Facile Borylation of Alkenes, Alkynes, Imines, Arenes and Heteroarenes with N-Heterocyclic Carbene-Boranes and a Heterogeneous Semiconductor Photocatalyst.

Although the development of radical chain and photocatalytic borylation reactions using N-heterocyclic carbene (NHC)-borane as boron source is remarkable, the persistent problems, including the use of hazardous and high-energy radical initiators or the recyclability and photostability issues of soluble homogeneous photocatalysts, still leave great room for further development in a sustainable manner. Herein, we report a conceptually different approach toward highly functionalized organoborane synthesis by using recoverable ultrathin cadmium sulfide (CdS) nanosheets as a heterogeneous photocatalyst, and a general and mild borylation platform that enables regioselective borylation of a wide variety of alkenes (arylethenes, trifluoromethylalkenes, α,ß-unsaturated carbonyl compounds and nitriles), alkynes, imines and electron-poor aromatic rings with NHC-borane as boryl radical precursor. Mechanistic studies and density functional theory (DFT) calculations reveal that both photogenerated electrons and holes on the CdS fully perform their own roles, thereby resulting in enhancement of photocatalytic activity and stability of CdS.

Relationship between apoA-I, chemerin, Procalcitonin and severity of hyperlipidaemia-induced acute pancreatitis.

The aim of this study was to investigate the relationship between apoA-I, chemerin, and Procalcitonin (PCT) and the severity of hyperlipidaemia-induced acute pancreatitis (HLAP), as well as the importance of their application in the diagnosis of severe HLAP. This study was conducted at the 363 Hospital, Chengdu City, China, from January 2016 to August 2020. There were significant differences in the levels of serum apoA-I, chemerin, and PCT among the three-mild, moderate and severe-groups (all p <0.001). Serum apoA-I was negatively correlated with chemerin and PCT levels in the severe group (p=0.006, p=0.011, respectively). Serum chemerin and PCT levels in the severe group was a positive correlation (p=0.032). Receiver Operating Characteristic (ROC) curve area of serum apoA-I in the diagnosis of severe HLAP was 0.808 (95% CI:0.727-0.888, p value <0.001), which was higher than that in serum chemerin and PCT, and its sensitivity and specificity were 0.628 and 0.814, respectively. Hence, in patients with HLAP, serum apoA-I, chemerin, and PCT are closely correlated. The efficacy of serum apoA-I in the diagnosis of severe HLAP is higher than that of serum chemerin and PCT.

Melatonin protects against thoracic aortic aneurysm and dissection through SIRT1-dependent regulation of oxidative stress and vascular smooth muscle cell loss.

Melatonin functions as an endogenous protective molecule in multiple vascular diseases, whereas its effects on thoracic aortic aneurysm and dissection (TAAD) and underlying mechanisms have not been reported. In this study, TAAD mouse model was successfully induced by ß-aminopropionitrile fumarate (BAPN). We found that melatonin treatment remarkably prevented the deterioration of TAAD, evidenced by decreased incidence, ameliorated aneurysmal dilation and vascular stiffness, improved aortic morphology, and inhibited elastin degradation, macrophage infiltration, and matrix metalloproteinase expression. Moreover, melatonin blunted oxidative stress damage and vascular smooth muscle cell (VSMC) loss. Notably, BAPN induced a decrease in SIRT1 expression and activity of mouse aorta, whereas melatonin treatment reversed it. Further mechanistic study demonstrated that blocking SIRT1 signaling partially inhibited these beneficial effects of melatonin on TAAD. Additionally, the melatonin receptor was involved in this phenomenon. Our study is the first to report that melatonin exerts therapeutic effects against TAAD by reducing oxidative stress and VSMC loss via activation of SIRT1 signaling in a receptor-dependent manner, thus suggesting a novel therapeutic strategy for TAAD.

Transplantation of mesenchymal stem cells overexpressing IL10 attenuates cardiac impairments in rats with myocardial infarction.

Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin-10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow-derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen-glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10-MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10-MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10-MSC treatment. IL10 overexpression and MSC may exert a synergistic anti-inflammatory effect to alleviate cardiac injury after MI.

