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Background: Previously, stage-IIIB non-small cell lung cancer (NSCLC) has been considered inoperable. In recent years, neoadjuvant immunotherapy has shown encouraging efficacy in the treatment of advanced stage NSCLC in several trials. However, the effectiveness and safety of neoadjuvant immunotherapy in treating stage-IIIB NSCLC are still unknown. Therefore, we conducted this retrospective study to examine the outcomes of surgery after neoadjuvant immunotherapy combined with chemotherapy for stage-IIIB NSCLC. Methods: Thirty patients with stage-IIIB NSCLC who were treated at the Department of Thoracic Surgery of Renji Hospital from January 2019 to September 2021 were analyzed retrospectively. Neoadjuvant immunotherapy combined with chemotherapy was administered prior to surgery. The curative effect was evaluated by imaging and pathological examinations. Results: The objective response rate (ORR) and disease control rate (DCR) of the patients after neoadjuvant therapy evaluated by imaging studies were 70% and 86.7%, respectively. Of the 30 patients, 19 (63%) underwent surgical resection, in which all achieved a complete R0 resection. The median operative time was 168 minutes (range, 75-295 minutes), and the average intraoperative blood loss was 215.3±258.4 mL. The median postoperative hospital stay was 8 days (range, 4-59 days). The major pathological response (MPR) rate was 73.7% (14/19), and the pathological complete response rate was 47.4% (9/19); 2/30 patients (6.7%) had postoperative complications, including two who developed bronchopleural fistulas and one mortality, from a postoperative pulmonary infection. The treatment-related adverse reactions were mainly grades 1-2. Only two patients had grade 3 anemia, and no grade 4 adverse reactions were observed. Conclusions: Neoadjuvant immunotherapy and chemotherapy combined with surgery in patients with stage-IIIB NSCLC is safe and feasible. The patient outcomes and optimal number of neoadjuvant treatment cycles need to be explored and studied further.
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In this study, BiVO4 nanosheets (BiVO4-NS) were prepared by a facile hydrothermal method. It is found that sonication-induced strain can effectively promote the H2 production over BiVO4-NS in the presence of pure water without any cocatalysts. With the assistance of the sonication, the H2 production over BiVO4-NS is 1.344 mmol·g-1 after 3 h simulated sunlight irradiation, which is 24.8 times higher than that of BiVO4-NS without sonication (0.054 mmol·g-1). In addition, the products of water oxidation are determined to be hydroxyl radicals and hydrogen peroxide. Moreover, BiVO4-NS also shows obviously enhanced photoactivity than that of the commercially available BiVO4 nanoparticles (BiVO4-C). The improved photoactivity of BiVO4-NS is attributed to the effective charge separation and low charge transfer resistance. The underlying mechanism of sonication-promoted water splitting is investigated by a variety of controlled experiments. The results show that ultrasonic waves can produce obvious strain inside the sample, which results in lattice distortion of BiVO4. Therefore, the conduction band of BiVO4 is obviously negative shifted, which is beneficial for H2 production. In addition, the strain in BiVO4 also produces local polarization of the sample, which effectively promotes the charge transfer and separation process. It is hoped that our study could provide a new strategy for achieving efficient photocatalytic water splitting.
