Tetramethylpyrazine Antagonizes the Subchronic Cadmium Exposure-Induced Oxidative Damage in Mouse Livers via the Nrf2/HO-1 Pathway.

Hepatic oxidative stress is an important mechanism of Cd-induced hepatotoxicity, and it is ameliorated by TMP. However, this underlying mechanism remains to be elucidated. To investigate the mechanism of the protective effect of TMP on liver injuries in mice induced by subchronic cadmium exposure, 60 healthy male ICR mice were randomly divided into five groups of 12 mice each, namely, control (CON), Cd (2 mg/kg of CdCl2), Cd + 100 mg/kg of TMP, Cd + 150 mg/kg of TMP, and Cd + 200 mg/kg of TMP, and were acclimatized and fed for 7 d. The five groups of mice were gavaged for 28 consecutive days with a maximum dose of 0.2 mL/10 g/day. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study show that compared with the Cd group, TMP attenuated CdCl2-induced pathological changes in the liver and improved the ultrastructure of liver cells, and TMP significantly decreased the MDA level (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection show that TMP significantly increased the levels of Nrf2 in the liver compared with the Cd group as well as the HO-1 and mRNA expression levels in the liver (p < 0.05). In conclusion, TMP could inhibit oxidative stress and attenuate Cd group-induced liver injuries by activating the Nrf2 pathway.

Clinical characteristics and prognosis of Klebsiella pneumoniae meningitis in adults.

Background: Klebsiella pneumoniae is a causative agent of bacterial meningitis in adults. However, there is little information regarding this infection. Therefore, this study comprehensively analyzed the clinical characteristics and prognosis of Klebsiella pneumoniae meningitis (KPM) patients. Methods: The clinical data of adult hospitalized patients with KPM were retrospectively collected from January 2015 to December 2022. The clinical characteristics and antibiotic resistance of KPM were evaluated. Meanwhile, a set of logistic regression models was constructed to identify prognostic factors for death. These prognostic factors were subsequently combined to develop a nomogram for predicting the risk of in-hospital mortality in individual patients. Finally, the receiver operating characteristic curve and calibrate plot were utilized to verify the performance of the nomogram. Results: This study included 80 adult patients with KPM, 58 (72.5%) of whom were males. The mortality rate was 45%. Among them, 74 (92.5%) were diagnosed with healthcare-associated meningitis. Thirty-seven carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were susceptible to tigecycline, polymyxin, and ceftazidime/avibactam. CRKP (OR = 9.825, 95%CI = 2.757-35.011, P < 0.001), length of stay (OR = 0.953, 95%CI = 0.921-0.986, P = 0.005), and C-reactive protein-to-prealbumin ratio (CRP/PA, OR = 3.053, 95%CI = 1.329-7.016, P = 0.009) were identified as predictive factors for mortality using multivariate logistic regression. Finally, a nomogram for death prediction was established. The area under the curve of this nomogram was 0.900 (95% CI = 0.828-0.971). Conclusions: KPM is a fatal disease associated with high incidence of healthcare-associated infections and carbapenem resistance. Moreover, CRKP, length of stay, and CRP/PA were found to be independent predictors of mortality.

Decoding human in vitro terminal erythropoiesis originating from umbilical cord blood mononuclear cells and pluripotent stem cells.

