 differentially expressed genes (DEGs) were identified in the examined fish groups. Among them, 60 genes were found to be significantly differentially expressed after trend analysis. GO annotation and enrichment results showed that they were mainly enriched into three categories: biological processes (12 subcategories), molecular functions (7 subcategories), and cellular components (7 subcategories). KEGG analysis results indicated that all significantly differentially expressed genes were annotated to 102 signaling pathways, including biological rhythm, cholesterol metabolism, glycerolipid metabolism, animal autophagy, FoxO signaling pathway, steroid biosynthesis, and regulation of adipocyte lipolysis and apoptosis. Four of them, namely: G6PC, GPX1, GCK, and HSPE1 were randomly selected for further qRT-PCR verification of data reliability obtained by RNA-Seq technology. In this study, we found that environmental acute cold stress mainly affected the black porgy's biological processes related to metabolism, apoptosis, and signal transduction. The data that we have reported provides baseline information for further studies concerning the genetic responses of the black porgy under cold stress conditions, the improvement of its aquaculture production, and other economically important matters regarding their limited tolerance to cold shock.

Exosomes: Mediators in microenvironment of colorectal cancer.

Tumor microenvironment, the soil where tumor thrives, plays a critical role in the development and progression of colorectal cancer (CRC). Various cell signaling molecules in the environment promote tumor angiogenesis, immune tolerance and facilitate immune escape. Exosomes, as messengers between tumor and host cells, are considered key mediators involved in the tumor-accelerating environment. However, the exosome-mediated communication networks in the CRC microenvironment are still largely unclear. In this review, we summarized the relationship between TME and CRC based on recent literature. Then, we revealed the unique impacts and signal molecules of exosomes on account of their regulatory role in the flora, hypoxia, inflammatory and immunological microenvironment of CRC. Finally, we summarized the therapeutically effective of exosomes in CRC microenvironment and discussed their current status and prospects, aiming to provide new molecular targets and a theoretical basis for the CRC treatment.

Dioscin induces M1 macrophage polarization through Connexin-43 Channels in Tumor-associated-macrophages-mediated melanoma metastasis.

BACKGROUND: Tumor-associated macrophages (TAMs) are important constituent parts of tumor microenvironment that connected with tumor metastasis in melanoma. Connexin 43 (Cx43) was expressed in all the immune cells which modulated different aspects of immune response. However, the concrete molecular mechanism maintains unclear. PURPOSE: The study aimed to find a natural drug monomer effectively reversed the polarity of tumor-associated macrophages inhibiting melanoma metastasis and improving survival time. METHODS: Flow cytometry was used to determine the effects of dioscin on the macrophage phenotype. Western bolt and ELISA were performed to explore the underlying mechanism of dioscin and a co-culture experiment in vitro was applied to assess the role of dioscin on TAMs-mediated melanoma proliferation, invasion and migration. Moreover, in vivo melanoma metastasis models were established for examining effects of dioscin on TAMs-mediated melanoma metastasis. RESULTS: Dioscin repolarized macrophages from M2 towards M1-like phenotype. Dioscin suppressed M2-like phenotype macrophages through enhanced the expression and transport function of Cx43. Furthermore, the stimulation IFN-γ/STAT1 pathway and suppression IL-4/JAK2/STAT3 pathway were major mechanism of dioscin. Importantly, dioscin suppressed Cx43G21R mutation TAMs induced proliferation, invasion, migration and metastasis of melanoma cells. It worthily noting that dioscin ameliorated tumor-associated-macrophages-mediated melanoma metastasis in vitro and vivo. CONCLUSION: Dioscin re-polarized macrophages from M2 to M1 phenotype through activation of Cx43-gap-junction-intercellular-communications (Cx43-GJs)/IFN-γ/STAT1 pathway and inhibition of Cx43-GJs/IL-4/JAK2/STAT3 suppressing migration, invasion and metastasis of melanoma, which provided a theoretical and experimental basis for treating melanoma metastasis.

Research on prognostic risk assessment model for acute ischemic stroke based on imaging and multidimensional data.

Accurately assessing the prognostic outcomes of patients with acute ischemic stroke and adjusting treatment plans in a timely manner for those with poor prognosis is crucial for intervening in modifiable risk factors. However, there is still controversy regarding the correlation between imaging-based predictions of complications in acute ischemic stroke. To address this, we developed a cross-modal attention module for integrating multidimensional data, including clinical information, imaging features, treatment plans, prognosis, and complications, to achieve complementary advantages. The fused features preserve magnetic resonance imaging (MRI) characteristics while supplementing clinical relevant information, providing a more comprehensive and informative basis for clinical diagnosis and treatment. The proposed framework based on multidimensional data for activity of daily living (ADL) scoring in patients with acute ischemic stroke demonstrates higher accuracy compared to other state-of-the-art network models, and ablation experiments confirm the effectiveness of each module in the framework.

Daily fluctuations in COVID-19 infection rates under Tokyo's epidemic prevention measures - new evidence from adaptive Fourier decomposition.

Background: The COVID-19 pandemic has witnessed widespread infections and variants. Particularly, Tokyo faced the challenge of seven waves of COVID-19, during which government interventions played a pivotal role. Therefore, gaining a comprehensive understanding of government control measures is of paramount importance, which is beneficial for health authorities in the policy development process. Method: Our study analysis the daily change data of the daily COVID-19 infection count in Tokyo from January 16, 2020 to September 30, 2022. We utilized adaptive Fourier decomposition (AFD) for analyzing the temporal trends within COVID-19 data. It extends the conventional AFD approach by constructing new components base on multiple individual components at various time-frequency scales. Furthermore, we conducted Pearson correlation assessments of the first to third-order synthesis results, along with comparative analyses against other signal analysis techniques. Ultimately, these new components are integrated with policy data spanning different time periods for a comprehensive analysis. Result: The analysis of daily COVID-19 data in Tokyo using AFD reveals how various government policies impacted infection rates across seven distinct fluctuation periods. In the decomposition results, the reduction of business hours policy correlated with high-frequency components in the first four waves, while the low-frequency components for the sixth wave suggested a decline in its relevance. The vaccination policy initially displayed a mid-frequency correlation with the fifth wave and continued with a low-frequency correlation in the last wave. Moreover, our statistical analysis (value of p < 0.05) demonstrated that 75% of the third-order AFD components exhibited significant positive correlations with the original infections, while the correlation coefficients of most components in EMD and VMD did not attain significance. Conclusion: In the time-frequency domain, AFD demonstrates superior performance compared to EMD and VMD in capturing crucial data related to epidemic control measures. The variations in daily COVID-19 infection counts during these seven periods under various policies are evident in distinct third-order AFD components. These findings guide the formulation of future public health policies and social measures.