Nr4a1 marks a distinctive ILC2 activation subset in the mouse inflammatory lung.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are critical sources of type 2 cytokines and represent one of the major tissue-resident lymphoid cells in the mouse lung. However, the molecular mechanisms underlying ILC2 activation under challenges are not fully understood. RESULTS: Here, using single-cell transcriptomics, genetic reporters, and gene knockouts, we identify four ILC2 subsets, including two non-activation subsets and two activation subsets, in the mouse acute inflammatory lung. Of note, a distinct activation subset, marked by the transcription factor Nr4a1, paradoxically expresses both tissue-resident memory T cell (Trm), and effector/central memory T cell (Tem/Tcm) signature genes, as well as higher scores of proliferation, activation, and wound healing, all driven by its particular regulons. Furthermore, we demonstrate that the Nr4a1+ILC2s are restrained from activating by the programmed cell death protein-1 (PD-1), which negatively modulates their activation-related regulons. PD-1 deficiency places the non-activation ILC2s in a state that is prone to activation, resulting in Nr4a1+ILC2 differentiation through different activation trajectories. Loss of PD-1 also leads to the expansion of Nr4a1+ILC2s by the increase of their proliferation ability. CONCLUSIONS: The findings show that activated ILC2s are a heterogenous population encompassing distinct subsets that have different propensities, and therefore provide an opportunity to explore PD-1's role in modulating the activity of ILC2s for disease prevention and therapy.

Incorporating environmental capacity considerations to prioritize control factors for the management of heavy metals in soil.

Heavy metals (HMs) pollution threatens food security and human health. While previous studies have evaluated source-oriented health risk assessments, a comprehensive integration of environmental capacity risk assessments with pollution source analysis to prioritize control factors for soil contamination is still lacking. Herein, we collected 837 surface soil samples from agricultural land in the Nansha District of China in 2019. We developed an improved integrated assessment model to analyze the pollution sources, health risks, and environmental capacities of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn. The model graded pollution source impact on environmental capacity risk to prioritize control measures for soil HMs. All HMs except Pb exceeded background values and were sourced primarily from natural, transportation, and industrial activities (31.26%). Approximately 98.92% (children), 97.87% (adult females), and 97.41% (adult males) of carcinogenic values exceeded the acceptable threshold of 1E-6. HM pollution was classified as medium capacity (3.41 kg/hm2) with mild risk (PI = 0.52). Mixed sources of natural backgrounds, transportation, and industrial sources were identified as priority sources, and As a priority element. These findings will help prioritize control factors for soil HMs and direct resources to the most critical pollutants and sources of contamination, particularly when resources are limited.

SNHG1, a KLF4-upregulated gene, promotes glioma cell survival and tumorigenesis under endoplasmic reticulum stress by upregulating BIRC3 expression.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the resistance to endoplasmic reticulum (ER) stress in many cancers. However, ER stress-regulated lncRNAs are still unknown in glioma. In the present study, we investigated the altered lncRNAs upon ER stress in glioma and found that small nucleolar RNA host gene 1 (SNHG1) was markedly increased in response to ER stress. Increased SNHG1 suppressed ER stress-induced apoptosis and promoted tumorigenesis in vitro and in vivo. Further mechanistic studies indicated that SNHG1 elevated BIRC3 mRNA stability and enhanced BIRC3 expression. We also found that KLF4 transcriptionally upregulated SNHG1 expression and contributed to the ER stress-induced SNHG1 increase. Collectively, the present findings indicated that SNHG1 is a KLF4-regulated lncRNA that suppresses ER stress-induced apoptosis and facilitates gliomagenesis by elevating BIRC3 expression.

Transmissible Gastroenteritis Virus Nucleocapsid Protein Interacts with Na+/H+ Exchanger 3 To Reduce Na+/H+ Exchanger Activity and Promote Piglet Diarrhea.

