ROS and Ca2+ signaling involved in important lipid changes of Chlorella pyrenoidosa under nitrogen stress conditions.

MAIN CONCLUSION: Nitrogen stress altered important lipid parameters and related genes in Chlorella pyrenoidosa via ROS and Ca2+ signaling. The mutual interference between ROS and Ca2+ signaling was also uncovered. The changed mechanisms of lipid parameters (especially lipid classes and unsaturation of fatty acids) in microalgae are not completely well known under nitrogen stress. Therefore, Chlorella pyrenoidosa was exposed to 0, 0.5, 1 and 1.5 g L-1 NaNO3 for 4 days. Then, the physiological and biochemical changes were measured. It was shown that the total lipid contents, neutral lipid ratios as well as their related genes (accD and DGAT) increased obviously while the polar lipid ratios, degrees of unsaturation as well as their related genes (PGP and desC) decreased significantly in nitrogen stress groups. The obvious correlations supported that gene expressions should be the necessary pathways to regulate the lipid changes in C. pyrenoidosa under nitrogen stress. The changes in ROS and Ca2+ signaling as well as their significant correlations with corresponding genes and lipid parameters were analyzed. The results suggested that ROS and Ca2+ may regulate these gene expressions and lipid changes in C. pyrenoidosa under nitrogen stress conditions. This was verified by the subordinate tests with an ROS inhibitor and calcium reagents. It also uncovered the clues of mutual interference between ROS and Ca2+ signaling. To summarize, this study revealed the signaling pathways of important lipid changes in microalgae under N stress.

Second Near-Infrared Macrophage-Biomimetic Nanoprobes for Photoacoustic Imaging of Neuroinflammation.

Neuroinflammation is a significant pathological event involving the neurodegenerative process associated with many neurological disorders. Diagnosis and treatment of neuroinflammation in its early stage are essential for the prevention and management of neurological diseases. Herein, we designed macrophage membrane-coated photoacoustic (PA) probes (MSINPs), with targeting specificities based on naturally existing target-ligand interactions for the early diagnosis of neuroinflammation. The second near-infrared dye, IR1061, was doped into silica as the core and was encapsulated with a macrophage membrane. In vitro as well as in vivo, the MSINPs could target inflammatory cells via the inflammation chemotactic effect. PA imaging was used to trace the MSINPs in a neuroinflammation mouse model and showed a great targeted effect of MSINPs in the prefrontal cortex. Therefore, the biomimetic nanoprobe prepared in this study offers a new strategy for PA molecular imaging of neuroinflammation, which can enhance our understanding of the evolution of neuroinflammation in specific brain regions.

Modulating the Catalytic Properties of Polyoxovanadates with Transition-Metal-Complex Units for Selective Oxidation of Sulfides.

Selective oxidation of sulfides to sulfoxides is of great significance in the synthesis of pharmaceuticals, desulfurization of fuels, and detoxification of sulfur mustard chemical warfare agents. Designing selective catalysts to achieve the efficient transformation of sulfides to sulfoxides is thus highly desired. Herein, we report three transition metal-complex-functionalized polyoxovanadates, [Zn2(BPB)2][V4O12]·0.5BPB·H2O (1), [Ni(BPB)(H2O)][V2O6]·2H2O (2), and [Co(HBPB)2][V4O12] (3) (BPB = 1,4-bis(pyrid-4-yl)benzene)), and explore their applications for selective oxidation of sulfides using H2O2 as an oxidant. All three compounds were catalytically effective for the oxidation of methyl phenyl sulfide to methyl phenyl sulfoxide, with 1 being best-performing with complete conversion and a selectivity of 96.7%. In the selective oxidation of a series of aromatic and aliphatic sulfides to corresponding sulfoxides, 1 also showed satisfactory performance; in particular, the chemical warfare agent stimulant 2-chloroethyl ethyl sulfide can be completely and selectively oxidized to the nontoxic 2-chloroethyl ethyl sulfoxide within 20 min at room temperature. Catalyst 1 can be recycled and reused at least six times with uncompromised performance. The perfect performance of 1 is attributed to the synergistic effect of coordinatively unsaturated V and Zn sites in bimetallic oxide, as revealed by comparative structural and catalytic studies.

No evidence for a genetic causal effect of breast cancer on venous thromboembolism: a mendelian randomization study.

