Cu(II)-Mediated Sulfonylation of (Hetero)arenes with TosMIC Using Monodentate Directing Groups.

Monodentate chelation-assisted direct ortho-C-H sulfonylation of (hetero)arenes using TosMIC as the novel sulfonylating reagent has been developed. A broad range of substrates, including indolines, indoles, 2-phenylpyridines, and others were well tolerated to afford the corresponding products in moderate to good yields. Mechanistic studies revealed that the sulfonyl radical might be involved. Inspired by the above discovery, preliminary para-C-H sulfonylation of naphthalene substrate was also successfully realized. The current protocol featured with cheap metal catalysis, good functional group compatibility, and operational convenience.

Application of trauma-focused cognitive behavioral therapy among children and adolescents with childhood household dysfunction. / 创伤聚焦的认知行为疗法在童年家庭功能障碍儿童和青少年中的应用.

Childhood household dysfunction (CHD) is a common adverse childhood experience, which brings the heavy physical and mental afflictions to children and adolescents. Trauma-focused cognitive behavioral therapy (TF-CBT) is an evidence-based psychotherapy that helps children and adolescents who have experienced childhood trauma with traumatic memories. It aims to enhance the coping abilities of CHD children and adolescents, thereby improving the negative effects caused by trauma and effectively reducing psychological burden. TF-CBT can effectively improve post-traumatic stress disorder, emotional and behavioral problems, and family function in children and adolescents with CHD. It is recommended to conduct high-quality original research in the future, develop targeted TF-CBT intervention plans based on potential predictive factors, adopt a combination of online and offline methods, and construct TF-CBT interventions suitable for the Chinese CHD population to meet the mental health service needs of CHD children and adolescents.

Asymmetric Epoxidation of Alkenes Catalyzed by a Cobalt Complex.

Asymmetric epoxidation of alkenes catalyzed by nonheme chiral Mn-O and Fe-O catalysts has been well established, but chiral Co-O catalysts for the purpose remain virtually undeveloped due to the oxo wall. Herein is first reported a chiral cobalt complex to realize the enantioselective epoxidation of cyclic and acyclic trisubstituted alkenes by using PhIO as the oxidant in acetone, wherein the tetra-oxygen-based chiral N,N'-dioxide with sterically hindered amide subunits plays a crucial role in supporting the formation of the Co-O intermediate and enantioselective electrophilic oxygen transfer. Mechanistic studies, including HRMS measurements, UV-vis absorption spectroscopy, magnetic susceptibility, as well as DFT calculations, were carried out, confirming the formation of Co-O species as a quartet Co(III)-oxyl tautomer. The mechanism and the origin of enantioselectivity were also elucidated based on control experiments, nonlinear effects, kinetic studies, and DFT calculations.

Amine-Imine Nickel Catalysts with Pendant O-Donor Groups for Ethylene (Co)Polymerization.

The introduction of a secondary interaction is an efficient strategy to modulate transition-metal-catalyzed ethylene (co)polymerization. In this contribution, O-donor groups were suspended on amine-imine ligands to synthesize a series of nickel complexes. By adjusting the interaction between the nickel metal center and the O-donor group on the ligands, these nickel complexes exhibited high activities for ethylene polymerization (up to 3.48 × 106 gPE·molNi-1·h-1) with high molecular weight up to 5.59 × 105 g·mol-1 and produced good polyethylene elastomers (strain recovery (SR) = 69-81%). In addition, these nickel complexes can catalyze the copolymerization of ethylene with vinyl acetic acid, 6-chloro-1-hexene, 10-undecylenic, 10-undecenoic acid, and 10-undecylenic alcohol to prepare the functionalized polyolefins.

CXCL5 promotes tumorigenesis and angiogenesis of glioblastoma via JAK-STAT/NF-κb signaling pathways.

