Aggregation-induced enhancement of pyrene-based metal-organic framework as a new electrochemiluminescence emitter for ultrasensitive detection of sulfadimethoxine.

In this study, a signal-on electrochemiluminescence (ECL) aptasensor for ultrasensitive detection of sulfadimethoxine (SDM) was constructed based on a competitive aptamer strategy. Specifically, cerium-metal-organic framework (Ce-MOF) with large specific surface area and excellent electrical conductivity was combined with gold nanoparticles (AuNPs) to form a substrate, followed by the immobilisation of double-stranded DNA (dsDNA) via AuN bonds. In the presence of SDM, the aptamer tended to form an aptamer-SDM complex, which caused dsDNA to dissociate. After release of the aptamer, the capture probe (CP) combined with the tracer label to enhance the ECL signal. As expected, the prepared sensor displayed an ideal linear response range from 10.0 fg mL-1 to 100 ng mL-1 with a limit of detection (LOD) of 1.28 fg mL-1 and successfully detected SDM in milk and quality control samples.

Metformin induces tolerogenicity of dendritic cells by promoting metabolic reprogramming.

Dendritic cells (DCs) can mediate immune responses or immune tolerance depending on their immunophenotype and functional status. Remodeling of DCs' immune functions can develop proper therapeutic regimens for different immune-mediated diseases. In the immunopathology of autoimmune diseases (ADs), activated DCs notably promote effector T-cell polarization and exacerbate the disease. Recent evidence indicates that metformin can attenuate the clinical symptoms of ADs due to its anti-inflammatory properties. Whether and how the therapeutic effects of metformin on ADs are associated with DCs remain unknown. In this study, metformin was added to a culture system of LPS-induced DC maturation. The results revealed that metformin shifted DC into a tolerant phenotype, resulting in reduced surface expression of MHC-II, costimulatory molecules and CCR7, decreased levels of proinflammatory cytokines (TNF-α and IFN-γ), increased level of IL-10, upregulated immunomodulatory molecules (ICOSL and PD-L) and an enhanced capacity to promote regulatory T-cell (Treg) differentiation. Further results demonstrated that the anti-inflammatory effects of metformin in vivo were closely related to remodeling the immunophenotype of DCs. Mechanistically, metformin could mediate the metabolic reprogramming of DCs through FoxO3a signaling pathways, including disturbing the balance of fatty acid synthesis (FAS) and fatty acid oxidation (FAO), increasing glycolysis but inhibiting the tricarboxylic acid cycle (TAC) and pentose phosphate pathway (PPP), which resulted in the accumulation of fatty acids (FAs) and lactic acid, as well as low anabolism in DCs. Our findings indicated that metformin could induce tolerance in DCs by reprogramming their metabolic patterns and play anti-inflammatory roles in vitro and in vivo.

Management of cognitive frailty: A network meta-analysis of randomized controlled trials.

OBJECTIVES: We aimed to compare the effectiveness of interventions in cognitive function and frailty status and rank these interventions. METHODS: Data Sources-We searched PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, Central Register of Controlled Trials (CENTRAL), CNKI, Wanfang, VIP and Google scholar. Data synthesis-The risk of bias was assessed using the Cochrane risk bias assessment tool. Statistical heterogeneity was assessed using the Chi-square test and quantified by I2 . The results were pooled using the standardized mean difference (SMD). The rank probability for each intervention was calculated using the surface under the cumulative ranking curve (SUCRA). Additionally, the quality of the evidence was evaluated using the GRADE approach. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 1110 patients were included in our analysis. The network map of cognitive function comprised 9 RCTs with 1347 participants, examining eight different interventions. Nutritional support (SUCRA = 99.9%, SMD = 3.02, 95% CI: 2.53, 3.51) may be the most effective intervention to improve cognitive function. The network map of frailty (including 9 RCTs with 1017 participants and 9 interventions) suggested that multicomponent exercises (SUCRA = 96.4%, SMD = -5.10, 95% CI: -5.96, -4.23) tended to have a greater effect. CONCLUSIONS: Community-based multicomponent exercises have shown significant benefits for improving cognitive function and frailty status in older adults, with moderate certainty. For hospitalized older patients with Cognitive frailty (CF), current evidence suggests that nutritional support yields the most improvement. Additionally, aerobic exercise and dual-task training have proven effective in managing CF. Further studies are needed to validate these preliminary findings and exploring more accessible and effective physical and cognitive interventions to prevent CF in aging.

Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer characterized by dominant driver mutations, including p53. Consequently, there is an urgent need to search for novel therapeutic agents to treat HCC. Andrographolide (Andro), a clinically available anti-inflammatory phytochemical agent, has shown inhibitory effects against various types of cancer, including HCC. However, the underlying molecular mechanisms of its action remain poorly understood. PURPOSE: This study aims to investigate the molecular mechanisms by which p53 and p62 collectively affect Andro-induced HCC cell death, using both in vitro and in vivo models. METHODS: In vitro cellular experiments were conducted to examine the effects of Andro on cell viability and elucidate its mechanisms of action. In vivo xenograft experiments further validated the anti-cancer effects of Andro. RESULTS: Andro induced dose- and time-dependent HCC cell death while sparing normal HL-7702 hepatocytes. Furthermore, Andro caused DNA damage through the generation of reactive oxygen species (ROS), a critical event leading to cell death. Notably, HCC cells expressing p53 exhibited greater resistance to Andro-induced cell death compared to p53-deficient cells, likely due to the ability of p53 to induce G2/M cell cycle arrest. Additionally, Andro-induced p62 aggregation led to the proteasomal degradation of RAD51 and 53BP1, two key proteins involved in DNA damage repair. Consequently, silencing or knocking out p62 facilitated DNA damage repair and protected HCC cells. Importantly, disruption of either p53 or p62 did not affect the expression of the other protein. These findings were further supported by the observation that xenograft tumors formed by p62-knockout HCC cells displayed increased resistance to Andro treatment. CONCLUSION: This study elucidates the mechanistic basis of Andro-induced HCC cell death. It provides valuable insights for repurposing Andro for the treatment of HCC, regardless of the presence of functional p53.

Functional Characterization of Two NAC Transcription Factors HfNAP1 and HfNAC090 Associated with Flower Programmed Cell Death in Daylily (Hemerocallis fulva).

Daylily (Hemerocallis fulva) is one of the most widely used perennial flowers, but its ornamental and economic value is greatly limited due to its ephemeral flowering period. In general, the flower senescence is regulated by the developmental signals and considered as an irreversible process of programmed cell death (PCD). However, the molecular mechanism of flower PCD in daylily still remains unclear. In this study, two NAC transcription factors, namely HfNAP1 and HfNAC090, are first identified and found to be upregulated significantly in both the age-induced and the ABA-induced flower PCD processes in daylily. Then, the functions of HfNAP1 and HfNAC090 in regulating the flower PCD are investigated through transgenic phenotypes analysis. The results demonstrate that the ectopic and transient overexpression of these two genes can effectively regulate the flower PCD in tobacco and daylily. While the overexpression of HfNAP1 accelerates the flower PCD process, the overexpression of HfNAC090 significantly delays that. Furthermore, the yeast two-hybrid assay is performed to discover potential interactions related to these two genes, and the results demonstrate that HfNAP1 and HfNAC090 can interact with each other, or interact with other flower aging-related genes. Additionally, the yeast one-hybrid assay suggests that HfNAP1 and HfNAC090 can bind directly to the promoters of downstream senescence-associated genes HfSAG39 and HfSAG15. Taken overall, this study provides sufficient evidences to confirm that HfNAP1 and HfNAC090 play dominant roles in regulating the flower PCD in daylily, supporting the development of new strategies to prolong the longevity of daylily flowers.

Long-term care status for the elderly with different levels of physical ability: a cross-sectional survey in first-tier cities of China.

