MYB2 and MYB108 regulate lateral root development by interacting with LBD29 in Arabidopsis thaliana.

AUXIN RESPONSE FACTOR 7 (ARF7)-mediated auxin signaling plays a key role in lateral root (LR) development by regulating downstream LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcription factor genes, including LBD16, LBD18, and LBD29. LBD proteins are believed to regulate the transcription of downstream genes as homodimers or heterodimers. However, whether LBD29 forms dimers with other proteins to regulate LR development remains unknown. Here, we determined that the Arabidopsis thaliana (L.) Heynh. MYB transcription factors MYB2 and MYB108 interact with LBD29 and regulate auxin-induced LR development. Both MYB2 and MYB108 were induced by auxin in an ARF7-dependent manner. Disruption of MYB2 by fusion with an SRDX domain severely affected auxin-induced LR formation and the ability of LBD29 to induce LR development. By contrast, overexpression of MYB2 or MYB108 resulted in greater LR numbers, except in the lbd29 mutant background. These findings underscore the interdependence and importance of MYB2, MYB108, and LBD29 in regulating LR development. In addition, MYB2-LBD29 and MYB108-LBD29 complexes promoted the expression of CUTICLE DESTRUCTING FACTOR 1 (CDEF1), a member of the GDSL (Gly-Asp-Ser-Leu) lipase/esterase family involved in LR development. In summary, this study identified MYB2-LBD29 and MYB108-LBD29 regulatory modules that act downstream of ARF7 and intricately control auxin-mediated LR development.

Application of neutrophil-to-lymphocyte-to-monocyte ratio in predicting mortality risk in adult patients with septic shock: A retrospective cohort study conducted at a single center.

Background: Sepsis is a life-threatening condition characterized by an aberrant host response to infection, resulting in multi-organ dysfunction. The application of currently available prognostic indicators for sepsis in primary hospitals is challenging. In this retrospective study, we established a novel index, the neutrophil-to-lymphocyte-to-monocyte ratio (NLMR), based on routine blood examination upon admission, and assessed its prognostic value for early mortality risk in adult patients with septic shock. Methods: This study included clinical data from adult patients with septic shock who were admitted to the hospital between January 1, 2018, and December 31, 2022. Training and validation sets were constructed, and patients were categorized into "survival" and "death" groups based on their survival status within the 28-day hospitalization period. Baseline data, including demographic characteristics and comorbidities, and laboratory results, such as complete blood count parameters, were collected for analysis. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were documented.The NLMR was determined through the utilization of multivariate binary logistic regression analysis, leading to the development of a risk model aimed at predicting early mortality in adult patients suffering from septic shock. Results: Overall, 112 adult patients with septic shock were enrolled in this study, with 84 and 28 patients in the training and validation sets, respectively. Multivariate binary logistic analysis revealed that the neutrophil, lymphocyte, and monocyte counts independently contributed to the mortality risk (odds ratios = 1.22, 0.08, and 0.16, respectively). The NLMR demonstrated an area under the receiver operating characteristic curve (ROC-AUC) of 0.83 for internal validation in the training set and 0.97 for external validation in the validation set. Both overall model quality values were significantly high at 0.74 and 0.91, respectively (P < 0.05). NLMR exhibited a higher ROC-AUC value of 0.88 than quick SOFA (ROC-AUC = 0.71), SOFA (ROC-AUC = 0.83), and APACHE II (ROC-AUC = 0.78). Conclusion: NLMR may be a potential marker for predicting the risk of early death in adult patients with septic shock, warranting further exploration and verification.

Development and validation of a clinical prediction model for early ventilator weaning in post-cardiac surgery.

Background: Weaning patients from mechanical ventilation is a critical clinical challenge post cardiac surgery. The effective liberation of patients from the ventilator significantly improves their recovery and survival rates. This study aimed to develop and validate a clinical prediction model to evaluate the likelihood of successful extubation in post-cardiac surgery patients. Method: A predictive nomogram was constructed for extubation success in individual patients, and receiver operating characteristic (ROC) and calibration curves were generated to assess its predictive capability. The superior performance of the model was confirmed using Delong's test in the ROC analysis. A decision curve analysis (DCA) was conducted to evaluate the clinical utility of the nomogram. Results: Among 270 adults included in our study, 107 (28.84%) experienced delayed extubation. A predictive nomogram system was derived based on five identified risk factors, including the proportion of male patients, EuroSCORE II, operation time, pump time, bleeding during operation, and brain natriuretic peptide (BNP) level. Based on the predictive system, five independent predictors were used to construct a full nomogram. The area under the curve values of the nomogram were 0.880 and 0.753 for the training and validation cohorts, respectively. The DCA and clinical impact curves showed good clinical utility of this model. Conclusion: Delayed extubation and weaning failure, common and potentially hazardous complications following cardiac surgery, vary in timing based on factors such as sex, EuroSCORE II, pump duration, bleeding, and postoperative BNP reduction. The nomogram developed and validated in this study can accurately predict when extubation should occur in these patients. This tool is vital for assessing risks on an individual basis and making well-informed clinical decisions.

Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells.

Background: The tumor microenvironment (TME) plays a pivotal role in the progression and metastasis of lung adenocarcinoma (LUAD). However, the detailed characteristics of LUAD and its associated microenvironment are yet to be extensively explored. This study aims to delineate a comprehensive profile of the immune cells within the LUAD microenvironment, including CD8+ T cells, CD4+ T cells, and myeloid cells. Subsequently, based on marker genes of exhausted CD8+ T cells, we aim to establish a prognostic model for LUAD. Method: Utilizing the Seurat and Scanpy packages, we successfully constructed an immune microenvironment atlas for LUAD. The Monocle3 and PAGA algorithms were employed for pseudotime analysis, pySCENIC for transcription factor analysis, and CellChat for analyzing intercellular communication. Following this, a prognostic model for LUAD was developed, based on the marker genes of exhausted CD8+ T cells, enabling effective risk stratification in LUAD patients. Our study included a thorough analysis to identify differences in TME, mutation landscape, and enrichment across varying risk groups. Moreover, by integrating risk scores with clinical features, we developed a new nomogram. The expression of model genes was validated via RT-PCR, and a series of cellular experiments were conducted, elucidating the potential oncogenic mechanisms of GALNT2. Results: Our study developed a single-cell atlas for LUAD from scRNA-seq data of 19 patients, examining crucial immune cells in LUAD's microenvironment. We underscored pDCs' role in antigen processing and established a Cox regression model based on CD8_Tex-LAYN genes for risk assessment. Additionally, we contrasted prognosis and tumor environments across risk groups, constructed a new nomogram integrating clinical features, validated the expression of model genes via RT-PCR, and confirmed GALNT2's function in LUAD through cellular experiments, thereby enhancing our understanding and approach to LUAD treatment. Conclusion: The creation of a LUAD single-cell atlas in our study offered new insights into its tumor microenvironment and immune cell interactions, highlighting the importance of key genes associated with exhausted CD8+ T cells. These discoveries have enabled the development of an effective prognostic model for LUAD and identified GALNT2 as a potential therapeutic target, significantly contributing to the improvement of LUAD diagnosis and treatment strategies.

Inhibition of colon C5a/C5a receptor signalling pathway confers protection against LPS-induced acute kidney injury via gut microbiota-kidney axis.

Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of the C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing on the colon's C5a/C5a receptor pathway, intestinal barrier integrity, and gut microbiota. Our findings demonstrate that W54011 effectively ameliorated kidney injury in the LPS-induced AKI model by selectively inhibiting the colon's C5a/C5a receptor signalling pathway. Additionally, C5a receptor blockade resulted in the inhibition of colonic inflammation and the reconstruction of the intestinal mucosal barrier. Furthermore, W54011 administration significantly impacted the composition and stability of the gut microbiota, restoring the abundance of dominant bacteria to levels observed in the normal state of the intestinal flora and reducing the abundance of potentially harmful bacterial groups. In conclusion, W54011 alleviates LPS-induced AKI by modulating the interplay between the colon, gut microbiota, and kidneys. It preserves the integrity of the intestinal barrier and reinstates gut microbiota, thereby mitigating AKI symptoms. These findings suggest that targeting the colon and gut microbiota could be a promising therapeutic strategy for AKI treatment.

Transesophageal echocardiography-guided percutaneous closure of the patent foramen ovale only uses the sheath.