Active cancer is known to contribute to venous thromboembolism (VTE), but the cause-and-effect association of breast cancer on VTE is not yet clear. In order to investigate the possible causal relationships, we used a Mendelian randomization analysis. Data for generically predicted breast cancer were identified based on the BCAC consortium. A meta-analysis of genome-wide association study (GWAS) comprising 1,500,861 participants for VTE as well as data from the FinnGen study for VTE, DVT and PE was used for the causal-effect estimation. Our primary method was inverse-variance weighted (IVW), and our supplementary methods included weighted median and MR-Egger. We also carried out sensitivity analysis for the study. No evidence of causal-effect was detected of overall breast cancer on VTE in both the GWAS meta-analysis (OR=1.01, 95%CI:0.98-1.04, p = 0.495) and the FinnGen consortium (OR=1.00,95%CI:0.96-1.04, p = 0.945). In addition, the presence of ER-positive or ER-negative disease did not significantly influence the incidence of VTE and its subtypes. In conclusion, no genetic cause-and-effect of breast cancer on VTE risk was detected in the large MR analysis.

A mitochondrion-targeted cyanine agent for NIR-II fluorescence-guided surgery combined with intraoperative photothermal therapy to reduce prostate cancer recurrence.

Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.

Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome.

OBJECTIVE: Gitelman syndrome (GS) is an autosomal recessive tubulopathy resulting from inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). To date, more than 500 mutations have been identified in the SLC12A3 gene. In this study, we identified two new mutations in the SLC12A3 gene in two Chinese GS pedigrees. DESIGN, PATIENTS AND MEASUREMENTS: The clinical characteristics and laboratory examination of two suspected GS patients in our hospital were analyzed. In addition, two pedigrees including 11 members and 2 patients underwent SLC12A3 gene analysis. RESULTS: Both patients were middle-aged women with characteristics of hypokalemic metabolic alkalosis, hypomagnesemia, low level of urinary calcium and the elevated levels of renin-angiotensin-aldosterone system. So, they were clinically diagnosed as GS. Patient 2 also had type 2 diabetes and Graves' disease. Both patients were found to carry two mutations of SLC12A3 gene by Sanger direct sequencing, which were all compound heterozygous mutations. We identified three mutations in these two Chinese GS pedigrees, one of which was c.179C>T (Thr60Met). The novel c.2159G>T (p. Gly720Val) and c.2675T>C (p. Leu892Pro) mutations were strongly predicted to be pathogenic using four network programs-Polyphen-2, SIFT, Mutation Taster and LRT. CONCLUSIONS: We identified two novel SLC12A3 genetic variant [c.2159G>T (p.Gly720Val) and c.2675T>C (p.Leu892Pro)] in two Chinese GS pedigrees. The discovery of new mutations has enriched the spectrum of SLC12A3 genotypes.

Biomimetic Nanoparticles Loaded with Ulinastatin for the Targeted Treatment of Acute Pancreatitis.

Ulinastatin is commonly used in the clinic to treat acute pancreatitis (AP), but its therapeutic effect was limited by the presence of the blood-pancreas barrier (BPB) and low specificity. Here, we prepared a macrophage biomimetic nanoparticle (MU) that delivered ulinastatin to address the above issues. Macrophage membrane was used as a shell for a mixture of PEG-PLGA and ulinastatin. It was found that MU showed good stability and biocompatibility in vitro and in vivo. According to in vivo fluorescence imaging, MU displayed a great inflammation targeting effect both in a subcutaneous inflammation model and in situ pancreatitis mouse model, which was ascribed to the presence of adhesion proteins. In vitro and in vivo results demonstrated that MU have a superior AP treatment effect by inhibiting pro-inflammatory factors and keeping cells viability. It was suggested the MU could provide a new strategy for targeted AP treatment.

Solvent- and Additive-Free Dehydrogenation of N-Heterocycles with Oxygen Catalyzed by Polyoxovanadate-Based Metal-Organic Frameworks.