BACKGROUND: The tumor microenvironment contains chemokines that play a crucial role in various processes, such as tumorigenesis, inflammation, and therapy resistance, in different types of cancer. CXCL5 is a significant chemokine that has been shown to promote tumor proliferation, invasion, angiogenesis, and therapy resistance when overexpressed in various types of cancer. This research aims to investigate the impact of CXCL5 on the biological functions of glioblastoma (GBM). METHODS: The TCGA GBM and GEO databases were utilized to perform transcriptome microarray analysis and oncogenic signaling pathway analysis of CXCL5 in GBM. Validation of CXCL5 expression was performed using RT-qPCR and Western Blot. The impact of CXCL5 on cell proliferation, tumorigenesis, and angiogenesis in GBM was assessed through various methods, including cell proliferation assay, cloning assay, intracranial xenograft tumor models, and tube formation assay. Clinical prognosis was evaluated in 59 samples of gliomas with varying degrees of malignancy (grades 2, 3, and 4) and the TCGA GBM database, based on CXCL5 expression levels. The activities of the JAK-STAT and NF-κB signaling pathways were detected using Western Blot. RESULTS: The expression of CXCL5 was highly enriched in GBM. Moreover, the inhibition of CXCL5 showed a significant efficacy in suppressing cellular proliferation and angiogenesis, resulting in extended survival rates in xenograft mouse models in comparison to the control group. Notably, pretreatment with dapsone exhibited a reversal of the impact of CXCL5 on the formation of colonies and tubes in GBM cells. Elevated expression of CXCL5 was correlated with poor outcomes in GBM patients. Furthermore, the overexpression of CXCL5 has been associated with the activation of JAK-STAT and NF-κB signaling pathways. CONCLUSIONS: CXCL5 plays an important role in tumorigenesis and angiogenesis, indicating the potential for novel therapies targeting CXCL5 in GBM.

Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling.

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 µM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor ß-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.

Tailored Supramolecular Cage for Efficient Bio-Labeling.

Fluorescent chemosensors are powerful imaging tools used in a broad range of biomedical fields. However, the application of fluorescent dyes in bioimaging still remains challenging, with small Stokes shifts, interfering signals, background noise, and self-quenching on current microscope configurations. In this work, we reported a supramolecular cage (CA) by coordination-driven self-assembly of benzothiadiazole derivatives and Eu(OTf)3. The CA exhibited high fluorescence with a quantum yield (QY) of 38.57%, good photoluminescence (PL) stability, and a large Stokes shift (153 nm). Furthermore, the CCK-8 assay against U87 glioblastoma cells verified the low cytotoxicity of CA. We revealed that the designed probes could be used as U87 cells targeting bioimaging.

Clinical application of double V-Y advancement mucosal flap to repair tongue defect. / 双V-Y推进黏膜瓣修复舌部缺损的临床应用.

OBJECTIVES: The repair of small- and medium-sized defects in the oral tongue has always been a challenge, and the effect of free flap and distal pedicle flap is still far from satisfactory. Tongue flap is an ideal choice for repairing small- and medium-sized defects. However, the disadvantages such as poor local morphology restricts the development of this operation.This study aims to investigate the efficacy of double V-Y advancement mucosal flap in repair of small- and medium-sized defects of the tongue defect. METHODS: The clinical data of 15 patients with tongue defect lesions who were hospitalized in the Department of Stomatology, Third Xiangya Hospital of Central South University from March 2019 to May 2022 were retrospectively analyzed. After the lesions were completely excised, the mucosa and part of the tongue defect were left. One V-Y advancement mucosal flap was designed anteriorly and posteriorly to the defect. The superficial mucosa was incised gradually all around, preserving the deep median muscle tip. The 2 flaps were freed toward the middle of the defect, and the anterior and posterior flaps were sutured together at the middle of the defect, with the donor area directly pulled together and sutured. RESULTS: The double V-Y advancement mucosal flap survived in 15 patients, and the wounds healed at stage I. The postoperative follow-up time was 12-22 months, and the patients had no recurrence, with symmetrical tongue shape, and no traction and deformation in the affected tongue organs. Meanwhile, the intraoral flap was thin and flat, and healed well with the surrounding mucosa, without obvious flap contracture or tongue bite. CONCLUSIONS: Double V-Y advancement mucosal flap has the advantages of flexible design, simple preparation, reliable blood supply, and good protection of the donor site, which may be one of the effective methods for repairing small- and medium-sized defects in the anterior tongue mucosa.