Background: Percutaneous closure of the patent foramen ovale (PFO) is primarily guided by fluoroscopy in the catheter room, during which procedure both the guidewire and sheath need to pass through the PFO. We performed PFO closure using a transesophageal echocardiography (TEE)-guided approach and only the sheath was passed through the PFO during the procedure. This study aimed to evaluate the feasibility and safety of PFO closure using this technique. Methods: A retrospective observational study was performed. A total of 117 consecutive adult patients underwent percutaneous PFO closure without fluoroscopy, under the sole guidance of TEE in our hospital between December 2018 and December 2021. The data of each patient consisted of preoperative, operative, and postoperative variables collected. The primary outcome is that the occluder was successfully released. The secondary outcomes included perioperative and follow-up transthoracic echocardiography (TTE), Headache impact test-6 (HIT-6) score and clinical symptoms. Results: Transvenous PFO closure under TEE guidance was successful in all cases. The sample consisted of 93 females and 24 males with an average age of 42.3±7.8 years. There were 28 patients with preoperative cerebral infarction [Risk of Paradoxical Embolism (RoPE) score >6 points] and 89 patients with migraine. All patients underwent a preoperative TEE to confirm the presence of PFO, and contrast-enhanced transcranial Doppler (c-TCD) acoustic contrast suggested grades 3 to 4. The average time of surgery for patients (puncture to removal of the sheath) was 32 minutes. Three cases of vagus nerve reflex manifestations during surgery and two cases of transient ventricular arrhythmia all improved after symptomatic treatment. There were no instances of metal allergy, hemolysis, or other acute vascular procedural complications. For all 89 patients with migraine, significant relief or resolution was achieved during the first six-month follow-up (P<0.001). Conclusions: As a monotherapy, percutaneous closure of PFO guided by TEE where only the sheath passes through the PFO during the operation is an effective procedure with a high success rate and a low complication rate.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Macrophage polarization states in atherosclerosis.

Atherosclerosis, a chronic inflammatory condition primarily affecting large and medium arteries, is the main cause of cardiovascular diseases. Macrophages are key mediators of inflammatory responses. They are involved in all stages of atherosclerosis development and progression, from plaque formation to transition into vulnerable plaques, and are considered important therapeutic targets. Increasing evidence suggests that the modulation of macrophage polarization can effectively control the progression of atherosclerosis. Herein, we explore the role of macrophage polarization in the progression of atherosclerosis and summarize emerging therapies for the regulation of macrophage polarization. Thus, the aim is to inspire new avenues of research in disease mechanisms and clinical prevention and treatment of atherosclerosis.

Tunable Nanoparticles with Aggregation-Induced Emission Heater for Precise Synergistic Photothermal and Thermodynamic Oral Cancer Therapy of Patient-Derived Tumor Xenograft.

The fluorophores in the second near-infrared (NIR-II) biological window (1000 - 1700 nm) show great application prospects in the fields of biology and optical communications. However, both excellent radiative transition and nonradiative transition cannot be achieved simultaneously for the majority of traditional fluorophores. Herein, tunable nanoparticles formulated with aggregation-induced emission (AIE) heater are developed rationally. The system can be implemented via the development of an ideal synergistic system that can not only produce photothermal from nonspecific triggers but also trigger carbon radical release. Once accumulating in tumors and subsequently being irradiated with 808 nm laser, the nanoparticles (NMB@NPs) encapsulated with NMDPA-MT-BBTD (NMB) are splitted due to the photothermal effect of NMB, leading to the decomposition of azo bonds in the nanoparticle matrix to generate carbon radical. Accompanied by second near-infrared (NIR-II) window emission from the NMB, fluorescence image-guided thermodynamic therapy (TDT) and photothermal therapy (PTT) which significantly inhibited the growth of oral cancer and negligible systemic toxicity is achieved synergistically. Taken together, this AIE luminogens-based synergistic photothermal-thermodynamic strategy brings a new insight into the design of superior versatile fluorescent NPs for precise biomedical applications and holds great promise to enhance the therapeutic efficacy of cancer therapy.

MicroRNA-205-5p plays a suppressive role in the high-fat diet-induced atrial fibrosis through regulation of the EHMT2/IGFBP3 axis.

