Synthesis and characterization of thermo-responsive polyethers

Hyaluronic acid (HA) hydrogels are interesting biomaterials for drug delivery and tissue engineering applications. Glycidyl ether derivatives have gained much interests due to their thermo-responsive properties. Thermo-responsive random copolymers of glycidyl methyl ether (GME) and epoxyhexane (EH) were synthesized. Once their properties were studied, they were grafted onto hyaluronic acid to obtain gelation at temperatures above the phase transition temperature of poly (GME-EH). PGME is a water-soluble polymer at low temperatures, but phase separates at 57.3oC. The transition temperature of PGME is too high to be utilized in medical applications. Thus a hydrophobic monomer EH was used to decrease the transition temperature of PGME via copolymerization. Several samples of random copolymers poly (GME-EH) were successfully synthesized by anionic ring opening polymerization (AROP). The transition temperature of copolymers was characterized by NMR, turbidimetry and micro-calorimetry respectively to study the phase transition behavior. Tetraoctylammonium bromide was used as initiator resulting with a bromide as the end group. Bromide was substituted by azide group to be used in click chemistry reaction with alkyne-functional HA. The reaction of the azide group on the end of copolymer chain was detected by FT-IR spectroscopy. Grafting was achieved by click chemistry following copper-catalyzed azide-alkyne cycloaddition (CuAAC) procedure. Rheology was used to study the gelation of the final product: thermo-responsive hyaluronic acid hydrogel. However, for different reasons the final product failed to form a gel

The long noncoding RNA THRIL knockdown protects hypoxia-induced injuries of H9C2 cells through regulating miR-99a

Background: Myocardial infarction (MI) is a leading cause of disease with high morbidity and mortality worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved inheart disease pathogenesis. This study aimed to investigate the effect and the molecular basis of THRIL on hypoxia-injured H9C2 cells. Methods: THRIL, miR-99a and Brahma-related gene 1 (Brg1) expressions in H9C2 cells were altered by transient transfections. The cells were subjected to hypoxia for 4 h, and then the levels of THRIL, miR-99a and Brg1 were investigated. Cell viability, migration and invasion, and apoptotic cells were respectively measured by trypan blue exclusion assay, transwell migration assay and flow cytometry assay. Dual luciferase reporter assay was conducted to verify the interaction between miR-99a and THRIL. Furthermore, levels of apoptosis-, PI3K/AKT and mTOR pathways-related factors were measured by western blotting. Results: Hypoxia induced an increase of THRIL but a reduction of miR-99a and Brg1. THRIL inhibition significantly attenuated hypoxia-induced cell injuries, as increased cell viability, migration and invasion, and decreased cell apoptosis. THRIL negatively regulated miR-99a expression through sponging with miR-99a binding site, and miR-99a inhibition abolished the protective effects of THRIL knockdown against hypoxia-induced injury in H9C2 cells. Furthermore, miR-99a positively regulated the expression of Brg1. Brg1 inhibition promoted hypoxia-induced cell injuries, while Brg1 overexpression alleviated hypoxia-induced cell injuries. Moreover, Brg1 overexpression activated PI3K/AKT and mTOR pathways. Conclusions: This study demonstrated that THRIL inhibition represented a protective effect againsthypoxia-induced injuries in H9C2 cells by up-regulating miR-99a expression

Structured Sparsity Learning for Efficient Video Super-Resolution

The high computational costs of video super-resolution (VSR) models hinder their deployment on resource-limited devices, (e.g., smartphones and drones). Existing VSR models contain considerable redundant filters, which drag down the inference efficiency. To prune these unimportant filters, we develop a structured pruning scheme called Structured Sparsity Learning (SSL) according to the properties of VSR. In SSL, we design pruning schemes for several key components in VSR models, including residual blocks, recurrent networks, and upsampling networks. Specifically, we develop a Residual Sparsity Connection (RSC) scheme for residual blocks of recurrent networks to liberate pruning restrictions and preserve the restoration information. For upsampling networks, we design a pixel-shuffle pruning scheme to guarantee the accuracy of feature channel-space conversion. In addition, we observe that pruning error would be amplified as the hidden states propagate along with recurrent networks. To alleviate the issue, we design Temporal Finetuning (TF). Extensive experiments show that SSL can significantly outperform recent methods quantitatively and qualitatively. We will release codes and models

Serum vitamin D deficiency in children and adolescents is associated with type 1 diabetes mellitus

Background: To investigate the relationship 25-hydroxy vitamin D (25OHD) level among children and in children with type 1 diabetes mellitus (T1DM). Methods: A case–control study was conducted to compare the serum 25OHD levels between cases and controls. This study recruited 296 T1DM children (106 newly diagnosed T1DM patients and 190 established T1DM patients), and 295 age- and gender-matched healthy subjects as controls. Results: The mean serum 25OHD in T1DM children was 48.69 ± 15.26 nmol/L and in the controls was 57.93 ± 19.03 nmol/L. The mean serum 25OHD in T1DM children was lower than that of controls (P 0.05). Conclusion: Vitamin D deficiency is common in T1DM children, and it should be worthy of attention on the lack of vitamin D in established T1DM children

Neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer: A new era for anal preservation