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Sulforaphane (SFN) is an organosulfur compound categorized as an isothiocyanate (ITC), primarily extracted from cruciferous vegetables like broccoli and cabbage. The molecular formula of sulforaphane (SFN) is C6H11NOS2. SFN is generated by the hydrolysis of glucoraphanin (GRP) through the enzyme myrosinase, showing notable properties including anti-diabetic, anti-inflammatory, antimicrobial, anti-angiogenic, and anticancer attributes. Ongoing clinical trials are investigating its potential in diseases such as cancer, neurodegenerative diseases, diabetes-related complications, chronic kidney disease, cardiovascular disease, and liver diseases. Several animal carcinogenesis models and cell culture models have shown it to be a very effective chemopreventive agent, and the protective effects of SFN in ophthalmic diseases have been linked to multiple mechanisms. In murine models of diabetic retinopathy and age-related macular degeneration, SFN delays retinal photoreceptor cell degeneration through the Nrf2 antioxidative pathway, NF-κB pathway, AMPK pathway, and Txnip/mTOR pathway. In rabbit models of keratoconus and cataract, SFN has been shown to protect corneal and lens epithelial cells from oxidative stress injury by activating the Keap1-Nrf2-ARE pathway and the Nrf-2/HO-1 antioxidant pathway. Oral delivery or intraperitoneal injection at varying concentrations are the primary strategies for SFN intake in current preclinical studies. Challenges remain in the application of SFN in eye disorders due to its weak solubility in water and limited bioavailability because of the presence of blood-ocular barrier systems. This review comprehensively outlines recent research on SFN, elucidates its mechanisms of action, and discusses potential therapeutic benefits for eye disorders such as age-related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and other ophthalmic diseases, while also indicating directions for future clinical research to achieve efficient SFN treatment for ophthalmic diseases.
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Premature ovarian insufficiency (POI) or premature ovarian failure (POF) is a multifactorial disorder occurring in reproductive-age women, characterized by elevated levels of follicle-stimulating hormone (FSH) and irregular or absent menstrual cycles, often accompanied by perimenopausal symptoms and infertility. While assisted reproductive technology can address the reproductive aspirations of some POI-affected women, it is hindered by issues such as exorbitant expenses, substantial risks, and poor rates of conception. Encouragingly, extensive research is exploring novel approaches to enhance fertility, particularly in the realm of stem cell therapy, showcasing both feasibility and significant potential. Human amniotic epithelial cells (hAECs) from discarded placental tissues are crucial in regenerative medicine for their pluripotency, low immunogenicity, non-tumorigenicity, accessibility, and minimal ethical concerns. Preclinical studies highlight the underlying mechanisms and therapeutic effects of hAECs in POI treatment, and current research is focusing on innovative interventions to augment hAECs' efficacy. However, despite these strides, overcoming application challenges is essential for successful clinical translation. This paper conducted a comprehensive analysis of the aforementioned issues, examining the prospects and challenges of hAECs in POI, with the aim of providing some insights for future research and clinical practice.
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Amnios , Células Epiteliales , Insuficiencia Ovárica Primaria , Humanos , Insuficiencia Ovárica Primaria/terapia , Femenino , Células Epiteliales/trasplante , Amnios/citología , Amnios/trasplanteRESUMEN
INTRODUCTION: Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate. METHODS: Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. RESULTS: A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues. CONCLUSIONS: These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.
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Metilación de ADN , Endometrio , Quistes Ováricos , Ovario , Femenino , Humanos , Quistes Ováricos/genética , Quistes Ováricos/patología , Quistes Ováricos/metabolismo , Endometrio/metabolismo , Endometrio/patología , Adulto , Ovario/metabolismo , Ovario/patología , Endometriosis/genética , Endometriosis/patología , Endometriosis/metabolismo , Epigénesis GenéticaRESUMEN
To explore the effects of tracking linkage self-management mode on the compliance of prenatal examinations and delivery modes in primiparas. A total of 270 primiparas undergoing prenatal examinations in Shijiazhuang Obstetrics and Gynecology Hospital were enrolled for prospective study between January 2021 and January 2022. They were divided into control group and observation group, 135 cases in each group. The control group was given routine management mode, while observation group was given tracking linkage self-management mode. All were intervened till discharge. The compliance (time and frequency of prenatal examinations), cognition of prenatal examinations, score of exercise of self-care agency scale, self-rating anxiety scale and self-rating depression scale, delivery modes and the occurrence of neonatal adverse outcomes were compared between the 2 groups. After intervention, total compliance rate of prenatal examinations in observation group was higher than that in control group (84.44% vs 72.59%) (Pâ <â .05). The scores of pregnancy care, genetic diseases counseling, prevention of birth defects and reasonable nutrition during pregnancy in observation group were higher than those in control group (Pâ <â .05), scores of health cognition, self-care skills, self-care responsibility and self-concept were higher than those in control group (Pâ <â .05), scores of self-rating anxiety scale and self-rating depression scale were lower than those in control group (Pâ <â .05), natural delivery rate was higher than that in control group (85.93% vs 74.81%) (Pâ <â .05), and incidence of neonatal adverse outcomes was lower than that in control group (0.74% vs 5.93%) (Fisher exact probabilityâ =â 0.036). The application of tracking linkage self-management mode can significantly improve cognition to prenatal examinations, improve compliance of prenatal examinations and self-care ability, relieve anxiety and depression, increase natural delivery rate and reduce the incidence of neonatal adverse outcomes in primiparas.
