DrugSK: A Stacked Ensemble Learning Framework for Predicting Drug Combinations of Multiple Diseases.

Combination therapy is an important direction of continuous exploration in the field of medicine, with the core goals of improving treatment efficacy, reducing adverse reactions, and optimizing clinical outcomes. Machine learning technology holds great promise in improving the prediction of drug synergy combinations. However, most studies focus on single disease-oriented collaborative predictive models or involve excessive feature categories, making it challenging to predict the majority of new drugs. To address these challenges, the DrugSK comprehensive model was developed, which utilizes SMILES-BERT to extract structural information from 3492 drugs and trains on reactions from 48,756 drug combinations. DrugSK is an integrated learning model capable of predicting interactions among various drug categories. First, the primary learner is trained from the initial data set. Random forest, support vector machine, and XGboost model are selected as primary learners and logistic regression as secondary learners. A new data set is then "generated" to train level 2 learners, which can be thought of as a prediction for each model. Finally, the results are filtered using logistic regression. Furthermore, the combination of the new antibacterial drug Drafloxacin with other antibacterial agents was tested. The synergistic effect of Drafloxacin and Isavuconazonium in the fight against Candida albicans has been confirmed, providing enlightenment for the clinical treatment of skin infection. DrugSK's prediction is accurate in practical application and can also predict the probability of the outcome. In addition, the tendency of Drafloxacin and antifungal drugs to be synergistic was found. The development of DrugSK will provide a new blueprint for predicting drug combination synergies.

Affinity Purification of Angiotensin Converting Enzyme Inhibitory Peptides from Wakame (Undaria Pinnatifida) Using Immobilized ACE on Magnetic Metal Organic Frameworks.

Angiotensin-I-converting enzyme (ACE) inhibitory peptides derived from marine organism have shown a blood pressure lowering effect with no side effects. A new affinity medium of Fe3O4@ZIF-90 immobilized ACE (Fe3O4@ZIF-90-ACE) was prepared and used in the purification of ACE inhibitory peptides from Wakame (Undaria pinnatifida) protein hydrolysate (<5 kDa). The Fe3O4@ZIF-90 nanoparticles were prepared by a one-pot synthesis and crude ACE extract from pig lung was immobilized onto it, which exhibited excellent stability and reusability. A novel ACE inhibitory peptide, KNFL (inhibitory concentration 50, IC50 = 225.87 µM) was identified by affinity purification using Fe3O4@ZIF-90-ACE combined with reverse phase-high performance liquid chromatography (RP-HPLC) and MALDI-TOF mass spectrometry. Lineweaver-Burk analysis confirmed the non-competitive inhibition pattern of KNFL, and molecular docking showed that it bound at a non-active site of ACE via hydrogen bonds. This demonstrates that affinity purification using Fe3O4@ZIF-90-ACE is a highly efficient method for separating ACE inhibitory peptides from complex protein mixtures and the purified peptide KNFL could be developed as a functional food ingredients against hypertension.

Synthesis and evaluation of 3-(4-(phenoxymethyl)phenyl)propanoic acid and N-phenylbenzenesulfonamide derivatives as FFA4 agonists.

Free fatty acid receptor 4 (FFA4) has been recognized as an attractive target in metabolic diseases. To find potent and selective FFA4 agonist, 28 compounds of 3-(4-(phenoxymethyl)phenyl)propanoic acid and N-phenylbenzenesulfonamide derivatives were designed and synthesized, featuring OC and SO2-N linkage. For the OC linkage compounds, 1g showed the most potent FFA4 agonistic activity with a pEC50 of 5.81 ± 0.04 and exhibited at least 64-fold selectivity against FFA1. For SO2-N linkage agonists, 2m had a pEC50 of 5.66 ± 0.04 and displayed>46-fold selectivity against FFA1. Among these two series of compounds, 1g was the most potent agonist at FFA4 and the best selectivity against FFA1, demonstrated by docking simulation. Moreover, 1g showed receptor selectivity on other seven GPCRs. In anti-diabetic evaluation, 1g dose-dependently reduced blood glucose, which was better than a clinical phase III drug TAK875. This study provides guidance for FFA4 ligand design and drug optimization.