Ex vivo red blood cell (RBC) production generates unsatisfactory erythroid cells. A deep exploration into terminally differentiated cells is required to understand the impairments for RBC generation and the underlying mechanisms. Here, we mapped an atlas of terminally differentiated cells from umbilical cord blood mononuclear cells (UCBMN) and pluripotent stem cells (PSC) and observed their dynamic regulation of erythropoiesis at single-cell resolution. Interestingly, we detected a few progenitor cells and non-erythroid cells from both origins. In PSC-derived erythropoiesis (PSCE), the expression of haemoglobin switch regulators (BCL11A and ZBTB7A) were significantly absent, which could be the restraint for its adult globin expression. We also found that PSCE were less active in stress erythropoiesis than in UCBMN-derived erythropoiesis (UCBE), and explored an agonist of stress erythropoiesis gene, TRIB3, could enhance the expression of adult globin in PSCE. Compared with UCBE, there was a lower expression of epigenetic-related proteins (e.g., CASPASE 3 and UBE2O) and transcription factors (e.g., FOXO3 and TAL1) in PSCE, which might restrict PSCE's enucleation. Moreover, we characterized a subpopulation with high proliferation capacity marked by CD99high in colony-forming unit-erythroid cells. Inhibition of CD99 reduced the proliferation of PSC-derived cells and facilitated erythroid maturation. Furthermore, CD99-CD99 mediated the interaction between macrophages and erythroid cells, illustrating a mechanism by which macrophages participate in erythropoiesis. This study provided a reference for improving ex vivo RBC generation.

Combined effects of high-intensity ultrasound treatment and hydrogen peroxide addition on the thermal stabilities of myofibrillar protein emulsions at low ionic strengths.

In this study, the effects of high-intensity ultrasound (HIU) treatment combined with hydrogen peroxide (H2O2) addition on the thermal stability of myofibrillar protein (MP)-stabilized emulsions in low-salt conditions were investigated. Results showed that compared to using either HIU or H2O2 treatment alone, HIU treatment combined with H2O2 was most effective in enhancing the physical stability of emulsions. Moreover, the emulsion stabilized by MPs co-treated with HIU and H2O2 exhibited the most uniform distribution, highest absolute zeta potential, and optimal rheological properties upon heating. This combination effect during heating was caused by the inhibition of disulfide bond cross-linking of myosin heads by H2O2 and the dissociation of filamentous myosin structures using the HIU treatment. In addition, the results of oxidative stability analysis indicated that the addition of H2O2 increased the content of oxidation products; however, the overall influence on the oxidative stability of emulsions was not significant. In conclusion, the combination of HIU and H2O2 treatment is a promising approach to suppress heat-induced MP aggregation and improve the thermal stability of corresponding emulsions.

Enhanced hypoglycemic effects of konjac glucomannan combined with Polygonatum cyrtonema Hua polysaccharide in complete nutritional liquid diet fed type 2 diabetes mice.

In our aging society, dysphagia and malnutrition are growing concerns, necessitating intervention. Liquid nutrition support offers a practical solution for traditional dietary issues, but it raises a key issue: the potential for post-meal glucose spikes impacting efficacy. This study examined the effects of supplementation of Polygonatum cyrtonema Hua polysaccharide (PCP), konjac glucomannan (KGM) and their combination on acute phase postprandial glycemic response and long-term glucose metabolism in T2DM mice on a complete nutritional liquid diet. KGM was more effective in reducing postprandial glucose response, while PCP was more prominent in ameliorating long-term glucose metabolism. The KGM-PCP combination demonstrated superior outcomes in fasting blood glucose, insulin, and glucose homeostasis. PCP and KGM also influenced the composition and abundance of the gut microbiome, with the H-PCP group showing optimal performance. Moreover, the KGM-PCP combination improved body weight, lipid homeostasis, and liver health the most. PCP potentially regulates glycemia through metabolic pathways, while KGM improves glycemic metabolism by reducing postprandial glucose levels in response to viscous intestinal contents. This research identifies the structure, viscosity properties, and hypoglycemic effects of KGM and PCP in complete nutritional liquid diet fed T2DM mice, enabling their strategic utilization as hypoglycemic components in nutritional administration and glycemic regulation.

Insights into the emulsifying effect and oxidation stability of myofibrillar protein-diacylglycerol emulsions containing catechin at different ionic strengths.

