Calcineurin controls proximodistal blastema polarity in zebrafish fin regeneration.

Planarian flatworms regenerate their heads and tails from anterior or posterior wounds and this regenerative blastema polarity is controlled by Wnt/ß-catenin signaling. It is well known that a regeneration blastema of appendages of vertebrates such as fish and amphibians grows distally. However, it remains unclear whether a regeneration blastema in vertebrate appendages can grow proximally. Here, we show that a regeneration blastema in zebrafish fins can grow proximally along the proximodistal axis by calcineurin inhibition. We used fin excavation in adult zebrafish to observe unidirectional regeneration from the anterior cut edge (ACE) to the posterior cut edge (PCE) of the cavity and this unidirectional regeneration polarity occurs as the PCE fails to build blastemas. Furthermore, we found that calcineurin activities in the ACE were greater than in the PCE. Calcineurin inhibition induced PCE blastemas, and calcineurin hyperactivation suppressed fin regeneration. Collectively, these findings identify calcineurin as a molecular switch to specify the PCE blastema of the proximodistal axis and regeneration polarity in zebrafish fin.

Design, Synthesis and Bioactivities of Novel Pyridyl Containing Pyrazole Oxime Ether Derivatives.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 µg/mL, and some title compounds were active towards Nilaparvata lugens at 500 µg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 µg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 µg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.

Possible genetic cross-talk between Down syndrome and obstructive sleep apnea revealed by transcriptomic analysis.

PURPOSE: Down syndrome (DS) is linked to a higher prevalence of obstructive sleep apnea (OSA) than in the general population, which in turn contributes to worse cognitive impairment in DS. However, the shared pathogenic mechanisms for DS and OSA remain incompletely illustrated. This study was designed to decipher the genetic cross-talk between DS and OSA by bioinformatics approach. METHODS: Transcriptomic datasets of DS (GSE59630) and OSA (GSE135917) were accessed from the Gene Expression Omnibus (GEO) repository. After screening out the common differentially expressed genes (DEGs) for DS and OSA, gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out. A protein-protein interaction (PPI) network was then constructed to determine essential modules and hub genes. Finally, based on hub genes, transcriptional factor (TF)-gene interaction and TF-miRNA regulatory networks were constructed. RESULTS: DS and OSA showed 229 DEGs. Functional analyses revealed how oxidative stress and inflammatory response were critical in the progression of DS and OSA. Ten significant hub genes were identified, including TLR4, SOD1, IGF1, FGF2, NFE2L2, PECAM1, S100A8, S100A9, FCGR3A, and KCNA1, which were candidate targets for DS and OSA. CONCLUSIONS: We found that DS and OSA display similarities in their pathogenesis. Key genes and signaling pathways revealed to be in common between the two conditions could lead us to new therapeutic targets for DS and OSA.

Analysis of the Current Situation and Factors Influencing the Clinical Thinking Ability of Nursing Undergraduates.

Context: Clinical thinking encompasses the critical analysis, judgment, and decision-making pertaining to the existing or potential nursing problems of patients. It plays a pivotal role in effectively executing clinical nursing work in alignment with the prescribed nursing procedures. Proficient clinical thinking empowers nurses with the capability to identify, analyze, and resolve problems. Objective: The study intended to investigate the current situation of clinical thinking ability of nursing students and its influencing factors, so as to improve their clinical thinking ability. Methods: This was a cross-sectional study and the research took place at Taizhou University in Taizhou, Zhejiang province, China in the Faculty of Nursing. 143 full-time undergraduate nursing students at the University were selected for the cross-sectional survey, including a general questionnaire and a clinical thinking ability questionnaire for undergraduate nursing students. The respondents included nursing students in their sophomore, junior and senior years. Results: The survey results obtained between the first and the third year of study were included. Age of the participants ranged from 18 to 24 years, with an average age of 21.58 ± 2.45 years. The professional knowledge score of undergraduate nursing students in this survey was found to be 52.59 ± 13.93; ​the score of professional emotion was 14.21 ± 2.40; ​the score of professional will was 19.51 ± 2.15; ​the score of professional values was 14.40 ± 2.31; ​the professional skill score was 18.52 ± 2.06; the professional expectation was found to be 12.73 ± 1.30; and ​the total score was (99.26 ± 7.96). All dimensions and total scores of clinical ability of thinking among undergraduate nursing students in this survey were found to be average. Conclusions: Clinical thinking of undergraduate nursing students is found to be of a medium level, and the main influencing factors are grade and the satisfaction of teachers. Nursing colleges and practice hospitals should unite to adopt various ways to help nursing undergraduates cultivate and improve their clinical thinking ability.