OBJECTIVE: MicroRNAs (miRNAs) targeting has been revealed to be an appealing strategy for the treatment and management of atrial fibrillation (AF). In this research, we aimed to explore the mechanisms of miR-205-5p in reducing the high-fat diet (HFD)-induced atrial fibrosis through the EHMT2/IGFBP3 axis. METHODS: Expression levels of miR-205-5p, IGFBP3 and EHMT2 were determined in AF patients, cell fibrosis models and mouse atrial fibrosis models. Luciferase activity and RIP assays were performed to detect the binding between miR-205-5p and EHMT2, and ChIP assays were implemented to detect the enrichment of H3K9me2 and H3K4me3 in the promoter region of IGFBP3 in cells. The related experiments focusing on the inflammatory response, atrial fibrosis, mitochondrial damage, and metabolic abnormalities were performed to figure out the roles of miR-205-5p, IGFBP3, and EHMT2 in cell and mouse atrial fibrosis models. RESULTS: Low expression levels of miR-205-5p and IGFBP3 and a high expression of EHMT2 were found in AF patients, cell fibrosis models and mouse atrial fibrosis models. Upregulation of miR-205-5p reduced the expression of TGF-ß1, α-SMA, Col III and other fibrosis-related proteins. miR-205-5p overexpression targeted EHMT2 to regulate the methylation of H3 histones to promote IGFBP3 expression, which in turn affected the fibrosis of atrial muscle cells. In HFD-induced atrial fibrosis mice, upregulated miR-205-5p or elevated IGFBP3 alleviated atrial fibrosis, mitochondrial damage, and metabolic abnormalities. CONCLUSION: This study suggests that miR-205-5p attenuates HFD-induced atrial fibrosis via modulating the EHMT2/IGFBP3 axis. miR-205-5p alleviates high-fat diet-induced atrial fibrosis in mice via EHMT2/IGFBP3.

Protective Effects of MicroRNA-200b-3p Encapsulated by Mesenchymal Stem Cells-Secreted Extracellular Vesicles in Myocardial Infarction Via Regulating BCL2L11.

Background Extracellular vesicles (EVs) are a popular treatment candidate for myocardial injury. This work investigated the effects of mesenchymal stem cells (MSCs)-secreted EVs-derived miR-200b-3p on cardiomyocyte apoptosis and inflammatory response after myocardial infarction (MI) through targeting BCL2L11 (Bcl-2-like protein 11) . Methods and Results EVs from MSCs were isolated and identified. EVs from MSCs with transfection of miR-200b-3p for overexpression were injected into MI mice. The effect of miR-200b-3p on cardiac function, infarction area, myocardial fibrosis, cardiomyocyte apoptosis, and inflammatory response was determined in MI mice. The targeting relationship between miR-200b-3p and BCL2L11 was verified, and the interaction between BCL2L11 and NLR family pyrin domain containing 1 (NLRP1) was also verified. MI mice were injected with an overexpressing BCL2L11 lentiviral vector to clarify whether BCL2L11 can regulate the effect of miR-200b-3p on MI mice. EVs from MSCs were successfully extracted. MSCs-EVs improved cardiac function and reduced infarction area, apoptosis of cardiomyocytes, myocardial fibrosis, and inflammation in MI mice. Upregulation of miR-200b-3p further enhanced the effects of MSCs-EVs on the myocardial injury of MI mice. BCL2L11 was targeted by miR-200b-3p and bound to NLRP1. Upregulation of BCL2L11 negated the role of miR-200b-3p-modified MSCs-EVs in MI mice. Conclusions A summary was obtained that miR-200b-3p-encapsulated MSCs-EVs protect against MI-induced apoptosis of cardiomyocytes and inflammation via suppressing BCL2L11.

The application of del Nido cardioplegia for myocardial protection in adult coronary artery bypass grafting: a cohort study.

BACKGROUND: Del Nido cardioplegia is widely used in adult cardiopulmonary bypass surgery and has a satisfying cardioprotective effect for about 90 minutes by single dose, but the effect in patients with coronary heart disease remains confused. The purpose of this study was to examine the cardioprotective effect of del Nido cardioplegia in adult multivessel coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: This retrospective comparative analysis included 124 consecutive patients undergoing isolated on-pump CABG performed by a single surgeon between January 2017 and December 2020. The demographic characteristics and medical history of the included patients were collected. The included patients were divided into two groups: a del Nido cardioplegia (DN) group and a conventional multidose blood cardioplegia (BC) group. Perioperative, intraoperative, and postoperative indicators and complications were compared. RESULTS: Compared with the BC group, CPB and aortic cross-clamp time were significantly shorter in the DN group. In the early postoperative period, the hemoglobin concentration in the DN group was significantly higher than that in the BC group (P<0.05). CONCLUSIONS: This study demonstrated that the application of del Nido cardioplegia in adult on-pump CABG could lead to a significantly shorter aortic cross-clamp and CPB time, as well as a higher hemoglobin concentration in the early postoperative period. The myocardial protective effect of del Nido cardioplegia is not inferior to that of conventional blood perfusion in adult on-pump CABG.