The purpose of this study was to investigate the effects of different ionic strengths on the emulsifying and oxidation stabilities of myofibrillar protein-diacylglycerol emulsions containing catechin (MP-DAG-C), in which lard, unpurified glycerolytic lard (UGL), and purified glycerolytic lard (PGL) were used as oil phases in this study, respectively. Results revealed that emulsifying ability was significantly improved by UGL and PGL (P < 0.05). Meanwhile, the emulsifying activity and stability, absolute ξ-potential value, shear viscosity, and dynamic rheological characteristic of emulsions increased with the increase of ionic strength (P < 0.05) remarkablely, which reached the maximum value at 0.6-M sodium chloride (NaCl). The droplets of emulsions at 0.6-M ionic strength were smallest and distributed most uniformly compared to other NaCl conditions. The formation of thiobarbituric acid substances and carbonyls increased, and the total sulfydryl contents decreased as the extension of storage days (P < 0.05). However, the oxidation stability of MP-DAG-C emulsions was insignificantly decreased by ionic strengths (P > 0.05). The above results showed that MP-DAG-C emulsions could keep excellent emulsifying effects and oxidation stability under high ionic strengths. This study provides data support for the application of MP-DAG-C emulsions in emulsified meat products, which is benefit for promoting the development of high-quality emulsified meat products.

Genetic insights into the gut microbiota and risk of facial skin aging: A Mendelian randomization study.

BACKGROUND: A growing number of experimental studies have shown an association between the gut microbiota (GM) and facial skin aging. However, the causal relationship between GM and facial skin aging remains unclear to date. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between GM and facial skin aging. MR analysis was mainly performed using the inverse-variance weighting (IVW) method, complemented by the weighted median (MW) method, MR-Egger regression, and weighted mode, and sensitivity analysis was used to test the reliability of MR analysis results. RESULTS: Eleven GM taxa associated with facial skin aging were identified by IVW method analysis, Family Victivallaceae (p = 0.010), Genus Eubacterium coprostanoligenes group (p = 0.038), and Genus Parasutterella (p = 0.011) were negatively associated with facial skin aging, while Phylum Verrucomicrobia (p = 0.034), Family Lactobacillaceae (p = 0.017) and its subgroups Genus Lactobacillus (p = 0.038), Genus Parabacteroides (p = 0.040), Genus Eggerthella (p = 0.049), Genus Family XIII UCG001 (p = 0.036), Genus Phascolarctobacterium (p = 0.027), and Genus Ruminococcaceae UCG005 (p = 0.012) were positively associated with facial skin aging. At Class and Order levels, we did not find a causal relationship between GM and facial skin aging. Results of sensitivity analyses did not show evidence of pleiotropy and heterogeneity. CONCLUSION: Our findings confirm the causal relationship between GM and facial skin aging, providing a new perspective on delaying facial aging.

Energy-Saving Electrochemical Hydrogen Production Coupled with Biomass-Derived Isobutanol Upgrading.

The widespread application of electrochemical hydrogen production faces significant challenges, primarily attributed to the high overpotential of the oxygen evolution reaction (OER) in conventional water electrolysis. To address this issue, an effective strategy involves substituting OER with the value-added oxidation of biomass feedstock, reducing the energy requirements for electrochemical hydrogen production while simultaneously upgrading the biomass. Herein, we introduce an electrocatalytic approach for the value-added oxidation of isobutanol, a high energy density bio-fuel, coupled with hydrogen production. This approach offers a sustainable route to produce the valuable fine chemical isobutyric acid under mild condition. The electrodeposited Ni(OH)2 electrocatalyst exhibits exceptional electrocatalytic activity and durability for the electro-oxidation of isobutanol, achieving an impressive faradaic efficiency of up to 92.4 % for isobutyric acid at 1.45 V vs. RHE. Mechanistic insights reveal that side reactions predominantly stem from the oxidative C-C cleavage of isobutyraldehyde intermediate, forming by-products including formic acid and acetone. Furthermore, we demonstrate the electro-oxidation of isobutanol coupled with hydrogen production in a two-electrode undivided cell, notably reducing the electrolysis voltage by approximately 180 mV at 40 mA cm-2 . Overall, this work represents a significant step towards improving the cost-effectiveness of hydrogen production and advancing the conversion of bio-fuels.