BACKGROUND: Long term care (LTC) services for functionally impaired senior citizens are crucial for addressing the challenges of aging. However, research on eligibility criteria and coverage of LTC in China is lacking. Our objective is to assess the current status of LTC and explore eligibility criteria and coverage for the elderly. METHODS: This is a cross-sectional study conducted in two first-tier cities in China. Residents aged 65 or over were recruited from a nursing home and four primary hospitals. Participants were divided into three groups (bedridden, domestic, and community), then six grades (grade one to six) according to the Longshi Scale, and their functional ability was assessed using the Modified Barthel Index. Information such as diseases, complications, and daily care needs were collected. Nursing staff were invited to indicate patients' needs for care. A one-way ANOVA test, Kruskal Wallis H test and Mann-Whitney U test were used to explore the differences of variables in three Longshi groups or Longshi grades. RESULTS: Among all 1157 participants, with an average age of 80.54, 69.3% were in the bedridden group. The most common diagnosis was stroke (71.4%), with the most prevalent complication being pulmonary infection (25.2%). In the nursing assessment, basic health care, disease care, activity care, complication prevention care and psychosocial care were summarized as the five main aspects of LTC for the elderly. Feeding, bathing, drinking, bowel management and bladder management were identified as the basic care which fulfills participants' basic physical needs in each Longshi group. Mouth care, artificial airway management, and body reposition, which can prevent immobility complications, were highly demanded by bedridden elderly. CONCLUSIONS: The elderly in grade one to three are the ones in need of LTC most. The content of LTC for elderly should include basic care which fulfills their basic physical needs and complication care which can prevent immobility complications. The evidence of this research may contribute to the design of LTC in China. TRIAL REGISTRATION: The study design was registered in the Chinese Clinical Trial Registry (ChiCTR-2000034067, Registered 22 Jun 2020, http://www.chictr.org.cn/showproj.aspx?proj=54770 ).

Patterns and Trends in Mortality Associated With and Due to Diabetes Mellitus in a Transitioning Region With 3.17 Million People: Observational Study.

BACKGROUND: Diabetes mellitus (DM) imposes a significant disease burden in economically transitioning regions. Most transitioning regions share similar experience in urbanization processes. Shanghai's Pudong district serves as a representative area of such regions. OBJECTIVE: We aimed to assess the burden of and trends in DM mortality in Shanghai's Pudong district and analyze the impact of aging and multimorbidity. METHODS: A longitudinal, population-based study was conducted to analyze DM mortality in Pudong from 2005 to 2020. We used joinpoint regression to analyze epidemiological features and long-term trends in crude mortality rate (CMR), age-standardized mortality rate worldwide (ASMRW), and years of life lost (YLL). Furthermore, the decomposition method was used to evaluate the contribution of demographic and nondemographic factors associated with mortality. RESULTS: There were 49,414 deaths among individuals with DM, including 15,512 deaths due to DM. The CMR and ASMRW were 109.55/105 and 38.01/105 person-years, respectively. Among the mortality associated with and due to DM, the total annual ASMRW increased by 3.65% (95% CI 3.25%-4.06%) and 1.38% (95% CI 0.74%-2.02%), respectively. Additionally, the total annual YLL rate increased by 4.98% (95% CI 3.92%-6.05%) and 2.68% (95% CI 1.34%-4.04%). The rates of YLL increase in persons aged 30 to 44 years (3.98%, 95% CI 0.32%-7.78%) and 45 to 59 years (4.31%, 95% CI 2.95%-5.69%) were followed by the increase in persons aged 80 years and older (10.53%, 95% CI 9.45%-11.62%) for deaths associated with DM. The annual CMR attributable to demographic factors increased by 41.9% (95% CI 17.73%-71.04%) and 36.72% (95% CI 16.69%-60.2%) for deaths associated with and due to DM, respectively. Hypertension, cerebrovascular disease, and ischemic heart disease were the top 3 comorbidities. CONCLUSIONS: Aging and multimorbidity played essential roles in changing the burden of DM in an urbanizing and transitioning region. There is an increasing disease burden among young and middle-aged people, emphasizing the need for greater attention to these groups. Health management is an emerging method that holds important implications for alleviating the future burden of DM.

Changes of the acute myocardial infarction-related resident deaths in a transitioning region: a real-world study involving 3.17 million people.

Background: The impact of acute myocardial infarction (AMI) on the life span of residents in a transitioning region has not been studied in depth. Therefore, we aimed to evaluate the changes in AMI-related resident deaths in a transitioning region in China. Methods: A longitudinal, population-based study was performed to analyze the deaths with/of AMI in Pudong New Area (PNA), Shanghai from 2005 to 2021. The average annual percentage change (AAPC) of AMI in crude mortality rates (CMR), age-standardized mortality rates worldwide (ASMRW), and rates of years of life lost (YLLr) were calculated by the joinpoint regression. The impact of demographic and non-demographic factors on the mortality of residents who died with/of AMI was quantitatively analyzed by the decomposition method. Results: In 7,353 residents who died with AMI, 91.74% (6,746) of them were died of AMI from 2005 to 2021. In this period, the CMR and ASMRW of residents died with/of AMI were 15.23/105 and 5.17/105 person-years, the AAPC of CMR was 0.01% (95% CI: -0.71,0.72, p = 0.989) and 0.06% (95% CI: -0.71,0.84, p = 0.868), and the ASMRW decreased by 2.83% (95% CI: -3.66,-2.00, p < 0.001) and 2.76% (95% CI: -3.56,-1.95, p < 0.001), respectively. The CMR of people died of AMI showed a downward trend (all p < 0.05) in people ≥60 years but an upward trend [AAPC = 2.47% (95% CI: 0.07,4.94, p = 0.045)] in people of 45-59 years. The change in CMR of people died with/of AMI caused by demographic factors was 28.70% (95% CI: 12.99,46.60, p = 0.001) and 28.07% (95% CI: 12.71,45.52, p = 0.001) per year, respectively. Conclusion: Preventative strategies for AMI should be applied to enhance the health management of residents aged 45-59 years or with comorbidities in the transitioning region.