Somatic mutations combined with clinical features can predict the postoperative prognosis of stage IIIA lung adenocarcinoma.

Background: Prognostic factors for stage IIIA lung adenocarcinoma (LUAD) are unclear. The current main treatment for stage IIIA LUAD is still controversial. Some Clinicians advocate synchronous chemoradiotherapy as the main treatment for stage IIIA LUAD. In contrast, some clinicians argue that there are still certain patients with stage IIIA LUAD who have a better postoperative prognosis. This study aimed to analyze preoperative factors as well as the association between somatic mutations and prognosis in stage IIIA LUAD [including overall survival (OS) time and the risk of postoperative recurrence]. Methods: This study retrospectively reviewed the data of patients with stage IIIA LUAD who underwent radical resection of lung cancer in the thoracic surgery department of Tianjin Chest Hospital from January 01, 2011 to September 30, 2016. All patients involved in the study provided written informed consent. The associations between OS and DFS and the clinical characteristics as well as somatic mutations of patients were analyzed separately. The Kaplan-Meier method was used for univariate analysis, and survival curves were drawn. Multivariate analysis was performed by the Cox regression model. Results: For univariate analysis, the prognostic factors of OS were the level of preoperative CYFRA21-1, the number of metastatic lymph node stations (NMLS), maximum tumor diameter, EGFR (epidermal growth factor receptor) classical base mutations, and the number of copies of POLE (polymerase epsilon) mutation (NCPM). Preoperative total protein level, preoperative CYFRA21-1 level, the number of metastatic lymph nodes (NMLN), maximum tumor diameter, the number of mutated genes (NMG) in tumor samples, TP53 mutations, and the number of copies of POLE mutation (NCPM) were associated with disease-free survival (DFS). The multivariate analysis showed that the preoperative CYFRA21-1 level, the number of metastatic lymph node stations (NMLS), and EGFR typical base mutations were independent prognostic factors of OS. The number of mutated genes (NMG), EGFR classical base mutations, preoperative NSE level, maximum tumor diameter, and the number of metastatic lymph node stations (NMLS) were independent prognostic factors for DFS. Conclusions: The preoperative level of tumor markers, the number of metastatic lymph node stations, and EGFR typical base mutations are important factors for the prognosis of patients with resectable stage IIIA LUAD.

The association between different hormone replacement therapy use and the incidence of lung cancer: a systematic review and meta-analysis.

Background: Many peri- and postmenopausal women use hormone replacement therapy (HRT) to relieve menopausal symptoms. However, the side effects of different HRT use (ever/current/former vs. never HRT use) on lung cancer risk in women were not completely consistent. Thus, we conducted this meta-analysis to examine the connection between current, former or ever HRT use and the incidence of lung cancer among women. Methods: We systematically searched the PubMed, Web of Science, EMBASE, Cochrane Library, SCOPUS, China National Knowledge Infrastructure, Wanfang and VIP databases to identify relevant articles published from the inception of the respective databases to February 18, 2022. On the relationship between different HRT use and the incidence of lung cancer among women. Relevant risk estimates [relative risks (RRs), odds ratio (OR)] were combined based on specific study types. The Newcastle-Ottawa Scale was used to evaluate the quality of included studies. This analysis has been registered in the International prospective register of systematic reviews (PROSPERO; CRD42020219728). Publication bias was tested based on Egger's and Begg's tests. Results: A total of 22 studies (13 prospective cohort studies and 9 case-control studies) were included, comprising 911,194 participants and 17,329 patients. Compared to never HRT users, in pooled cohort studies, current HRT users had a statistically decreased risk of lung cancer [RR 0.91, 95% confidence interval (CI): 0.86-0.97, I2=22.9%], and similar results were found among the postmenopausal women with current HRT use (RR 0.91, 95 CI: 0.85-0.98, I2=36%), while in pooled case-control studies, ever HRT users had a decreased risk of incidence of lung cancer [odds ratio (OR) 0.75, 95% CI: 0.69-0.81, I2=0%] as did female non-smokers with ever HRT use (OR 0.76, 95% CI: 0.66-0.87, I2=36.8%). Conclusions: Current or ever HRT use is partly correlated with the decreased incidence of lung cancer in women. Concerns about the incidence of lung cancer can be reduced when perimenopausal and postmenopausal women use current HRT to reduce menopausal symptoms. Meanwhile, given the roles of hormone receptors and relevant genes single nucleotide polymorphism (SNPs) among females, HRT use should be cautiously administered and individualized.