Effects of MTNR1B Genetic Variants on Individual Susceptibility to Gestational Diabetes Mellitus: A Meta-Analysis.

OBJECTIVE: Whether melatonin receptor 1B (MTNR1B) variants are implicated in gestational diabetes mellitus (GDM) remains unclear. Therefore, we performed this meta-analysis to obtain a more conclusive result on associations between MTNR1B variants and GDM. STUDY DESIGN: Literature research was performed in PubMed, Web of Science, Embase, and China National Knowledge Infrastructure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 17 studies were eligible for analyses. Pooled overall analyses showed that rs1387153 (dominant model: p = 0.0002, OR = 0.78, 95% CI: 0.68-0.89; recessive model: p < 0.0001, OR = 1.46, 95% CI: 1.24-1.73; allele model: p < 0.0001, OR = 0.78, 95% CI: 0.72-0.84), rs4753426 (recessive model: p = 0.01, OR = 1.75, 95% CI: 1.14-2.68; allele model: p = 0.01, OR = 0.69, 95% CI: 0.51-0.93), and rs10830963 (dominant model: p < 0.0001, OR = 0.72, 95% CI: 0.65-0.78; recessive model: p < 0.0001, OR = 1.56, 95% CI: 1.40-1.74; allele model: p < 0.0001, OR = 0.73, 95% CI: 0.69-0.78) variants were all significantly associated with the susceptibility to GDM. Further subgroup analyses by ethnicity of participants yielded similar positive results. CONCLUSION: Our findings indicated that MTNR1B rs1387153, rs4753426, and rs10830963 variants might serve as genetic biomarkers of GDM.

Modified kyphoplasty with controllable balloon dilatation for treatment of thoracolumbar osteoporotic vertebral compression fractures.

PURPOSE: To investigate the surgical effects of modified kyphoplasty with controllable balloon dilatation for treatment of thoracolumbar osteoporotic vertebral compression fractures (OVCF). METHODS: From April 2013 to October 2017, a total of 53 patients with thoracolumbar OVCF were treated with controllable balloon percutaneous kyphoplasty (C-PKP). Peri-operative parameters including days from injury to operation, operation time, injected cement volume, cement leakage and complications were collected. Visual analogue scale (VAS) and Cobb angle before and after operation were applied to evaluate surgical effects. Moreover, a total of 53 cases treated with traditional balloon of percutaneous kyphoplasty were retrospectively analyzed and compared with C-PKP in above parameters. RESULTS: C-PKP achieved significant fewer events of cement leakage (type C) than that of traditional PKP (5/53 vs 13/53, p < 0.01). The patients were followed up for 10.8 ± 4.2 months; VAS and Cobb angle of the injured vertebra in both two groups at three days and final follow-up were significantly improved compared with that before surgery (p < 0.05), while there were no significant differences between the two groups regarding the VAS and Cobb angle at corresponding time points (p > 0.05). CONCLUSIONS: C-PKP technology is a safe and efficient way for the treatment of thoracolumbar OVCF, and it can reduce cement leakage.

[Correlations between lipid ratio/oxidative stress status in COPD patients and pulmonary hypertension as well as prognosis].