Current Situation and Factors Influencing the Disaster Response Capability of Undergraduate Nursing Students.

Context: China is a country in which frequent natural disasters occur, but there is a lack of disaster education in Chinese institutions of higher education. Nursing students should receive disaster and emergency training in addition to their professional medical training. Objective: Our study aimed to investigate the current situation and disaster knowledge and training needs of nursing students and to increase the disaster first aid knowledge of college nursing students. Design: This was a cross-sectional study. Setting: The study took place at Taizhou University in Taizhou, Zhejiang, China. Participants: Participants were 443 full-time undergraduate nursing students at Taizhou University in China. Outcome Measures: This cross-sectional survey included a general questionnaire and an undergraduate nursing student disaster nursing ability questionnaire. Results: The survey results were from the first to the third year of study. Students were age 20 to 23 years, with an average age of 20.57±1.85 years. The largest group (35.44%) was made up of juniors. The scores of 3 dimensions of this survey were: dimension of physical and mental quality dimension (3.76 ± 0.71), theoretical system dimension (3.00 ± 0.57) and practical competencies dimension (2.89 ± 0.68). The ability to adapt to rescue needs at the disaster site and whether or not the student had heard of the term "disaster nursing" is the dominant factor affecting the disaster nursing skills of undergraduate nursing students. Conclusions: The disaster relief of male undergraduate nursing student seniors is more positive and their physical and mental quality is better than female nursing students, but knowledge of disaster prevention and practical capability in disaster relief remain weak and there is a lack of a corresponding theoretical system and competence in practical knowledge and skills. It is recommended that systematic disaster nursing education at universities be improved. Knowledge of disaster rescue should be taught systematically to improve awareness of disaster procedures and response and improve the level of practical skills in disaster rescue. We should learn from the educational approach and models of disaster nursing training in developed countries in order to establish a disaster nursing education model in China.

Oxygen Therapy Confers Little Benefit in Patients with Acute ST-Segment Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis.

Objective: We aimed to investigate the clinical benefit of oxygen therapy in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: We searched PubMed, Embase and the Cochrane Library from database inception to June 2020 to identify randomized controlled trials (RCTs) on oxygen therapy in acute STEMI. Literature screening, data extraction and study quality assessment were independently carried out by the 2 investigators according to the predefined eligibility criteria, and RevMan 5.3 analysis software was utilized for all analyses. Results: Finally, 5 RCTs with a total of 4824 patients with STEMI were eligible for further meta-analysis. The RCT results demonstrated that oxygen therapy exerted non-significant effects in reducing the risks for short-term all-cause mortality (risk ratio [RR] = 1.21; 95% CI, 0.80-1.53; P = .53), cardiac arrest (RR = 1.20; 95% CI, 0.94-1.54; P = .79), recurrent myocardial infarction (MI) (RR = 0.68; 95% CI, 0.43-1.08; P = .10) and cardiogenic shock (RR = 0.81; 95% CI, 0.58-1.15; P = .24) and the incidence of other outcome indicators of acute STEMI. Conclusions: Oxygen therapy does not provide more benefits than adverse effects in patients with acute STEMI. Personalized oxygen treatment based on dynamic oxygen saturation is recommended in patients with hypoxia. Supplemental oxygen in patients with acute STEMI has no effect on reducing infarct size, and has no benefit in all-cause mortality, cardiogenic shock, etc.

