Since bacterial infections seriously threaten human's health, considerable attention is devoted to the design of nanoscale antibacterial materials. Among them, metal nanoparticles cannot meet the ...requirements of durable antibacterial effects and are harmful to biological environments. In this study, environmentally friendly nanogels with durable antibacterial and antiadhesion properties are prepared by copolymerization of styrene, polycaprolactone‐hydroxyethyl methacrylate, and polyhexamethylene guanidine hydrochloride methacrylate. The resultant nanogels possess regular spherical morphologies with the size of about 200 nm. The nanogels exhibit a strong ability to kill bacteria and the mechanism is different from that of conventional antibacterial agent loaded nanoparticles. In addition, anti‐infection experiments explored by a wound model confirm the nanogels have the capability to prevent infection. Furthermore, the nanogels grafted on the surface of cotton fibers display good thermal stability, which is essential for finishing of fabrics. The cotton fabrics finished with nanogels can prevent the adhesion of bacteria by enhancing the hydrophobicity and the bacteriostatic rate. The antibacterial fabrics against Staphylococcus aureus and Escherichia coli are still more than 86% active after 50 times of mechanical washing. The biocompatible nanogels are unleachable from the antibacterial fabrics which demonstrate that they are ideal candidates for durable and environmental‐friendly nanoscaled antimicrobial materials.
In this study, environmentally friendly nanogels with durable antibacterial and antiadhesion properties are prepared by copolymerization of guanidine groups based monomers. The resultant inherent guanidine spherical nanogels can kill bacteria effectively and have the capability to prevent infection. Furthermore, the nanogels grafted on cotton fibers display good thermal stability. The cotton fabrics finished with nanogels can prevent the adhesion of bacteria permanently.
Herein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen‐centered radicals (NCRs). By ...changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C−N versus N−N bond formation reaction. Hence, pyrido1,2‐abenzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition‐metal‐ and exogenous oxidant‐free strategy with broad generality. Bioactivity assays demonstrated that pyrido1,2‐abenzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.
Tunable C−N versus N−N bond formation of nitrogen‐centered radicals was achieved by an electrochemical dehydrogenative dearomatization strategy. Control experiments, DFT calculations, and investigations of the electrode material elucidated the origin of the chemoselectivity. Bioactivity assays demonstrated that pyrido1,2‐abenzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells.
Oxidative stress is recognized as free radical dyshomeostasis, which has damaging effects on proteins, lipids and DNA. However, during cell differentiation and proliferation and other normal ...physiological processes, free radicals play a pivotal role in message transmission and are considered important messengers. Organisms maintain free radical homeostasis through a sophisticated regulatory system in which these “2‐faced” molecules play appropriate roles under physiological and pathological conditions. Reactive oxygen species (ROS), including a large number of free radicals, act as redox signalling molecules in essential cellular signalling pathways, including cell differentiation and proliferation. However, excessive ROS levels can induce oxidative stress, which is an important risk factor for diabetes, cancer and cardiovascular disease. An overall comprehensive understanding of ROS is beneficial for understanding the pathogenesis of certain diseases and finding new therapeutic treatments. This review primarily focuses on ROS cellular localization, sources, chemistry and molecular targets to determine how to distinguish between the roles of ROS as messengers and in oxidative stress.
Human milk oligosaccharides (HMOs) are a unique class of non-digestible carbohydrates present in the mother milk, which play a key role in the development of infant gut microbiota, epithelial barrier ...and immune function. The deficiency of HMOs in the bovine milk-based infant formula has been widely recognized as a major culprit for the much higher incidence of immune disorders of formula-fed infants. This report was to give an up-to-date review on the structure characteristics of HMOs and the possible mechanisms, and strategies for their cellular uptake, and metabolism by the gut bacteria and the associated effects on the infant gut microbiome, and immune function. Most previous studies have been carried out in animals or in vitro model systems on the utilization strategies for HMOs in infant bacteria and their roles in infant microbiome, and gut immune function. A few HMO molecules have been synthesized artificially and applied in infant formulas.
•HMOs have diverse structures mostly composed of five sugar residues with a DP of 3–32.•HMOs play important roles in development of infant microbiome and immune function.•HMOs are degraded extra-/intra-cellularly and utilized selectively by infant gut bacteria.•A few HMOs have been synthesized and applied in infant formula milk.•Much more effort is needed to understand the function and mechanism of HMOs in infant health.