OBJECTIVE: To investigate the correlations between lipid ratio/oxidative stress status in chronic obstructive pulmonary disease (COPD) patients and pulmonary hypertension as well as the prognosis.
 Methods: A total of 120 patients with COPD were randomly selected and served as the COPD group and 30 healthy persons were selected as the control group. The ratios of low density lipoprotein (LDL)/high-density lipoprotein (HDL), triglyceride (TG)/HDL and total cholesterol (TC)/HDL were measured. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) level in the control group and COPD patients were detected. Pulmonary hypertension incidence and 3-year survival rate for COPD patients were statistically analyzed. Spearman rank correlation method was used to analyze relationship between lipid ratio /oxidative stress status and pulmonary hypertension.
 Results: Compared with control group, the ratios of LDL/HDL, TG/HDL and TC/HDL, and the serum MDA level in the COPD group were increased, while the serum SOD and T-AOC level in the COPD group were decreased; compared with stable period, lipid ratios and MDA levels in the acute period were elevated, while serum SOD and T-AOC levels were reduced (P<0.05). Pulmonary hypertension incidence and 3-year survival rates in the COPD group were 56.67% and 81.67% respectively; the lipid ratios and serum MDA levels in COPD patients with pulmonary hypertension were elevated compared with that in COPD patients without pulmonary hypertension; the serum SOD and T-AOC levels in COPD patients with pulmonary hypertension were reduced compared with that in patients without pulmonary hypertension (P<0.05). Spearman rank correlation analysis showed that ratios of LDL/HDL, TG/HDL and TC/HDL, and the serum MDA levels in COPD patients were positively correlated with 3-years pulmonary hypertension incidence (r=0.752, 0.748, 0.752, 0.748; P<0.05), and negatively correlated with 3-years survival rate (r=-0.722, -0.751, -0.736, -0.748; P<0.05); serum SOD and T-AOC levels in COPD patients were negatively correlated with 3-years pulmonary hypertension (r=-0.711, -0.734; P<0.05), and positively correlated with 3-year survival rate (r=0.726, 0.733; P<0.05). 
 Conclusion: Blood lipid ratio and oxidative stress levels in COPD patients are elevated while antioxidant abilities were attenuated. The lipid ratio and oxidative stress status in COPD patients is closely related to the prognosis of pulmonary hypertension. Therefore, blood lipid ratio and oxidative stress status may be used in evaluation of pulmonary hypertension and prognosis for COPD patients.

[Plasma level of chemerin in COPD patients and the relationship between chemerin and lipid metabolism].

OBJECTIVE: To explore the change of plasma level of chemerin in chronic obstructive pulmonary disease (COPD) patients and its relationship with lipid metabolism. 
 METHODS: A total of 150 COPD patients were randomly selected and set as the COPD group and 30 healthy persons were set as the control group. The COPD group was further divided into a thin group (BMI<18.5 kg/m2, n=116) and a normal weight group (BMI≥18.5 kg/m2, n=34) according to their body mass index (BMI). Enzyme-linked immunosorbent (ELISA) was used in detection of plasma chemerin, total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high-density lipoprotein (HDL). The hospitalization rate in a half year and the mortality was statistically analyzed. Pearson correlation analysis was applied to analyze the relationship between plasma level of chemerin and levels of blood lipids, and Spearman rank correlation method was used to analyze the relationship between the plasma levels of chemerin or lipids and the prognosis. 
 RESULTS: Compared with the control group, plasma levels of TC, TG and HDL in the COPD group in acute exacerbation and remission stage were reduced, while plasma levels of chemerin and LDL was elevated; compared with the thin group, plasma levels of TC, TG and HDL in the normal weight group were elevated, while plasma levels of chemerin and LDL were decreased. The hospitalization rate in half year and the mortality in the thin group were higher than that in the normal weight group, and the plasma levels of TC, TG and HDL in the COPD patients with hospitalization in half year or death were lower than that in COPD patients without hospitalization, while the plasma levels of chemerin and LDL was increased (P<0.05). Pearson correlation analysis showed that plasma level of chemerin in COPD patients was negatively correlated with plasma levels of TC, TG and HDL (r=-0.695, -0.748, -0.695, P<0.05), while positively correlated with plasma levels of LDL (r=0.668, P<0.05). Spearman rank correlation analysis showed that plasma levels of TC, TG and HDL in COPD patients and hospitalization rate in half year as well as the mortality were negatively correlated (TC: r=-0.716, -0.737; TG: r=-0.748, -0.753; HDL: r=-0.736, -0.728, P<0.05), while the plasma level of chemerin or LDL and hospitalization rate in half year and the mortality were positively correlated (chemerin: r=0.753, 0.766; LDL: r=0.742, 0.755, P<0.05).
 CONCLUSION: Plasma levels of chemerin in the COPD patients are correlated with lipid metabolism. Plasma levels of chemerin and lipid are related to prognosis of COPD. The plasma levels of chemerin in patients with COPD may reflect the lipid metabolism and could be served as the index for prognostic evaluation.