MicroRNA-132 is involved in morphine dependence via modifying the structural plasticity of the dentate gyrus neurons in rats.

Repeated morphine exposure has been shown to induce neuronal plasticity in reward-related areas of the brain. miR-132, a CREB-induced and activation-dependent microRNA, has been suggested to be involved in the neuronal plasticity by increasing neuronal dendritic branches and spinogenesis. However, it is still unclear whether miR-132 is related to morphine dependence. Here, we investigate whether miR-132 is involved in morphine dependence and whether it is related to the structural plasticity of the dentate gyrus (DG) neurons. Sprague-Dawley rats are treated with increasing doses of morphine injection for six consecutive days to develop morphine dependence. Our results show that dendritic branching and spinogenesis of the DG neurons of morphine dependent rats are increased. Morphine treatment (24 h) promotes the differentiation of N2a cells stably expressing µ-opioid receptor by up-regulating miR-132 expression. Moreover, inhibiting miR-132 3p (but not 5p) of the DG neurons can reverse the structural plasticity and disrupt the formation of morphine dependence in rats. These findings indicate that miR-132 in the DG neurons is involved in morphine dependence via modifying the neuronal plasticity.

Altered gut microbiota correlates with cognitive impairment in Chinese children with Down's syndrome.

Down's syndrome (DS), a common chromosomal disease caused by chromosome 21 trisomy, is the main cause of cognitive impairment in children worldwide. Emerging evidence suggests that the microbiota-gut-brain axis plays a potential role in cognitive impairment. However, data regarding gut microbiota alterations in DS patients remain scarce, especially data from children with DS. This case-control study was conducted to explore the gut microbiota composition in Chinese DS children. Additionally, the potential association between gut microbiota and cognitive function in DS was evaluated. Microbiota communities in the feces of 15 DS subjects and 15 matched controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of 16S rRNA gene. The relationships between gut microbiota composition and DS cognitive function scores were analyzed. The structure and richness of the gut microbiota differed between DS patients and healthy controls. The abundance of Acidaminococcaceae was decreased in DS patients. Moreover, the Kyoto Encyclopedia of Genes and Genomes analysis showed increased modules related to peptidases and pyrimidine metabolism. Overall, we confirmed that gut microbiota alterations occurred in Chinese patients with DS. Additionally, the fecal microbiota was closely related to DS cognitive impairment. Larger cohorts are needed to confirm these findings and to clarify the mechanisms involved. Elucidating these novel findings in the field of microbiota-gut-brain axis will provide a promising strategy for future studies of DS cognitive impairment.

AMPA Receptor in Ventromedial Prefrontal Cortex Plays Different Roles in the Recent and Remote Retrieval of Morphine-Associated Memory.

Previous studies demonstrate that drug addiction can share the neural circuits in the brain with normal learning and memory. Re-exposure to drug-associated contexts, one way to retrieve the drug-associated memory, can trigger strong psychic craving and even relapse in addicts after prolonged abstinence. The ventromedial prefrontal cortex (vmPFC) has been shown to be involved in time-dependent reinstatement of drug self-administration. This work is designed to investigate the role of AMPA receptor (AMPAR) in the vmPFC in the recent and remote retrieval of morphine-associated memory. Rats were re-exposed to the morphine-paired context 1 day (recent) and 3 weeks (remote) after morphine conditioned place preference (CPP) training. Results showed that membrane expression of GluA1 and GluA2 in the vmPFC was decreased following the recent retrieval, while the membrane expression of GluA1 and GluA2 in the vmPFC was increased following the remote retrieval of morphine-associated memory. Furthermore, the microinfusion of Tat-GluA2-3Y, a GluA2 endocytosis inhibitor, into the vmPFC impaired the recent retrieval of morphine-associated memory. The microinfusion of AMPAR antagonist NBQX into the vmPFC prevented the remote retrieval of morphine-associated memory. Taking together, the present study proved that AMPAR in the vmPFC played different roles in the recent and remote retrieval of morphine-associated memory.