Mesenchymal stem cells (MSCs) repair infarcted heart through paracrine mechanism. We sought to compare the effectiveness of MSCs and MSC-derived exosomes (MSC-Exo) in repairing infarcted hearts and ...to identify how MSC-Exo mediated cardiac repair is regulated. In a rat myocardial infarction model, we found that MSC-Exo inhibited cardiac fibrosis, inflammation, and improved cardiac function. The beneficial effects of MSC-Exo were significantly superior compared to that of MSCs. To explore the potential mechanisms underlying MSC-Exo’s effects, we performed several in vitro experiments and miRNA-sequence analysis. MSC-Exo stimulated cardiomyocyte H9C2 cell proliferation, inhibited apoptosis induced by H2O2, and inhibited TGF-β induced transformation of fibroblast cell into myofibroblast. Importantly, novel miRNA sequencing results indicated that MSC-Exo and MSCs have similar miRNA expression profile, which could be one of the reasons that MSC-Exo can replace MSCs for cardiac repair. In addition, the expression of several miRNAs from MSC-Exo was significantly different from that of MSCs, which may explain why MSC-Exo has better therapeutic effect than MSCs. In conclusion, this study demonstrates that MSC-Exo could be used alone to promote cardiac repair and are superior to MSCs in repairing injured myocardium.
Background LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in ...patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. Methods LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 x 10.sup.6 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. Results As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced greater than or equal to 1 adverse events (AEs). Grade greater than or equal to 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade greater than or equal to 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. Conclusions The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285. Keywords: Multiple myeloma, Chimeric antigen receptor therapy, B cell maturation antigen, Safety, Efficacy
Background: Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth ...most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.
This study was carried out to evaluate the effects of power ultrasound (US) on the molecular weight and rheological properties of a food polysaccharide, konjac glucomannan (KGM). Upon the exposure of ...KGM solution (1% w/v in water) to US at a relatively high power intensity (50 W/cm2), the apparent viscosity decreased rapidly from about 50 Pa s to a negligible level within 10–20 min. The intrinsic viscosity (η) of KGM solution decreased gradually during the US exposure with a time course closely fitted to the first-order polymer degradation kinetics (random chain scission). The US treatment also caused a significant reduction of particle size (Zavg) of KGM aggregates and changes in the rheological properties including the decrease of storage modulus (G′) and loss modulus (G″), and the increase in phase angle (tan δ = G″/G′). Nevertheless, no change in primary structure was detected by Fourier transformation infrared (FT-IR) analysis. The results suggested that high intensity US was an effective means for KGM degradation without significant structural destruction.
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•Ultrasound (US) was effective for partial degradation of konjac glucomannan (KGM).•US power and treatment period were major factors affecting the degradation.•High-intensity US treatment caused dramatic reduction of KGM solution viscosity.•US degradation of KGM followed the first-order polymer degradation kinetics.
Endothelial glycocalyx degradation, critical for increased pulmonary vascular permeability, is thought to facilitate the development of sepsis into the multiple organ failure. Maresin conjugates in ...tissue regeneration 1 (MCTR1), a macrophage‐derived lipid mediator, which exhibits potentially beneficial effects via the regulation of bacterial phagocytosis, promotion of inflammation resolution, and regeneration of tissue. In this study, we show that MCTR1 (100 ng/mouse) enhances the survival of mice with lipopolysaccharide (LPS)‐induced (15 mg/kg) sepsis. MCTR1 alleviates LPS (10 mg/kg)‐induced lung dysfunction and lung tissue inflammatory response by decreasing inflammatory cytokines (tumor necrosis factor‐α, interleukin‐1β IL‐1β, and IL‐6) expression in serum and reducing the serum levels of heparan sulfate (HS) and syndecan‐1. In human umbilical vein endothelial cells (HUVECs) experiments, MCTR1 (100 nM) was added to the culture medium with LPS for 6 hr. MCTR1 treatment markedly inhibited HS degradation by downregulating heparanase (HPA) protein expression in vivo and in vitro. Further analyses indicated that MCTR1 upregulates sirtuin 1 (SIRT1) expression and decreases NF‐κB p65 phosphorylation. In the presence of BOC‐2 or EX527, the above effects of MCTR1 were abolished. These results suggest that MCTR1 protects against LPS‐induced sepsis in mice by attenuating pulmonary endothelial glycocalyx injury via the ALX/SIRT1/NF‐κB/HPA pathway.
Maresin conjugates in tissue regeneration 1 (MCTR1) protects against lipopolysaccharide (LPS)‐induced sepsis in mice by attenuating pulmonary endothelial glycocalyx injury via the ALX/SIRT1/NF‐κB/HPA pathway.
Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic ...malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. CAR T cells were i.v. infused after lymphodepleting chemotherapy. Two delivery methods, three infusions versus one infusion of the total CAR T dose, were tested in, respectively, 8 and 9 cases. No response differences were noted among the two delivery subgroups. Together, after CAR T cell infusion, 10 cases experienced a mild cytokine release syndrome (CRS), 6 had severe but manageable CRS, and 1 died of a very severe toxic reaction. The abundance of BCMA and cytogenetic marker del(17p) and the elevation of IL-6 were the key indicators for severe CRS. Among 17 cases, the overall response rate was 88.2%, with 13 achieving stringent complete response (sCR) and 2 reaching very good partial response (VGPR), while 1 was a nonresponder. With a median follow-up of 417 days, 8 patients remained in sCR or VGPR, whereas 6 relapsed after sCR and 1 had progressive disease (PD) after VGPR. CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.
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