Interaction of the extracellular protease from Staphylococcus xylosus with meat proteins elucidated via spectroscopic and molecular docking.

This study aimed to assess the effect of an external protease secreted by Staphylococcus (S.) xylosus on the hydrolysis and flavor properties of meat protein. The results indicated that the protease significantly increased the solubility of myofibrillar proteins (MPs) and sarcoplasmic proteins (SPs) in water (P < 0.05), and altered their surface hydrophobicity and secondary structure. The results of micromorphological and free amino acids analyses suggested that the protease degraded the large and insoluble meat protein aggregates into small molecular proteins with uniform distribution and amino acids, especially glycine, glutamic acid, leucine, and cysteine. Moreover, the protease-catalyzed hydrolysis promoted the formation of some volatile compounds in the MPs and SPs. Additionally, molecular docking analysis suggested that hydrogen bond and hydrophobic interaction promoted the formation of a S. xylosus protease/meat protein complex. These results provided a basis for the future application of S. xylosus protease in meat products.

Association of peritumoral region features assessed on breast MRI and prognosis of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Increasing attention has been given to the peritumoral region. However, conflicting findings have been reported regarding the relationship between peritumoral region features on MRI and the prognosis of breast cancer. PURPOSE: To evaluate the relationship between peritumoral region features on MRI and prognosis of breast cancer. MATERIALS AND METHODS: A retrospective meta-analysis of observational studies comparing either qualitative or quantitative assessments of peritumoral MRI features on breast cancer with poor prognosis and control subjects was performed for studies published till October 2022. Pooled odds ratios (ORs) or standardized mean differences and 95% confidence intervals (CIs) were estimated by using random-effects models. The heterogeneity across the studies was measured using the statistic I2. Sensitivity analyses were conducted to test this association according to different study characteristics. RESULTS: Twenty-four studies comprising 1853 breast cancers of poor prognosis and 2590 control participants were included in the analysis. Peritumoral edema was associated with non-luminal breast cancers (OR=3.56; 95%CI: 2.17, 5.83; p=.000), high expression of the Ki-67 index (OR=3.70; 95%CI: 2.41, 5.70; p =.000), high histological grade (OR=5.85; 95%CI: 3.89, 8.80; p=.000), lymph node metastasis (OR=2.83; 95%CI: 1.71, 4.67; p=.000), negative expression of HR (OR=3.15; 95%CI: 2.03, 4.88; p=.000), and lymphovascular invasion (OR=1.72; 95%CI: 1.28, 2.30; p=.000). The adjacent vessel sign was associated with greater odds of breast cancer with poor prognosis (OR=2.02; 95%CI: 1.68, 2.44; p=.000). Additionally, breast cancers with poor prognosis had higher peritumor-tumor ADC ratio (SMD=0.67; 95%CI: 0.54, 0.79; p=.000) and peritumoral ADCmean (SMD=0.29; 95%CI: 0.15, 0.42; p=.000). A peritumoral region of 2-20 mm away from the margin of the tumor is recommended. CONCLUSION: The presence of peritumoral edema and adjacent vessel signs, higher peritumor-tumor ADC ratio, and peritumoral ADCmean were significantly correlated with poor prognosis of breast cancer. CLINICAL RELEVANCE STATEMENT: MRI features of the peritumoral region can be used as a non-invasive index for the prognostic evaluation of invasive breast cancer. KEY POINTS: • Peritumoral edema was positively associated with non-luminal breast cancer, high expression of the Ki-67 index, high histological grade, lymph node metastasis, negative expression of HR, and lymphovascular invasion. • The adjacent vessel sign was associated with greater odds of breast cancers with poor prognosis. • Breast cancers with poor prognosis had higher peritumor-tumor ADC ratio and peritumoral ADCmean.

