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DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.

Digital urban-rural sharing of social public resources (SPRs) is an effective way to narrow the urban-rural gap and promote integrated urban-rural development. Applying the method of the Grounded theory, 122 documents such as interview data and policy texts, and news reports are collected. And open codes, axial codes, and selective codes are developed to systematically examine the main factors affecting digital urban-rural sharing of SPR in China, and 23 categories and 6 main categories including government guarantee, talent support, technical support, resource supply, innovation drive, and social demand are obtained. On this basis, we construct a model of factors influencing the digital urban-rural sharing of SPR in China, analyze their effect mechanisms, and propose targeted countermeasures to enhance the digital urban-rural sharing of SPR in China.

PAA as an additive enhances perovskite film crystallinity, enlarges grain boundaries, passivates defects, and improves efficiencies and stability of PSCs.

Kai Dong,1,2 Shu-Jing Deng,2 Bin-Yang He,2 Zi-Yang Guo,2 Ze-Lin Guan,2 Xue Leng,2 Rui-Rui Ma,2 Dan-Yang Wang,2 Jian-Feng Xing,2 Cui-Yu You1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Jian-Feng Xing, School of Pharmacy, Xi’an Jiaotong University, 76 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China, Tel +86-29-82655139, Fax +86-29-82655139, Email xajdxjf@mail.xjtu.edu.cn Cui-Yu You, Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Tel +86-29-85323241, Fax +86-29-85323240, Email ycy720123@163.comBackground: As the first-line drug to treat ulcerative colitis (UC), long-term use of glucocorticoids (GCs) produces severe toxic and side effects. Local administration as enema can increase the local GCs concentrations and reduce systemic exposure to high oral doses by directly delivering GCs to the inflammation site in the distal colorectum. However, UC patients are often accompanied by diarrhea, leading to the short colonic residence time of GCs and failure to exert their function fully.Purpose: A kind of mucoadhesive nanoparticles (NPs) loading different dexamethasone derivatives (DDs) were developed, which could attach to the positively charged inflammatory colonic mucosa through electrostatic adsorption after administered by enema, thereby improving the local concentration and achieving effective targeted therapy for UC.Methods: Two DDs, dexamethasone hemisuccinate and dexamethasone phosphate, were synthesized. In NPs preparation, The core PEI-DDs NPs were built by the electrostatic adsorption of DDs and the cationic polymer polyethyleneimine (PEI). Then, the natural polyanionic polysaccharide sodium alginate (SA) was electronically coated around NPs to construct the final SA-PEI-DDs NPs, followed by the in vitro stability and release tests, in vitro and in vivo colonic mucosal adhesion tests. In the in vivo anti-UC test, the experimental colitis mice were induced by 2,4,6-trinitrobenzenesulfonic acid. The body weight and disease activity index changes were measured, and the myeloperoxidase activity, pro-inflammatory cytokines concentration, and hematoxylin and eosin staining were also investigated to evaluate the therapeutic effect of NPs.Results: The structures of two DDs were demonstrated by 1H-NMR and MS. Both NPs were negatively charged and achieved high loading efficiency of DDs, while their particle sizes were significantly different. NPs showed good stability and sustained release properties in the simulated colonic environment. Moreover, the negative charge on the of NPs surface made them easier to adhere to the positively charged inflammatory colonic mucosa, thereby enhancing the enrichment and retention of DDS in the colitis site. Furthermore, the NPs exhibited better therapeutic effects than free Dex on the experimental colitis mice induced by TNBS through the enema rectal.Conclusion: These results indicated the mucoadhesive NPs as a kind of novel nano-enema showed great potential to achieve efficient treatment on UC.Keywords: ulcerative colitis, glucocorticoids, mucoadhesive, polyethyleneimine, sodium alginate

A novel strategy for the organocatalytic asymmetric synthesis of spiro-δ-lactam oxindoles was developed via a [3 + 3] annulation of 3-carboxamide oxindoles and β,γ-unsaturated α-keto esters with excellent diastereoselectivities and enantioselectivities.

Electrical impedance tomography (EIT) is an imaging technique that non-invasively acquires the electrical conductivity distribution within a field. The ill-posed and nonlinear nature of the image reconstruction process results in lower quality of the obtained images. To solve this problem, an EIT image reconstruction method based on DenseNet with multi-scale convolution named MS-DenseNet is proposed. In the proposed method, three different multi-scale convolutional dense blocks are incorporated to replace the conventional dense blocks; they are placed in parallel to improve the generalization ability of the network. The connection layer between dense blocks adopts a hybrid pooling structure, which reduces the loss of information in the traditional pooling process. A learning rate setting achieves reduction in two stages and optimizes the fitting ability of the network. The input of the constructed network is the boundary voltage data, and the output is the conductivity distribution of the imaging area. The network was trained and tested on a simulated dataset, and it was further tested using actual measurement data. The images reconstructed via this method were evaluated by employing root mean square error, structural similarity index measure, mean absolute error and image correlation coefficient in comparison with conventional DenseNet and Gauss-Newton. The results show that the method improves the artifact and edge blur problems, achieves higher values on the image metrics and improves the EIT image quality.

ZnO–nano-ZnO@porous carbon (ZnO–nZnO@PC) was in situ fabricated through the Ostwald ripening mechanism and facile pyrolysis process, which demonstrated the performance of piezo-photocatalytic degradation efficiency of 99.4%.