MicroRNA-188-5p regulates contribution of bone marrow-derived cells to choroidal neovascularization development by targeting MMP-2/13.

Our previous investigations have shown that bone marrow-derived cells (BMCs), including mesenchymal stem cells (MSCs), contribute to the development of choroidal neovascularization (CNV) as sources of cells and angiogenic factors. Two main steps for circulating BMCs to integrate into CNV lesions are extracellular matrix remodeling and consequential cell migration. MicroRNAs (miRNAs) were found to be involved in CNV development; however, little is known about whether miRNAs regulate the contribution of BMCs to CNV. In the present study, we found that the expression of miR-188-5p was decreased in cultured hypoxic MSCs and BMCs within laser-induced CNV in mice. Matrix metalloproteinase 2 (MMP-2) and MMP-13 were both discovered as targets of miR-188-5p by bioinformatics predictions and dual-luciferase reporter system. Accordingly, increased expression of MMP-2/13 was found in hypoxic MSCs and BMCs in CNV lesions. Furthermore, miR-188-5p mimic transfection caused downregulation of MMP-2/13 in hypoxic MSCs and decreased tube formation of co-cultured vascular endothelial cells. Intravitreal injections of a miR-188-5p agomir attenuated the severity of CNV and inhibited the migration of BMCs into CNV lesions in mice. Our study suggests that miR-188-5p regulates the contribution of BMCs to CNV development by targeting MMP-2/13-mediated extracellular matrix degeneration, and miR-188-5p serves as a therapeutic target to treat CNV-related diseases.

A Temporal Adaptive Access Mechanism for Data Fusion in an IoT Environment.

Data fusion in the Internet of Things (IoT) environment demands collecting and processing a wide variety of data with mixed time characteristics, both real-time and non-real-time data. Most of the previous research on data fusion was about the data processing aspect; however, successful data transmission is a prerequisite for high-performance data fusion in IoT. On the other hand, research on data transmissions in IoT mainly focuses on networking without sufficiently considering the special requirements of the upper-layer applications, such as the data fusion process, that are consuming the transmitted data. In this paper, we tackle the problem of data transmission for data fusion in an IoT environment by proposing a distributed scheduling mechanism VD-CSMA in wireless sensor networks, which considers the values for data fusion, as well as the delay constraints of packets when determining their priority levels for transmission. Simulation results have shown that VD-CSMA may enhance both throughput and delay performance of data transmission as compared to the typical scheduling schemes used for data fusion in IoT.

Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis.

Sirtuins are a family of highly evolutionarily conserved nicotinamide adenine nucleotide-dependent histone deacetylases. Sirtuin-3 (SIRT3) is a member of the sirtuin family that is localized primarily to the mitochondria and protects against oxidative stress-related diseases, including myocardial ischemia/reperfusion (MI/R) injury. Melatonin has a favorable effect in ameliorating MI/R injury. We hypothesized that melatonin protects against MI/R injury by activating the SIRT3 signaling pathway. In this study, mice were pretreated with or without a selective SIRT3 inhibitor and then subjected to MI/R operation. Melatonin was administered intraperitoneally (20 mg/kg) 10 minutes before reperfusion. Melatonin treatment improved postischemic cardiac contractile function, decreased infarct size, diminished lactate dehydrogenase release, reduced the apoptotic index, and ameliorated oxidative damage. Notably, MI/R induced a significant decrease in myocardial SIRT3 expression and activity, whereas the melatonin treatment upregulated SIRT3 expression and activity, and thus decreased the acetylation of superoxide dismutase 2 (SOD2). In addition, melatonin increased Bcl-2 expression and decreased Bax, Caspase-3, and cleaved Caspase-3 levels in response to MI/R. However, the cardioprotective effects of melatonin were largely abolished by the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine (3-TYP), suggesting that SIRT3 plays an essential role in mediating the cardioprotective effects of melatonin. In vitro studies confirmed that melatonin also protected H9c2 cells against simulated ischemia/reperfusion injury (SIR) by attenuating oxidative stress and apoptosis, while SIRT3-targeted siRNA diminished these effects. Taken together, our results demonstrate for the first time that melatonin treatment ameliorates MI/R injury by reducing oxidative stress and apoptosis via activating the SIRT3 signaling pathway.

Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC-1ß: In vivo and in vitro studies.

Melatonin, a circadian molecule secreted by the pineal gland, confers a protective role against cardiac hypertrophy induced by hyperthyroidism, chronic hypoxia, and isoproterenol. However, its role against pressure overload-induced cardiac hypertrophy and the underlying mechanisms remains elusive. In this study, we investigated the pharmacological effects of melatonin on pathological cardiac hypertrophy induced by transverse aortic constriction (TAC). Male C57BL/6 mice underwent TAC or sham surgery at day 0 and were then treated with melatonin (20 mg/kg/day, via drinking water) for 4 or 8 weeks. The 8-week survival rate following TAC surgery was significantly increased by melatonin. Melatonin treatment for 8 weeks markedly ameliorated cardiac hypertrophy. Compared with the TAC group, melatonin treatment for both 4 and 8 weeks reduced pulmonary congestion, upregulated the expression level of α-myosin heavy chain, downregulated the expression level of ß-myosin heavy chain and atrial natriuretic peptide, and attenuated the degree of cardiac fibrosis. In addition, melatonin treatment slowed the deterioration of cardiac contractile function caused by pressure overload. These effects of melatonin were accompanied by a significant upregulation in the expression of peroxisome proliferator-activated receptor-gamma co-activator-1 beta (PGC-1ß) and the inhibition of oxidative stress. In vitro studies showed that melatonin also protects against angiotensin II-induced cardiomyocyte hypertrophy and oxidative stress, which were largely abolished by knocking down the expression of PGC-1ß using small interfering RNA. In summary, our results demonstrate that melatonin protects against pathological cardiac hypertrophy induced by pressure overload through activating PGC-1ß.

Bone marrow-derived cells in ocular neovascularization: contribution and mechanisms.

Ocular neovascularization often leads to severe vision loss. The role of bone marrow-derived cells (BMCs) in the development of ocular neovascularization, and its significance, is increasingly being recognized. In this review, we discuss their contribution and the potential mechanisms that mediate the effect of BMCs on the progression of ocular neovascularization. The sequence of events by which BMCs participate in ocular neovascularization can be roughly divided into four phases, i.e., mobilization, migration, adhesion and differentiation. This process is delicately regulated and liable to be affected by multiple factors. Cytokines such as vascular endothelial growth factor, granulocyte colony-stimulating factor and erythropoietin are involved in the mobilization of BMCs. Studies have also demonstrated a key role of cytokines such as stromal cell-derived factor-1, tumor necrosis factor-α, as well as vascular endothelial growth factor, in regulating the migration of BMCs. The adhesion of BMCs is mainly regulated by vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and vascular endothelial cadherin. However, the mechanisms regulating the differentiation of BMCs are largely unknown at present. In addition, BMCs secrete cytokines that interact with the microenvironment of ocular neovascularization; their contribution to ocular neovascularization, especially choroidal neovascularization, can be aggravated by several risk factors. An extensive regulatory network is thought to modulate the role of BMCs in the development of ocular neovascularization. A comprehensive understanding of the involved mechanisms will help in the development of novel therapeutic strategies related to BMCs. In this review, we have limited the discussion to the recent progress in this field, especially the research conducted at our laboratory.

The roles of nanocarriers on pigment epithelium-derived factor in the differentiation of human cardiac stem cells.

Over the past decade, adult stem cells have attracted great attention because of their ability to potentially regenerate desired tissues or entire organs. With the emergence of nanomaterial-based gene therapy, adult stem cells have been considered as a proper tool for the biomedical field. In this study, we utilized organically modified silica (ORMOSIL) nanoparticles to deliver small interfering RNA (siRNA) against pigment epithelium-derived factor (PEDF) and induce the differentiation of human cardiac stem cells (CSCs). We found that the down-regulation of PEDF can inhibit the proliferation of human CSCs and induce cell differentiation. To further study the mechanism, we have tested the Notch signalling pathway genes, Hes1 and Hes5, and found that their expressions were inhibited by the PEDF down-regulation. Furthermore, with the restoration of PEDF, both the proliferation of human CSCs and expressions of Hes1 and Hes5 were recovered. Our results suggest for the first time the use of ORMOSIL as nanocarriers for the delivery of PEDF siRNA in human CSCs, and demonstrated the cooperation between PEDF and the Notch signalling pathway in maintaining the self-renewal and pluripotency of stem cells. PEDF as the essential controller in differentiation may be a promising target for the regulation of cardiac homeostasis and damage repair, which opens new treatment strategies using nanomaterials for heart disease therapy.

