A novel microdeletion of 517 kb downstream of the PAX6 gene in a Chinese family with congenital aniridia.

BACKGROUND: To identify the disease-causing gene in a Chinese family affected with congenital aniridia. METHODS: Patients underwent systematic ophthalmic examinations such as anterior segment photography, fundus photography, optical coherence tomography, and fundus fluorescein angiography. The proband was screened for pathogenic variants by whole exome sequencing (WES) and copy number variant (CNV) analysis. Real-time quantitative PCR (RT-qPCR) was applied to confirm the CNV results. Breakpoints were identified by long-range PCR followed by Sanger sequencing. RESULTS: All seven members of this Chinese family, including four patients and three normal individuals, were recruited for this study. All patients showed bilateral congenital aniridia with nystagmus, except the son of the proband, who presented with bilateral partial coloboma of the iris. A novel heterozygous deletion (chr11:31,139,019-31,655,997) containing the 3' regulatory enhancers of the PAX6 gene was detected in this family. We also reviewed the reported microdeletions downstream of PAX6 in patients with aniridia. CONCLUSIONS: We identified a novel microdeletion, 517 kb in size located about 133 kb downstream of the PAX6 gene, responsible for congenital aniridia in this Chinese family, which expands the spectrum of aniridia-associated mutations in PAX6.

Detection of Corporate Environmental Information Disclosure Falsification Based on Support Vector Machine.

Environmental information disclosure (EID) is an important embodiment of corporate social responsibility. With the awakening of public awareness of environmental protection and the increasing pressure of environmental preservation, enterprises tend to strategically manipulate environmental information for the pursuit of profit, which will consequently lead to environmental information disclosure falsification (EIDF) and disruption of both the market regulatory order and the development of green economy. In this article, support vector machine (SVM) technique is applied to construct the detection model of corporate EIDF. Based on the theory of "public pressure," the detection indicators will be improved from three aspects: public pressure, corporate governance, and financial indicators. The training set and test set are constructed by combining the manually collected cases of environmental administrative penalties from 2015 to 2019 with the indicator information of nonfinancial listed enterprises in China's A-share market, and the SVM detection performance is compared with the logistic regression of the benchmark model. To solve the problem of category imbalance, we have introduced the Borderline-SMOTE oversampling technique. Based on the detection results of SVM and Borderline-SMOTE, we find that the Borderline-SMOTE-SVM model has the best detection performance, surpassing the SVM and logistic regression models. These conclusions have constructive policy implications for regulatory agencies, investors, the third-party service sector, enterprises, and government policy-making to achieve high-quality corporate EID.

Using Amphiphilic Polymer Micelles as the Templates of Antisolvent Crystallization to Produce Drug Nanocrystals.

Biocompatible and biodegradable amphiphilic polymeric micelles (PLA-CMCS-g-OA) were prepared by surface grafting of oleic acid and polylactic acid onto carboxymethyl chitosan and were used as templates for the crystallization of camptothecin. The camptothecin (CPT) nanocrystals prepared by the novel micelle-templated antisolvent crystallization (mt-ASC) method demonstrated higher crystallinity, narrower particle size distribution, and slower release characteristic than those prepared by conventional antisolvent crystallization (c-ASC) using a high initial concentration and fast addition rate. In particular, the CPT release behavior of mt-ASC products in phosphate buffer solutions presented a pH-responsive characteristic with the increasing release rate of CPT under lower pH conditions. This work confirmed that amphiphilic nanomicelle-templated crystallization was an effective method for preparing drug nanocrystals.

Catalytic Transformation of PET and CO2 into High-Value Chemicals.

Polyethylene terephthalate (PET) and CO2 , two chemical wastes that urgently need to be transformed in the environment, are converted simultaneously in a one-pot catalytic process through the synergistic coupling of three reactions: CO2 hydrogenation, PET methanolysis and dimethyl terephthalate (DMT) hydrogenation. More interestingly, the chemical equilibria of both reactions were shifted forward due to a revealed dual-promotion effect, leading to significantly enhanced PET depolymerization. The overall methanol yield from CO2 hydrogenation exceeded the original thermodynamic equilibrium limit since the methanol was in situ consumed in the PET methanolysis. The degradation of PET by a stoichiometric ratio of methanol was significantly enhanced because the primary product, DMT was hydrogenated to dimethyl cyclohexanedicarboxylate (DMCD) or p-xylene (PX). This synergistic catalytic process provides an effective way to simultaneously recycle two wastes, polyesters and CO2 , for producing high-value chemicals.