Image detection of aortic dissection complications based on multi-scale feature fusion.

Background: Aortic dissection refers to the true and false two-lumen separation of the aortic wall, in which the blood in the aortic lumen enters the aortic mesomembrane from the tear of the aortic intima to separate the mesomembrane and expand along the long axis of the aorta. Purpose: In view of the problems of individual differences, complex complications and many small targets in clinical aortic dissection detection, this paper proposes a convolution neural network MFF-FPN (Multi-scale Feature Fusion based Feature Pyramid Network) for the detection of aortic dissection complications. Methods: The proposed model uses Resnet50 as the backbone for feature extraction and builds a pyramid structure to fuse low-level and high-level feature information. We add an attention mechanism to the backbone network, which can establish inter-dependencies between feature graph channels and enhance the representation quality of CNN. Results: The proposed method has a mean average precision (MAP) of 99.40% in the task of multi object detection for aortic dissection and complications, which is higher than the accuracy of 96.3% on SSD model and 99.05% on YoloV7 model. It greatly improves the accuracy of small target detection such as cysts, making it more suitable for clinical focus detection. Conclusions: The proposed deep learning model achieves feature reuse and focuses on local important information. By adding only a small number of model parameters, we are able to greatly improve the detection accuracy, which is effective in detecting small target lesions commonly found in clinical settings, and also performs well on other medical and natural datasets.

Kinetic Model for Denitration Reaction Process of Cylindrical Single-Base Gun Propellant.

As a new type of progressive energy release propellant, nitro gradiently distributed propellant (NGDP) was prepared by a denitration reaction between a denitration reagent and the propellant to remove the energy-containing functional group (-O-NO2) from the surface of the propellant. The kinetics of the denitration reaction determines distribution of the nitrate group in the surface layer of NGDP, which further affects the combustion progressivity. In this paper, the kinetic model for the denitration reaction process of the cylindrical single-base gun propellant was studied by the shrinking unreacted core model (SUC model). The energy change of the propellant particles before and after the denitration reaction was used to evaluate the denitration rates, which were used to fit the proposed SUC cylindrical model. The results show that the rate-controlling step of the denitration reaction process is largely dependent on the concentration of the denitration reagent. At low concentrations (the concentration of the denitration reagent was 6%), the denitration reaction process was controlled by the chemical reaction, and the activation energy was found to be 48.40 kJ·mol-1. When the concentration increased (the concentration of the denitration reagent was 15%), the rate-controlling step changed to a solid product layer diffusion control with an activation energy of 84.77 kJ·mol-1. The kinetic models obtained in this study can provide theoretical guidance for the controlled preparation of NGDP with good combustion progressivity.

Synergy of metal nanoparticles and organometallic complex in NAD(P)H regeneration via relay hydrogenation.

Most, if not all, of the hydrogenation reactions are catalyzed by organometallic complexes (M) or heterogeneous metal catalysts, but to improve both the activity and selectivity simultaneously in one reaction via a rational combination of the two types of catalysts remains largely unexplored. In this work, we report a hydrogenation mode though H species relay from supported metal nanoparticles (NPs) to M, where the former is responsible for H2 dissociation, and M is for further hydride transferring to reactants. The synergy between metal NPs and M yields an efficient NAD(P)H regeneration system with >99% selectivity and a magnitude higher activity than the corresponding metal NPs and M. The modularizing of hydrogenation reaction into hydrogen activation with metal NPs and substrate activation with metal complex paves a new way to rationally address the challenging hydrogenation reactions.