Membrane receptor-dependent Notch1/Hes1 activation by melatonin protects against myocardial ischemia-reperfusion injury: in vivo and in vitro studies.

Melatonin confers profound protective effect against myocardial ischemia-reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also ameliorates MI/RI. We hypothesize that melatonin attenuates MI/RI-induced oxidative damage by activating Notch1/Hes1 signaling pathway with phosphatase and tensin homolog deleted on chromosome 10 (Pten)/Akt acting as the downstream signaling pathway in a melatonin membrane receptor-dependent manner. Male Sprague Dawley rats were treated with melatonin (10 mg/kg/day) for 4 wk and then subjected to MI/R surgery. Melatonin significantly improved cardiac function and decreased myocardial apoptosis and oxidative damage. Furthermore, in cultured H9C2 cardiomyocytes, melatonin (100 µmol/L) attenuated simulated ischemia-reperfusion (SIR)-induced myocardial apoptosis and oxidative damage. Both in vivo and in vitro study demonstrated that melatonin treatment increased Notch1, Notch1 intracellular domain (NICD), Hes1, Bcl-2 expressions, and p-Akt/Akt ratio and decreased Pten, Bax, and caspase-3 expressions. However, these protective effects conferred by melatonin were blocked by DAPT (the specific inhibitor of Notch1 signaling), luzindole (the antagonist of melatonin membrane receptors), Notch1 siRNA, or Hes1 siRNA administration. In summary, our study demonstrates that melatonin treatment protects against MI/RI by modulating Notch1/Hes1 signaling in a receptor-dependent manner and Pten/Akt signaling pathways are key downstream mediators.

Reduced silent information regulator 1 signaling exacerbates myocardial ischemia-reperfusion injury in type 2 diabetic rats and the protective effect of melatonin.

Diabetes mellitus (DM) increases myocardial oxidative stress and endoplasmic reticulum (ER) stress. Melatonin confers cardioprotective effect by suppressing oxidative damage. However, the effect and mechanism of melatonin on myocardial ischemia-reperfusion (MI/R) injury in type 2 diabetic state are still unknown. In this study, we developed high-fat diet-fed streptozotocin (HFD-STZ) rat, a well-known type 2 diabetic model, to evaluate the effect of melatonin on MI/R injury with a focus on silent information regulator 1 (SIRT1) signaling, oxidative stress, and PERK/eIF2α/ATF4-mediated ER stress. HFD-STZ treated rats were exposed to melatonin treatment in the presence or the absence of sirtinol (a SIRT1 inhibitor) and subjected to MI/R surgery. Compared with nondiabetic animals, type 2 diabetic rats exhibited significantly decreased myocardial SIRT1 signaling, increased apoptosis, enhanced oxidative stress, and ER stress. Additionally, further reduced SIRT1 signaling, aggravated oxidative damage, and ER stress were found in diabetic animals subjected to MI/R surgery. Melatonin markedly reduced MI/R injury by improving cardiac functional recovery and decreasing myocardial apoptosis in type 2 diabetic animals. Melatonin treatment up-regulated SIRT1 expression, reduced oxidative damage, and suppressed PERK/eIF2α/ATF4 signaling. However, these effects were all attenuated by SIRT1 inhibition. Melatonin also protected high glucose/high fat cultured H9C2 cardiomyocytes against simulated ischemia-reperfusion injury-induced ER stress by activating SIRT1 signaling while SIRT1 siRNA blunted this action. Taken together, our study demonstrates that reduced cardiac SIRT1 signaling in type 2 diabetic state aggravates MI/R injury. Melatonin ameliorates reperfusion-induced oxidative stress and ER stress via activation of SIRT1 signaling, thus reducing MI/R damage and improving cardiac function.