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Cooperación del Paciente , Atención Prenatal , Automanejo , Humanos , Femenino , Embarazo , Adulto , Automanejo/métodos , Estudios Prospectivos , Cooperación del Paciente/estadística & datos numéricos , Cooperación del Paciente/psicología , Atención Prenatal/métodos , Parto Obstétrico/métodos , Parto Obstétrico/psicología , Paridad , Autocuidado/métodosRESUMEN
The inequality in CO2 emissions from agricultural energy consumption is a major challenge for coordinating low-carbon agricultural development across regions in China. However, the evolutionary characteristics and driving factors of inequality in China's agricultural energy-related CO2 emissions are poorly understood. In response, the Kaya-Theil model was adopted to examine the three potential factors influencing CO2 emission inequality in China's agricultural energy consumption. The results revealed that, from 1997 to 2021, agricultural energy-related CO2 emissions per capita showed a significant upward trend, with prominent polarization and right-tailing phenomena. Overall, the inequality was on a downward trend, with the Theil index falling from 0.4109 in 1997 to 0.1957 in 2021. Meanwhile, the decomposition of the national inequality revealed that the within-group inequality declined from 0.3991 to 0.1634, which was greater than between-group inequality, based on zoning the 28 provinces into three grain production functional areas. As for the three kaya factors, the energy intensity contributed the most to the overall inequality, followed by the agricultural economic development and CO2 emission intensity. Based on these results, this study provided some potential strategies to reduce agricultural-related CO2 emissions.
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AIM: To evaluate the role of semaphorin 7A (Sema7A) and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells (HCEs). METHODS: Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0, 125, 250, or 500 ng/mL for 24, 48, or 72h in vitro. Transepithelial electrical resistance (TEER) as well as Dextran-fluorescein isothiocyanate (FITC) permeability assays were conducted to assess barrier function. To quantify tight junctions (TJs) such as occludin and zonula occludens-1 (ZO-1) at the mRNA level, reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. Immunoblotting was used to examine the activity of the nuclear factor-kappa B (NF-κB) signaling pathway and the production of TJs proteins. Immunofluorescence analyses were employed to localize the TJs. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were utilized to observe changes in interleukin (IL)-1ß levels. To investigate the role of NF-κB signaling activation and IL-1ß in Sema7A's anti-barrier mechanism, we employed 0.1 µmol/L IκB kinase 2 (IKK2) inhibitor IV or 500 ng/mL IL-1 receptor (IL-1R) antagonist. RESULTS: Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time- and dose-dependent manner, as well as altering the localization of TJs. Furthermore, Sema7A stimulated the activation of inhibitor of kappa B alpha (IκBα) and expression of IL-1ß. The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists. CONCLUSION: Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins, as well as the expression of IL-1ß. These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.
