Polyphosphide anion-mediated simultaneous P, Au co-alloying with Pd for anti-poisoning formic acid oxidation.

An innovative polyphosphide route is developed to synthesize a series of P-doped PdAu ternary alloys. The alloying of P and Au optimizes the electronic structure and reduces the back-donation of d electrons to CO. Meanwhile, the generation of CO is largely inhibited by the highly selective direct pathway arising from the synergistic electron/ligand effect of Au and P, leading to a remarkable anti-poisoning capability for formic acid oxidation.

Ni/Mn-Complex-Tethered Tetranuclear Polyoxovanadates: Crystal Structure and Inhibitory Activity on Human Hepatocellular Carcinoma (HepG-2).

Polyoxometalates (POMs) exhibit unique structural characteristics and excellent physical and chemical properties, which have attracted significant attention from scholars in the fields of anticancer research and chemotherapy. Herein, we successfully synthesized and structurally characterized two novel polyoxovanadates (POVs), denoted as POVs-1 and POVs-2, where [M(1-vIM)4]2[VV4O12]·H2O (M: NiII and MnII, 1-vinylimidazole abbreviated as 1-vIM) serve as ligands. The two POVs are isomeric and consist of fundamental structural units, each comprising one [V4O12]4- cluster, two [M(1-vIM)4]2+ cations, and one water molecule. Subsequently, we evaluated the cell viability of human hepatocellular carcinoma (HepG-2) cells treated with the synthesized POVs using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide) assay. And the changes in cell nucleus morphology, mitochondrial membrane potential (Δψm), and reactive oxygen species levels in HepG-2 exposed to POVs were monitored using specific fluorescent staining techniques. Both hybrid POVs showed potent inhibitory activities, induing apoptosis in HepG-2 cells along with significant mitochondria dysfunction and a burst of reactive oxygen species. Notably, the inhibitory effects of POVs-2 were more pronounced than those of POVs-1, which is primarily attributed to the different transition metal ions present. These findings underscore the intricate relationship between the metal components, structural characteristics, and the observed antitumor activities in HepG-2 cells.

Synthesis, Characterization and Application of Amine-Functionalized Hierarchically Micro-Mesoporous Silicon Composites for CO2 Capture in Flue Gas.

An efficient CO2 adsorbent with a hierarchically micro-mesoporous structure and a large number of amine groups was fabricated by a two-step synthesis technique. Its structural properties, surface groups, thermal stability and CO2 adsorption performance were fully investigated. The analysis results show that the prepared CO2 adsorbent has a specific hierarchically micro-mesoporous structure and highly uniformly dispersed amine groups that are favorable for the adsorption of CO2. At the same time, the CO2 adsorption capacity of the prepared adsorbent can reach a maximum of 3.32 mmol-CO2/g-adsorbent in the actual flue gas temperature range of 303-343 K. In addition, the kinetic analysis results indicate that both the adsorption process and the desorption process have rapid adsorption/desorption rates. Finally, the fitting of the CO2 adsorption/desorption experimental data by Avrami's fractional kinetic model shows that the CO2 adsorption rate is mainly controlled by the intra-particle diffusion rate, and the temperature has little effect on the adsorption rate.

Translation initiation site of mRNA is selected through dynamic interaction with the ribosome.

Initiation of protein synthesis from the correct start codon of messenger RNA (mRNA) is crucial to translation fidelity. In bacteria, the start codon is usually preceded by a 4- to 6-mer adenosine/guanosine-rich Shine­Dalgarno (SD) sequence. Both the SD sequence and the start codon comprise the core ribosome-binding site (RBS), to which the 30S ribosomal subunit binds to initiate translation. How the rather short and degenerate information inside the RBS can be correctly accommodated by the ribosome is not well understood. Here, we used single-molecule techniques to tackle this long-standing issue. We found that the 30S subunit initially binds to mRNA through the SD sequence, whereas the downstream RBS undergoes dynamic motions, especially when it forms structures. The mRNA is either dissociated or stabilized by initiation factors, such as initiation factor 3 (IF3). The initiator transfer RNA (tRNA) further helps the 30S subunit accommodate mRNA and unwind up to 3 base pairs of the RBS structure. Meanwhile, the formed complex of the 30S subunit with structured mRNA is not stable and tends to disassociate. IF3 promotes dissociation by dismissing the bound initiator tRNA. Thus, initiation factors may accelerate the dynamic assembly­disassembly process of 30S­mRNA complexes such that the correct RBS can be preferentially selected. Our study provides insights into how the bacterial ribosome identifies a typical translation initiation site from mRNA.