Krüppel-like factor 4 regulates the expression of inducible nitric oxide synthase induced by TNF-α in human fibroblast-like synoviocyte MH7A cells.

Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, has been implicated in the inflammation mediated by macrophages and endothelial cells by regulating the expression of inflammatory mediators. Here, we investigated whether KLF4 affects the expression of inducible nitric oxide synthase (iNOS), an important inflammatory mediator, in the human RA fibroblast-like synovial cell line MH7A. A pcDNA3.1-KLF4 plasmid or short interfering RNA KLF4 was transfected into MH7A cells, and the iNOS expression and nitric oxide (NO) production were analyzed by quantitative PCR, immunoblotting, and nitrite measurement. The iNOS promoter activity was determined by luciferase assay. The results showed overexpression of KLF4 increased iNOS expression and NO production in the presence or absence of TNF-α. Conversely, KLF4 knockdown markedly reduced iNOS expression and NO production induced by TNF-α. KLF4 activated the transcription activity of iNOS promoter in MH7A cells stimulated by TNF-α. This study indicates that KLF4 is important for regulating the expression of iNOS by TNF-α in human synoviocytes.

Phosphorylated SNAP25 in the CA1 regulates morphine-associated contextual memory retrieval via increasing GluN2B-NMDAR surface localization.

Although our previous studies have demonstrated both protein kinase C (PKC) and GluN2B-containing N-methyl-d-aspartate receptor (GluN2B-NMDAR) play crucial roles in morphine-associated learning and memory, the relationship between them remains unexplored. In this study, we validated the enhanced PKC and membrane GluN2B protein expression in the hippocampal CA1 after morphine conditioned place preference (CPP) expression in rats. Interestingly, we also found that phosphorylation of SNAP25 at Ser187 (pSer187-SNAP25), a PKC-activated target, was significantly increased following morphine CPP expression. Blocking the pSer187-SNAP25 by intra-CA1 injection of an interfering peptide impaired morphine CPP expression and accompanied by the reduced ratio of GluN2B membrane/total in the CA1. In addition, intra-CA1 blockade of pSer187-SNAP25 did not affect natural learning and memory process as evidenced by intact sucrose-induced CPP expression and normal locomotor activity in rats. Therefore, our results reveal that enhanced pSer187-SNAP25 by PKC recruits GluN2B-NMDAR to the membrane surface in the hippocampal CA1 and mediates context-induced addiction memory retrieval. Our findings in this study fill in the missing link and provide better understanding of the molecular mechanisms involved in morphine-associated contextual memory retrieval.

mGluR5 in the nucleus accumbens shell regulates morphine-associated contextual memory through reactive oxygen species signaling.

Emerging evidence indicates that metabotropic glutamate receptor 5 (mGluR5) critically modulates drug and drug-related behaviors. However, the role of mGluR5 in the opiate-induced contextual memory remains unclear. Here, we found that microinfusion of the mGluR5 antagonist 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) into the nucleus accumbens (NAc) shell, but not into the core, significantly attenuated the expression of morphine conditioned place preference (CPP) in rats. Following the expression of morphine CPP, the protein level of membrane mGluR5 was selectively increased in the NAc shell. In primary striatal neurons, we observed that treatment with the mGluR5 agonist CHPG increased the phosphorylation level of extracellular signal-regulated kinase (ERK), which was dependent on the mGluR5-inositol-1,4,5-trisphosphate-reactive oxygen species (ROS) pathway. Moreover, the microinjection of the ROS scavenger Tempol into the NAc shell of rats blocked the expression of morphine CPP. Further, the administration of t-BOOH, a ROS donor, into the NAc shell rescued the retrieval impairment of morphine CPP produced by MTEP. Our previous study demonstrated that the expression of morphine CPP increased the phosphorylation of ERK selectively in the NAc shell. Thus, results of the present study suggest that mGluR5 in the NAc shell, but not in the core, is essential for the retrieval of morphine contextual memory, which is mediated at least in part, through the ROS/ERK signaling pathway. Uncovering the molecular basis of opiate contextual memory will benefit the development of new therapeutic approaches for the treatment of opiate addiction.

n-3 polyunsaturated fatty acids alleviate the progression of obesity-related osteoarthritis and protect cartilage through inhibiting the HMGB1-RAGE/TLR4 signaling pathway.