Transmissible gastroenteritis virus (TGEV) is member of the family Coronaviridae and mainly causes acute diarrhea. TGEV infection is characterized by vomiting, watery diarrhea, and severe dehydration, resulting in high mortality rates in neonatal piglets. TGEV infection symptoms are related to an imbalance of sodium absorption in small intestinal epithelial cells; however, the etiology of sodium imbalance diarrhea caused by TGEV remains unclear. In this study, we performed transcriptomic analysis of intestinal tissues from infected and healthy piglets and observed that the expression of NHE3, encoding Na+/H+ exchanger 3 (NHE3), the main exchanger of electroneutral sodium in intestinal epithelial cells, was significantly reduced upon TGEV infection. We also showed that specific inhibition of intestinal NHE3 activity could lead to the development of diarrhea in piglets. Furthermore, we revealed an interaction between TGEV N protein and NHE3 near the nucleus. The binding of TGEV N to NHE3 directly affected the expression and activity of NHE3 on the cell surface and affected cellular electrolyte absorption, leading to diarrhea. Molecular docking and computer-aided screening techniques were used to screen for the blocker of the interaction between TGEV N and NHE3, which identified irinotecan. We then demonstrated that irinotecan was effective in relieving TGEV-induced diarrhea in piglets. These findings provide new insights into the mechanism of TGEV-induced sodium imbalance diarrhea and could lead to the design of novel antiviral strategies against TGEV. IMPORTANCE A variety of coronaviruses have been found to cause severe diarrhea in hosts, including TGEV; however, the pathogenic mechanism is not clear. Therefore, prompt determination of the mechanism and identification of efficient therapeutic agents are required, both for public health reasons and for economic development. In this study, we demonstrated that NHE3 is the major expressed protein of NHEs in the intestine, and its expression decreased by nearly 70% after TGEV infection. Also, specific inhibition of intestinal NHE3 resulted in severe diarrhea in piglets. This demonstrated that NHE3 plays an important role in TGEV-induced diarrhea. In addition, we found that TGEV N directly regulates NHE3 expression and activity through protein-protein interaction, which is essential to promote diarrhea. Molecular docking and other techniques demonstrated that irinotecan could block the interaction and diarrhea caused by TGEV. Thus, our results provide a basis for the development of novel therapeutic agents against TGEV and guidance for the development of drugs for other diarrhea-causing coronaviruses.

Bioinformatic analysis of the S protein of human respiratory coronavirus.

The present study aimed to apply bioinformatic methods to analyze the structure of the S protein of human respiratory coronaviruses, including severe respiratory disease syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus HKU1 (HCoV-HKU1), and severe respiratory disease syndrome coronavirus type 2 (SARS-CoV-2). We predicted and analyzed the physicochemical properties, hydrophilicity and hydrophobicity, transmembrane regions, signal peptides, phosphorylation and glycosylation sites, epitopes, functional domains, and motifs of the S proteins of human respiratory coronaviruses. All four S proteins contain a transmembrane region, which enables them to bind to host cell surface receptors. All four S proteins contain a signal peptide, phosphorylation sites, glycosylation sites, and epitopes. The predicted phosphorylation sites might mediate S protein activation, the glycosylation sites might affect the cellular orientation of the virus, and the predicted epitopes might have implications for the design of antiviral inhibitors. The S proteins of all four viruses have two structural domains, S1 (C-terminal and N-terminal domains) and S2 (homology region 1 and 2). Our bioinformatic analysis of the structural and functional domains of human respiratory coronavirus S proteins provides a basis for future research to develop broad-spectrum antiviral drugs, vaccines, and antibodies.

Knockdown of CENPN Inhibits Glucose Metabolism and Induces G1 Arrest in Esophageal Cancer Cells by Regulating PI3K/AKT Signaling Pathway.

Esophageal carcinoma (ESCA) is a deadly malignancy with an increasing incidence year by year. The purpose of this study was to explore the function of CENPN in ESCA. Based on TCGA public data platform, the transcription level of CENPN in ESCA was analyzed. Subsequently, ESCA cells with CENPN overexpression or knockdown were constructed. The proliferation and migration levels of ESCA cells were evaluated by CCK-8, colony formation assay, and transwell analysis. Western blotting was used to detect protein levels associated with CyclinD1, CDK2, GLUT1, and PI3K/AKT signaling pathways. Cell cycle distribution was measured by flow cytometry. Glucose consumption and lactate production in ESCA cells were measured. CENPN was overexpressed in ESCA. In vitro experiments showed that CENPN promoted the proliferation and migration of ESCA cells, and upregulated the levels of CyclinD1, CDK2, and GLUT1, promoting the cell cycle process, increasing glucose consumption and lactic acid production. In addition, CENPN overexpression increased the phosphorylation levels of PI3K and AKT. The results suggest that the abnormal expression of CENPN in ESCA may enhance the malignant phenotype of ESCA cells by activating the PI3K/AKT signaling pathway. CENPN is expected to be a new target for ESCA treatment.