Accurately Controlled Delivery of Temozolomide by Biocompatible UiO-66-NH2 Through Ultrasound to Enhance the Antitumor Efficacy and Attenuate the Toxicity for Treatment of Malignant Glioma.

BACKGROUND: Glioma is the most common and malignant primary brain tumour in adults and has a dismal prognosis. Temozolomide (TMZ) is the only clinical first-line chemotherapy drug for malignant glioma up to present. Due to poor aqueous solubility and toxic effects, TMZ is still inefficient and limited for clinical glioma treatment. METHODS: UiO-66-NH2 nanoparticle is a zirconium-based framework, constructed by Zr and 2-amino-1,4-benzenedicarboxylic acid (BDC-NH2) with octahedral microporous structure, which can be decomposed by the body into an ionic form to discharge. We prepared the nanoscale metal-organic framework (MOF) of UiO-66-NH2 to load TMZ for therapy of malignant glioma, TMZ is released from UiO-66-NH2 through a porous structure. The ultrasound accelerates its porous percolation and promotes the rapid dissolution of TMZ through low-frequency oscillations and cavitation effect. The biological safety and antitumor efficacy were evaluated both in vitro and in vivo. RESULTS: The prepared TMZ@MOF exhibited excellent biocompatibility and biosafety due to minimal drug leakage without ultrasound intervention. We further used the flank model of glioblastoma to verify the in vivo therapeutic effect. TMZ@UiO-66-NH2 nanocomposites could be well delivered to the tumour tissue, which led to local enrichment of the TMZ concentration. Furthermore, TMZ@UiO-66-NH2 nanocomposites under ultrasound demonstrated much more efficient inhibition for tumor growth than TMZ@UiO-66-NH2 nanocomposites and TMZ alone. Meanwhile, the bone marrow suppression side effects of TMZ were significantly reduced by TMZ@UiO-66-NH2 nanocomposites. CONCLUSION: In this work, TMZ@UiO-66-NH2 nanocomposites with ultrasound mediation could effectively improve the killing effect of malignant glioma and decrease TMZ-induced toxicity in normal tissues, demonstrating great potential for the delivery of TMZ in the clinical treatment of malignant gliomas.

A biocompatible theranostic agent based on stable bismuth nanoparticles for X-ray computed tomography/magnetic resonance imaging-guided enhanced chemo/photothermal/chemodynamic therapy for tumours.

Cancer is a leading cause of death worldwide and seriously threatens the health of humans. The current clinical treatments for cancer are not efficient and always lead to significant side effects. Herein, a biocompatible and powerful theranostic agent (Bi@mSiO2@MnO2/DOX) is fabricated using a facile stepwise reaction method. The Bi nanoparticles (NPs) are coated by mesoporous silica to protect the Bi NPs from oxidation, which guarantees the stable photothermal effect of the Bi NPs. When the Bi@mSiO2@MnO2/DOX nanocomposites (NCs) accumulate in the tumour site, hyperthermia is generated by Bi NPs under near-infrared (NIR) light irradiation for photothermal therapy (PTT), and the generated heat triggers the release of DOX for chemotherapy in the tumour. In addition, the MnO2 of the NCs responsively catalyses endogenous H2O2 to generate O2, raising the oxygen level to enhance the effect of chemotherapy in the tumour microenvironment (TME), and consumes glutathione (GSH) to produce Mn2+ for magnetic resonance (MR) imaging. Under acidic TME conditions, H2O2 and Mn2+ also produce toxic hydroxyl radical (·OH) for chemodynamic therapy (CDT). Furthermore, the Bi NPs can also be used as excellent contrast agents for X-ray computed tomography (CT) imaging of tumours with a high CT value (6.865 HU mM-1). The Bi@mSiO2@MnO2/DOX NCs exhibit a powerful theranostic performance for CT/MR imaging-guided enhanced PTT/CDT/chemotherapy, which opens a new prospect to rationally design theranostic agents for tumour imaging.

Association Between Sensory Loss and Falls Among Middle-Aged and Older Chinese Population: Cross-Sectional and Longitudinal Analyses.