Selective inhibition reveals the regulatory function of DYRK2 in protein synthesis and calcium entry.

The dual-specificity tyrosine phosphorylation-regulated kinase DYRK2 has emerged as a critical regulator of cellular processes. We took a chemical biology approach to gain further insights into its function. We developed C17, a potent small-molecule DYRK2 inhibitor, through multiple rounds of structure-based optimization guided by several co-crystallized structures. C17 displayed an effect on DYRK2 at a single-digit nanomolar IC50 and showed outstanding selectivity for the human kinome containing 467 other human kinases. Using C17 as a chemical probe, we further performed quantitative phosphoproteomic assays and identified several novel DYRK2 targets, including eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and stromal interaction molecule 1 (STIM1). DYRK2 phosphorylated 4E-BP1 at multiple sites, and the combined treatment of C17 with AKT and MEK inhibitors showed synergistic 4E-BP1 phosphorylation suppression. The phosphorylation of STIM1 by DYRK2 substantially increased the interaction of STIM1 with the ORAI1 channel, and C17 impeded the store-operated calcium entry process. These studies collectively further expand our understanding of DYRK2 and provide a valuable tool to pinpoint its biological function.

Boosting the anti-poisoning ability of palladium towards electrocatalytic formic acid oxidation via polyphosphide chemistry.

In this work, we reported a novel polyphosphide strategy for the synthesis of phosphorus doped Pd (P-Pd) using red phosphorus as the starting material at quasi-ambient conditions. Polyphophide anions, as the key reaction intermediates, served as the reducing agent and phosphorus source to modulate the surface electronic structure of Pd. The P-Pd obtained exhibited topmost CO tolerance and electrocatalytic activity to formic acid oxidation among the state-of-arts reports. The mass activity and turnover frequency of P-Pd reached 4413 mA mg-1Pd and 16.04 s-1 at 0.8 V, which were 23.7 and 6.4 times that of commercial Pd/C respectively. After 1000 repeated cycles, 82% initial activity was reserved. Combined with the electrochemical analysis and the density functional theory calculation, the boosted electrochemical performances can be attributed to the size and electronic effects induced by the P doping, which increase the surface actives sites, inhibit the adsorption of CO and change the reaction pathway to favorable CO2 route. A full cell was also assembled to demonstrate the practical potential of the P-Pd, which showed a maximum power density of 21.56 mW cm-2. This polyphophide-based reaction route provides a new strategy for the preparation of efficient and durable phosphorus doped alloys for electrocatalysis.

Bone marrow-derived mesenchymal stem cells-secreted exosomal microRNA-192-5p delays inflammatory response in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease closely correlated to synovial tissue inflammation. Exosomes are known to transfer microRNAs (miRNAs) between cells and have been validated as the vehicles for delivery of therapeutic molecules. AIM AND SCOPE: The current study was set to examine the functional values of bone marrow-derived mesenchymal stem cells (BMSCs)-secreted exosomal miR-192-5p (exo-miR-192-5p) on inflammation in RA. METHODS: Following the screening of differentially expressed genes in RA and miRNA-mRNA target prediction, BMSCs were infected with lentivirus expressing miR-192-5p to obtain miR-192-5p-overexpressed exosomes. To study the effect of exo-miR-192-5p on the expression of ras-related C3 botulinum toxin substrate 2 (RAC2), collagen-induced arthritis (CIA) rat models were established, and the clinical and histopathological changes were evaluated in the rats injected with exosomes. Subsequently, the expression patterns of pro-inflammatory factors were determined by ELISA. RESULTS: miR-192-5p was found to be down-regulated, while RAC2 was up-regulated in RA samples. Bioinformatics prediction revealed that the up-regulated RAC2 in RA may be regulated by miR-192-5p, which was further confirmed by dual luciferase reporter gene assay. The clinical arthritic scores, joint destruction, and inflammatory response were reduced after the injection of exosomes in rats with CIA targeting RAC2, and the treatment efficacy was even better with miR-192-5p-overexpressed exosomes. CONCLUSION: Our study established that the BMSCs-secreted exosomal miR-192-5p can delay the event of the inflammatory response in RA and may represent a possible therapeutic strategy for the treatment of RA.

Bouveret syndrome: A case report.