Osteoarthritis (OA) is a common joint degenerative disease. There is currently no cure for OA. Dietary fatty acids have potential value in the prevention and treatment of OA. n-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory effects, but their anti-OA mechanism remains unclear. High-mobility group box 1 (HMGB1) promotes inflammation and participates the pathogenesis of OA. The purpose of this study was to investigate the protective effect of n-3 PUFAs on cartilage and whether n-3 PUFAs could exert an anti-OA effect through inhibiting HMGB1-RAGE/TLR4 signaling pathway. We established an obesity-related post-traumatic OA mice model and an in vitro study was conducted to explore the regulatory mechanism of n-3 PUFAs on HMGB1 and its signal pathway against OA. We found that diet rich in n-3 PUFAs alleviated OA-like lesions of articular cartilage with the decrease of HMGB1-RAGE/TLR4 signaling protein in mice. In SW1353 cells, DHA significantly reduced the expression of HMGB1-RAGE/TLR4 signaling protein which was up-regulated by IL-1ß stimulation. HMGB1 overexpression reversed the inhibitory effect of DHA on HMGB1-RAGE/TLR4 signaling pathway. The activation of SIRT1 may participate the inhibitory effect of DHA on HMGB1-RAGE/TLR4 signaling pathway. In conclusion, n-3 PUFAs could attenuate the progression of obesity-related OA and exert protective effect on cartilage by inhibiting HMGB1-RAGE/TLR4 signaling pathway, which may be associated with the activation of SIRT1. Dietary n-3 PUFAs supplements can be considered as a potential therapeutic substance for OA.

Discovery of RGT-018: a Potent, Selective and Orally Bioavailable SOS1 Inhibitor for KRAS-driven Cancers.

KRAS is the most frequently dysregulated oncogene with high prevalence in NSCLC, colorectal cancer, and pancreatic cancer. FDA-approved sotorasib and adagrasib provide breakthrough therapies for cancer patients with KRASG12C mutation. However, there is still high unmet medical need for new agents targeting broader KRAS-driven tumors. An emerging and promising opportunity is to develop a pan KRAS inhibitor by suppressing the upstream protein SOS1. SOS1 is a key activator of KRAS and facilitates the conversion of GDP-bound KRAS state to GTP-bound KRAS state. Binding to its catalytic domain, small molecule SOS1 inhibitor has demonstrated the ability to suppress KRAS activation and cancer cell proliferation. RGT-018, a potent and selective SOS1 inhibitor, was identified with optimal drug-like properties. In vitro, RGT-018 blocked the interaction of KRAS:SOS1 with single digit nM potency and is highly selective against SOS2. RGT-018 inhibited KRAS signaling and the proliferation of a broad spectrum of KRAS-driven cancer cells as a single agent in vitro. Further enhanced anti-proliferation activity was observed when RGT-018 was combined with MEK, KRASG12C, EGFR or CDK4/6 inhibitors. Oral administration of RGT-018 inhibited tumor growth and suppressed KRAS signaling in tumor xenografts in vivo. Combination with MEK or KRASG12C inhibitors led to significant tumor regression. Furthermore, RGT-018 overcame the resistance to the approved KRASG12C inhibitors caused by clinically acquired KRAS mutations either as a single agent or in combination. RGT-018 displayed promising pharmacological properties for combination with targeted agents to treat a broader KRAS-driven patient population.

Cryo-EM structures reveal two allosteric inhibition modes of PI3KαH1047R involving a re-shaping of the activation loop.