Synergistic ultrasound pulsed electric field extraction of litchi peel polyphenols and determination of their properties.

The effects of pulsed electric field combined with ultrasound (PEF-US) on the recovery of polyphenols from litchi peels were investigated. In addition, the optimal purification parameters for polyphenol extracts and their biological activities were also explored in this study. Single-factor and orthogonal experiments were used to optimize the extraction conditions of polyphenols. After optimization, the total phenol content (TPC) of the sample extracted by PEF-US was 2.30 times higher than that of the sample extracted by traditional hot-water extraction. The mechanism of PEF-US enhancing polyphenol recovery was also revealed by morphological analysis of the powder surface. LX-7 was the best resin by comparing the purification effect of nine macroporous resins. The optimum conditions for purification of litchi peel polyphenols by LX-7 resin were also optimized through adsorption and desorption experiments. UHPLC-MS and HPLC results revealed that gentisic acid, catechin, procyanidin A2 and procyanidin B1 are four main substances in purified samples. The results of bioactivity experiments showed that the purified polyphenol samples had strong antioxidant and antibacterial activity. Overall, PEF-US is an efficient method for recovering polyphenols from litchi peels. Our study also provides a strategy for the comprehensive utilization of fruit processing waste.

Selective recovery of lithium from spent lithium iron phosphate batteries.

The recovery of lithium from spent lithium iron phosphate (LiFePO4) batteries is of great significance to prevent resource depletion and environmental pollution. In this study, through active ingredient separation, selective leaching and stepwise chemical precipitation develop a new method for the selective recovery of lithium from spent LiFePO4 batteries by using sodium persulphate (Na2S2O8) to oxidize LiFePO4 to FePO4. The impact of various variables on the efficiency of lithium leaching was investigated. Moreover, a combination of thermodynamic analysis and characterization techniques such as X-ray diffraction and X-ray photoelectron spectroscopy was employed to elucidate the leaching mechanism. It was found that 98.65% of lithium could be selectively leached in just 35 minutes at 60°C with only 0.2 times excess of Na2S2O8. This high leaching efficiency can be attributed to the stability and lack of structural damage during the oxidation leaching process. The proposed process is economically viable and environmentally friendly, thus showing great potential for the large-scale recycling of spent LiFePO4 batteries.

Discovery of (2S)-N-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-3-(6-(4-cyanophenyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-hydroxy-2-methylpropanamide as a Highly Potent and Selective Topical Androgen Receptor Antagonist for Androgenetic Alopecia Treatment.

Androgenetic alopecia (AGA) is the most prevalent form of progressive hair loss disorder in both men and women, significantly impacting their appearance and overall quality of life. Overactivation of the AR signaling pathway in dermal papilla cells (DPCs) plays a crucial role in the development and progression of AGA. Considering the severe systemic side effects associated with oral AR antagonists, the idea of developing of topical AR antagonists with rapid metabolic deactivation properties emerged as a promising approach. Herein, through systematic structural optimization, we successfully identified compound 30a as a potent and selective AR antagonist with favorable pharmacokinetic properties, resulting in high skin exposure and low plasma exposure following topical administration. Importantly, in both hair-growth and AGA mouse models, compound 30a showed potent hair-growth-promoting effects without any noticeable toxicity. These findings suggest that compound 30a holds significant potential as a topical AR antagonist for treating AGA patients.

Coastal distribution and driving factors for blue carbon fractions in the surface soil of a warm-temperate salt marsh in China.