BACKGROUND: Bouveret syndrome is a rare complication of cholelithiasis, with only 315 cases reported in the literature between 1967 and 2016. Delay in diagnosis is associated with a high mortality rate. Diagnosis is based upon clinical manifestations, gastroscopy, and imaging studies such as abdominal computed tomography and magnetic resonance cholan-giopancreatography. Endoscopic stone extraction or lithotripsy is the preferred choice for treatment as it is safe and minimally invasive with few complications. However, if endoscopy fails, surgery is required. CASE SUMMARY: A 61-year-old female patient presented with recurrent epigastric pain for more than 6 mo. On endoscopy, a large amount of food residue was present in the stomach with multiple stones and ulcers in the antro-pyloric region. Based on these findings, a diagnosis of gastrolithiasis was made. However, computed tomography of the abdomen revealed the correct diagnosis of Bouveret syndrome. Initially, endoscopic treatment was attempted but it failed. Later, she was successfully managed by cholecystectomy with duodenal stone extraction and fistula repair (one-step method). At the last follow-up 6 mo after surgery, the patient was symptom-free. CONCLUSION: Bouveret syndrome is a rare complication of gallstones that requires prompt endoscopic or surgical treatment to prevent mortality.

Coordination among tertiary base pairs results in an efficient frameshift-stimulating RNA pseudoknot.

Frameshifting is an essential process that regulates protein synthesis in many viruses. The ribosome may slip backward when encountering a frameshift motif on the messenger RNA, which usually contains a pseudoknot structure involving tertiary base pair interactions. Due to the lack of detailed molecular explanations, previous studies investigating which features of the pseudoknot are important to stimulate frameshifting have presented diverse conclusions. Here we constructed a bimolecular pseudoknot to dissect the interior tertiary base pairs and used single-molecule approaches to assess the structure targeted by ribosomes. We found that the first ribosome target stem was resistant to unwinding when the neighboring loop was confined along the stem; such constrained conformation was dependent on the presence of consecutive adenosines in this loop. Mutations that disrupted the distal base triples abolished all remaining tertiary base pairs. Changes in frameshifting efficiency correlated with the stem unwinding resistance. Our results demonstrate that various tertiary base pairs are coordinated inside a highly efficient frameshift-stimulating RNA pseudoknot and suggest a mechanism by which mechanical resistance of the pseudoknot may persistently act on translocating ribosomes.

A novel monoclonal antibody against cannabinoid receptor 1.

The cannabinoid receptor 1 (CBR1) is being widely investigated because of its specific structure and functions compared with other cannabinoid receptors. In this study, we immunized BALB/c mice with synthesized human CBR1 polypeptide and obtained a novel monoclonal antibody (MAb) against human CBR1. Analysis through enzyme-linked immunosorbent assay (ELISA), spot-ELISA, Western blot, and immunohistochemistry revealed that the MAb was specifically against recombinant human CBR1 protein, and its subtype and affinity constant (Kaff) were IgG2b/k and 7.85 × 10(8) M/L, respectively. Using this MAb we found that CBR1 is expressed on HL-7702 cells and lipid tissue, raising the possibility that the CBR1 may take a role in glucose and lipid metabolism. Thus, this antibody might facilitate studies for pathophysiology of diseases associated with glucose and lipid metabolism abnormality.

Overexpression of the c-Myb but not its leukemogenic mutant DNA-binding domain increased adipogenic differentiation in mesenchymal stem cells.

The c-Myb protein is a vital transcription factor that regulates the differentiation of hematopoietic cells. Previous works have noticed that c-Myb is involved in an epigenetic control mechanism, in which the c-Myb DNA-binding domain (DBD) binds to the N-terminal histone tail of H3 to facilitate it acetylation and activate endogenous differentiation genes, while the leukemogenic mutant of c-Myb does not have these functions. However, whether c-Myb has corresponding biologic functions on the differentiation of other cells except for hematopoietic cells has not been explored. In our studies, we constructed the c-Myb wild type and its leukemogenic mutant DBD recombinant adenovirus with replication-defective adenoviral vectors carrying the GFP gene. We compared their roles on adipogenic differentiation efficiency in human bone marrow-derived mesenchymal stem cells (hMSCs). Our results demonstrated that the overexpression of c-Myb could enhance adipogenic differentiation in hMSCs, while the overexpression of its leukemogenic mutant blocked the adipogenic differentiation to a certain extent. These suggest that c-Myb play an important role in the hMSCs differentiation too, which is consistent with the epigenetic control mechanism of c-Myb.

p38 MAPK and NF-kappaB pathways are involved in naphtho[1,2-b] furan-4,5-dione induced anti-proliferation and apoptosis of human hepatoma cells.