Circular RNA circ_0001006 aggravates cardiac hypertrophy via miR-214-3p/PAK6 axis.

AIM: Circular RNAs (circRNAs) control gene expression in a series of physiological and pathological processes, but their role in heart disease is unknown. This research illustrates the role and potential mechanism of circRNA in cardiac hypertrophy. METHODS AND RESULTS: In this report, we found that circular RNA hsa_circ_0001006 (circ_0001006) was upregulated in cardiac hypertrophy mice and cardiomyocytes treated with angiotensin II (Ang II). Next, we noticed that gain of function circ_0001006 could induce cardiomyocyte hypertrophy; oppositely, knockdown of circ_0001006 remitted Ang II-induced cardiomyocyte hypertrophy. Biotin-coupled miRNA and RNA-pull down assays showed that miR-214-3p could bind with circ_0001006 and gain the function of miR-214-3p abrogated the pro-hypertrophy effect of circ_0001006. Furthermore, Further, dual-luciferase reporter assay showed that miR-214-3p could interact with 3'UTRs of the PAK6 gene, and circRNA_0001006 could block the above interactions. Additionally, PAK6 expression is inhibited by miR-214-3p mimic in cardiomyocytes but enhanced by over-expression of circRNA_000203 in vitro. CONCLUSIONS: Our data demonstrated that circRNA_0001006 exacerbates cardiac hypertrophy via suppressing miR-214-3p leading to enhanced PAK6 levels.

Application of grading evaluation method of water radioactivity level in Chongqing section of Yangtze River.

The major rivers in a region are usually vital sources of drinking water for local populations, and the concentration of radionuclides in the water is intimately tied to people's health. The varying concentration limits set by the World Health Organization are appropriate as screening values for determining the pollution of water sources, but their capacities as regulatory or early warning limits are restricted. In daily management, the regulatory authority needs to manage water bodies by level based on the concentration of radionuclide to indicate the potential pollution risks. From 2017 to 2019, a statistical analysis and dosage evaluation were conducted on the water radioactivity level in the Chongqing section of the Yangtze River in this study. The Modified Nemerow Index method based on the dose conversion coefficients was applied for the grading evaluation of the water radioactivity level, allowing the grading effect discussed. The results showed that the concentration of radionuclides in the Chongqing section of the Yangtze River and its contribution to the annual effective dose of the human body were lower than the limits stated in the Guidelines for Drinking Water Quality (Fourth Edition). And the samples in the section were 52.94% in Grade Ⅰand 47.06% in Grade Ⅱ, meaning few potential radioactive pollution risks exist there. Compared with other methods. The Modified Nemerow Index method combines the Traditional Nemerow Index method with the dose conversion coefficient of nuclides making it more realistic for the early warning and control of radioactive pollution in water bodies, which is worth popularizing and implementing.

LncRNA SOX2-OTinhibitionprotects against myocardialischemia/reperfusion-inducedinjury via themicroRNA-186-5p (miR-186-5p)/Yin Yang 1 (YY1)pathway.

Long noncoding RNAs (lncRNAs) exert essential effects in regulating myocardial ischemia/reperfusion (MI/R)-induced injury. This work intended to explore the functions of lncRNA SOX2-OT and its regulatory mechanism within MI/R-induced injury. In this study, gene expression was determined by RT-qPCR. Western blotting was applied for the detection of protein levels. Pro-inflammatory cytokine concentrations, cardiomyocyte viability, and apoptosis were detected via ELISA, CCK-8 and flow cytometry. In the in vitro model, SOX2-OT and YY1 were both upregulated, while miR-186-5p was downregulated. SOX2-OT knockdown attenuated oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cardiomyocyte dysregulation through relieving inflammation, promoting proliferation, and reducing apoptosis in OGD/R-treated H2C9 cells. SOX2-OT positively regulated YY1 expression via miR-186-5p. Moreover, miR-186-5p inhibition or YY1 upregulation abolished the effects of SOX2-OT blocking on the inflammatory responses, proliferation, and apoptosis of OGD/R-challenged H2C9 cells. In conclusion, our results, for the first time, demonstrated that SOX2-OT inhibition attenuated MI/R injury in vitro via regulating the miR-186-5p/YY1 axis, offering potential therapeutic targets for MI/R injury treatment.

