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A nickel/Lewis acid cooperatively catalyzed intramolecular dearomative arylcyanation of indoles is presented. The reaction proceeds through a C-CN bond activation, dearomatization, and benzylic cyanation sequence, affording 3-cyano fused indolinyl heterocycles in good to excellent yields and excellent diastereoselectivity. The asymmetric version of the reaction can be established in moderate enantioselectivity by using a chiral ligand.

Objective Functional tricuspid regurgitation(FTR) levels can vary over time and its longitudinal changing patterns may predict right ventricular dysfunction(RVD) risk. We aim to identify different trajectories of FTR in those who received mitral valve replacement(MVR) and investigate the association between longitudinal trajectory groups and RVD risk in a cohort study. Methods and results A prospective cohort study, reported usual FTR levels at baseline in 2005–2015 and the participants of MVR have been followed up for 5~6 years, approximately every one years, and so far, the data have been collected across five subsequent phases. Five-year longitudinal trajectories of FTR were identified using group-based trajectory modelling(GBTM). We identified 3 distinct trajectories using a GBTM, labeled by initial value and changing pattern: stable group(258/378, 68.2%), increasing-slow group(67/378, 17.6%) and increasing-fast group(53/378, 14.2%). Treating the stable group as the reference, the age- and sex-adjusted odds ratio(OR) was 25.84 (95% confidence interval, 11.78-56.65) for the increasing-slow group and 139.94(95% confidence interval, 45.47-430.68) for the increasing-fast group by logistic regression model. After adjustment for every potential confounding factors, the OR is 14.21(95% confidence interval, 4.36-46.33)、49.34(95% confidence interval, 8.88-273.87) respectively. Conclusions The longitudinal trajectories of worsening FTR were mostly associated with increased risk of RVD outcomes, which is independent of other factors including FTR levels. These findings have implications for intervention and prevention of RVD among individuals who received MVR.

As clean renewable energy with strong advantages, hydropower plays an extremely important role in promoting green development and energy allocation patterns. Hydropower project construction is characterized by long duration, large scale, high cost, many participants, and complex construction conditions, and is closely related to the economy, society, and ecological environment, and its construction management mode and construction risk management have become the focus of extensive attention from all walks of life. In this paper, the risk evaluation index system of hydropower engineering EPC project is constructed, and the linear weighted combination method is introduced to determine the comprehensive weights based on the calculation of weights by sequential relationship method and entropy weight method, and the improved fuzzy normal distribution is introduced as the subordinate function distribution of fuzzy evaluation level based on DS evidence theory and fuzzy theory. The risk evaluation model of a hydropower engineering EPC project is also established. Meanwhile, the model was analyzed with hydropower project examples to verify the accuracy and practicality of the model, which can guide hydropower project stakeholders to manage hydropower project risks comprehensively, collaboratively, and efficiently, and provide decision support for hydropower project construction risk management.

The exopolysaccharides (EPS) produced by Lactobacillus and other probiotics are associated with many benefits, such as immune regulation, antioxidant properties, antitumor effect, and regulation of intestinal microbe homeostasis. In the present study, the modulatory effect of EPS produced by Lactobacillus rhamnosus ZFM231 on the intestinal flora of mice with inflammatory bowel disease induced by dextran sulfate solution was investigated.Results indicated that weight loss, colonic length, the disease activity index score and colonic tissue damage in mice were significantly improved by EPS treatment. Compared with the model group, in the EPS-treated group, the diversity of and the composition of gut microbiota at both phylum and genus levels were found to recover to the levels of normal group, indicating the effective modulation on gut microbiota by EPS; short-chain fatty acids, including acetic acid, propionic acid and butyric acid produced by intestinal microbial metabolism, increased significantly; the level of anti-inflammatory factor transforning growth factor-β significantly increased and the level of pro-inflammatory factor tumor necrosis factor-α significantly decreased in the colonic cells of EPS-treated mice.It is clear that EPS produced by L. rhamnosus ZFM231 could find application in functional foods with the property of anti-ulcerative colitis. The experimental results provide new insights into the probiotic effect of EPS. © 2022 Society of Chemical Industry.

In this study, the effects of Nb and O contents on the negative thermal expansion behaviors including the coefficient of negative thermal expansion and matensite (α) stability of cold rolled (CR) Ti-34Nb alloys was investigated by optical microscopy, X-ray diffraction and Thermomechanical analysis. Results show that texture strength of CR-Ti-xNb-xO alloys is related to β stability, the addition of Nb and O (β stabilizers) enhances the texture strength. XRD results indicate that Nb and O inhibit the formation of α. The coefficient of negative thermal expansion of CR-Ti-xNb-xO alloys decrease with the increase of Nb and O contents. Moreover, cyclic thermal expansion results reveal that Nb and O promote the decomposition of α.