Naphtho[1,2-b] furan-4,5-dione (NFD) was investigated for its anti-proliferation effect on human hepatocellular carcinoma (HCC), Hep3B, HepG(2), and Huh-7 cells. The effect of NFD on inhibiting proliferation and apoptosis was correlated with up-regulation of pro-apoptotic protein and down-regulation of pro-survival proteins. Remarkably, we found that NFD inhibited the nuclear translocation of NF-kappaB, likely accounting for the down-regulation of pro-survival Bcl-2 family. Furthermore, suppression of p38 MAPK activity by a specific inhibitor significantly rescued the cell proliferation inhibited by NFD. These findings suggest that signaling imbalance between p38 MAPK and NF-kappaB by NFD results in the proliferative inhibition and apoptosis of HCC tumor cells.

The c-Myb functions as a downstream target of PDGF-mediated survival signal in vascular smooth muscle cells.

Apoptosis of vascular smooth muscle cell (VSMC) is one of the major pathologic features in atherosclerosis. The platelet-derived growth factor (PDGF) pathway has been shown to provide survival signals in VSMCs and PDGF receptors are also highly expressed in VSMCs contained in the plaques of atherosclerosis. However, the downstream targets of PDGF signaling are unclear. In the current study, we show that PDGF signals stimulate the protein expression of c-Myb in human arterial VSMCs. Inhibition of c-Myb function in VSMCs enhanced apoptosis in PDGF treated VSMCs. Our data suggest that c-Myb functions as a downstream target of the PDGF survival pathway and suggest that c-Myb plays an essential role in adult VSMC survival.

[Relationship between apoptosis of rat hippocampus cells induced by aluminum and the copy of the bcl-2 as well as bax mRNA].

OBJECTIVE: To explore the effects of aluminum chloride (AlCl3) on the apoptosis of rat hippocampus cells and the relationship between the apoptosis and the expression of the bcl-2 as well as bax mRNA. METHODS: 40 SD rats, adult and healthy, were divided into 4 groups randomly: normal saline, Al3+ 2.5 mg/kg, 5 mg/kg, 10 mg/kg. They were exposed to AlCl, by intraperitioneal injection at the dose of 0.2 ml/d for 60 days. After exposure, the apoptosis of hippocampus cells were measured by method of TUNEL. The expression of bcl-2 mRNA and bax mRNA in rats' hippocampus were measured by RT-PCR. The results were analyzed by the gelatum analyzing system. RESULTS: The rates of apoptosis in hippocampus cells in Al3+ 5 mg/kg group and Al3+ 10 mg/kg group were significantly higher than that of controls (P < 0.05). But Al3+ 2.5 mg/kg group was not significantly higher than that of control (P > 0.05), and was significantly decreased in hippocampus cells in Al3+ 5 mg/kg and 10 mg/kg group compared with the control group (P < 0.05). The expression of bcl-2 mRNA was significantly decreased in every aluminum treatment group compared with the control group (P < 0.05). The expression of bax mRNA was significantly increased in every aluminum treatment group compared with the control group (P < 0.05). There was negative correlation between AI and the expression of Bcl-2 (r = -0.909, P < 0.01). There was positive correlation between Al and the expression of Bax (r = 0.871, P < 0.01). CONCLUSION: Aluminum can induce apoptosis in rat hippocampus cells through the downwards regulation of bcl-2 mRNA, the upwards regulation of bax mRNA expression.

[Alteration of neurobehavioral and autonomic nervous function in aluminum electrolytic workers].

In order to explore the impairment of Aluminum on the neurobehavioral, autonomic nervous function. Neurobehavioral test battery (NCTB) recommended by WHO and autonomic nervous system (ANS) function test recommended by Ewing DJ were conducted in 32 Al electrolytic workers and 34 controls. Results showed that the scores of confusion-bewilderment and tension-anxious in Al exposed workers were higher than that of control group, while the scores of POMSA, POMSD, POMSF and POMSV in Al-exposed group had no obvious change. The scores of DSY, PA and PAC were lower than that of control group. The scores of DSPF, DDSPB, DSP, SANN, SANP and BVR had no significant alteration. R-R interval variability of maximin ratio of immediate standing up, which reflects parasympathetic nervous modification ability in aluminum electrolytic workers, was lower than that of the control group. This implied that Al exposure had adverse impact on workers' mood state, neurobehavioral and parasympathetic nervous function.