Cx43 Facilitates Mesenchymal Transition of Endothelial Cells Induced by Shear Stress.

OBJECTIVES: This study aimed to determine the function of Cx43 in the endothelial-to-mesenchymal transition (EndMT) process of endothelial cells (ECs) and to explore the potential signaling pathways underlying these functions. METHODS: ECs were extracted from rat aorta. ECs were transfected with Cx43 cDNA and Cx43 siRNA and then exposed to 5 or 12 dyne/cm2. Immunofluorescence staining was used to detect the expression of SM22α, Cx43, and acetylated α-tubulin in ECs. Western blotting was used to detect the protein expression of α-SMA, CD31, Cx43, H1-calponin, Ift88, and p-smad3 in ECs. RESULTS: The expression of αSMA, SM22α, and Cx43 was significantly increased, and CD31 was markedly decreased in ECs treated with laminar shear stress at 5 dyn/cm2. The Cx43 cDNA transfection could induce the expression of SM22α or H1-calponin and attenuate CD31 expression in ECs. Also, Cx43 overexpression harms cilia formation in ECs exposed to 5 dyn/cm2, accompanied with the regulated Ift88 and smad signaling. CONCLUSIONS: This study found that laminar shear stress at 5 dyn/cm2 would increase the expression of Cx43 to facilitate the EndMT process of ECs, associated with morphological changes in primary cilia and the decreased expression of Ift88 in ECs.

Changes in sleep quality of children with epilepsy and anxiety of their caregivers after COVID-19 infection: a case-series report.

Objective: To study the changes in epileptic seizures and sleep quality in children with epilepsy (CWE) and the changes in anxiety of their caregivers after infection with COVID-19. Methods: Outpatients and inpatients of CWEs were selected as subjects and a questionnaire survey was used to carry out this case-series study. The demographic information of the CWEs and their caregivers, information about epilepsy, and information about the vaccination, infection, and treatment of COVID-19 were collected. The changes in sleep quality of CWEs and the changes in anxiety of their caregivers were assessed by the Child Sleep Habits Questionnaire (CSHQ) and Caregiver Anxiety Scale (CAS). Risk factors affecting sleep habits in CWEs and caregiver anxiety were further analyzed by one-way analysis of variance. Results: A total of 312 children were included in the study. Among them, 134 patients (42.9%) were female. The average age of the children was 9.30 ± 3.88 years, and the duration of epilepsy was 4.59 ± 3.36 years. A total of 221 of the 312 children were infected with COVID-19, and all the infected children developed fever, which lasted for 1.71 ± 1.13 days. 10 children were satisfied with controlled seizures for more than 1 year and relapsed after COVID-19 infection (4.2%), 4 cases (3.6%) with increased seizures, and 8 children with reduced seizures (7.7%), 17 children (7.7%) had no change in seizures, and 182 children (82.3%) remained seizure-free after the COVID-19 infection. The average sleep time of the CWEs was 9.25 ± 1.04 h and the average total score of the CSHQ was 37.25 ± 5.19, among which 44 cases (14.1%) had more than 41 points. As the result of the CAS, 16 of them (5.13%) scored above 50 and the average total score was 31.49 ± 8.09. The control of seizures, age of onset, types of anti-seizure medicines (ASMs), and seizure duration were risk factors affecting sleep quality. Accordingly, the score of CAS was significantly lower when there was more than one caregiver who cared for the CWE. Conclusions: COVID-19 infection did not cause an increase in seizures in CWEs, nor did it worsen their sleep quality of them or aggravate the anxiety of their caregivers.

CaMKII autophosphorylation but not downstream kinase activity is required for synaptic memory.