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BACKGROUND: Gut microbiota is significantly influenced by altitude. However, the dynamics of gut microbiota in relation to altitude remains undisclosed. METHODS: In this study, we investigated the microbiome profile of 610 healthy young men from three different places in China, grouped by altitude, duration of residence, and ethnicity. We conducted widely targeted metabolomic profiling and clinical testing to explore metabolic characteristics. RESULTS: Our findings revealed that as the Han individuals migrated from low altitude to high latitude, the gut microbiota gradually converged towards that of the Tibetan populations but reversed upon returning to lower altitude. Across different cohorts, we identified 51 species specifically enriched during acclimatization and 57 species enriched during deacclimatization to high altitude. Notably, Prevotella copri was found to be the most enriched taxon in both Tibetan and Han populations after ascending to high altitude. Furthermore, significant variations in host plasma metabolome and clinical indices at high altitude could be largely explained by changes in gut microbiota composition. Similar to Tibetans, 41 plasma metabolites, such as lactic acid, sphingosine-1-phosphate, taurine, and inositol, were significantly elevated in Han populations after ascending to high altitude. Germ-free animal experiments demonstrated that certain species, such as Escherichia coli and Klebsiella pneumoniae, which exhibited altitude-dependent variations in human populations, might play crucial roles in host purine metabolism. CONCLUSIONS: This study provides insights into the dynamics of gut microbiota and host plasma metabolome with respect to altitude changes, indicating that their dynamics may have implications for host health at high altitude and contribute to host adaptation. Video Abstract.
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Pueblos del Este de Asia , Microbioma Gastrointestinal , Animales , Masculino , Humanos , Microbioma Gastrointestinal/genética , Altitud , Multiómica , MetabolomaRESUMEN
An unprecedented solvent-tuned electrochemical method for selective C(sp3)-H bond activation towards the synthesis of C3 functionalized chromone derivatives has been developed. This electrosynthesis protocol provides an efficient and green way to access various C3-functionalized chromones by avoiding traditionally employed transition metals and high temperatures. The swappable chemoselectivity was controlled mainly by altering the solvent and the current. A plausible reaction mechanism has been proposed with the help of radical capture and cyclic voltammetry experiments.
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Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.
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Intervertebral disc degeneration (IVDD) is one of the most prevalent causes of chronic low back pain. The role of m6A methylation modification in disc degeneration (IVDD) remains unclear. We investigated immune-related m6A methylation regulators as IVDD biomarkers through comprehensive analysis and experimental validation of m6A methylation regulators in disc degeneration. The training dataset was downloaded from the GEO database and analysed for differentially expressed m6A methylation regulators and immunological features, the differentially regulators were subsequently validated by a rat IVDD model and RT-qPCR. Further screening of key m6A methylation regulators based on machine learning and LASSO regression analysis. Thereafter, a predictive model based on key m6A methylation regulators was constructed for training sets, which was validated by validation set. IVDD patients were then clustered based on the expression of key m6A regulators, and the expression of key m6A regulators and immune infiltrates between clusters was investigated to determine immune markers in IVDD. Finally, we investigated the potential role of the immune marker in IVDD through enrichment analysis, protein-to-protein network analysis, and molecular prediction. By analysising of the training set, we revealed significant differences in gene expression of five methylation regulators including RBM15, YTHDC1, YTHDF3, HNRNPA2B1 and ALKBH5, while finding characteristic immune infiltration of differentially expressed genes, the result was validated by PCR. We then screen the differential m6A regulators in the training set and identified RBM15 and YTHDC1 as key m6A regulators. We then used RBM15 and YTHDC1 to construct a predictive model for IVDD and successfully validated it in the training set. Next, we clustered IVDD patients based on the expression of RBM15 and YTHDC1 and explored the immune infiltration characteristics between clusters as well as the expression of RBM15 and YTHDC1 in the clusters. YTHDC1 was finally identified as an immune biomarker for IVDD. We finally found that YTHDC1 may influence the immune microenvironment of IVDD through ABL1 and TXK. In summary, our results suggest that YTHDC1 is a potential biomarker for the development of IVDD and may provide new insights for the precise prevention and treatment of IVDD.