Highly Conjugated Two-dimensional Covalent Organic Frameworks for Efficient Iodine Uptake.

Radioactive iodine in nuclear waste would be harmful to nature and human health. The design of adsorbents for iodine capture with high efficiency still remains a challenge. Herein, two highly conjugated two-dimensional covalent organic frameworks (TFPB-BPTA-COF and TFPB-PyTTA-COF) have been successfully constructed. Both COFs possess high porosity, stability, and a high π-conjugated framework. Impressively, TFPB-PyTTA-COF exhibits an excellent iodine uptake value of up to 5.6 g g-1 , which is superior to most reported COF-based adsorbents for iodine capture.

The promotion effect of π-π interactions in Pd NPs catalysed selective hydrogenation.

The utilization of weak interactions to improve the catalytic performance of supported metal catalysts is an important strategy for catalysts design, but still remains a big challenge. In this work, the weak interactions nearby the Pd nanoparticles (NPs) are finely tuned by using a series of imine-linked covalent organic frameworks (COFs) with different conjugation skeletons. The Pd NPs embedded in pyrene-COF are ca. 3 to 10-fold more active than those in COFs without pyrene in the hydrogenation of aromatic ketones/aldehydes, quinolines and nitrobenzene, though Pd have similar size and surface structure. With acetophenone (AP) hydrogenation as a model reaction, systematic studies imply that the π-π interaction of AP and pyrene rings in the vicinity of Pd NPs could significantly reduce the activation barrier in the rate-determining step. This work highlights the important role of non-covalent interactions beyond the active sites in modulating the catalytic performance of supported metal NPs.

Covalent organic frameworks with high quantum efficiency in sacrificial photocatalytic hydrogen evolution.

Organic semiconductors offer a tunable platform for photocatalysis, yet the more difficult exciton dissociation, compared to that in inorganic semiconductors, lowers their photocatalytic activities. In this work, we report that the charge carrier lifetime is dramatically prolonged by incorporating a suitable donor-acceptor (ß-ketene-cyano) pair into a covalent organic framework nanosheet. These nanosheets show an apparent quantum efficiency up to 82.6% at 450 nm using platinum as co-catalyst for photocatalytic H2 evolution. Charge carrier kinetic analysis and femtosecond transient absorption spectroscopy characterizations verify that these modified covalent organic framework nanosheets have intrinsically lower exciton binding energies and longer-lived charge carriers than the corresponding nanosheets without the donor-acceptor unit. This work provides a model for gaining insight into the nature of short-lived active species in polymeric organic photocatalysts.

The Fabrication of Pd Single Atoms/Clusters on COF Layers as Co-catalysts for Photocatalytic H2 Evolution.

The particle size of co-catalysts significantly affects the activity of semiconductors in photocatalysis. Herein, we report that the photocatalytic H2 evolution (PHE) activity of a visible light responsive covalent organic framework (COF) layer supported on SiO2 nanoparticles was greatly promoted from 47.7 to 85.5 µmol/h by decreasing the particle size of the Pd co-catalyst from 3.3 nm to single atoms/clusters. A PHE rate of 156 mmol gCOF-1 h-1 and apparent quantum efficiency up to 7.3% were achieved with the Pd SAs/Cs co-catalyst. The relationship between the activity of Pd in H2 dissociation, proton reduction, and PHE rate suggests that the promotion effect of Pd SAs/Cs is mainly attributed to their enhancement in charge separation of COF layers rather than proton reduction. Furthermore, a photoactive film was fabricated and steady production of H2 was achieved under visible light irradiation and static conditions. The optimization of the particle size of co-catalysts provides an efficient method for enhancing the photocatalytic activity of semiconductors.