Positive rate and quantification of amyloid pathology with [18F]florbetapir in the urban Chinese population.

OBJECTIVES: Amyloid deposition is considered the initial pathology in Alzheimer's disease (AD). Personalized management requires investigation of amyloid pathology and the risk factors for both amyloid pathology and cognitive decline in the Chinese population. We aimed to investigate amyloid positivity and deposition in AD patients, as well as factors related to amyloid pathology in Chinese cities. METHODS: This cross-sectional multicenter study was conducted in Shanghai and Zhengzhou, China. All participants were recruited from urban communities and memory clinics. Amyloid positivity and deposition were analyzed based on amyloid positron emission tomography (PET). We used partial least squares (PLS) models to investigate how related factors contributed to amyloid deposition and cognitive decline. RESULTS: In total, 1026 participants were included: 768 participants from the community-based cohort (COMC) and 258 participants from the clinic-based cohort (CLIC). The overall amyloid-positive rates in individuals with clinically diagnosed AD, mild cognitive impairment (MCI), and normal cognition (NC) were 85.8%, 44.5%, and 26.9%, respectively. The global amyloid deposition standardized uptake value ratios (SUVr) (reference: cerebellar crus) were 1.44 ± 0.24, 1.30 ± 0.22, and 1.24 ± 0.14, respectively. CLIC status, apolipoprotein E (ApoE) ε4, and older age were strongly associated with amyloid pathology by PLS modeling. CONCLUSION: The overall amyloid-positive rates accompanying AD, MCI, and NC in the Chinese population were similar to those in published cohorts of other populations. ApoE ε4 and CLIC status were risk factors for amyloid pathology across the AD continuum. Education was a risk factor for amyloid pathology in MCI. Female sex and age were risk factors for amyloid pathology in NC. CLINICAL RELEVANCE STATEMENT: This study provides new details about amyloid pathology in the Chinese population. Factors related to amyloid deposition and cognitive decline can help to assess patients' AD risk. KEY POINTS: • We studied amyloid pathology and related risk factors in the Chinese population. •·The overall amyloid-positive rates in individuals with clinically diagnosed AD, MCI, and NC were 85.8%, 44.5%, and 26.9%, respectively. • These overall amyloid-positive rates were in close agreement with the corresponding prevalence for other populations.

Prioritization of control factors for heavy metals in groundwater based on a source-oriented health risk assessment model.

Heavy metals (HMs) in groundwater seriously threaten ecological safety and human health. To facilitate the effective management of groundwater contamination, priority control factors of HMs in groundwater need to be categorized. A total of 86 groundwater samples were collected from the Huangpi district of Wuhan city, China, during the dry and wet seasons. To determine priority control factors, a source-oriented health risk assessment model was applied to compare the pollution sources and health risks of seven HMs (Cu, Pb, Zn, Cr, Ni, As, and Fe). The results showed that the groundwater had higher As and Fe contents. The sources of HM pollution during the wet period were mainly industrial and agricultural activities and natural sources. During the dry period, origins were more complex due to the addition of domestic discharges, such as sewage wastewater. Industrial activities (74.10% during the wet period), agricultural activities (53.84% during the dry period), and As were identified as the priority control factors for groundwater HMs. The results provide valuable insights for policymakers to coordinate targeted management of HM pollution in groundwater and reduce the cost of HM pollution mitigation.

Palladium Catalyzed Direct Carbonylative Thiomethylation of Aryldiazonium Salts and Amines with 4-(Methylthio)-2-Butanone as (Methylthio) Transfer Agent.

Herein, an interesting palladium-catalyzed procedure for the direct carbonylative thiomethylation of aromatic amine derivatives with 4-methylthio-2-butanone is developed. Using 4-methylthio-2-butanone as (methylthio) transfer agent, a variety of corresponding thioesters are obtained with moderate to good yields under base-free condition. In addition, good functional group tolerance can be observed.

Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity.

BACKGROUND: Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function. METHODS: Immunohistochemical staining and/or autoradiography staining were used to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and TH levels in the striatum. Using a stereotyped behavior rating scale, we evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization. RESULTS: Repeated METH administration induced obvious stereotyped behavior and neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly attenuated METH-induced stereotyped responses, and interdicted METH-induced changes in the levels of DAT, D2R and TH expression. Treatment with JTT after METH administration restored DAT, D2R and TH expression to normal levels. CONCLUSIONS: Our results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.

Effects of Jitai tablet, a traditional Chinese medicine, on spontaneous withdrawal symptoms and modulation of dopaminergic functions in morphine-dependent rats.

Chronic opioid abuse can cause damage to dopamine neurons. However, there are currently no effective pharmacotherapies to reverse this damage, even though progress has been made in the development of therapeutic strategies for opioid dependence. The Jitai tablet (JTT) is a traditional Chinese medicine formulation most commonly used for opioid addiction treatment in China. In a morphine spontaneous withdrawal rat model we investigated the effects of JTT, either given before (pre-treatment) or after (post-treatment) morphine administration, on the dopamine system. Our study has shown the following: (1) pre- and post-treatment with JTT were effective at alleviating the wet dog shakes and episodes of writhing; (2) pre-treatment with JTT inhibited the morphine-induced decreases in dopamine transporter (DAT), dopamine D2 receptor (D2 R) and tyrosine hydroxylase (TH) levels in the striatum (p < 0.01, compared with morphine group) and maintained them at normal levels; and (3) post-treatment with JTT restored the densities of DAT, D2 R and TH in the striatum to normal levels (p < 0.01, compared with morphine group). These results support the notion that modulation of the dopamine system in the striatum may play a role for JTT's therapeutic effect on the alleviation of opioid withdrawal symptoms.

Corydaline alleviates Parkinson's disease by regulating autophagy and GSK-3ß phosphorylation.

BACKGROUND: Jitai tablet, a traditional Chinese medicine, has a neuroprotective effect on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mice. As one of the main active ingredients in the Jitai tablet, corydaline (Cory) has analgesic and anti-allergic effects, but it has not been studied in PD. Here, we investigated the role and mechanism of Cory in PD. METHODS: The PD model was induced by MPTP. Cell viability was measured by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide assay. The Pole test and traction test were performed to detect the behaviors of mice. The expression of tyrosine hydroxylase (Th) was detected by immunohistochemistry and Western blot. Immunofluorescence staining, monodansylcadaverine staining, and Western blot were conducted to assess autophagy. A lactic dehydrogenase release assay was used to detect cytotoxicity. Network pharmacology was used to screen the targets. RESULTS: There existed cytotoxicity when the concentration of Cory reached 40 µg/mL. Cory (not exceeding 20 µg/mL) could alleviate MPTP-induced cell damage. In vivo experiments indicated that Cory could improve the motor coordination of mice with PD. Besides, Cory could increase LC3-II/LC3-I levels both in vivo and in vitro. In addition, the Th levels reduced in the striatum and middle brain tissues of Parkinson's mice were recovered by Cory injection. We also found that Cory decreased the phosphorylation of glucogen synthase kinase-3 beta (GSK-3ß) at Tyr216 and increased the phosphorylation of GSK-3ß at Ser9 not only in primary neurons and SH-SY5Y cells but also in the striatum and middle brain tissues. Furthermore, Cory increased LC3-II/LC3-I levels and decreased p62 levels by regulating GSK-3ß. CONCLUSION: Cory enhanced autophagy, attenuated MPTP-induced cytotoxicity, and alleviated PD partly through the regulation of GSK-3ß phosphorylation.

Comparative Effects of Umbilical Cord Mesenchymal Stem Cell Treatment via Different Routes on Lipopolysaccharide-Induced Acute Lung Injury.