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Degeneración del Disco Intervertebral , Humanos , Animales , Ratas , Degeneración del Disco Intervertebral/genética , Adenina , Metilación , BiomarcadoresRESUMEN
BACKGROUND: Programmed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC. METHODS: From July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes. RESULTS: A total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients. CONCLUSIONS: nCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined. TRIAL REGISTRATION NUMBER: NCT04437212.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Linfopenia , Trombocitopenia , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Cisplatino/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Terapia Neoadyuvante , Carcinoma de Células Escamosas/tratamiento farmacológico , Resultado del Tratamiento , Recurrencia Local de Neoplasia , Paclitaxel , Antígenos HLA-DR , Células Epiteliales/patologíaRESUMEN
BACKGROUND: Tolerogenic dendritic cells (TolDCs) have been evidenced to trigger regulatory T cell's (Treg's) differentiation and be involved in the pathogenesis of Crohn's disease (CD). Aryl hydrocarbon receptor (AhR) plays a crucial role in the differentiation of TolDCs, although the mechanism remains vague. This study aimed to evaluate the role of AhR in TolDCs formation, which may affect Th17/Treg balance in CD. METHODS: Colon biopsy specimens were obtained from healthy controls and patients with CD. Wild type (WT) and AhR-/- mice were induced colitis by drinking dextran sulphate sodium (DSS) with or without 6-formylindolo 3,2-b carbazole (FICZ) treatment. Wild type and AhR-/- bone marrow-derived cells (BMDCs) were cultured under TolDCs polarization condition. Ratios of DCs surface markers were determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify the levels of interleukin (IL)-1ß, transforming growth factor (TGF)-ß and IL-10. Tolerogenic dendritic cells differentiated from BMDCs of WT or AhR-/- mice were adoptively transferred to DSS-induced WT colitis mice. RESULTS: Patients with CD showed less AhR expression and activation in their inflamed colon regions. Compared with WT mice, AhR-/- mice experienced more severe colitis. Tolerogenic dendritic cells and Tregs were both decreased in the colon of AhR-/- colitis mice, while Th17 cells were upregulated. In vitro, compared with WT DCs, AhR-deficient DCs led to less TolDC formation. Furthermore, intestinal inflammation in WT colitis mice, which transferred with AhR-/- TolDCs, showed no obvious improvement compared with those transferred with WT TolDCs, as evidenced by no rescues of Th17/Treg balance. CONCLUSIONS: Activation of AhR attenuates experimental colitis by modulating the balance of TolDCs and Th17/Treg. The AhR modulation of TolDCs may be a viable therapeutic approach for CD.
Deletion of AhR aggravated colitis in mice, while AhR activation ameliorated colitis by promoting TolDCs formation which in turn restored Th17/Treg balance in colons. Thus, induction of TolDCs via regulating AhR may supply a therapeutic target for CD.
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The non-homogeneous structure and high-density ash composition of biochar matrix pose significant challenges in characterizing the dynamic changes of heavy metal adsorption onto biochar with micro-computed tomography (Micro-CT). A novel in-situ registration subtraction image segmentation method (IRS) was developed to enhance micro-CT characterization accuracy. The kinetics of Cu(II) adsorption onto pellet biochar derived from corn stalks were tested. Respectively, the IRS and traditional K-means algorithms were used for image segmentation to the in-situ three-dimensional (3D) visual characterization of the Cu(II) adsorption onto biochar. The results indicated that the IRS algorithm reduced interference from high-density biochar composition, and thus achieved more precise results (R2 = 0.95) than that of K-means (R2 = 0.72). The visualized dynamic migration of Cu(II) from surface adsorption to intraparticle diffusion reflexed the complex mechanism of heavy metal adsorption. The developed Micro-CT method with high generalizability has great potential for studying the process and mechanism of biochar heavy metal adsorption.