Synthesis of Sulfonated Porous Organic Polymers with a Hydrophobic Core for Efficient Acidic Catalysis in Organic Transformations.

Synthesis of sulfonated porous polymers with improved hydrophobicity and stability is of extreme importance in both academic research and industrial applications. However, there is often a trade-off between acidity and surface hydrophobicity of sulfonated polymers. In this study, we report a strategy for the synthesis of sulfonated porous organic polymers (S-PT) with improved hydrophobicity via free radical polymerization method by using a rigid and large multidentate monomer, 1,3,5-tri(4-vinylphenyl)-benzene, having a hydrophobic core. The results of vapor adsorption measurement show that S-PT has more hydrophobic properties than sulfonated poly(divinylbenzene) (S-PD), attributed to the hydrophobic core of its multidentate monomer. Furthermore, the optimization of sulfonation time established a balance between surface acidity and hydrophobicity. Under optimized conditions, S-PT afforded up to 113 mmol g-1 h-1 TOF in the esterification of oleic acid with methanol, more active than commercial Amberlyst-15 with TOF of 15 mmol g-1 h-1 and Nafion NR50 with TOF of 7 mmol g-1 h-1 . We believe that the findings of this study will provide useful insights to advance the design and synthesis of solid acid catalysts for organic transformations.

Hydrogenation of benzoic acid derivatives over Pt/TiO2 under mild conditions.

Hydrogenation of benzoic acid (BA) to cyclohexanecarboxylic acid (CCA) has important industrial and academic significance, however, the electron deficient aromatic ring and catalyst poisoning by carboxyl groups make BA hydrogenation a challenging transformation. Herein, we report that Pt/TiO2 is very effective for BA hydrogenation with, to our knowledge, a record TOF of 4490 h-1 at 80 °C and 50 bar H2, one order higher than previously reported results. Pt/TiO2 catalysts with electron-deficient and electron-enriched Pt sites are obtained by modifying the electron transfer direction between Pt and TiO2. Electron-deficient Pt sites interact with BA more strongly than electron-rich Pt sites, helping the dissociated H of the carboxyl group to participate in BA hydrogenation, thus enhancing its activity. The wide substrate scope, including bi- and tri-benzoic acids, further demonstrates the high efficiency of Pt/TiO2 for hydrogenation of BA derivatives.

Non-covalent and covalent immobilization of papain onto Ti3C2 MXene nanosheets.

Papain was immobilized onto Ti3C2 MXene nanosheets by physical adsorption and physical adsorption combined with covalent crosslinking with glutaraldehyde. Ti3C2 MXene nanosheets were prepared by hydrofluoric acid etching method. The resulting products were well characterized by SEM, BET, XRD, FTIR, XPS. The optimized immobilization conditions are pH 6.5, immobilization time of 20 h, immobilization temperature of 10℃, and 10 mL 2 mg mL-1 papain, the amount of papain immobilized was 156 mg g-1, the activity of the immobilized papain determined was 1701 U∙g-1. The immobilized papain exhibited enhanced pH and temperature endurances, immobilized papain also showed improved storage stability (39.25 % and 65.57 % after 20 days of storage at 4 °C). papain reusability was significantly improved after immobilization and it retained more than 50 % of its initial activity after 5 repeated cycles. Interestingly, the results of immobilized enzymes demonstrated that the immobilization of enzymes on Ti3C2 MXene is feasible. Such approach could be transferred to other support systems for anchoring enzyme.