Potential energy surfaces for the HBr(+) + CO2 → Br + HOCO(+) reaction in the HBr(+) (2)Π3/2 and (2)Π1/2 spin-orbit states.

Quantum mechanical (QM) + molecular mechanics (MM) models are developed to represent potential energy surfaces (PESs) for the HBr(+) + CO2 → Br + HOCO(+) reaction with HBr(+) in the (2)Π3/2 and (2)Π1/2 spin-orbit states. The QM component is the spin-free PES and spin-orbit coupling for each state is represented by a MM-like analytic potential fit to spin-orbit electronic structure calculations. Coupled-cluster single double and perturbative triple excitation (CCSD(T)) calculations are performed to obtain "benchmark" reaction energies without spin-orbit coupling. With zero-point energies removed, the "experimental" reaction energy is 44 ± 5 meV for HBr(+)((2)Π3/2) + CO2 → Br((2)P3/2) + HOCO(+), while the CCSD(T) value with spin-orbit effects included is 87 meV. Electronic structure calculations were performed to determine properties of the BrHOCO(+) reaction intermediate and [HBr⋯OCO](+) van der Waals intermediate. The results of different electronic structure methods were compared with those obtained with CCSD(T), and UMP2/cc-pVTZ/PP was found to be a practical and accurate QM method to use in QM/MM direct dynamics simulations. The spin-orbit coupling calculations show that the spin-free QM PES gives a quite good representation of the shape of the PES originated by (2)Π3/2HBr(+). This is also the case for the reactant region of the PES for (2)Π1/2 HBr(+), but spin-orbit coupling effects are important for the exit-channel region of this PES. A MM model was developed to represent these effects, which were combined with the spin-free QM PES.

Increased expression of pigment epithelium-derived factor in aged mesenchymal stem cells impairs their therapeutic efficacy for attenuating myocardial infarction injury.

AIMS: Mesenchymal stem cells (MSCs) can ameliorate myocardial infarction (MI) injury. However, older-donor MSCs seem less efficacious than those from younger donors, and the contributing underlying mechanisms remain unknown. Here, we determine how age-related expression of pigment epithelium-derived factor (PEDF) affects MSC therapeutic efficacy for MI. METHODS AND RESULTS: Reverse transcriptase-polymerized chain reaction  and enzyme-linked immunosorbent assay analyses revealed dramatically increased PEDF expression in MSCs from old mice compared to young mice. Morphological and functional experiments demonstrated significantly impaired old MSC therapeutic efficacy compared with young MSCs in treatment of mice subjected to MI. Immunofluorescent staining demonstrated that administration of old MSCs compared with young MSCs resulted in an infarct region containing fewer endothelial cells, vascular smooth muscle cells, and macrophages, but more fibroblasts. Pigment epithelium-derived factor overexpression in young MSCs impaired the beneficial effects against MI injury, and induced cellular profile changes in the infarct region similar to administration of old MSCs. Knocking down PEDF expression in old MSCs improved MSC therapeutic efficacy, and induced a cellular profile similar to young MSCs administration. Studies in vitro showed that PEDF secreted by MSCs regulated the proliferation and migration of cardiac fibroblasts. CONCLUSIONS: This is the first evidence that paracrine factor PEDF plays critical role in the regulatory effects of MSCs against MI injury. Furthermore, the impaired therapeutic ability of aged MSCs is predominantly caused by increased PEDF secretion. These findings indicate PEDF as a promising novel genetic modification target for improving aged MSC therapeutic efficacy.

The Efficacy and Safety of Anlotinib Plus Etoposide with Cisplatin/Carboplatin in the First-Line Treatment of Lung Cancer: A Phase II Clinical Study.