CaMKII plays a critical role in long-term potentiation (LTP), a well-established model for learning and memory through the enhancement of synaptic transmission. Biochemical studies indicate that CaMKII catalyzes a phosphotransferase (kinase) reaction of both itself (autophosphorylation) and of multiple downstream target proteins. However, whether either type of phosphorylation plays any role in the synaptic enhancing action of CaMKII remains hotly contested. We have designed a series of experiments to define the minimal requirements for the synaptic enhancement by CaMKII. We find that autophosphorylation of T286 and further binding of CaMKII to the GluN2B subunit are required both for initiating LTP and for its maintenance (synaptic memory). Once bound to the NMDA receptor, the synaptic action of CaMKII occurs in the absence of kinase activity. Thus, autophosphorylation, together with binding to the GluN2B subunit, are the only two requirements for CaMKII in synaptic memory.

Why green absorptive capacity and managerial environmental concerns matter for corporate environmental entrepreneurship?

Balancing environmental sustainability and green business growth is one of the primary goals of corporate environmental entrepreneurship, while green entrepreneurship orientation (GEO) represents balanced approaches to maximize green business value-added and maintain environmental performance (EP). Green innovation (GI) strengthens green business efficiencies and drives GEO achievements. Building on the natural resource-based view (NRBV) and dynamic capability view (DCV), this research addressed the critical role of GEO and GI on EP. In addition, the effect of green absorptive capacity (GAC) and managerial environmental concern (MEC) on EP is estimated. The results indicated that GEO significantly affects MEC and GI. While GI positively influences MEC, the relationship between GI and GAC was insignificant. Additionally, GAC and MEC positively and greatly influenced EP. As GAC partially mediates the effect of GEO and GI on EP, MEC also partly mediates the relationship between GI and EP. In the context of the environment, this study presents three quantitative achievements, namely (1) it confirms the vital role of green dynamic capabilities such as GAC to balance GEO's green business agenda and maintain environmental performance, (2) GAC converts knowledge creation to knowledge applications focusing on the development of eco-friendly products and processes to reduce environmental pollution, and (3) MEC determine and focus on GI core competencies to support GEO strategies, (4) GAC level up firms green dynamic capabilities to the level of GEO, and thus maintaining ecosystem and eco-business sustainability. In light of the study outcomes, theoretical and managerial implications were highlighted.

[Distribution and Biotoxicity of Endogenous Pollutants in Pennisetum sp. Biochar from Different Polluted Areas].

Due to the wide sources of biomass raw materials and the lack of limits for the endogenous pollutants in biochar and their dosage, some biochar with high endogenous pollutants may be used for environmental remediation, which results in potential environmental risks. In this study, three biochars were prepared from the straws of Pennisetum sp. grown in clean, moderately polluted and highly polluted soils, respectively. The total endogenous copper (Cu) and cadmium (Cd), acid-soluble fraction, and persistent free radical (PFRs) distribution in biochars were investigated, and their biotoxicities were evaluated based on wheat root elongation inhibition rate and antioxidant enzyme activity. The results indicated that total Cu in Jiuniu biochar from the highly polluted soil and total Cd in Shuiquan biochar from the moderately-polluted soil were 3.73 and 4.43 times higher than that in Hongrang biochar from the clean soil, respectively. Moreover, acid-soluble Cu in Jiuniu biochar was 3.32 and 2.84 times higher than that in Shuiquan and Hongrang biochar, respectively, and acid-soluble Cd in Shuiquan and Jiuniu biochar was 7.95 and 5.11 times higher than that in Hongrang biochar, respectively. All three biochars had PFRs with adjacent oxygen atoms centered on carbon and followed the order of Hongrang>Jiuniu>Shuiquan. Three biochar leaching solutions significantly inhibited wheat root elongation but enhanced the enzyme activities of SOD, POD, and CAT for the wheat seedlings compared with that in the control. In particular, the highest inhibition rate (27.7%) was found in Jiuniu biochar. This study indicated that the interaction of endogenous heavy metals and PFRs in biochar exhibited significant biotoxicity to wheat seedlings. In the future, more attention should be paid to the potential environmental toxicity of endogenous pollutants from biochar to avoid new environmental pollution problems.

Recent progress in the development of ursolic acid derivatives as anti-diabetes and anti-cardiovascular agents.