ZL-n-91, a specific Phosphodiesterase-4 inhibitor, suppresses the growth of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that frequently develops resistance to chemotherapy. A new approach to treating TNBC is required to improve patient survival. Phosphodiesterase-4 (PDE4) is an enzyme that is predominantly involved in the modulation of intracellular signaling mediated by cAMP. Although the efficacy of PDE4 inhibitors in several human inflammatory diseases is well documented, their clinical utility has been limited by side effects, including nausea and emesis. Recently, PDE4 has been used as a potential therapeutic target for different cancer types. In the present study, we investigated the anticancer effects of a novel PDE4 inhibitor ZL-n-91 on TNBC and the underlying mechanism. We showed that ZL-n-91 inhibited the proliferation of TNBC cells, induced cell apoptosis, and caused cell cycle arrest. Western blot analysis showed that ZL-n-91 increased Bax level and reduced Bcl-2 expression. Furthermore, downregulation of the cell cycle-related proteins, such as CDK2, CDK4, cyclin D1, PCNA, p-RB, and ZL-n-91, significantly inhibited the transcription of DNA repair genes and triggered an intracellular DNA damage response. Moreover, ZL-n-91 prevented the growth of the transplanted MDA-MB-231 tumor xenograft in nude mice and increased the γ-H2AX expression. These data demonstrate the anticancer effects of ZL-n-91 on TNBC cells and suggest its potential use in anticancer therapy.

LncRNA MYMLR promotes pituitary adenoma development by upregulating carbonyl reductase 1 via sponging miR-197-3p.

Long noncoding RNAs (lncRNAs) have been demonstrated to participate in various biological processes and play key roles in tumorigenesis and metastasis. Pituitary adenoma (PA) is one of the most common malignancies in central nervous system. Recently, multiple lncRNAs have been identified to regulate PA initiation, progression and metastasis. we aimed to elucidate the expression pattern and function of lncRNA MYMLR in PA development. The expression of lncRNA MYMLR in PA tissues and cells was examined by real-time quantitative PCR. Knockdown of MYMLR expression was achieved by using shRNA. The function of MYMLR and regulatory network were analyzed using CCK-8 assay, wound-healing assay, migration assay and Annexin V/PI staining. Xenograft tumor model was used to explore the function of MYMLR in vivo . Bioinformatics analysis and luciferase reporter assay were conducted to investigate the interaction between MYMLR and its regulatory network. LncRNA MYMLR was highly expressed in PA tissues compared with that in normal tissues. Knockdown of MYMLR suppressed cell proliferation, migration and invasion, while promoting PA cell apoptosis. Mechanistically, MYMLR functioned as a competing endogenous RNA (ceRNA) sponging microRNA miR-197-3p. Furthermore, miR-197-3p exerted its tumor inhibitory role via negatively regulating carbonyl reductase 1 (CBR1). Overexpression of CBR1 antagonized the inhibitory effect of lncRNA MYMLR knockdown or miR-197-3p overexpression. In addition, xenograft tumor model revealed that knockdown of lncRNA MYMLR suppressed PA tumor development in vivo via regulating CBR1. Our findings suggest a regulatory network of lncRNA MYMLR/miR-197-3p/CBR1, which benefits the understanding of PA development and provides a promising lncRNA-direct therapeutic strategy against PA.

Copper-catalyzed regioselective C2-H chlorination of indoles with para-toluenesulfonyl chloride.

A copper-catalyzed, pyrimidine directed regioselective C-H chlorination of indoles with para-toluenesulfonyl chloride (TsCl) has been developed. The reactions proceeded smoothly in the presence of 20 mol% of Cu(OAc)2 as the catalyst and TsCl as the chlorine source, delivering C2-chlorinated indoles with structural diversity in moderate to excellent yields. Mechanistic studies suggested that single electron transfer (SET) from Cu(II) to TsCl accompanied by the release of the p-toluenesulfonyl radical and the related Cu(III)Cl species might be involved in the reactions.

Synthesis and biological evaluation of aminobenzamides containing purine moiety as class I histone deacetylases inhibitors.

The aminobenzamide is selective to class I histone deacetylases (HDACs) and displays unique tight-binding/slow-off HDAC-binding mechanism. Herein, we report a series of 9-substituted purine aminobenzamides that selectively inhibit class I HDACs. The activities in vitro showed compound 9d exhibited 12 folds more potent than MS-275 against HDAC1 isoform and showed excellent inhibitory activity on cancer cells, including HCT-116, MDA-MB-231, K562 cell lines. The metabolic stability of 9d was much better than that of the well-known HDAC inhibitor SAHA. Pulse exposure test of western blot assay demonstrated that 9a, 9d induced histone acetylation in a similar manner to MS-275. Further biological validation demonstrated that 9d prevented cell transition from G1 phase to S phase by reducing Cyclin D1, CDK2 and lifting p21, induced early apoptosis by upregulating BAX and downregulating Bcl-2 in HCT-116 cells.

Potential influencing factors of aortic diameter at specific segments in population with cardiovascular risk.