Background: The primary aim of this phase II clinical study was to assess the safety and efficacy of combining anlotinib, etoposide, and platinum-based drugs as a first-line treatment for ES-SCLC. Methods: Patients underwent the standard chemotherapeutic regimen, consisting of four courses of etoposide plus cisplatin/carboplatin. Additionally, each patient received a 2-week intervention with anlotinib (12 mg/day, once daily). Anlotinib was continued until disease progression, occurrence of unbearable adverse events (AEs), or withdrawal from the research. Progression-free survival (PFS) served as the primary prognostic measure. Secondary measures included the disease control rate (DCR), objective response rate (ORR), overall survival time (OS), and the incidence of AEs. Results: The DCR and ORR were 97.6% and 91.0%, respectively. Estimated PFS and OS were 5.0 months (95% CI: 1.0-10.8 months) and 13.0 months (95% CI: 8.4-18.6 months), respectively. No unexpected adverse effects were reported during the trial. The most common adverse reactions included anemia (42.22%), hypertension (53.33%), alopecia (40.00%), elevated transaminase (24.40%), and elevated alkaline phosphatase (24.44%). Sixteen cases (35.56%) were classified as AEs of grades 3-5. No deaths attributed to treatment-related causes occurred in any patient during the trial. Conclusion: Combination chemotherapy is currently the first-line therapy for extensive small-cell lung cancer (ES-SCLC). Combining anlotinib with conventional platinum-based chemotherapy demonstrated promising therapeutic outcomes and prognosis in the management of ES-SCLC.

Frailty and long-term survival of patients with gastric cancer: a meta-analysis.

Background: The relationship between frailty and the long-term clinical outcome of gastric cancer (GC) patients has not yet been established, although frailty is associated with a poor short-term outcome. The impact of frailty on long-term survival of GC patients was investigated through a systematic review and meta-analysis. Methods: Observational studies with longitudinal follow-ups for a minimum of one year were identified through a search of the PubMed, Embase, Cochrane Library, and Web of Science databases, in accordance with the objective of the meta-analysis. Combining the findings was achieved using a random-effects model, which accounted for inter-study heterogeneity. Results: Ten datasets from nine cohort studies were included, which involved 7613 patients with GC. A total of 2074 patients (27.2%) were with frailty at baseline, and the mean follow-up duration was 48.1 months. A pooled analysis of the results showed that frailty was linked to a poor long-term overall survival in GC patients (risk ratio [RR]: 1.65, 95% confidence interval [CI]: 1.27 to 2.13, p < 0.001; I2 = 80%). Sensitivity analysis showed consistent results in older patients (≥ 65 years, RR: 1.51, p = 0.002) and the oldest old (≥ 80 years, RR: 1.41, p = 0.01). In addition, frailty was also associated with poor long-term progression-free survival (RR: 1.65, 95% CI: 1.39 to 1.96, p < 0.001; I2 = 0%) and disease-specific survival (RR: 1.71, 95% CI: 1.23 to 2.37, p = 0.001; I2 = 4%). Conclusion: Frailty is associated with poor long-term survival of patients with GC.

Oxidative cleavage and ammoxidation of organosulfur compounds via synergistic Co-Nx sites and Co nanoparticles catalysis.

The cleavage and functionalization of C-S bonds have become a rapidly growing field for the design or discovery of new transformations. However, it is usually difficult to achieve in a direct and selective fashion due to the intrinsic inertness and catalyst-poisonous character. Herein, for the first time, we report a novel and efficient protocol that enables direct oxidative cleavage and cyanation of organosulfur compounds by heterogeneous nonprecious-metal Co-N-C catalyst comprising graphene encapsulated Co nanoparticles and Co-Nx sites using oxygen as environmentally benign oxidant and ammonia as nitrogen source. A wide variety of thiols, sulfides, sulfoxides, sulfones, sulfonamides, and sulfonyl chlorides are viable in this reaction, enabling access to diverse nitriles under cyanide-free conditions. Moreover, modifying the reaction conditions also allows for the cleavage and amidation of organosulfur compounds to deliver amides. This protocol features excellent functional group tolerance, facile scalability, cost-effective and recyclable catalyst, and broad substrate scope. Characterization and mechanistic studies reveal that the remarkable effectiveness of the synergistic catalysis of Co nanoparticles and Co-Nx sites is crucial for achieving outstanding catalytic performance.

Oxidative Cleavage and Ammoxidation of Unsaturated Hydrocarbons via Heterogeneous Auto-Tandem Catalysis.