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder, characterized by reciprocal translocation t(9,22) (q34; q11), leading to increased myeloid proliferation. Most cases are diagnosed in the chronic phase (CP). However, a minority of cases can be present in the blastic phase (BP). In most patients with CML-BP, the blasts have a myeloid phenotype, however, in 20–30% of cases, the blasts have a lymphoid phenotype, mostly a B-cell phenotype. It is challenging to differentiate CML B-lymphoblastic phase (CML-BLP) from Ph + primary B-acute lymphoblastic leukemia (B-ALL) especially when the CML-BLP is the initial presentation of the disease, which is uncommon. We report here an unusual case of CML-BLP as an initial presentation of the disease without typical CML morphological findings. This case demonstrates diagnostic challenges and emphasizes the importance of an integrated approach using morphology, multiparametric flow cytometry, cytogenetic studies, and molecular studies to render an accurate diagnosis.

Brown and beige adipocytes dissipate energy in a nonshivering thermogenesis manner, exerting beneficial effects on metabolic homeostasis. CHCHD10 is a nuclear-encoded mitochondrial protein involved in cristae organization; however, its role in thermogenic adipocytes remains unknown. We identify CHCHD10 as a novel regulator for adipocyte thermogenesis. CHCHD10 is dramatically upregulated during thermogenic adipocyte activation by PPARγ-PGC1α and positively correlated with UCP1 expression in adipose tissues from humans and mice. We generated adipocyte-specific Chchd10 knockout mice (Chchd10-AKO) and found that depleting CHCHD10 leads to impaired UCP1-dependent thermogenesis and energy expenditure in the fasting state, with no effect in the fed state. Lipolysis in adipocytes is disrupted by CHCHD10 deficiency, while augmented lipolysis through ATGL overexpression recovers adipocyte thermogenesis in Chchd10-AKO mice. Consistently, overexpression of Chchd10 activates thermogenic adipocytes. Mechanistically, CHCHD10 deficiency results in the disorganization of mitochondrial cristae, leading to impairment of oxidative phosphorylation complex assembly in mitochondria, which in turn inhibits ATP generation. Decreased ATP results in downregulation of lipolysis by reducing nascent protein synthesis of ATGL, thereby suppressing adipocyte thermogenesis. As a result, Chchd10-AKO mice are prone to develop high-fat diet–induced metabolic disorders. Together, our findings reveal an essential role of CHCHD10 in regulating lipolysis and the thermogenic program in adipocytes.

Backgroud To explore whether monitoring of non-invasive urine oxygen tension (PuO2) for 3 consecutive days can reflect renal medulla microcirculation injury early and whether changes in PuO2 (△PuO2) have reliable early diagnostic value for sepsis-associated acute kidney injury (SA-AKI). Methods Twenty-four patients who were hospitalised for more than 48 h in our hospital and were diagnosed with sepsis were retrospectively divided into non-SA-AKI group and SA-AKI group according to the occurrence of acute kidney injury (AKI). The general and oxygen metabolism data of the two groups were compared. The results of urine analysis (PuO2, PuCO2, and urinary lactic acid) for 3 consecutive days were compared with common clinical kidney injury indices, and a changing trend was observed. Results In the PICU, a total of 24 patients with sepsis were included (14 males, 58.33%; mean age, 5 years), with 15 cases in the non-SA-AKI group and 9 cases in the SA-AKI group, with incidence of SA-AKI being 37.5%. PuO2 gradually decreased from D0 to D2 in the SA-AKI group; PuCO2 increased naturally. The variation trend of PuO2 was statistically significant in D1-D0, D2-D0, and D2-D1 (PConclusions Three consecutive days of PuO2 monitoring can reflect early renal medullary microcirculation injury, and △PuO2 has early diagnostic value for SA-AKI.