N-heteroarenes are a family of organics with significant chemical and pharmaceutical applications. They are generally prepared by the catalytic oxidative dehydrogenation (ODH) of partially saturated N-heterocycles. In this work, we prepare and demonstrate the catalytic ODH applications of two polyoxovanadate-based metal-organic frameworks of the general formula {[MII(bibp)1.5][VV2O6]}·H2O (M = Ni 1, Co 2; bibp = 4,4'-bis(imidazol-1-ylmethyl)biphenyl). They are based on nonprecious metals, need no additives or organic solvents typically required for catalytic ODH, and utilize molecular O2 as the oxidant, thus possessing all the traits desirable for practical catalysis. Catalyst 1 shows tolerance for a range of substrates with different electronic and steric features, including 2,3-dihydro-1H-indole and tetrahydroquinolines substituted with various functional groups. Mechanistic studies supported primarily by evidence from electron paramagnetic resonance and X-ray photoelectron spectra suggest that the VV sites in 1 are catalytically responsible, first enabling the formation of the substrate-based radical species by a single electron transfer event while being converted into its mixed-valence form, followed by the production of the superoxide radical anion (O2•-) upon contact with O2. The reaction mixture containing O2•- and the initially formed substrate-based radical then undergoes a series of steps, including the hydrogen abstraction and formation of the hydroperoxyl radical, the production and tautomerization of the partially dehydrogenated intermediate, and finally a repeating cycle of the aforementioned steps, to achieve the high-yield conversion of substrates to the corresponding N-heteroarenes.

Retraction: Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides.

Retraction of 'Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides' by Yingying Pan et al., Org. Biomol. Chem., 2019, 17, 4230-4233, https://doi.org/10.1039/C9OB00628A.

Expression and bioinformatics analysis of RPL38 protein and mRNA in gastric cancer.

We aimed to clarify the expression of RPL38 in gastric cancer, explore the relationship between the expression level of RPL38 and the clinicopathological parameters and prognosis of gastric cancer patients, and explore whether RPL38 has the potential to be used as a therapeutic target for gastric cancer and a biomarker for assessing prognosis. The mRNA and protein expression of RPL38 in gastric cancer tissues and normal tissues were compared by TIMER, Kaplan-Meier plotter, CCLE and UALCAN databases, respectively. Next, the relationship between the expression level of RPL38 in gastric cancer tissues and clinicopathological features was analysed using the UALCAN database. The Kaplan-Meier plotter database was then used to predict the prognostic value of RPL38 in gastric cancer patients, and overall survival curves were plotted based on the follow-up information of clinical specimens. The relationship between RPL38 expression and the level of immune infiltration in gastric cancer was explored using the TIMER database. Finally, co-expression analysis as well as enrichment analysis of RPL38 was performed using LinkedOmics database and GSEA, respectively. Through comprehensive bioinformatics analysis and immunohistochemistry experiments, we comprehensively concluded that RPL38 was highly expressed in gastric cancer. Univariate analysis showed that TNM stage (P=0.008), radiotherapy (P=0.02), and RPL38 expression level (P=0.0006) were associated with prognosis. Multifactorial analysis showed that RPL38 expression level (P=0.019), TNM stage (P=0.015) and radiotherapy (P=0.039) were independent risk factors affecting the prognosis of gastric cancer. Gastric cancer patients with high expression of RPL38 had poorer OS. In addition, RPL38 was associated with immune infiltration in gastric cancer. RPL38 is highly expressed in gastric cancer tissues, and RPL38 protein plays an important role in the development of gastric cancer, which is one of the important factors in assessing the prognosis of gastric cancer patients.

An Analysis of Infection Prevention and Control Practices in Designated Hospitals that Treat COVID-19: A Systematic Review and Meta-Analysis.

Objective: The present investigation aims to conduct a comprehensive examination of the infection prevention and control efforts in hospitals of Xinjiang Production and Construction Corps designated for COVID-19 treatment. Methods: By searching the Cochrane Library, PubMed, Embase, Chinese Academic Journal, Full Text Database, Chinese Biomedical Literature Database (CBM), VIP Chinese Scientific, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (CECDB), and using Review Manager 5.2 software, the quality assessment, data extraction, and meta-analysis were carried out for the included literature. Results: Between both the experimental and the control groups, there was a statistically significant difference in the level of public awareness of COVID-19 prevention and control [OR = 1.61, 95% confidence interval (CI) (1.31, 1.99), P < .00001, I2 = 32%, Z = 4]; public concern about COVID-19 prevention and control [OR = 1.56, 95% CI (1.28, 1.90), P < .0001, I2 = 0%, Z = 4.35]; public anxiety on COVID-19 prevention and control [OR = 1.67, 95% CI (1.37, 2.03), P < .00001, I2 = 32%, Z = 5.13]. Conclusion: Chinese prophylaxis and controlling measures for COVID-19 are mainly to protect vulnerable populations, cut off transmission routes, and control the source of infection. Therefore, we must also do our best to prevent and control novel coronavirus pneumonia to protect our health and reduce the burden on our country.