A better understanding of blue carbon (BC) sequestration can not only contribute to a better elucidation of global carbon cycle processes but can also lay the foundation for the incorporation of BC ecosystems into regional and global carbon offset schemes. In this study, the surface soils of seven plots along a landward to seaward distance gradient were analyzed for the concentrations and stocks of soil organic carbon (SOC), soil inorganic carbon (SIC), dissolved organic carbon (DOC), and dissolved inorganic carbon (DIC), as well as soil physical (bulk density, texture, moisture), chemical (pH, electrical conductivity), and microbiological (phospholipid fatty acid) properties in the coastal wetlands. Correlation, variation partition and random forest (RF) analyses were used to identify key variables correlating with BC fraction distribution patterns. The results suggested that SIC, DIC, and DOC, exhibited similar landward-increasing trends but the driving factors were distinct from each other. Based on correlation and RF analysis, both SIC and DIC were closely related to soil moisture and clay contents, but microbial indicators of arbuscular mycorrhizal fungi and actinomycete, were found to be associated with SIC, and abiotic properties played less important but still substantial roles in predicting DIC dynamics. In contrast with the other three investigated BC fractions, SOC showed a slight tendency toward enrichment in the seaward direction, and SIC was identified as the main driving factor. DOC showed no significant correlations with the other BC fractions, and its variation could not be explained well by the selected edaphic parameters. The soils in the YRD's tidal Suaeda salsa salt marshes showed a significant negative coupled SOC-SIC correlation, which was potentially related to divergent sedimentary processes and potential biotransformation between SOC and SIC. These results highlight the importance of integrating multiple BC fractions and their interactions into attempts to explore key mechanisms of BC cycling.

The role of tumor-associated macrophages in hepatocellular carcinoma progression: A narrative review.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, with complex etiology and mechanism, and a high mortality rate. Tumor-associated macrophages (TAMs) are an important part of the HCC tumor microenvironment. Studies in recent years have shown that TAMs are involved in multiple stages of HCC and are related to treatment and prognosis in HCC. The specific mechanisms between TAMs and HCC are gradually being revealed. This paper reviews recent advances in the mechanisms associated with TAMs in HCC, concentrating on an overview of effects of TAMs on drug resistance in HCC and the signaling pathways linked with HCC, providing clues for the treatment and prognosis determination of HCC.

A novel telomere-related genes model for predicting prognosis and treatment responsiveness in diffuse large B-cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease with diverse clinical and molecular features. Telomere maintenance is widely present in tumors, but there is a lack of relevant reports on the role of telomere-related genes (TRGs) in DLBCL. In this study, we used consensus clustering based on TRGs expression to identify two molecular clusters with distinct prognoses and immune cell infiltration. We developed a TRGs scoring model using univariate Cox regression and LASSO regression in the GSE10846 training cohort. DLBCL patients in the high-risk group had a worse prognosis than those in the low-risk group, as revealed by Kaplan-Meier curves. The scoring model was validated in the GSE10846 testing cohort and GSE87371 cohort, respectively. The high-risk group was characterized by elevated infiltration of activated DCs, CD56 dim natural killer cells, myeloid-derived suppressor cells, monocytes, and plasmacytoid DCs, along with reduced infiltration of activated CD4 T cells, Type 2 T helper cells, γδ T cells, NK cells, and neutrophils. Overexpression of immune checkpoints, such as PDCD1, CD274, and LAG3, was observed in the high-risk group. Furthermore, high-risk DLBCL patients exhibited increased sensitivity to bortezomib, rapamycin, AZD6244, and BMS.536924, while low-risk DLBCL patients showed sensitivity to cisplatin and ABT.263. Using RT-qPCR, we found that three protective model genes, namely TCEAL7, EPHA4, and ELOVL4, were down-regulated in DLBCL tissues compared with control tissues. In conclusion, our novel TRGs-based model has great predictive value for the prognosis of DLBCL patients and provides a promising direction for treatment optimization.

A novel strategy for improving the stability of myofibrillar protein emulsions at low ionic strength using high-intensity ultrasound combined with non-enzymatic glycation.