The biogeography research of orchids through species distribution models (SDMs), a vital tool in the biogeography field, is critical to understanding the fundamental geographic distribution patterns and identifying conservation priorities. The correspondence between species occurrence and environmental information is crucial to the model’s performance. However, ecological preferences unique to different orchid species, such as their life forms, are often overlooked during the modeling process. This oversight can introduce bias and increase model uncertainty. Additionally, human activities, as an important potential predictor, have not been quantified in any orchid SDMs. Taking the Hengduan Mountains as an example, we preprocessed all orchid species’ occurrences based on physiological characteristics. Choosing five spatial factors related to human activities to quantify the interference and enter into models as HI factor. Using different modeling methods (GLM, MaxEnt, and RF) and evaluation indices (AUC, TSS, and Kappa), diverse modeling strategies have been constructed in the study. A double-ranking method has been adopted to select the critical orchid distribution regions. The results showed that classification models based on physiological characteristics significantly improved the model’s accuracy while adding the HI factor had the same effect but the absence of enough significance. Suitability maps indicated that highly heterogeneous mountainous areas were vital for the distribution of orchids in the Hengduan Mountains. Different distribution patterns and critical regions existed between various orchid life forms geographically - terrestrial orchids were dominant in the mountain, and mycoherterophical orchids were primarily located in the north, more influenced by vegetation and temperature. Critical regions of epiphytic orchids were in the south due to a greater dependence on precipitation and temperature. These studies are informative for understanding the orchids’ geographic distribution patterns in the Hengduan Mountains, promoting conservation, and providing references for similar research beyond orchids.

Background The cognitive benefits of early non-pharmacological approaches have been demonstrated in older adults with mild cognitive impairment (MCI). However, older adults living in nursing homes have more severe cognitive impairment problems and lower initiative and compliance to participate in complex interventions. Hence, it important to investigate more attractive and sustainable methods to prevent or delay cognitive decline. The present study adopts the self-determination theory (SDT) as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes in China and aims to evaluate its effects on cognitive function, mental health, and other health-related outcomes. Methods The study is a nursing home-based, cluster randomised controlled trial (RCT) that targets older adults (aged ≥ 60 years) with MCI in Fuzhou City, China. All nursing homes in the area covered by Fuzhou City are invited to participate. Eligible nursing homes are randomised to one of two groups: intervention group (receive a 14-week, 27-session intervention) and waitlist control group (receive the usual care). The SDT-based integrated creative art (SDTICA) program reasonably adopts the SDT as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes. The primary (global cognitive function and psychological indicator) and secondary (daily activity function, social function, and specific domains of cognitive function) outcomes will be measured at baseline, after the intervention, and during follow-up. Discussion This study aims to evaluate the effects of SDTICA program on neuropsychological outcomes in older adults with MCI and provide scientific evidence for art-based non-pharmacologic interventions in nursing homes, which may reduce dementia risk in older adults with MCI. Trial registration The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR2200061681 on 30 June 2022.

Objective: This study aimed to explore the prevalence and associated factors of medication adherence among infertile women undergoing frozen-thawed embryo transfer (FET) cycle.Methods: A cross-sectional study was conducted with 556 infertile women undergoing FET cycle in total. The Self-efficacy for Appropriate Medication Use Scale (SEAMS), Herth Hope Index (HHI) scale, and Social Support Rating Scale (SSRS) were used to evaluate the patients. Data were described by univariate and multivariate analyses. Logistic regression method was performed to analyse the factors potentially associated with medication adherence.Results: The average score of Self-efficacy for Appropriate Medication Use Scale (SEAMS) was 30.38 ± 6.65, and 65.3% of participants showed non-adherence. Multiple regression analysis indicated that first-time FET cycle, treatment stage, methods of daily medication, social support and hope level were the main associated factors of the medication adherence among infertile women undergoing FET cycle (p < 0.001).Conclusion: This study revealed the medication adherence is at medium level among infertile women undergoing FET cycle, especially in patients with repeated FET cycles. The study also suggested that improving the hope level and social support of infertile women undergoing FET cycle may increase medication adherence.

Ménière’s disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière’s disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière’s disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1β production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk−/− mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière’s disease pathogenesis.

Macrophages are involved in the whole process of atherosclerosis, which is characterized by accumulation of lipid and inflammation. Presently, clinically used lipid-lowering drugs cannot completely retard the progress of atherosclerosis. Liver X receptor (LXR) plays a key role in regulation of lipid metabolism and inflammation. Accumulating evidence have demonstrated that synthetic LXR agonists can significantly retard the development of atherosclerosis. However, these agonists induce sever hypertriglyceridemia and liver steatosis. These side effects have greatly limited their potential application for therapy of atherosclerosis. The rapid development of drug delivery system makes it possible to delivery interested drugs to special organs or cells using nanocarriers. Macrophages express various receptors which can recognize and ingest specially modified nanocarriers loaded with LXR agonists. In the past decades, a great progress has been made in this field. These macrophage-targeted nanocarriers loaded with LXR agonists are found to decrease atherosclerosis by reducing cholesterol accumulation and inflammatory reactions. Of important, these nanocarriers can alleviate side effects of LXR agonists. In this article, we briefly review the roles of macrophages in atherosclerosis, mechanisms of action of LXR agonists, and focus on the advances of macrophage-targeted nanocarriers loaded with LXR agonists. This work may promote the potential clinical application of these nanocarriers.