Ursolic acid (UA) is a pentacyclic triterpenoid, which exhibits many biological activities, particularly in anti-cardiovascular and anti-diabetes. The further application of UA is greatly limited due to its low bioavailability and poor water solubility. Up to date, various UA derivatives have been designed to overcome these shortcomings. In this paper, the authors reviewed the development of UA derivatives as the anti-diabetes anti-cardiovascular reagents.

Progress in the development of TRPV1 small-molecule antagonists: Novel Strategies for pain management.

Transient receptor potential vanilloid 1 (TRPV1) channels are widely distributed in sensory nerve endings, the central nervous system, and other tissues, functioning as ion channel proteins responsive to thermal pain and chemical stimuli. In recent years, the TRPV1 receptor has garnered significant interest as a potential therapeutic approach for various pain-related disorders, particularly TRPV1 antagonists. The present review offers a comprehensive, systematic exploration of both first- and second-generation TRPV1 antagonists in the context of pain management. Antagonists are categorized and explicated according to their structural characteristics. Detailed examination of binding modes, structural features, and pharmacological activities, alongside a critical appraisal of the advantages and limitations inherent to typical compounds within each structural category, are undertaken. Detailed discussions of the binding modes, structural features, pharmacological activities, advantages, and limitations of typical compounds within each structural category offer valuable insights and guidance for the future research and development of safer, more effective, and more targeted TRPV1 antagonists.

Anti-reflux effects of a novel esophagogastric asymmetric anastomosis technique after laparoscopic proximal gastrectomy.

BACKGROUND: Reflux esophagitis is a common postoperative complication of proximal gastrectomy. There is an urgent need for a safer method of performing esophageal-gastric anastomosis that reduces the risk of reflux after proximal gastrectomy. We hypothesize that a novel technique termed esophagogastric asymmetric anastomosis (EGAA) can prevent postoperative reflux in a safe and feasible manner. AIM: To observe a novel method of EGAA to prevent postoperative reflux. METHODS: Initially, we employed a thermal stress computer to simulate and analyze gastric peristalsis at the site of an esophagogastric asymmetric anastomosis. This was done in order to better understand the anti-reflux function and mechanism. Next, we performed digestive tract reconstruction using the EGAA technique in 13 patients who had undergone laparoscopic proximal gastrectomy. Post-surgery, we monitored the structure and function of the reconstruction through imaging exams and gastroscopy. Finally, the patients were followed up to assess the efficacy of the anti-reflux effects. RESULTS: Our simulation experiments have demonstrated that the clockwise contraction caused by gastric peristalsis and the expansion of the gastric fundus caused by the increase of intragastric pressure could significantly tighten the anastomotic stoma, providing a means to prevent the reverse flow of gastric fluids. Thirteen patients with esophagogastric junction tumors underwent laparoscopic proximal gastrectomy, with a mean operation time of 304.2 ± 44.3 min. After the operation, the upper gastroenterography in supine/low head positions showed that eight patients exhibited no gastroesophageal reflux, three had mild reflux, and two had obvious reflux. The abdominal computed tomography examination showed a valve-like structure at the anastomosis. During follow-up, gastroscopy revealed a closed valve-like form at the anastomosis site without stenosis or signs of reflux esophagitis in 11 patients. Only two patients showed gastroesophageal reflux symptoms and mild reflux esophagitis and were treated with proton pump inhibitor therapy. CONCLUSION: EGAA is a feasible and safe surgical method, with an excellent anti-reflux effect after proximal gastrectomy.

CircCCL22 Regulates CDC25A via Sponging miR-543 and Promotes Proliferation and Metastasis in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecological tumor. Circular RNAs are a novel type of non-coding RNA that have important regulatory functions, particularly in the pathogenic progression of cancer. In this study, we investigated the function of circCCL22, and elucidated its molecular mechanism in EC progresssion. The expression of circCCL22, miR-543 and CDC25A in EC tissues and cells were determined by qRT-PCR and western blot. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing and transwell assays were executed to assess the cell viability, proliferation, migration and invasion. Dual-luciferase report assay was utilized to investigate the interaction of miR-543 with circCCL22 and CDC25A. The role of circCCL22 in EC in vivo was investigated by xenograft assay. CircCCL22 was notably upregulated in EC tissues and cells. Functionally, circCCL22 knockdown suppressed EC cell proliferation, migration and invasion in vitro, and inhibited tumor growth in vivo. Mechanistically, circCCL22 acted as "miR-543 sponges" to regulate its targeted gene CDC25A expression in EC cells. The inhibiting effect induced by circCCL22 knockdown on EC cell proliferation, migration and invasion was greatly reversed by miR-543 inhibition or CDC25A overexpression. Our results revealed that circCCL22 regulated EC progression through targeting miR-543/CDC25A axis, and it could be a novel therapeutic target of EC.