For locally advanced (T3-4/N+M0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment. It was demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. And the demand for anus preservation and better quality of life increases in recent years. Radiotherapy and immunotherapy can be supplement to each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. It was reported that these trials achieved promising short-term efficacy in both MSI-H and MSS rectal cancers, which could further improve the rate of clinical complete response (cCR) and pathological complete response (pCR), so that increase the possibility of ‘Watch and Wait (W&W)’ approach. However, the cCR and pCR is not always consistent, which occurs more frequent when nCRT is combined with immunotherapy. Thus, the efficacy evaluation after neoadjuvant therapy is an important issue for patient selection of W&W approach. Evaluating the cCR accurately needs the combination of multiple traditional examinations, new detective methods, such as PET-CT, ctDNA-MRD and various omics studies. And finding accurate biomarkers can help guide the risk stratification and treatment decisions. And large-scale clinical trials need to be performed in the future to demonstrate the surprising efficacy and to explore the long-term prognosis

Thermo-reversible cellulose micro phase-separation in mixtures of methyltributylphosphonium acetate and γ-valerolactone or DMSO

We have identified cellulose solvents, comprised of binary mixtures of molecular solvents and ionic liquids that rapidly dissolve cellulose to high concentration and show upper-critical solution temperature (UCST)-like thermodynamic behaviour - upon cooling and micro phase-separation to roughly spherical microparticle particle-gel mixtures. This is a result of an entropy-dominant process, controllable by changing temperature, with an overall exothermic regeneration step. However, the initial dissolution of cellulose in this system, from the majority cellulose I allomorph upon increasing temperature, is also exothermic. The mixtures essentially act as 'thermo-switchable' gels. Upon initial dissolution and cooling, micro-scaled spherical particles are formed, the formation onset and size of which are dependent on the presence of traces of water. Wide-angle X-ray scattering (WAXS) and C-13 cross-polarisation magic-angle spinning (CP-MAS) NMR spectroscopy have identified that the cellulose micro phase-separates with no remaining cellulose I allomorph and eventually forms a proportion of the cellulose II allomorph after water washing and drying. The rheological properties of these solutions demonstrate the possibility of a new type of cellulose processing, whereby morphology can be influenced by changing temperature.Peer reviewe

Revolutionizing anti-tumor therapy: unleashing the potential of B cell-derived exosomes

B cells occupy a vital role in the functioning of the immune system, working in tandem with T cells to either suppress or promote tumor growth within the tumor microenvironment(TME). In addition to direct cell-to-cell communication, B cells and other cells release exosomes, small membrane vesicles ranging in size from 30-150 nm, that facilitate intercellular signaling. Exosome research is an important development in cancer research, as they have been shown to carry various molecules such as major histocompatibility complex(MHC) molecules and integrins, which regulate the TME. Given the close association between TME and cancer development, targeting substances within the TME has emerged as a promising strategy for cancer therapy. This review aims to present a comprehensive overview of the contributions made by B cells and exosomes to the tumor microenvironment (TME). Additionally, we delve into the potential role of B cell-derived exosomes in the progression of cancer

Genetic and Clinical Profiles of Disseminated Bacillus Calmette-Guérin Disease and Chronic Granulomatous Disease in China

Background: Disseminated Bacillus Calmette-Guérin disease (D-BCG) in children with chronic granulomatous disease (CGD) can be fatal, while its clinical characteristics remain unclear because both diseases are extremely rare. The patients with CGD receive BCG vaccination, because BCG vaccination is usually performed within 24 h after delivery in China.Methods: We prospectively followed-up Chinese patients with CGD who developed D-BCG to characterize their clinical and genetic characteristics. The diagnoses were based on the patients' clinical, genetic, and microbiological characteristics.Results: Between September 2009 and September 2016, we identified 23 patients with CGD who developed D-BCG. Their overall 10-year survival rate was 34%. We created a simple dissemination score to evaluate the number of infected organ systems and the survival probabilities after 8 years were 62 and 17% among patients with simple dissemination scores of ≤3 and >3, respectively (p = 0.0424). Survival was not significantly associated with the CGD stimulation index or interferon-γ treatment. Eight patients underwent umbilical cord blood transplantation and 5 of them were successfully treated. The genetic analyses found mutations in CYBB (19 patients), CYBA (1 patient), NCF1 (1 patient), and NCF2 (1 patient). We identified 6 novel highly likely pathogenic mutations, including 4 mutations in CYBB and 2 mutations in NCF1.Conclusions: D-BCG is a deadly complication of CGD. The extent of BCG spreading is strongly associated with clinical outcomes, and hematopoietic stem cell transplantation may be a therapeutic option for this condition

Unveiling the Electro‐Chemo‐Mechanical Failure Mechanism of Sodium Metal Anodes in Sodium–Oxygen Batteries by Synchrotron X‐Ray Computed Tomography

Rechargeable sodium–oxygen batteries (NaOBs) are receiving extensive research interests because of their advantages such as ultrahigh energy density and cost efficiency. However, the severe failure of Na metal anodes has impeded the commercial development of NaOBs. Herein, combining in situ synchrotron X-ray computed tomography (SXCT) and other complementary characterizations, a novel electro-chemo-mechanical failure mechanism of sodium metal anode in NaOBs is elucidated. It is visually showcased that the Na metal anodes involve a three-stage decay evolution of a porous Na reactive interphase layer (NRIL): from the initially dot-shaped voids evolved into the spindle-shaped voids and the eventually-developed ruptured cracks. The initiation of this three-stage evolution begins with chemical-resting and is exacerbated by further electrochemical cycling. From corrosion science and fracture mechanics, theoretical simulations suggest that the evolution of porous NRIL is driven by the concentrated stress at crack tips. The findings illustrate the importance of preventing electro-chemo-mechanical degradation of Na anodes in practically rechargeable NaOBs