The Metabolism of Reactive Oxygen Species and Their Effects on Lipid Biosynthesis of Microalgae.

Microalgae have outstanding abilities to transform carbon dioxide (CO2) into useful lipids, which makes them extremely promising as renewable sources for manufacturing beneficial compounds. However, during this process, reactive oxygen species (ROS) can be inevitably formed via electron transfers in basal metabolisms. While the excessive accumulation of ROS can have negative effects, it has been supported that proper accumulation of ROS is essential to these organisms. Recent studies have shown that ROS increases are closely related to total lipid in microalgae under stress conditions. However, the exact mechanism behind this phenomenon remains largely unknown. Therefore, this paper aims to introduce the production and elimination of ROS in microalgae. The roles of ROS in three different signaling pathways for lipid biosynthesis are then reviewed: receptor proteins and phosphatases, as well as redox-sensitive transcription factors. Moreover, the strategies and applications of ROS-induced lipid biosynthesis in microalgae are summarized. Finally, future perspectives in this emerging field are also mentioned, appealing to more researchers to further explore the relative mechanisms. This may contribute to improving lipid accumulation in microalgae.

Gene alternation of cerebrospinal fluid in patients with leptomeningeal metastases of lung adenocarcinoma using next-generation sequencing.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide a better prognosis in EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the outcome of leptomeningeal metastasis (LM) remains poor. In addition, due to limited access to intracranial tumour tissue, gene alterations associated with leptomeningeal metastasis from lung adenocarcinoma (LM-LUAD) are unclear. METHODS: Forty-five patients with LM-LUAD from May 2019 to June 2021 in Guangdong Sanjiu Brain Hospital were enrolled in this study. Seventy-five percent (34/45) of patients with LM harbored EGFR mutations, and patients with progressive disease (PD) of LM had 3rd-generation EGFR-TKI therapy and were defined as Cohort 1; those without 3rd-generation EGFR-TKI therapy were defined as Cohort 2. Next-generation targeted panel sequencing (NGS) was performed in each cerebrospinal fluid (CSF) sample of the two cohorts, and 9/45 LM-LUAD patients had matched plasma (PLA). RESULTS: The common gene alterations discovered in the CSF of LM-LUAD were EGFR mutation (34/45, 75%), TP53 (25/45, 56%), CDKN2A (9/45, 20%), ALK (7/45, 16%), CTNNB1 (6/45, 13%), MET (5/45, 11%), APC (4/45, 9%), FGF4 (4/45, 9%), FGF3 (4/45, 9%), ERBB2 (4/45, 9%), and PIK3CG (4/45, 9%). Cooccurring mutations of TP53 and EGFR were found in 49% (22/45) of patients and correlated with poor prognosis. CDKN2A was identified in 20% (9/45) of patients and presented slightly shorter overall survival (OS) than those without (7.1 versus 8.8 months, p = 0.2). Cohort 1 had more genes associated with poor prognosis, consisting of CDK4, CDKN2A, PIK3CG, or PIK3CA, and YES1 and MET were more likely to be detected in cohort 2. The alteration of EGFR was comparable between CSF and matched PLA. Incidences of gene alterations such as CDK4, CDKN2A, MET, SOX2, JAK2, BRAF, and PIK3CG were more likely to be identified in CSF. All mutant allele frequencies (MAF) were much higher in CSF than in matched PLA. CONCLUSIONS: CSF could be a potential candidate for the genetic profiling of LM-LUAD, demonstrating the genetic characteristics of LM in EGFR-mutated lung adenocarcinoma on diverse EGFR-TKI therapies.

Progress and Prospects of Research Ideas and Methods in the Network Pharmacology of Traditional Chinese Medicine.

In recent years, the emerging network pharmacology has been extensively applied to the field of traditional Chinese medicine and has made great contributions to the modernization of TCM. Therefore, this paper provides an overview of the progress of research ideas and methods in the network pharmacology in the last few years in the field of traditional Chinese medicine and presents insights into future research methods and ideas in the network pharmacology. Problems with the current network pharmacology are discussed and prospects of its future development are put forward.