Dexmedetomidine Provides Protection Against Hippocampal Neuron Apoptosis and Cognitive Impairment in Mice with Alzheimer's Disease by Mediating the miR-129/YAP1/JAG1 Axis.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that leads to progressive cognitive, memory, and learning dysfunction that affects the aging population. Dexmedetomidine (Dex) might be beneficial for postoperative cognitive function in elderly patients. However, the exact mechanism underlying the protective role of Dex against cognitive impairment requires further elucidation. The present study aims to determine whether miR-129 is involved in the protective effect of Dex against Aß1-42-induced hippocampal neuron apoptosis and cognitive impairment in mice. In our study, Y-shaped maze and water maze tests were conducted to evaluate the cognitive function of AD mice, while neuronal apoptosis was measured by Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick-End Labeling (TUNEL) staining. The findings showed that Dex administration resulted in the enhancement of miR-129 expression with declined hippocampal neuron apoptosis and attenuated cognitive impairment in Aß1-42-injected mice. miR-129 targeted YAP1 and disrupted its interaction with JAG1, leading to a decline in hippocampal neuron apoptosis and attenuated cognitive impairment in Aß1-42-injected mice. In conclusion, the miR-129/YAP1/JAG1 axis could potentially be the mechanism by which Dex protects AD mice from cognitive impairment.

microRNA-222-Mediated VHL Downregulation Facilitates Retinoblastoma Chemoresistance by Increasing HIF1α Expression.

Purpose: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemoresistance is the major obstacle for treatment of these tumors. This study aims to determine whether or not downregulating microRNA-222 (miR-222) could serve as a potential therapeutic target for preventing chemoresistance in RB treatment. Methods: Differentially expressed miR-222 in RB samples and its downstream target genes were predicted using bioinformatics methods. The expression of miR-222 was altered by mimic or inhibitor to examine its role in RB cell in response to the chemotherapeutic agent vincristine (VCR). Further bioinformatic analysis predicted involvement of the stability of hypoxia-inducible factor 1α (HIF1α) protein in regulation of the von Hippel-Lindau (VHL) tumor suppressor, followed by characterization of the effect of VHL on the ubiquitin-proteasome degradation of HIF1α. Next, VHL or HIF1α was overexpressed to determine their effects on RB cell activities after VCR treatment. In vivo assays were performed on nude mice to further verify the in vitro results. Results: miR-222 is highly expressed in RB tissues and cells and was found to facilitate resistance of RB cells to VCR. Of note, miR-222 specifically bound to and negatively regulated VHL. VHL could inhibit the stability of HIF1α and promote the degradation of ubiquitin-proteasome, thus reducing HIF1α expression to attenuate VCR resistance in RB cells. Moreover, inhibition of miR-222 in combination with VCR suppressed tumor formation in nude mice. Conclusions: miR-222 promotes the expression of HIF1α by targeting VHL, thus accelerating the resistance of RB cells to the chemotherapeutic agent VCR.

Structural Engineering of Two-Dimensional Covalent Organic Frameworks for Visible-Light-Driven Organic Transformations.

Covalent organic frameworks (COFs) emerging as a novel kind of visible light-responsive organic semiconductor have attracted extensive research attention in the field of photocatalytic organic transformations. However, the key parameters affecting their photocatalytic properties are still not clear. In this work, a series of [3 + 3] COFs with similar two-dimensional hexagonal structure but different compositions are synthesized and employed as model materials for investigating the key factors affecting the photocatalytic properties in the visible-light-driven reductive dehalogenation reaction and the aerobic cross-dehydrogenative coupling reaction. In comparison with -H and -CF3, the -OH substituent in the aromatic ring could narrow the band gap of the COFs. The COFs with a triazine skeleton in the framework usually boost the photocatalytic activity, possibly because of the enhanced charge separation efficiency by the formation of a donor-acceptor domain. As a combined result of the narrow band gap, efficient charge separation, and high conductivity, the COF possessing both a -OH group and triazine skeleton shows the highest activity in the photocatalytic reductive dehalogenation reaction. Notably, COFs could be easily recovered and reused several times without the loss of crystallinity. Our primary results may shed light on the design of efficient COF-based semiconductors for photocatalytic organic transformations.