Generation of an induced pluripotent stem cell line from an Ohtahara syndrome patient with the hemizygous mutation p.Q503Afs*28 (c.1507_1508del) in the ARX gene.

Aristaless-related homeobox (ARX)-related disorders are recessive X-linked intellectual disability disorders. We encountered a patient with a hemizygous mutation (c.1507_1508del) showing intellectual disability, early-onset epileptic encephalopathy and Ohtahara syndrome. The patient had female genitals, but an XY karyotype. We established an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a six-month Chinese child with a hemizygous mutation (c.1507_1508del) in ARX. The PBMCs were reprogrammed with Sendai viral vectors. The iPSCs showed stable amplification, pluripotency-related gene expression, and trilineage differentiation potential. Karyotype analysis of the iPSCs showed 23 pairs of chromosomes with normal structure and sex chromosome is XY.

miRNA-19b-3p Stimulates Cardiomyocyte Apoptosis Induced by Myocardial Ischemia Reperfusion via Downregulating PTEN.

OBJECTIVE: To clarify the function of miRNA-19b-3p in accelerating myocardial ischemia-reperfusion injury- (MIRI-) induced cardiomyocyte apoptosis by downregulating gene of phosphate and tension homology deleted on chromsome ten (PTEN), thus influencing the progression of acute myocardial infarction. MATERIALS AND METHODS: miRNA-19b-3p and PTEN levels in HCM cells undergoing hypoxia/reoxygenation (H/R) were determined. Meanwhile, activities of myocardium injury markers [lactate dehydrogenase (LDH), malondialdehyde; malonic dialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX)] in H/R-induced HCM cells were tested. Through dual-luciferase reporter gene assay, the binding between miRNA-19b-3p and PTEN was verified. Regulatory effects of miRNA-19b-3p and PTEN on apoptotic rate and apoptosis-associated gene expressions (proapoptotic protein Bcl-2 associated X protein (Bax), antiapoptotic protein B-cell lymphoma-2 (Bcl-2), and cytochrome C) in H/R-induced human cardiac myocytes (HCM) cells were examined. RESULTS: miRNA-19b-3p was upregulated, while PTEN was downregulated in H/R-induced HCM cells. Knockdown of miRNA-19b-3p decreased activities of LDH, MDA, and GSH-PX, but increased SOD level in H/R-induced HCM cells. The binding between miRNA-19b-3p and PTEN was confirmed. More importantly, knockdown of miRNA-19b-3p reduced apoptotic rate, downregulated proapoptosis gene expressions (Bax and cytochrome C), and upregulated antiapoptosis gene expression (Bcl-2), which were reversed by silence of PTEN. CONCLUSIONS: miRNA-19b-3p is upregulated in HCM cells undergoing hypoxia and reoxygenation, which accelerates MIRI-induced cardiomyocyte apoptosis through downregulating PTEN.

A narrative review of prognosis prediction models for non-small cell lung cancer: what kind of predictors should be selected and how to improve models?

OBJECTIVE: To discover potential predictors and explore how to build better models by summarizing the existing prognostic prediction models of non-small cell lung cancer (NSCLC). BACKGROUND: Research on clinical prediction models of NSCLC has experienced explosive growth in recent years. As more predictors of prognosis are discovered, the choice of predictors to build models is particularly important, and in the background of more applications of next-generation sequencing technology, gene-related predictors are widely used. As it is more convenient to obtain samples and follow-up data, the prognostic model is preferred by researchers. METHODS: PubMed and the Cochrane Library were searched using the items "NSCLC", "prognostic model", "prognosis prediction", and "survival prediction" from 1 January 1980 to 5 May 2021. Reference lists from articles were reviewed and relevant articles were identified. CONCLUSIONS: The performance of gene-related models has not obviously improved. Relative to the innovation and diversity of predictors, it is more important to establish a highly stable model that is convenient for clinical application. Most of the prevalent models are highly biased and referring to PROBAST at the beginning of the study may be able to significantly control the bias. Existing models should be validated in a large external dataset to make a meaningful comparison.