BACKGROUND: Aortic diameter is a critical parameter for the diagnosis of aortic dilated diseases. Aortic dilation has some common risk factors with cardiovascular diseases. This study aimed to investigate potential influence of traditional cardiovascular risk factors and the measures of subclinical atherosclerosis on aortic diameter of specific segments among adults. METHODS: Four hundred and eight patients with cardiovascular risk factors were prospectively recruited in the observational study. Comprehensive transthoracic M-mode, 2-dimensional Doppler echocardiographic studies were performed using commercial and clinical diagnostic ultrasonography techniques. The aortic dimensions were assessed at different levels: (1) the annulus, (2) the mid-point of the sinuses of Valsalva, (3) the sinotubular junction, (4) the ascending aorta at the level of its largest diameter, (5) the transverse arch (including proximal arch, mid arch, distal arch), (6) the descending aorta posterior to the left atrium, and (7) the abdominal aorta just distal to the origin of the renal arteries. Multivariable linear regression analysis was used for evaluating aortic diameter-related risk factors, including common cardiovascular risk factors, co-morbidities, subclinical atherosclerosis, lipid profile, and hematological parameters. RESULTS: Significant univariate relations were found between aortic diameter of different levels and most traditional cardiovascular risk factors. Carotid intima-media thickness was significantly correlated with diameter of descending and abdominal aorta. Multivariate linear regression showed potential effects of age, sex, body surface area and some other cardiovascular risk factors on aortic diameter enlargement. Among them, high-density lipoprotein cholesterol had a significantly positive effect on the diameter of ascending and abdominal aorta. Diastolic blood pressure was observed for the positive associations with diameters of five thoracic aortic segments, while systolic blood pressure was only independently related to mid arch diameter. CONCLUSION: Aortic segmental diameters were associated with diastolic blood pressure, high-density lipoprotein cholesterol, atherosclerosis diseases and other traditional cardiovascular risk factors, and some determinants still need to be clarified for a better understanding of aortic dilation diseases.

Logistic Regression Analysis of Conventional Ultrasound, and Contrast-Enhanced Ultrasound Characteristics: Is It Helpful in Differentiating Benign and Malignant Superficial Lymph Nodes?

OBJECTIVES: This study aimed to screen the significant sonographic features for differentiation of benign and malignant superficial lymph nodes (LNs) by logistic regression analysis and fit a model to diagnose LNs. METHODS: A total of 204 pathological LNs were analyzed retrospectively. All the LNs underwent conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) examinations. A total of 16 suspicious sonographic features were used to assess LNs. All variables that were statistically related to the diagnosis of LNs were included in the logistic regression analysis in order to ascertain the significant features of diagnosing LNs, and to establish a logistic regression analysis model. RESULTS: The significant features in the logistic regression analysis model of diagnosing malignant LNs were absence of echogenic hilus, age, and absence of hilum after enhancement. According to the results of logistic regression analysis, the formula to predict whether LNs were malignant was established. The area under the receiver operating curve (ROC) was 0.908 and the accuracy, sensitivity, and specificity were 85.0%, 92.9%, and 85.3%, respectively. CONCLUSION: The logistic regression model for the significant sonographic features of conventional US and CEUS is an effective and accurate diagnostic tool for differentiating malignant and benign LNs.

Behavior Characteristics and Risk for Metabolic Syndrome Among Women in Rural Communities in China.

BACKGROUND: Rapid economic growth and lifestyle changes in China have resulted in increased metabolic syndrome (MetS) rates. Few investigators have examined sex-specific risk factors and the role of menopause, stress, and sleep on MetS among women in China. OBJECTIVE: In this study, we aimed to identify the risk factors for MetS among women in rural China. METHODS: A cross-sectional study design was used, and participants were recruited from rural areas in China. Female participants older than 18 years were eligible to participate. Participants had their weight, height, waist circumference, blood pressure, and fasting blood measured at study sites. They also completed validated questionnaires regarding sociodemographic information and MetS-related health behaviors. RESULTS: A total of 646 women were included in this study. The overall prevalence of MetS was 26.2%. The MetS group had a greater number of overweight/obese women than the non-MetS group did. For premenopausal women, a higher income, being overweight/obese, and eating salty/marinated food increased their risk for MetS (odds ratio [OR], 2.56, 4.55, and 3.1, respectively). For postmenopausal women, a low level of education (OR, 0.44) and being overweight/obese (OR, 4.98) increased their risk of MetS. CONCLUSION: Almost half of the women in this study were overweight/obese, and many of them did not meet the national recommendations for a healthy lifestyle, increasing their risk for MetS. Developing cultural and behavioral interventions tailored for overweight/obese women is critical in reducing MetS.