BACKGROUND: Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of UCMSC transplantation, such as infusion routes and doses, need to be further optimized. METHODS: In this study, we compared the therapeutic effects of UCMSCs transplanted via intravenous injection and intratracheal instillation on lipopolysaccharide-induced ALI using a rat model. Following transplantation, levels of inflammatory factors in serum; neutrophils, total white blood cells, and lymphocytes in bronchoalveolar lavage fluid (BALF); and lung damage levels were analyzed. RESULTS: The results indicated that UCMSCs administered via both intravenous and intratracheal routes were effective in alleviating ALI, as determined by analyses of arterial blood gas, lung histopathology, BALF contents, and levels of inflammatory factors. Comparatively, the intratracheal instillation of UCMSCs was found to result in lower levels of lymphocytes and total proteins in BALF, whereas greater reductions in the serum levels of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were detected in rats receiving intravenously injected stem cells. CONCLUSIONS: Our findings in this study provide convincing evidence to indicate the efficacy of UCMSC therapy in the treatment of ALI mediated via different delivery routes, thereby providing a reliable theoretical basis for further clinical studies. Moreover, these findings imply that the effects obtained using the two assessed delivery routes for UCMSC transplantation are mediated via different mechanisms, which could be attributable to different cellular or molecular targets.

Observation on efficacy and underlying mechanism of cheek acupuncture on ovulation induction for infertile women with PCOS: Case series.

RATIONALE: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of childbearing age and is the primary cause of anovulatory infertility, accounting for 70% to 80% of cases. Ovulation induction is the main treatment approach for infertile patients with PCOS. Commonly utilized medications for this purpose are clomiphene citrate (CC) and letrozole (LE). Clomiphene citrate administration results in an ovulation rate ranging from 60% to 85%, while the pregnancy rate is limited to 35% to 40%, and a further reduction is observed in live birth rates. Letrozole demonstrates a slightly higher pregnancy rate and live birth rate compared to clomiphene citrate, although challenges persist in terms of longer stimulation cycles, multiple pregnancies, and the risk of ovarian hyperstimulation syndrome (OHSS). Clinical reports indicate that acupuncture therapy shows promising efficacy in treating patients with PCOS-related infertility, despite a partially unclear understanding of its underlying mechanisms. PATIENT CONCERNS: In this study, one patient did not achieve pregnancy despite more than a year of ovulation induction using clomiphene citrate and letrozole. However, after 3 months of receiving cheek acupuncture therapy, she successfully conceived and gave birth to a liveborn baby. Another patient achieved natural conception and live birth after 2 months of exclusive cheek acupuncture therapy. DIAGNOSIS: PCOS. INTERVENTIONS: Cheek acupuncture therapy. OUTCOMES: Both of them successfully conceived and gave birth to a liveborn baby. LESSONS: These findings suggest that cheek acupuncture therapy can effectively stimulate follicle development and ovulation, potentially improving endometrial receptivity. According to holographic theory, there is a biologically holographic model within the cheek region that shares a homology with the human body structure. This model provides an explanation for the regulatory effects of cheek acupuncture point stimulation on the Hypothalamic-Pituitary-Ovarian axis (HPO), which subsequently influences follicle development and ovulation in patients. Consequently, when cheek acupuncture therapy is applied alone or in combination with ovulation induction medication, patients have the ability to achieve successful pregnancy and experience a smooth delivery.

Abnormal changes in metabolites caused by m6A methylation modification: The leading factors that induce the formation of immunosuppressive tumor microenvironment and their promising potential for clinical application.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation modifications have been widely implicated in the metabolic reprogramming of various cell types within the tumor microenvironment (TME) and are essential for meeting the demands of cellular growth and maintaining tissue homeostasis, enabling cells to adapt to the specific conditions of the TME. An increasing number of research studies have focused on the role of m6A modifications in glucose, amino acid and lipid metabolism, revealing their capacity to induce aberrant changes in metabolite levels. These changes may in turn trigger oncogenic signaling pathways, leading to substantial alterations within the TME. Notably, certain metabolites, including lactate, succinate, fumarate, 2-hydroxyglutarate (2-HG), glutamate, glutamine, methionine, S-adenosylmethionine, fatty acids and cholesterol, exhibit pronounced deviations from normal levels. These deviations not only foster tumorigenesis, proliferation and angiogenesis but also give rise to an immunosuppressive TME, thereby facilitating immune evasion by the tumor. AIM OF REVIEW: The primary objective of this review is to comprehensively discuss the regulatory role of m6A modifications in the aforementioned metabolites and their potential impact on the development of an immunosuppressive TME through metabolic alterations. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review aims to elaborate on the intricate networks governed by the m6A-metabolite-TME axis and underscores its pivotal role in tumor progression. Furthermore, we delve into the potential implications of the m6A-metabolite-TME axis for the development of novel and targeted therapeutic strategies in cancer research.