Oral-facial-digital syndrome (OFDS) is a multisystemic ciliopathic disorder with an autosomal recessive mode of inheritance. OFDS usually manifests with typical craniofacial anomalies and variable occurrence of polydactyly. Germline variants in CPLANE1 cause OFDS VI. In this study, we investigated a 26-year-old Chinese female patient who was 23

Objective: As one of the most prevalent psychiatric disorders, the exact pathogenesis of depression remains elusive. Therefore, there is an urgent need to identify novel antidepressants for effective treatment. MicroRNA-124 (miR-124), the most abundant miRNA in brain tissue, plays a key effect on adult neurogenesis and neuronal differentiation. However, the mechanism of miR-124 in depression has not been clarified so far. The aim of this study is to provide broad insight into the mechanisms underlying depression. Methods: In the study, we used the forced swim test (FST), the tail suspension test (TST), and a Chronic Social Defeat Stress (CSDS) mice model of depression. Quantitative real-time reverse transcription PCR (qRT-PCR), western blotting, immunofluorescence and virus-mediated gene transfer were used together. The level of plasma corticosterone in mice was analyzed by Enzyme Linked Immunosorbent Assay (ELISA). Results: It was found that CSDS robustly increased the level of miR-124 in the hippocampus. Genetic knockdown of hippocampal miR-124 produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, AAV-siR-124-EGFP treatment increased the level of plasma corticosterone in CSDS-induced mice. Moreover, it was found that the antidepressant-like effects induced by miR-124 inhibition required the hippocampal BDNF-TrkB system. Conclusion: Hippocampal miR-124 participated in the pathogenesis of depression by regulating BDNF biosynthesis and was a feasible antidepressant target.

Background: The objective was to develop and validate an individualized nomogram to predict severe functional tricuspid regurgitation (S-FTR) after mitral valve replacement (MVR) via retrospective analysis of rheumatic heart disease (RHD) patients’ pre-clinical characteristics. Methods: Between 2001-2015, 442 MVR patients of RHD were examined. Transthoracic echocardiography detected S-FTR, and logistic regression model analyzed its independent predictors. R software established a nomogram prediction model, and Bootstrap determined its theoretical probability, which subsequently was compared with the actual patient probability to calculate the area under the curve (AUC) and calibration plots. Decision curve analysis (DCA) identified its clinical utility. Results: Ninety-six patients developed S-FTR during the follow-up period. Both uni- and multivariate analyses found significant correlations between S-FTR occurrence with gender, age, atrial fibrillation (AF), pulmonary arterial hypertension (PH), left atrial diameter (LAD), and tricuspid regurgitation area (TRA). The individualized nomogram model had the AUC of 0.99 in internal verification. Calibration test indicated high agreement of predicted and actual S-FTR onset. DCA also showed that utilization of those six aforementioned factors was clinically useful. Conclusion: The nomogram for the patient characteristics of age, gender, AF, PH, LAD, and TRA found that they were highly predictive for future S-FTR onset within 5 years. This predictive ability therefore allows clinicians to optimize postoperative patient care and avoid unnecessary tricuspid valve surgeries.

Introduction: Cardiac magnetic resonance (CMR) is the gold standard for evaluating myocardial fibrosis. Few studies have explored the association between ventricular arrhythmias (VAs) and fibrosis in apparently normal hearts. We aimed to investigate the association between the occurrence and morphology of VAs and left ventricular late gadolinium enhancement (LV-LGE) in patients without known structural heart diseases. Methods: This study enrolled 78 patients with apparently normal hearts who underwent simultaneous 24-h ambulatory Holter electrocardiogram (ECG) and CMR examinations. The presence and extent of LGE was determined using CMR imaging and compared based on occurrence and morphology of VAs. The clinical characteristics were also recorded and calculated. Results: LV-LGE was observed in 19 (37.3%) and 4 (14.8%) patients with and without VAs, respectively (P=0.039). It was more frequently observed in patients with polymorphic VAs (P=0.024) and ST-segment depression (P=0.001), and its extent was greater in polymorphic VAs than monomorphic VAs, with a difference that approached significance (P=0.055). In multivariate analyses adjusted for other clinical variables, the presence of ST-segment depression (HR: 8.83; 95% CI: 2.23-35.50; P=0.002), drinking (HR: 6.84; 95% CI: 1.63-28.56; P=0.008), and polymorphic VAs (HR: 25.24; 95% CI: 3.88-164.06; P=0.001) were associated with greater prevalence of LV-LGE. Conclusion: In this cohort of patients without structural heart diseases, myocardial fibrosis was associated with multiple VA morphologies and ST-segment depression on Holter ambulatory ECG measurements.