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Metales Pesados , Contaminantes Químicos del Agua , Cobre/química , Microtomografía por Rayos X , Zea mays , Adsorción , Carbón Orgánico/química , Metales Pesados/química , Cinética , Contaminantes Químicos del Agua/químicaRESUMEN
An electrochemical multicomponent [2+2+1] cascade cyclization of enaminones and primary amines towards the synthesis of 4-acylimidazoles has been developed. In an undivided cell, enaminones and primary amines can smoothly participate in this reaction to provide a series of 1,2-disubstituted 4-acylimidazoles at room temperature. The reaction avoids the use of both transition-metal catalysts and oxidation reagents, which makes it more sustainable and renewable.
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This study constructed a moderated mediation model to examine whether increased army morale could reduce suicidal ideation. The mediating role of grit and the moderating role of social support were also examined. A total of 1029 male navy cadets in China were recruited to complete the survey. The measures used in the study included the Army Morale Scale, Grit Scale, Social Support Scale, and Self-rated Idea of Suicide Scale. The results indicated that: increased army morale could significantly reduce suicidal ideation; the impact of army morale on suicidal ideation could be partially mediated by grit; and social support moderated the impact of army morale on suicidal ideation. Specifically, relatively higher levels of social support could reduce suicidal ideation among individuals with lower levels of army morale, but the effect is not significant when the morale is at a high level. The study revealed that increased army morale could reduce suicidal ideation. Moreover, the mediating role of grit and the moderating role of social support were also revealed.
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Ideación Suicida , Suicidio , Humanos , Masculino , Moral , Apoyo Social , ChinaRESUMEN
The direct functionalization of ß-C(sp2)-H bonds in enamides has garnered increasing attention within the realm of organic synthesis. However, these remarkable advancements are predominantly dependent on transition metals; limited success has been achieved via organocatalytic catalysis. Herein, we report a CPA-catalyzed ß-C(sp2)-H functionalization of enamides cascade intramolecular cyclization to synthesize the chiral dihydropyrimido[1,6-a]indoles bearing gem-difluoromethylene. Moreover, this methodology enables the synthesis of diverse chiral dihydropyrimido[1,6-a]indoles with outstanding enantioselectivities in moderate to high yields.
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A novel and highly selective electrochemical method for the synthesis of diverse quinazolinone oximes via direct electrooxidation of primary amines/C(sp2)-H functionalization of oximes has been developed. The reaction is conducted in an undivided cell under constant current conditions and is oxidant-free, open-air, and eco-friendly. Notably, the protocol shows good functional group tolerance, providing versatile quinazolinone oximes in good yields. Moreover, the mechanism is investigated through control experiments and cyclic voltammogram (CV) experiments.
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Chlorogenic acid (CGA) has incredible potential for various pharmaceutical, nutraceutical, and agricultural applications. However, the traditional extraction approach from plants is time-consuming, further limiting its production. Herein, we design and construct the de novo biosynthesis pathway of CGA using modular coculture engineering in Escherichia coli, which is composed of MG09 and BD07 strains. To accomplish this, the phenylalanine-deficient MG09 strain was engineered to utilize xylose preferentially and to overproduce precursor caffeic acid, while the tyrosine-deficient BD07 strain was constructed to consume glucose exclusively to enhance another precursor quinic acid availability for the biosynthesis of CGA. Further pathway modularization and balancing in the context of syntrophic cocultures resulted in additional production improvement. The coculture strategy avoids metabolic flux competition in the biosynthesis of two CGA precursors, caffeic acid and quinic acid, and allows for production improvement by balancing module proportions. Finally, the optimized coculture based on the aforementioned efforts produced 131.31 ± 7.89 mg/L CGA. Overall, the modular coculture engineering strategy in this study provides a reference for constructing microbial cell factories that can efficiently biomanufacture complex natural products.