The roles of parental absence, life skills and personality traits in mental health status among adolescents in rural China.

PROBLEM: Mental health issues in adolescents are public health concerns worldwide including China. However, there is a lack of research examining the role of parental absence status, life skills, and personality traits on the mental health of adolescents in rural China. METHOD: The purpose of this cross-sectional study was to examine the role of parental absence status, life skills, and personality traits on the mental health of adolescents in rural China. This study used self-developed demographic questionnaire, Mental Health Test (MHT), Middle School Student Life Skills Rating Scale, and Eysenck Personality Questionnaire. Binary logistic regression analyses were performed to examine the associated factors on different domains of MHT. RESULTS: Adolescents in rural China reported high proportion of mental health disorders (MHDs), including learning anxiety, sensitiveness, self-accusation, and physical symptoms tendency. Although 75.6% experienced parental absence, this was not associated with MHT after controlling for all other variables. Better mental health was correlated with life skills including communication skills, interpersonal morality, self-efficacy, and stress coping. The instability-neuroticism personality trait was positively associated with MHDs. DISCUSSION: Adolescents in rural China reported high positive rates of MHDs. Communication skills, interpersonal morality, self-efficacy, ability to cope with stress and Instability-neuroticism were important associated factors of MHDs. APPLICATION TO PRACTICE: Life skills and personality are two important factors that should be considered when assessing the mental health status of adolescents and formulating interventions.

Synthesis of a Tetrahedral Metal-Organic Supramolecular Cage with Dendritic Carbazole Arms.

In recent years, incredible endeavors have been devoted to the design and self-assembly of discrete metal-organic cages (MOCs) with expanding intricacy and functionality. The controlled synthesis of metal-organic supramolecular cages with large branched chains remains an interesting and challenging work in supramolecular chemistry. Herein, a tetrahedral metal-organic supramolecular cage (ZnII4L4) containing 12 dendritic carbazole arms is unprecedentedly constructed through coordination-driven subcomponent self-assembly and characterized in different ways. Interestingly, tetrahedral supramolecular Cage-1 exhibited the potential for aggregation-induced emission (AIE) performance and stimulus-responsive luminescence features, and it achieved color-tunable photoluminescence due to the introduction of dendritic carbazole arms. Crucially, owing to the great photophysical properties of Cage-1 in solution, Cage-1 was enabled to act as a fluorescent ink for the vapor-responsive recording and wiping of information.

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As a global public health problem, adverse childhood experiences (ACEs) is an important factor leading to serious psychological and behavioral problems in children and adolescents. Mental health service plan based on mental health service needs is the key to effectively improve the psychological problems of children and adolescents with ACEs. Emotional support, life skills training, mental health education, and individualized psychological intervention can effectively improve the mental health of children and adolescents with ACEs. Among them, emotional support is an important way to help individual reduce psychological and behavioral problems; secondly, life skills training can significantly improve the individual's psychosocial ability; and mental health education is a necessary way to promote the development of individual mental health. Individualized psychological intervention can promote individual to obtain more professional mental health service and improve their psychological symptoms, which is crucial for preventing the occurrence of mental health problems. Future research can develop targeted mental health interventions based on the specific mental health service needs.

NaOH-Mediated Direct Synthesis of Quinoxalines from o-Nitroanilines and Alcohols via a Hydrogen-Transfer Strategy.

A NaOH-mediated sustainable synthesis of functionalized quinoxalines is disclosed via redox condensation of o-nitroamines with diols and α-hydroxy ketones. Under optimized conditions, various o-nitroamines and alcohols are well tolerated to generate the desired products in 44-99% yields without transition metals and external redox additives.

Iron-Mediated Selective Sulfonylmethylation of Aniline Derivatives with p-Toluenesulfonylmethyl Isocyanide (TosMIC).

An iron-mediated highly selective C-H sulfonylmethylation of aniline derivatives with p-toluenesulfonylmethyl isocyanide in a mixture solvent of H2O and PEG400 under an Ar atmosphere has been realized. This transformation proceeds with operational convenience, use of earth-abundant metal catalyst and nontoxic media, broad substrate scope, and good functional group tolerance. The current methodology could be applied to the regioselective C-H sulfonylmethylation of indolines, tetrahydroquinolines, and tertiary anilines.