A potential role of NFIL3 in atherosclerosis.

Nuclear factor interleukin-3(NFIL3), a proline- and acidic-residue-rich (PAR) bZIP transcription factor, is called the E4 binding protein 4 (E4BP4) as well, which is relevant to regulate the circadian rhythms and the viability of cells. More and more evidence has shown that NFIL3 is associated with different cardiovascular diseases. In recent years, it has been found that NFIL3 has significant functions in the progression of atherosclerosis via the regulation of inflammatory response, macrophage polarization, some immune cells and lipid metabolism. In this overview, we sum up the function of NFIL3 during the development of atherosclerosis and offer meaningful views how to treat cardiovascular disease related to atherosclerosis.

MiRNA-423 rs6505162 and miRNA-6811 rs2292879 SNP associated with lung cancer in Hainan, China.

BACKGROUND: MicroRNAs (miRNAs) are known to exert significant influence on various physiological processes and diseases, including cancers. The primary objective of this present study was to examine the impact of eight single-nucleotide polymorphisms (SNPs) in miRNA on the susceptibility to lung cancer (LC) within the Chinese Southern population. METHODS: The genotypes of these eight polymorphisms were determined in 132 LC patients and 214 cancer-free controls. RESULTS: In overall analyses, GG genotype of miRNA-6811 rs2292879 polymorphism was significantly correlated with increased risk of LC (GG vs. AA, adjusted OR = 5.10, 95% CI = 1.02-25.43, P=0.047), yet the genotype frequencies of rs2292879 SNP in controls did not met the Hardy-Weinberg equilibrium (HWE) (P=0.001) in present study. Stratified analyses by smoking revealed that miRNA-423 rs6505162 variants significantly decreased the LC risk in heterozygous (CA vs. CC, adjusted OR = 0.14, 95% CI = 0.03-0.81, P=0.028) and recessive (AA vs. CA + CC, adjusted OR = 0.17, 95% CI = 0.03-0.90, P=0.038) genetic models in smoking population. However, miRNA-196A2 rs11614913, miRNA-196A2 rs12304647, miRNA-146A rs2910164, miRNA-16-1 rs1022960, miRNA-608 rs4919510, and miRNA-27a rs895819 polymorphisms were not significantly associated with LC. CONCLUSION: The findings of our study indicate a potential decrease in LC risk among smokers with the miRNA-423 rs6505162 variants, while an increase in risk is associated with miRNA-6811 rs2292879 polymorphisms in the population of Southern Chinese. However, further well-designed research is necessary to fully understand the precise impact of these two SNPs on the development of LC.

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis developed after ovarian cancer cytoreduction surgery: a case report and literature review.

BACKGROUND: Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis (AE), is often found associated with tumors such as thymoma, lung cancer, ovarian tumors, and breast cancer, and the tumors were generally detected during the screening process after the encephalitis initiated. The tumor is considered a trigger of AE, but the mechanism remains unclear. CASE PRESENTATION: A 53-year-old woman presented short-term memory loss two days after the primary cytoreduction for high-grade serous ovarian cancer (HGSOC, FIGO stage IC3). Cell-based assay found AMPAR CluA2 IgG positive in both serum (1:3.2) and cerebrospinal fluid (1:32). Moreover, mild AMPAR GluA1 and strong GluA2 expressions were also found positive in the paraffin sections of ovarian tumor tissue, indicating the ovarian cytoreduction surgery might stimulate the release of receptor antigens into the circulation system. The patient's condition deteriorated within two weeks, developing consciousness and autonomic dysfunction, leading to ICU admission. With oral steroids, intravenous immunoglobulin, plasmapheresis, and rituximab treatment, the patient's consciousness markedly improved after three months. CONCLUSION: We presented the first case of anti-AMPAR encephalitis developed right after the primary cytoreduction of a patient with HGSOC and retrieved paraneoplastic anti-AMPAR encephalitis cases (n = 66). Gynecologists should pay attention to patients who develop cognitive dysfunction or psychiatric symptoms shortly after the ovarian tumor resection and always include AE in the differentiation diagnosis.