1,3,5-Trinitro-1,3,5-triazinane (RDX) has attracted considerable attention in energy-related fields. However, the safety performance of RDX needs to be improved in terms of various external stimuli. Herein, such issues of RDX could be well balanced through hydrothermal assembly with the assistance of insensitive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) in a low content of 10 wt% (named RT co-particles). The TATB spread outside and were embedded inside of the resultant RT co-particles, which were examined

Despite the great advances in target therapy, lung cancer remains the top cause of cancer-related death worldwide. G protein-coupled receptor neurokinin-1 (NK1R) is shown to play multiple roles in various cancers; however, the pathological roles and clinical implication in lung cancer are unclarified. Here we identified NK1R as a significantly upregulated GPCR in the transcriptome and tissue array of human lung cancer samples, associated with advanced clinical stages and poor prognosis. Notably, NK1R is co-expressed with epidermal growth factor receptor (EGFR) in NSCLC patients’ tissues and co-localized in the tumor cells. NK1R can crosstalk with EGFR by interacting with EGFR, transactivating EGFR phosphorylation and regulating the intracellular signaling of ERK1/2 and Akt. Activation of NK1R promotes the proliferation, colony formation, EMT, MMP2/14 expression, and migration of lung cancer cells. The inhibition of NK1R by selective antagonist aprepitant repressed cell proliferation and migration in vitro. Knockdown of NK1R significantly slowed down the tumor growth in nude mice. The sensitivity of lung cancer cells to gefitinib/osimertinib is highly increased in the presence of the selective NK1R antagonist aprepitant. Our data suggest that NK1R plays an important role in lung cancer development through EGFR signaling and the crosstalk between NK1R and EGFR may provide a potential therapeutic target for lung cancer treatment.

An N-glycosidic polysaccharide-peptide complex CMPS-80 from the fruiting body of C. militaris modulates ceRNA network in the liver of apoE(−/−) mice.

2,4,6-Trinitroresorcinol (TNR), one main by-product in the dinitrobenzene (DNB) production process, is self-reactive substance and has led to tragic explosion incidents in China. In this article, the formation mechanism of TNR during the DNB production process was studied employing HPLC and HPLC-MS technique. Thermal decomposition behavior of TNR was also systematically studied by differential scanning calorimeter (DSC). The decomposition kinetics of TNR were investigated employing both iso-conversional (Friedman and Ozawa method) and model-fitting method. The formation mechanism of TNR during the dinitrobenzene (DNB) production is confirmed: The two by-products of dinitrophenol (DNP) and trinitrophenol (TNP) produced in the benzene mononitration stage are further nitrated to form tetranitrophenol (TTNP) in the mononitrobenzene (MNB) nitration stage. Then most of TTNP will be hydrolyzed to form the TNR during the water washing process. The decomposition process of TNR has been proven to follow three consecutive steps (A→B1→B2→B). The former two steps present autocatalytic behavior while the last step obeys N-order reaction model. The accuracy of the developed decomposition model and the obtained model parameters have been demonstrated by the comparison of the simulated and experimental DSC data and the activation energy obtained by both the iso-conversional method and model-fitting method. The same trend of experimental and simulated results about isothermal reaction further verify the building model.

Myocardial ischemia/reperfusion (I/R) injury is still a lack of effective therapeutic drugs, and its molecular mechanism is urgently needed. Studies have shown that the intestinal flora plays an important regulatory role in cardiovascular injury, but the specific mechanism has not been fully elucidated. In this study, we found that an increase in Ang II in plasma was accompanied by an increase in the levels of myocardial injury during myocardial reperfusion in patients with cardiopulmonary bypass. Furthermore, Ang II treatment enhanced mice myocardial I/R injury, which was reversed by caveolin-1 (CAV-1)-shRNA or strengthened by angiotensin-converting enzyme 2 (ACE2)-shRNA. The results showed that CAV-1 and ACE2 have protein interactions and inhibit each other's expression. In addition, propionate, a bacterial metabolite, inhibited the elevation of Ang II and myocardial injury, while GPR41-shRNA abolished the protective effects of propionate on myocardial I/R injury. Clinically, the propionate content in the patient's preoperative stool was related to Ang II levels and myocardial I/R injury levels during myocardial reperfusion. Taken together, propionate alleviates myocardial I/R injury aggravated by Ang II dependent on CAV-1/ACE2 axis through GPR41, which provides a new direction that diet to regulate the intestinal flora for treatment of myocardial I/R injury.