Predictive value of live birth rate based on different intrauterine adhesion evaluation systems following TCRA.

OBJECTIVE: The aim of this study was to assess the predictive value of five different intrauterine adhesion (IUA) evaluation systems for live birth rate following transcervical resection of adhesion (TCRA). METHOD: This retrospective study included 128 women with IUA who desired for spontaneous conception after TCRA. All the patients were retrospectively scored by the American Fertility Society (AFS) classification, European Society of Gynecological Endoscopy (ESGE) classification, March's classification (March), Nasr classification (Nasr) and Chinese IUA diagnosis classification criteria (Chinese). The predictive value of these evaluation systems was determined by receiver operating characteristic (ROC) curves and area under a ROC curve (AUC). RESULTS: The correlation coefficients of AFS, ESGE, March, Nasr and Chinese classification and the live birth rate were 0.313, 0.313, 0.288, 0.380, and 0.336, respectively. Among women with hypomenorrhea and amenorrhea, as well as women with no infertility, the severities determined by all five evaluation systems were correlated with live birth rate (P <  0.001). All five scoring systems were efficient to predict live birth rate. Among them, Nasr classification showed the highest AUC (0.748) with the best predictive value. Multivariate logistic regression analyses showed that Nasr classification had the highest OR (OR, 6.523; 95% CI, 2.612, 18.263). And, Nasr's classification system also showed highest sensitivity (81.8%) and negative predictive value (96.7%) when divide the system into mild IUA vs. moderate and severe IUA. CONCLUSION: AFS, ESGE, March, Nasr and Chinese classification were demonstrated to be capable of predicting live birth following TCRA although the predictive capacities might be limited, and Nasr classification showed the highest predictive value of live birth.

Comparison of Combined Hemodialysis and Hemoperfusion with Hemoperfusion Alone in 106 Patients with Diabetic Ketoacidosis and Acute Renal Failure: A Retrospective Study from a Single Center in China.

BACKGROUND Acute kidney injury with acute renal failure is associated with severe diabetic ketoacidosis. This retrospective study was conducted at a single center in China and aimed to compare combined hemodialysis and hemoperfusion (hemodialysis+hemoperfusion) with hemoperfusion alone in 106 patients with diabetic ketoacidosis and acute renal failure. MATERIAL AND METHODS The 106 patients were divided into 2 groups according to different dialysis programs, with 53 cases in each group. Hemodialysis was performed using a single-pass 4008S FX8 HeLix-One hollow fiber hemodialyzer (Fresenius Medical Care, St. Wendel, Germany). Hemoperfusion was performed using HA130 resin adsorbents. RESULTS There were no significant differences in terms of sex, age, duration of diabetes, A1c, pH, and admission blood glucose between the 2 groups (P=0.54, 0.564, 0.53, 0.78, 0.82, 0.51). There were no significant differences in fasting blood glucose, blood urea nitrogen, osmotic pressure, and creatinine between the 2 groups before treatment (P=0.146, 0.978, 0.786, 0.983). After treatment, blood urea nitrogen and creatinine in the dual-treatment group were lower than in the control group, and the osmotic pressure was higher than that in the control group (P=0.000, 0.000, 0.000). The dual-treatment group experienced a lower prevalence of dizziness (5.7%), anemia (7.5%), bone pain (7.5%), hypertension (3.8%), and pruritus (5.7%) than the control group (P<0.05). CONCLUSIONS Compared with hemoperfusion alone, hemodialysis+hemoperfusion significantly reduced pruritus and anemia, improved renal function, and was associated with significantly fewer adverse events in patients with diabetic ketoacidosis and acute renal failure.

Nanostructured Iron Fluoride Derived from Fe-Based Metal-Organic Framework for Lithium Ion Battery Cathodes.