Introduction: Previous studies have suggested that sensory loss is linked to falls. However, most of these studies were cross-sectional designed, focused on single sensory loss, and were conducted in developed countries with mixed results. The current study aims to investigate the longitudinal relationship between hearing loss (HL), vision loss (VL) and dual sensory loss (DSL) with falls among middle-aged and older Chinese population over 7 years. Methods: The data was obtained from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 7,623 Chinese older adults aged over 45 were included at baseline 2011 in this study. Self-reported falls and HL/VL/DSL were accepted. Other confounding variables included age, sex, BMI, educational level, marital status, various physical disorders and lifestyles. The impact of baseline sensory status on baseline prevalence of falls and incident falls over 7 years were assessed using logistic regression analyses. A logistic mixed model was used to assess the association between time-varying sensory loss with incident falls over 7 years after adjusted with multi-confounding factors. Results: Single and dual sensory loss groups had significantly higher prevalence of falls compared to no sensory loss (NSL) group (DSL: 22.4%, HL: 17.4%, VL: 15.7%, NSL: 12.3%). Baseline HL (OR: 1.503, 95% CI: 1.240-1.820), VL (OR: 1.330, 95% CI: 1.075-1.646) and DSL (OR: 2.061, 95% CI: 1.768-2.404) were significantly associated with prevalence of falls. For longitudinal observation over 7 years, baseline HL/DSL and persistence of all types of sensory loss were associated with incidence of falls. Time-varying HL (OR: 1.203, 95% CI: 1.070-1.354) and DSL (OR: 1.479, 95% CI: 1.343-1.629) were associated with incident falls after adjusted with multi-confounders, while VL was not. Conclusion: HL and DSL are significantly associated with both onset and increased incidence of falls over 7 year's observation in middle-aged and elderly Chinese population. Persistence or amelioration of sensory loss status could exert divergent influences on incidence of falls, which should be considered in the development of falls-prevention public health policies for aging population.

Polyphenol-cisplatin complexation forming core-shell nanoparticles with improved tumor accumulation and dual-responsive drug release for enhanced cancer chemotherapy.

Cisplatin (CDDP) is a potent first-line antitumor drug but suffers severe side effects and poor pharmacokinetics. Its complexation with polycarboxylic acids, such as polyglutamic acids, is generally used to fabricate nanoformulations for CDDP delivery; however, the multiple strong complexations makes intracellular drug release slow. Herein, we report a novel polyphenol-metal coordination method to fabricate CDDP-incorporated core-shell nanoparticles, which are stable in blood circulation but dissociate in the tumor. Methoxyl-PEG terminated with one or two gallic acids (PEG-GA or PEG-GA2) complexed CDDP and produced well-defined nanoparticles (PEG-GAx/Pt) with CDDP loading contents as high as 17.7% to 29.8%. The PEG-GAx/Pt nanoparticles were very stable in the physiological conditions and had slow blood clearance and efficient tumor accumulation, but dissociated quickly and released CDDP in response to the tumor acidity or elevated levels of reactive oxygen species (ROS). PEG-GAx/Pt nanoparticles exhibited improved antitumor efficiency against 4 T1 breast cancer and A549 lung carcinoma with much-reduced toxicity compared to free CDDP. The work demonstrates a new strategy of cisplatin-polyphenol coordination for developing platinum drugs' nanomedicines.

Interfacial Fe5C2-Cu catalysts toward low-pressure syngas conversion to long-chain alcohols.

Long-chain alcohols synthesis (LAS, C5+OH) from syngas provides a promising route for the conversion of coal/biomass/natural gas into high-value chemicals. Cu-Fe binary catalysts, with the merits of cost effectiveness and high CO conversion, have attracted considerable attention. Here we report a nano-construct of a Fe5C2-Cu interfacial catalyst derived from Cu4Fe1Mg4-layered double hydroxide (Cu4Fe1Mg4-LDH) precursor, i.e., Fe5C2 clusters (~2 nm) are immobilized onto the surface of Cu nanoparticles (~25 nm). The interfacial catalyst exhibits a CO conversion of 53.2%, a selectivity of 14.8 mol% and a space time yield of 0.101 g gcat-1 h-1 for long-chain alcohols, with a surprisingly benign reaction pressure of 1 MPa. This catalytic performance, to the best of our knowledge, is comparable to the optimal level of Cu-Fe catalysts operated at much higher pressure (normally above 3 MPa).

Dual Pseudo and Chemical Crosslinked Polymer Micelles for Effective Paclitaxel Delivery and Release.