Diagnostic value of 18F-PSMA-1007 PET/CT for predicting the pathological grade of prostate cancer.

This study was designed to evaluate the diagnostic efficacy of relevant parameters of 18F-prostate-specific membrane antigen (PSMA)-1007 PET/CT in predicting the pathological grade of primary prostate cancer. Briefly, a prospective analysis was performed on 53 patients diagnosed with prostate cancer by systematic puncture biopsy, followed by 18F-PSMA-1007 PET/CT examination prior to treatment within 10 d. The patients were grouped in accordance with the Gleason grading system revised by the International Association of Urology Pathology (ISUP). They were divided into high-grade group (ISUP 4-5 group) and low-grade group (ISUP 1-3 group). The differences in maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), intraprostatic PSMA-derived tumor volume (iPSMA-TV), and intraprostatic total lesion PSMA (iTL-PSMA) between the high- and low-grade group were statistically significant (p < .001). No significant difference was found for mean standardized uptake value (SUVmean) between the high- and low-grade groups (Z = -1.131, p = .258). Besides, binary multivariate logistic regression analysis showed that only iPSMA-TV and iTL-PSMA were independent predictors of the pathological grading, for which the odds ratios were 18.821 [95% confidence interval (CI): 2.040-173.614, p = .010] and 0.758 (95% CI: 0.613-0.938, p = .011), respectively. The area under the ROC of this regression model was 0.983 (95% CI: 0.958-1.00, p < .001). Only iTL-PSMA was a significant parameter for distinguishing ISUP-4 and ISUP-5 groups (Z = -2.043, p = .041). In a nutshell, 18F-PSMA-1007 PET/CT has good application value in predicting the histopathological grade of primary prostate cancer. Three-dimensional volume metabolism parameters iPSMA-TV and iTL-PSMA were found to be independent predictors for pathological grade.

Clinical significance of leukotriene b4 and extracellular matrix metalloproteinase inducer in acute coronary syndrome.

PURPOSE: Leukotriene B4 (LTB4) and extracellular matrix metalloproteinase (EMMPRIN) have been suggested as modulators of atherosclerotic plaque instability. This study sought to evaluate the potential diagnostic implication of LTB4 and EMMPRIN in patients with acute coronary syndrome (ACS). METHODS: Patients (n=153) who underwent coronary angiography, including 105 patients diagnosed with ACS, were divided into four groups: stable angina pectoris (SAP, n=19), unstable angina pectoris (UAP, n=39), acute myocardial infarction (AMI, n=66) and control (with normal coronary angiography, n=29). EMMPRIN expression in peripheral blood mononuclear cells was determined by flow cytometry and serum LTB4 levels were measured by ELISA. To examine whether LTB4 can regulate the expression of EMMPRIN and matrix metalloproteinases (MMPs) in macrophages, differentiated THP-1 macrophages were stimulated with different concentrations of LTB4 (10-10-10-7mmol/L). Expression of EMMPRIN was evaluated by Western blotting. MMP-9 mRNA expression and enzymatic activity were determined by RT-PCR and SDS-PAGE gelatin zymography. RESULT: Serum LTB4 concentration was significantly higher in AMI and UAP groups, compared with control and SAP groups (p < 0.01). Subgroups analysis showed that LTB4 was significantly higher in the AMI < 24h group, compared with the AMI > 24h group. Expression of EMMPRIN on circulating monocytes was significantly higher in patients with UAP and AMI (> 24h), compared with control, SAP and AMI (< 24h) groups (p < 0.05). In vitro study showed LTB4 up-regulated the expression of EMMPRIN, as well as the expression and activity of MMP-9, in cultured THP-1-derived macrophages (p < 0.05). CONCLUSION: LTB4 and EMMPRIN are associated with the pathogenesis of ACS and may be potential biomarkers for patients with ACS.

Risk Factors for Negative Emotions in Patients Undergoing Radical Resection of Hilar Cholangiocarcinoma and Their Influence on Prognosis.