A comprehensive strategy for the morphological control of octahedral and spindle Fe-based metal-organic frameworks (Fe-MOFs) via microwave-assisted adjustment is proposed in this research. Afterward, in situ copyrolysis under N2 atmosphere contributes to the fabrication of two shape-maintained FeF3·0.33H2O nanostructures (named O-FeF3·0.33H2O and S-FeF3·0.33H2O, respectively) with confined hierarchical porosity and graphitized carbon skeleton. The lithium storage performances for the MOF-derived octahedral O-FeF3·0.33H2O and spindle S-FeF3·0.33H2O composites are investigated, and the prospective lithium storage mechanism is discussed. As a result, the main product of the porous O-FeF3·0.33H2O structure is found to be a promising cathode material for lithium ion batteries owing to its advantageous electrochemical capability. Even after being cycled over 1000 times at 2 C (1 C = 237 mAh g-1), the capacity attenuation rate of the as-prepared O-FeF3·0.33H2O electrode is as low as 0.039% per cycle. The combination of proper octahedral morphology and highly graphitized carbon modification can not only enhance the conductivity of the cathode but also promote the diffusion of Li+ effectively. The remarkable performance of octahedral O-FeF3·0.33H2O can be confirmed by the Li-ion diffusion coefficient (DLi+) calculation analysis and kinetics analysis of lithium storage behavior.

Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling-dependent manner.

Fibroblast growth factor 21 (FGF21) is important in glucose, lipid homeostasis and insulin sensitivity. However, it remains unknown whether FGF21 is involved in insulin expression and secretion that are dysregulated in type 2 diabetes mellitus (T2DM). In this study, we found that FGF21 was down-regulated in pancreatic islets of db/db mice, a mouse model of T2DM, along with decreased insulin expression, suggesting the possible involvement of FGF21 in maintaining insulin homeostasis and islet ß-cell function. Importantly, FGF21 knockout exacerbated palmitate-induced islet ß-cell failure and suppression of glucose-stimulated insulin secretion (GSIS). Pancreatic FGF21 overexpression significantly increased insulin expression, enhanced GSIS, improved islet morphology and reduced ß-cell apoptosis in db/db mice. Mechanistically, FGF21 promoted expression of insulin gene transcription factors and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, the major regulators of insulin secretion, as well as activating phosphatidylinositol 3-kinase (PI3K)/Akt signaling in islets of db/db mice. In addition, pharmaceutical inhibition of PI3K/Akt signaling effectively suppressed FGF21-induced expression of insulin gene transcription factors and SNARE proteins, suggesting an essential role of PI3K/Akt signaling in FGF21-induced insulin expression and secretion. Taken together, our results demonstrate a protective role of pancreatic FGF21 in T2DM mice through inducing PI3K/Akt signaling-dependent insulin expression and secretion.

Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides.

This work describes Ni-catalyzed cross-electrophile coupling of benzyl chloroformate derivatives with aryl iodides that generates a wide range of diaryl methane products. The mild reaction conditions merit the C-O bond radical fragmentation of benzyl chloroformates via halide abstraction or a single electron reduction by a Ni catalyst. This work offers a new substrate type for cross-electrophile couplings.

The Cardioprotective Effects of Remote Ischemic Conditioning in a Rat Model of Acute Myocardial Infarction.

BACKGROUND Cardiac remote ischemic conditioning (RIC) is a noninvasive cardioprotective method in ischemia-reperfusion injury and acute myocardial infarction (AMI). The aims of this study were to investigate the effects of RIC in a rat model of AMI. MATERIAL AND METHODS Adult male Sprague-Dawley rats included the AMI group that underwent ligation of the left anterior descending (LAD) coronary artery (n=24), the RIC group that consisted the AMI rat model treated with RIC once daily in the left hind limb until days 1, 7 and 14 (n=24), and the sham group (n=24). Myocardial infarct size was measured by routine histology with triphenyltetrazolium chloride (TTC) and Masson's trichrome histochemical staining for myocardial necrosis and fibrosis, respectively. Serum levels of Bcl-2, Bax, caspase-3, and inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptosis index was detected using the TUNEL assay. Spectrophotometry of the myocardium was used to identify mitochondrial complexes and myocardial ATP. RESULTS The RIC group showed improved cardiac hemodynamics, reduced the size of the myocardial infarction, upregulated expression of Bcl-2, and down-regulation of the levels of Bax, caspase-3, and iNOS, and reduced cardiac myocyte apoptosis and inhibited the opening of the mitochondrial permeability transition pore (MPTP). CONCLUSIONS In a rat model of AMI, RIC improved the hemodynamic index, reduce the levels of apoptosis and myocardial injury, and improved mitochondrial function.