The oxidative cleavage and functionalization of unsaturated C-C bonds are important processes for synthesis of carbonyl compounds from hydrocarbon feedstocks, yet there has been no report of direct amidation of unsaturated hydrocarbons via an oxidative cleavage of unsaturated C-C bonds with molecular oxygen as an environmentally benign oxidant. Herein, for the first time, we describe a manganese oxide-catalyzed auto-tandem catalysis strategy that enables direct synthesis of amides from unsaturated hydrocarbons by coupling oxidative cleavage with amidation. With oxygen as an oxidant and ammonia as a nitrogen source, a wide range of structurally diverse mono- and multisubstituted activated and unactivated alkenes or alkynes can smoothly undergo unsaturated C-C bond cleavage to deliver one- or multiple-carbon shorter amides. Moreover, a slight modification of the reaction conditions also allows for the direct synthesis of sterically hindered nitriles from alkenes or alkynes. This protocol features excellent functional group tolerance, a broad substrate scope, flexible late-stage functionalization, facile scalability, and a cost-effective and recyclable catalyst. Detailed characterizations reveal that the high activity and selectivity of the manganese oxides are attributed to the large specific surface area, abundant oxygen vacancies, better reducibility, and moderate acid sites. Mechanistic studies and density functional theory calculations indicate that the reaction proceeds through divergent pathways depending on the structure of substrates.

Correlation of Serum CA242, CA724, and TPA Levels with Clinicopathological Features and Prognosis in Patients with Inflammatory Bowel Disease Complicated with Rectal Cancer.

Objective: To investigate the correlation of serum cancer antigen 242 (CA242), cancer antigen 72-4 (CA724), and tissue polypeptide antigen (TPA) levels with clinicopathological features and prognosis in patients with inflammatory bowel disease (IBD) complicated with rectal cancer. Methods: The data of 120 patients with IBD were retrospectively analyzed. Patients were divided into the IBD group (without rectal cancer, n = 60) and the rectal cancer group (with rectal cancer, n = 60), and 60 healthy individuals receiving medical examination during the same period were selected as the healthy group. Serum CA242, CA724, and TPA levels of research subjects were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the clinical data of the patients were collected. The patients were followed up for 3 years and divided into the survival group and the dead group. The relationship between the levels of CA242, CA724, TPA, and prognosis was tested. Results: Significant differences were found in the serum CA242, CA724, and TPA levels among three groups (P < 0.001). CA242 was related to tumor size, histological stage, growth mode, and TNM stage in patients with IBD and rectal cancer. CA724 was related to histological stage, growth mode, depth of tumor invasion (T stage), lymph node metastasis (N stage), distant metastasis (M stage), and TNM stage in patients with IBD and rectal cancer. TPA was related to histological stage, T stage, M stage, and TNM stage in patients with IBD and rectal cancer. Serum CA242, CA724, and TPA levels in the survival group were significantly lower than those in the dead group after 3 years (P < 0.001). As for the combined prediction of serum CA242, CA724, and TPA for patients' prognosis, the confidence interval was 0.000-1.000, AUC was 0.875, standard error was 0.093, and sensitivity was 0.750. Conclusion: Serum CA242, CA724, and TPA levels are closely related to the clinicopathological features such as location, stage, and metastasis of rectal cancer. The combined detection of serum CA242, CA724, and TPA levels has a significant correlation with the prognosis of patients with rectal cancer, which can be used in monitoring the disease progression.

Protocol for the preparation of amorphous manganese oxide and its application as heterogeneous catalyst in the direct synthesis of amides and nitriles.

The cleavage and functionalization of carbon-carbon (C-C) bonds has emerged as a powerful tool for preparing value-added chemicals. In this protocol, we describe the preparation of amorphous manganese oxide and its application as a heterogeneous catalyst in the direct synthesis of amides via successive cleavage and amidation of C-C bonds in alcohols. Furthermore, we describe how a slight modification of reaction conditions allows for the cleavage and cyanation of alcohols to access sterically hindered nitriles. For complete details on the use and execution of this protocol, please refer to He et al. (2022).