Poor emulsification of myofibrillar proteins (MPs) limits the production of meat protein emulsion-type products, and it is related to the myosin self-assembles in low-salt settings. The effect of high-intensity ultrasound (HIU) pretreatment combined with non-enzymatic glycation on MP-stabilized emulsions in low-salt settings was investigated in this study, and the potential mechanism was revealed. The results indicated that, compared to using either HIU or glycation treatment alone, HIU pretreatment in combination with glycation significantly improves the physical stability of emulsions while increasing the distribution uniformity and reducing the droplet particle size from 18.05 µm to 2.54 µm (P < 0.05). Correspondingly, the emulsion prepared using this approach exhibited a relatively high absolute zeta potential (-23.58 mV) and a high interfacial protein content (38.78 %) (P < 0.05), promoting molecular rearrangement and forming a continuous and stable interfacial layer. HIU pretreatment combined with glycation could offer reinforced electrostatic repulsion and steric hindrance to depolymerize self-assembled filamentous polymers, thus enhancing the stability of droplets. Additionally, the thermal sensitivity of the glycated MPs pretreated by HIU was remarkably reduced, thus improving the thermal stability of the corresponding emulsions.

Metabolic influences on T cell in psoriasis: a literature review.

Psoriasis is a systemic inflammatory disease that frequently coexists with various other conditions, such as essential hypertension, diabetes, metabolic syndrome, and inflammatory bowel disease. The association between these diseases may be attributed to shared inflammatory pathways and abnormal immunomodulatory mechanisms. Furthermore, metabolites also play a regulatory role in the function of different immune cells involved in psoriasis pathogenesis, particularly T lymphocytes. In this review, we have summarized the current research progress on T cell metabolism in psoriasis, encompassing the regulation of metabolites in glucose metabolism, lipid metabolism, amino acid metabolism, and other pathways within T cells affected by psoriasis. We will also explore the interaction and mechanism between psoriatic metabolites and immune cells. Moreover, we further discussed the research progress of metabolomics in psoriasis to gain a deeper understanding of its pathogenesis and identify potential new therapeutic targets through identification of metabolic biomarkers associated with this condition.

The Future Landscape of Endothelial Cells Research in Psoriasis: Bibliometric Analysis and Literature Review.

Background: Psoriasis is a global health concern as a chronic inflammatory skin disease. Endothelial dysfunction has been implicated in psoriasis pathogenesis. Objective: This study aims to explore the scientific literature on the relationship between psoriasis and endothelial cells using bibliometric analysis, identifying research trends and public interest in this topic. Methods: We analyzed articles on the topic of endothelial cells and psoriasis in the Web of Science (WoS) Core Collection from 1987 to 2022, examining their distribution by publication year, country, organization, author, and journal. We used bibliometric software, including CiteSpace and R package bibliometrix, to visualize co-authorship relations, keyword citation burst analysis, co citation networks, keyword time zone map, burst references and cluster analysis. Results: Our analysis included 993 publications. The bibliometric analysis revealed a steady increase in the number of publications on psoriasis and endothelial cells over the past decade. The United States was the leading contributor to this field. The Journal of Investigative Dermatology was the most high-yield publication journal. Burst references analysis identified key articles that have significantly influenced the field, including studies on the role of endothelial dysfunction in psoriasis pathogenesis and the association between psoriasis severity and cardiovascular outcomes. 9 clusters were grouped in the key-word citation network. "Expression", "inflammation", "endothelial growth factor" and "angiogenesis" were the research focuses, while "cardiovascular disease", "atherosclerosis", "endothelial dysfunction", and "oxidative stress" might be the future research hotspots. Conclusion: This bibliometric analysis sheds light on the growing acknowledgement of the involvement of endothelial cells in psoriasis, with the United States taking the lead. It also emphasizes the necessity for additional research to unravel the underlying mechanisms connecting psoriasis, endothelial dysfunction, and cardiovascular comorbidities. Ultimately, this research will contribute to the development of enhanced management strategies for psoriasis patients.

CHSY1 promotes CD8+ T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening.

BACKGROUND: The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown. METHODS: We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments. RESULT: The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC. CONCLUSION: CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.