The fabrication of polymer micelles, both with ample intracorporeal circulation stability and fast release within cancerous cells, is still facing challenges. Herein, we fabricated a strategy to improve the stability of polymer micelles using pseudo- and chemical crosslinking jointly. To be specific, a star-shaped polymer (TMP-PGMA-g-PEG) with trimethylolpropane (TMP) as the inner core was synthesized with glycidyl methacrylate (GMA), followed by the graft reaction with amine-terminated poly(ethylene glycol) (mPEG-NH2). Star polymer micelle-based nanomedicines (TPP/paclitaxel (PTX)) were obtained using paclitaxel (PTX) as a model drug and polymer micelles (TPP) as carriers, which were constructed by TMP-PGMA-g-PEG. The star core and arms behaved as pseudo crosslinkers, which reduced their critical micelle concentration (CMC) values and improved their stability; profoundly, cystamine was used as a chemical crosslinker to react with the rest of the epoxy groups of TPP or TPP/PTX and further improve their stability. Finally, dual pseudo and chemical crosslinked star polymer micelles (CTPP) and micelle-based nanomedicines (CTPP/PTX) were obtained. The results demonstrated that CTPP/PTX with combined stability design presented excellent stability both in vitro and in vivo physiological conditions. Notably, cystamine not only served as a crosslinker but also had a reduction-responsive disulfide bond to achieve fast release inside cancer cells with a high level of glutathione (GSH). This smart design effectively resolved the antinomy that the polymer micelle delivery system could not cause rapid release in tumor sites when it possesses extreme stability resulted from chemical crosslinking. Both in vitro and in vivo experiments clearly stated the advantages of CTPP/PTX, including excellent stability, fast reduction-responsive release, and remarkable antitumor efficacy.

Dual Stable Nanomedicines Prepared by Cisplatin-Crosslinked Camptothecin Prodrug Micelles for Effective Drug Delivery.

A polymer micelle-based drug delivery system has faced many challenges due to the lack of stability especially after being diluted in blood, resulting in a premature release. Herein, we developed camptothecin (CPT)-conjugated prodrug (CPTP) micelles in which CPT was grafted to the poly(ethylene glycol)-poly(glutamic acid) block copolymer via a disulfide bond linker for a redox-triggered drug release. Then, the cisplatin (CDDP)-crosslinked CPT-prodrug micelles (CPTP/CDDP) with a hybrid complex as a stable structure were successfully established via the CDDP (Pt)-carboxyl (COOH) chelate interaction. The resulting dual CPTP/CDDP had an average hydrodynamic radius of about 50 nm with a narrow distribution, which was conducive to the promotion of solid tumor accumulation. Importantly, CPT chemical bonding to the polymer backbone obviously stabilizes the CPT-prodrug micelles and prolongs their circulation time. Moreover, both CPT and CDDP are clinically used antitumor drugs; CDDP not only behaves as an ancillary anticarcinogen but also serves as a crosslinker to restrain the untimely burst release of CPT and to achieve synergistic antitumor efficacy. In addition, the CPTP/CDDP also exhibited a sustained reduction responsive release of CPT accompanied by the dissociation of the CDDP-COOH complex. This design ingeniously solved the contradiction between the stability and release of polymer micelle-based nanomedicines. Both in vitro and in vivo tests demonstrated an amazing antineoplastic efficacy compared with free drugs (CPT or CDDP) and just their physical mixing, indicating great promise for cancer treatment.

Glycerol aerobic oxidation to glyceric acid over Pt/hydrotalcite catalysts at room temperature.

Glycerol (GLY) aerobic oxidation in an aqueous solution is one of the most prospective pathways in biomass transformation, where the supported catalysts based on noble metals (mainly Au, Pd, Pt) are most commonly employed. Herein, Pt nanoparticles supported on rehydrated MgxAl1-hydrotalcite (denoted as re-MgxAl1-LDH-Pt) were prepared via impregnation-reduction method followed by an in situ rehydration process, which showed high activity and selectivity towards GLY oxidation to produce glyceric acid (GLYA) at room temperature. The metal-support interfacial structure and catalyst basicity were modulated by changing the Mg/Al molar ratio of the hydrotalcite precursor, and the optimal performance was achieved on re-Mg6Al1-LDH-Pt with a GLY conversion of 87.6% and a GLYA yield of 58.6%, which exceeded the traditional activated carbon and oxide supports. A combinative study on structural characterizations (XANES, CO-FTIR spectra, and benzoic acid titration) proves that a higher Mg/Al molar ratio promotes the formation of positively charged Ptδ+ species at metal-support interface, which accelerates bond cleavage of α-C-H and improves catalytic activity. Moreover, a higher Mg/Al molar ratio provides a stronger basicity of support that contributes to the oxidation of terminal-hydroxyl and thus enhances the selectivity of GLYA. This catalyst with tunable metal-support interaction shows prospective applications toward transformation of biomass-based polyols.