In order to obtain the knowledge information of financial texts more efficiently and make the extracted information such as entity relation attribute more accurate, this paper studies the grammatical features of financial news texts and the semantic features of How Net, and puts forward the scheme of financial information extraction based on How Net. First, the phrase matching is carried out in the dictionary. Then the neural network is used for weighting, BiLSTM is used for character vector feature enhancement training, and then conditional random field (CRF) is used to complete named entity recognition, and then the relationship extraction of entity pairs from the dependency syntax is carried out to complete the research on the construction method of knowledge extraction of text in the financial field. The experimental results show that this model is superior to the other three models in entity recognition, and the overall performance is improved by about 1.2%. In relation extraction, the accuracy and recall rate of the model algorithm adopted in this paper are improved by 5% and 1.5% respectively, which shows that the improvement of the algorithm is effective.

Here, we introduce bio-piezoelectric platforms from the perspective of antitumor therapy, review their recent applications as nanomedicines and carriers in tumor diagnosis and treatment, and discuss future challenges and opportunities.

An electrochemical method for the direct synthesis of 1,2-diester derivatives from abundant and readily available olefins and carboxylic acids is described. The method is clean and highly atom- and step-economical.

This research provides an efficient hierarchical self-assembly approach to construct artificial LHSs featuring excellent energy transfer efficiency and high antenna effects with diverse architectures.

A photoinduced TBADT-catalyzed one-pot, three-component strategy for the synthesis of alkyl-alkyl sulfones was reported. The developed methodology could tolerate broad functional groups and allow for the late-stage modification of complex molecules.

Bacterial proliferation and the disordered extracellular matrix (ECM) at the wound site are the major reasons for delayed healing and abnormal scarring. The development of new multifunctional dressing materials that can effectively prevent scar formation without delaying wound healing remains a challenge. In this study, we construct a verteporfin-loaded biodegradable hydrogel (VP-gel) using hyaluronic acid and thiol-terminated 4-arm polyethylene glycol (PEG). The injectable VP-gel sustainably releases small doses of verteporfin in the wound microenvironment that generates reactive oxygen species (ROS) under red light irradiation to kill bacteria efficiently. Importantly, the sustained release of VP could also regulate TGF-β family-induced cellular responses and the downstream signaling molecule Smad2 in fibroblasts to reduce myofibroblast differentiation, promoting ECM reconstruction and scarless wound healing. Immunohistochemical examination of wound healing and histomorphology in a mouse full-thickness wound model demonstrates excellent acceleration effects of VP-gel for infected wound healing. Therefore, VP-gel with anti-scarring and antibacterial activity, as well as enhanced infection wound healing ability shows great potential in the clinical treatment of scar healing for infected wounds.

We consider the incremental subgradient algorithm employing dynamic step sizes for minimizing the sum of a large number of component convex functions. The dynamic step size rule was firstly introduced by Goffin and Kiwiel [Math. Program., 1999, 85(1): 207-211] for the subgradient algorithm, soon later, for the incremental subgradient algorithm by Nedic and Bertsekas in [SIAM J. Optim., 2001, 12(1): 109-138]. It was observed experimentally that the incremental approach has been very successful in solving large separable optimizations, and that the dynamic step sizes generally have better computational performance than others in the literature. In the present paper, we propose two modified dynamic step size rules for the incremental subgradient algorithm and analyse the convergence properties of them. At last, the assignment problem is considered and the incremental subgradient algorithms employing different kinds of dynamic step sizes are applied to solve the problem. The computational experiments show that the two modified ones converges dramatically faster and stabler than the corresponding one in [SIAM J. Optim., 2001, 12(1): 109-138]. Particularly, for solving large separable convex optimizations, we strongly recommend the second one (see Algorithm 3.3 in the paper) since it has interesting computational performance and is the simplest one.

We present the case of a 26-year-old woman with recurrent episodes of severe pain, weakness, and atrophy in her bilateral upper extremities during pregnancy and puerperium. She reported 2 similar episodes at ages 5 and 10 years, after which she fully recovered. On examination, we observed significant atrophy in her bilateral upper extremity muscles with decreased strength. Needle electromyography (EMG) revealed neurogenic damage in her bilateral upper limbs. The patient's clinical manifestations and auxiliary examination suggested a brachial plexopathy. Metabolic and immune factors that may occur during pregnancy and puerperium were evaluated. We also screened for paraneoplastic, neoplastic, and genetic factors. Finally, a hereditary form of disease was considered. This case emphasizes the importance of early diagnosis and avoidance of triggers.

Tyrosinase (TYR), an important biomarker for melanoma, offered significant information early detection of melanoma and may decrease the likelihood of mortality. Therefore, this article constructed a highly sensitive and selective green fluorescent functionalized carbon quantum dots (TYR-CQDs) for tyrosinase (TYR) activity detection by one-step hydrothermal protocol utilizing catechol, citric acid and urea as precursors. The prepared TYR-CQDs illustrated excellent linear relationship and broad linear range with a low detection limit, which exhibited high accuracy and recovery in quantitative determination of TYR in human serum samples. Furthermore, the TYR-CQDs had successfully realized intracellular TYR detection owing to excellent biocompatibility, high anti-interference ability and good cellular imaging capability, suggesting the potential biomedical applications in early diagnosis of melanoma and other tyrosinase-related diseases.