PI3Kα is a lipid kinase that phosphorylates PIP2 and generates PIP3. The hyperactive PI3Kα mutation, H1047R, accounts for about 14% of breast cancer, making it a highly attractive target for drug discovery. Here, we report the cryo-EM structures of PI3KαH1047R bound to two different allosteric inhibitors QR-7909 and QR-8557 at a global resolution of 2.7 Å and 3.0 Å, respectively. The structures reveal two distinct binding pockets on the opposite sides of the activation loop. Structural and MD simulation analyses show that the allosteric binding of QR-7909 and QR-8557 inhibit PI3KαH1047R hyper-activity by reducing the fluctuation and mobility of the activation loop. Our work provides a strong rational basis for a further optimization and development of highly selective drug candidates to treat PI3KαH1047R-driven cancers.

[Correlation Analysis between Thyroid Function Abnormality and Efficacy in Patients 
with Advanced Non-small Cell Lung Cancer after Immunotherapy].

BACKGROUND: Thyroid function abnormality (TFA) is one of the common adverse reactions in patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy, but the risk factors of TFA and its relationship with efficacy are not completely clear. The purpose of this study was to explore the risk factors of TFA and its relationship with efficacy in patients with advanced NSCLC after immunotherapy. METHODS: The general clinical data of 200 patients with advanced NSCLC in The First Affiliated Hospital of Zhengzhou University from July 1, 2019 to June 31, 2021 were collected and analyzed retrospectively. χ² test and multivariate Logistic regression were used to explore the risk factors of TFA. Kaplan-Meier curve was drawn and Log-rank test was used for comparison between groups. Univariate and multivariate Cox analysis was used to explore the efficacy factors. RESULTS: A total of 86 (43.0%) patients developed TFA. Logistic regression analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS), pleural effusion and lactic dehydrogenase (LDH) were factors influencing TFA (P<0.05). Compared with normal thyroid function group, the median progression-free survival (PFS) of patients in the TFA group was significantly longer (19.0 months vs 6.3 months, P<0.001), and the objective response rate (ORR) (65.1% vs 28.9%, P=0.020) and disease control rate (DCR) (100.0% vs 92.1%, P=0.020) of the TFA group were better than those of the normal thyroid function group. Cox regression analysis showed that ECOG PS, LDH, cytokeratin 19 fragment (CYFRA21-1) and TFA were factors influencing prognosis (P<0.05). CONCLUSIONS: ECOG PS, pleural effusion and LDH may be risk factors affecting the occurrence of TFA and TFA may be a predictor of the efficacy of immunotherapy. Patients with advanced NSCLC who have TFA after immunotherapy may obtain better efficacy.

Research on the dynamic evolution and convergence of collaborative capacity of pollution control and carbon reduction: from the perspective of whole-process governance.

Under the strategic goals of achieving peak carbon neutrality, deepening the battle against pollution, and building a beautiful China, improving the collaborative capacity of pollution control and carbon reduction is an important means to achieve comprehensive green and low-carbon transformation of the social economy. Starting from the essential requirements of improving the collaborative capacity of pollution control and carbon reduction, based on the whole-process governance perspective of "source-process-end-of-pipe," build an evaluation index system, measure the collaborative capacity, quantify the spatial differences, analyze the evolution characteristics, and explore the improvement path. The study found that China's collaborative capacity of pollution control and carbon reduction is characterized by homogeneous agglomeration and unbalanced regional development. Intra-regional differences are the main source of the differences, sorting by contribution is "Eastern > Western > Central > Northeast." After taking into account the factors of green transformation of industry, the input of scientific and technological elements, and opening to the outside world, the differences have gradually narrowed. Among them, the green transformation of industry is instrumentally in bridging the gap in eastern, central, and northeastern, the input of scientific and technological elements is instrumentally in bridging the gap between regions and the eastern and northeast, and opening to the outside world is instrumentally in bridging the gap between regions and the western. The scientific measurement and improvement of this capacity will provide the factual basis and path choice for achieving the task goal of "significantly improving China's collaborative capacity of pollution control and carbon reduction by 2030," which is of great practical significance for building a higher-quality, more sustainable, and greener pattern of the collaborative capacity of pollution control and carbon reduction.