Acid-base sites synergistic catalysis over Mg-Zr-Al mixed metal oxide toward synthesis of diethyl carbonate.

In heterogeneous catalysis processes, development of high-performance acid-base sites synergistic catalysis has drawn increasing attention. In this work, we prepared Mg/Zr/Al mixed metal oxides (denoted as Mg2Zr x Al1-x -MMO) derived from Mg-Zr-Al layered double hydroxides (LDHs) precursors. Their catalytic performance toward the synthesis of diethyl carbonate (DEC) from urea and ethanol was studied in detail, and the highest catalytic activity was obtained over the Mg2Zr0.53Al0.47MMO catalyst (DEC yield: 37.6%). By establishing correlation between the catalytic performance and Lewis acid-base sites measured by NH3-TPD and CO2-TPD, it is found that both weak acid site and medium strength base site contribute to the overall yield of DEC, which demonstrates an acid-base synergistic catalysis in this reaction. In addition, in situ Fourier transform infrared spectroscopy (in situ FTIR) measurements reveal that the Lewis base site activates ethanol to give ethoxide species; while Lewis acid site facilitates the activated adsorption of urea and the intermediate ethyl carbamate (EC). Therefore, this work provides an effective method for the preparation of tunable acid-base catalysts based on LDHs precursor approach, which can be potentially used in cooperative acid-base catalysis reaction.

Alkynyl-functionalization of hydroxypropyl cellulose and thermoresponsive hydrogel thereof prepared with P(NIPAAm-co-HEMAPCL).

A ternary system thermoresponsive hydrogel, poly(N-isopropylacrylamide-co-hydroxyethyl methylacrylate polycaprolactone)/hydroxypropyl cellulose (or P(NIPAAm-co-HEMAPCL)/HPC), was prepared via "alkynyl/azide" click chemistry between the azide modified graft copolymer P(NIPAAm-co-HEMAPCL-N3) and the alkynyl modified HPC (or alkynyl-HPC). The structures of P(NIPAAm-co-HEMAPCL-N3) and alkynyl-HPC were characterized by (1)H NMR, SEC and FT-IR, and the results demonstrated that the mole ratio of the alkynyl and azide functional groups, and the feed ratios of HPC, PCL, and PNIPAAm could be easily adjusted. The incorporation of PCL and HPC dramatically enhanced the compression modulus of the P(NIPAAm-co-HEMAPCL)/HPC hydrogel, which ranged from 500 to 1000 g/cm(2). Due to the immiscibility of HPC and PCL, a heterogeneous and semicontinuous structure was observed via SEM. The incorporation of HPC accelerated the water absorption rate and enhanced the hydrogel's ability to shed water. The swelling-deswelling and compressive properties could also be adjusted by changing the feeding ratio. The hydrogel exhibited reversible swelling-deswelling behavior after three "swelling-deswelling" cycles.

Synthesis of copolymers with cyclodextrin as pendants and its end group effect as superplasticizer.

In this paper, the efficient approach for the synthesis of ß-cyclodextrin (CD) based functional monomers was described. Based on the monovinyl ß-CD monomer (GMA-EDA-CD), a new type poly(AA-co-GMA-EDA-CD) (PCDs) copolymer bearing pendent CD groups was synthesized and used as superplasticizer. Their chemical compositions were characterized by FT-IR, NMR, MALDI-TOF and GPC. The effects of PCDs on dispersion and adsorption in cement mortars were detailed discussed. The results indicated that PCD copolymers behaved excellent dispersion ability and strong retarding effect. PCD2 with molar ratio (%) for monomer (AA:GMA-EDA-CD=80:20) had the best dispersion and dispersion maintaining abilities, which were mainly attributed to the synergistic effects of steric hindrance and electrostatic repulsive force, and the retarding effect of PCD copolymers resulted from steric hindrance repulsion of CD pendants and the large number of hydroxyl groups, which affected the hydration reaction of cement.