Background: Hilar cholangiocarcinoma (HCCA) is a common malignant tumor of the biliary system. Factors such as limited physical function, intractability, and high mortality caused by the tumor lead to negative emotions, such as anxiety and depression in patients. In this study, we investigated the risk factors for negative emotions in patients undergoing radical resection of HCCA during the perioperative period and its effect on prognosis to provide strategies for alleviating the negative emotional disorders of patients and improving prognosis. Methods: From September 2016 to August 2021, we retrospectively examined 205 patients with HCCA who underwent radical resection in our hospital. The incidence of negative emotions and the clinical parameters of patients were compared using Chi-square tests and t-tests. The independent risk factors for unfavorable feelings in patients during the perioperative period were determined using binary logistic regression. The key variables influencing the postoperative survival status of HCCA patients were identified using the log-rank univariate analysis and Cox proportional risk regression analysis. Results: The results of the binary logistic regression analysis showed that perioperative negative emotions were independently influenced by family monthly income (OR = 0.069), medical insurance (OR = 0.089), family care (OR = 0.013), sleep quality (OR = 0.071), TNF-α (OR = 5.851), and bile leakage (OR = 29.412) (P < 0.05). The age of the patient (OR = 2.003), preoperative CA19-9 (OR = 2.038), lymph node metastases (OR = 2.327), and negative mood (OR = 3.054) were independent risk variables that affected the survival status of patients, as determined by the results of Cox regression analysis (P < 0.05). Conclusion: In this study, we found that anxiety and depression in patients undergoing radical operation of HCCA are related to family monthly income, medical insurance, sleep quality, family care, TNF-α, and bile leakage; also, negative emotions have adverse effects on prognosis.

Large-scale renewable energy brings regionally disproportional air quality and health co-benefits in China.

Developing renewable energy could jointly reduce air pollution, greenhouse gas emissions, and bring air pollution-related health co-benefits. However, the temporal and sub-national distributions of investment costs and human health co-benefits from renewable energy deployment remain unclear. To investigate this gap, we linked multiple models for a more comprehensive assessment of the economic-environmental-health co-benefits of renewable energy development in China. The results show that developing renewable energy can avoid 0.6 million premature mortalities, 151 million morbidities, and 111 million work-loss days in 2050. Meanwhile, the human health and economic co-benefits vary substantially across regions in China. Renewable energy can undoubtedly bring health and economic co-benefits. Nevertheless, the economic benefits lag considerably behind the high initial investment cost, first negative in 2030 (-0.6 trillion Yuan) and then positive in 2050 (2.9 trillion Yuan). Hence, renewable energy deployment strategy must be carefully designed considering the regional disparities.

[Expressions and Clinical Significance of Notch1 and Hes1 in Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the expressions of Notch1 and Hes1 in diffuse large B-cell lymphoma (DLBCL), and their correlations with clinical features. METHODS: Immunohistochemistry (IHC) was performed on DLBCL samples (54 cases) and lymphadenitis tissues (20 cases) to evaluate the expressions of Notch1 and Hes1, and analyze their correlations with clinical characteristics of patients. Based on Oncomine database, the expressions of Notch1 and Hes1 mRNA and DNA were also explored. RESULTS: IHC result showed that the positive expression rates of Notch1 and Hes1 in DLBCL patients were significantly higher than those in the control group (P <0.05). In DLBCL patients, the expression of Notch1 was closely associated with B symptoms, Ann Arbor stage, lymphocyte count and the level of lactate dehydrogenase (P <0.05), while the expression level of Hes1 was significantly higher in patients with B symptoms (P <0.05). Notch+/Hes1+ expression was found in 21 DLBCL tissues (38.9%), and there was a correlation between Notch1 and Hes1 expression (r =0.296, P <0.05). Bioinformatics analysis (Oncomine database) showed that the mRNA expressions of Notch1 and Hes1 in the Brune dataset were significantly higher than those in the control tissues (P <0.05). CONCLUSION: The expressions of Notch1 and Hes1 in DLBCL are significantly higher than those in lymphadenitis, and correlated with B symptoms and Ann Arbor stage, suggesting that Notch1 and Hes1 play important roles in the occurrence and development of DLBCL.