Trait creativity, personality, and physical activity: a structural equation model.

BACKGROUND: Previous studies have shown that personality affects creativity, and physical activity and is associated with cognitive function. However, the relationship among physical activity, creativity, and personality remains unclear. This study sought to examine the relationship among personality, physical activity, and creativity to identify relevant risk factors of trait creativity. Structural equation modeling (SEM) was used to assess the effect of personality (extraversion, agreeableness, conscientiousness, neuroticism, and openness) on physical activity, the effect of physical activity on creativity traits. METHODS: A total of 296 university students were recruited for this study. The survey was administered by WeChat. The self-reported questionnaires included questions related to demographic information, creativity (from the Williams Creativity Assessment Packet), the Big Five personality traits, and physical activity. A correlation analysis was conducted and the structural equation models were constructed using SPSSAU. RESULTS: The SEM analysis showed that openness in personality was positively correlated with physical activity. Physical activity was negatively correlated with curiosity, challenging, risk-taking, and imagination. CONCLUSIONS: Among university students, openness may be a profound positive factor affecting physical activity. Moreover, physical activity was also associated with trait creativity. Consideration should be given to assessing personality traits and physical activity to ensure the selection of more creative students.

Histone H3 Acetylation Is Involved in Retinoid Acid-Induced Neural Differentiation through Increasing Mitochondrial Function.

Histone acetylation and mitochondrial function contribute importantly to neural differentiation, which is critically associated with neurodevelopmental disorders such as Down Syndrome (DS). However, whether and how histone acetylation regulates mitochondrial function and further affects neural differentiation has not been well described. In this study, when treated with retinoid acid (RA), the human neuroblastoma SH-SY5Y cell line was used as a neural differentiation model. We found that the acetylation of histone H3, especially H3 lysine 14 acetylation (H3K14ac), and mitochondrial function, including biogenesis and electron transport chain, were enhanced during neural differentiation. Specific inhibition of histone acetyltransferases (HATs) induced neural differentiation deficits, accompanied by downregulation of mitochondrial function. Furthermore, RA receptors (RARs) interacting with HATs were involved in the increased H3K14ac and the enhanced mitochondrial function during the neural differentiation process. Finally, receptor-interacting protein 140 (RIP140), a co-repressor of RARs, was also involved in regulating histone acetylation. RIP140 overexpression inhibited histone acetylation and mediated negative feedback on target genes which are involved in RA signaling. These findings evidenced that when interacting with RARs which had been negatively regulated by RIP140, RA promoted neural differentiation by promoting H3K14ac and enhanced mitochondrial function. This provides a molecular foundation for further investigations into abnormal neural development.

Diagnostic efficacy of metagenomic next generation sequencing in bronchoalveolar lavage fluid for proven invasive pulmonary aspergillosis.

Objective: To assess the diagnostic efficacy of metagenomic next generation sequencing (mNGS) for proven invasive pulmonary aspergillosis (IPA). Methods: A total of 190 patients including 53 patients who had been diagnosed with proven IPA were retrospectively analyzed. Using the pathological results of tissue biopsy specimens as gold standard, we ploted the receiver operating characteristic (ROC) curve to determine the optimal cut-off value of mNGS species-specific read number (SSRN) of Aspergillus in bronchoalveolar lavage fluid (BALF)for IPA. Furthermore, we evaluated optimal cut-off value of mNGS SSRN in different populations. Results: The optimal cut-off value of Aspergillus mNGS SSRN in BALF for IPA diagnosis was 2.5 for the whole suspected IPA population, and 1 and 4.5 for immunocompromised and diabetic patients, respectively. The accuracy of mNGS was 80.5%, 73.7% and 85.3% for the whole population, immunocompromised and diabetic patients, respectively. Conclusions: The mNGS in BALF has a high diagnostic efficacy for proven IPA, superioring to Aspergillus culture in sputum and BALF and GM test in blood and BALF. However, the cut-off value of SSRN should be adjusted when in different population.