Treatment of multiple myeloma: What is the impact on T-cell function?

Treatment of multiple myeloma (MM) has evolved remarkably over the past few decades. Autologous stem cell transplantation, as well as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has substantially improved the prognosis of patients with MM. Novel therapies, including chimeric antigen receptor-T cells, bispecific T-cell engagers, antibody-drug conjugates, histone deacetylase inhibitors, and nuclear export inhibitors, have provided more options. However, MM remains incurable. T cells are the principal weapons of antitumor immunity, but T cells display a broad spectrum of dysfunctional states during MM. The promising clinical results of T-cell-directed immunotherapies emphasize the significance of enhancing T-cell function in antimyeloma treatment. This review summarizes the potential effects of these antimyeloma agents on T-cell function and discusses possible optimized strategies for MM management by boosting T-cell immunity.

Sustainable process for fractionation of lignin by the microwave-assisted chemical additive approach: Towards sugarcane leaf biorefinery and characterization.

The microwave assisted pretreatment on sugarcane leaf (SCL) biomass for delignification was studied to enhance cellulose digestibility. In this work, microwave assisted with additives were used to delignification SCL for maximize sugar yield recovery. Single factorial and Central composite design (CCD) were employed to optimize the microwave assisted pretreatment conditions for improve delignification efficiency and the sugar yield recovery. The optimized pretreatment conditions were determined to be 4 min pre-treatment time, 500 W microwave power, 1.0 M Na2CO3 and 10 % biomass loading condition produce maximum reducing sugar yield (601 mg g-1) and glucose sugar yield (231 mg g-1) were achieved during saccharification. Pretreated biomass produced reducing sugar and glucose yields that were 4.5 and 4.1 times higher than those of untreated (native) SCL-N biomass, respectively. Additionally, the recyclability study of black liquor, obtained from optimized conditioned treatment of SCL-MSC (Microwave-assisted sodium carbonate pretreated SCL) resulted in considerable saccharification yield up to three pretreatment cycles. The 1H NMR and 13C NMR spectra studies illustrate that aromatic units present in SCL fractionated lignin samples. The variations of structure features and chemical compositions of the raw and pretreated SCL biomass were analyzed by SEM, XRD and XPS analysis. Overall, SCL-MSC pretreatment condition significantly delignification of SCL and led to the maximum sugar production optimized strategies pretreatment conditions was produced maximum amount of sugar, which is great potential for bio-refinery product development.

Current optimized strategies for stem cell-derived extracellular vesicle/exosomes in cardiac repair.

Ischemic heart diseases remain the leading cause of death globally, and stem cell-based therapy has been investigated as a potential approach for cardiac repair. Due to poor survival and engraftment in the cardiac ischemic milieu post transplantation, the predominant therapeutic effects of stem cells act via paracrine actions, by secreting extracellular vesicles (EVs) and/or other factors. Exosomes are nano-sized EVs of endosomal origin, and now viewed as a major contributor in facilitating myocardial repair and regeneration. However, EV/exosome therapy has major obstacles before entering clinical settings, such as limited production yield, unstable biological activity, poor homing efficiency, and low tissue retention. This review aims to provide an overview of the biogenesis and mechanisms of stem cell-derived EV/exosomes in the process of cardiac repair and discuss the current advancements in different optimized strategies to produce high-yield EV/exosomes with higher bioactivity, or engineer them with improved homing efficiency and therapeutic potency. In particular, we outline recent findings toward preclinical and clinical translation of EV/exosome therapy in ischemic heart diseases, and discuss the potential barriers in regard to clinical translation of EV/exosome therapy.

Optimized strategies of green and grey infrastructures for integrated control objectives of runoff, waterlogging and WWDP in old storm drainages.

Frequent waterlogging occurs in old high-density urban areas where the sewage is inappropriately connected to storm drainages, resulting in serious wet weather discharge pollution (WWDP). To address urban waterlogging and runoff, the optimization of green infrastructures (GIs) and grey infrastructures (GRs) has been proposed to improve rainwater management efficiency. However, most strategies neglect WWDP and fail to achieve integrated control of runoff, waterlogging, and discharge pollution. In the present study, a new optimization method was introduced to identify optimal solutions for renovating outdated storm drainage systems, considering the management of discharge pollution in wet weather. A case study in Shanghai, China was conducted to demonstrate the application of the method. The cost-benefit index (CBI) of optimized GIs (0.06) was lower than that of optimized GRs (2.78) under 22.2 mm rainfall (no runoff and WWDP), but the costs of the former were only half those of the latter. In a 5-year return period storm (no waterlogging), optimized GIs had a significantly higher CBI (2.85 times) compared to optimized GRs, costing only 44 % of the latter. When WWDP reached the control objective (COD≤70 mg/L), the optimized GIs needed to be further optimized with GRs. The CBI of optimized GI-GRs was higher than GRs by 2.50, and the cost was 58% of the latter. In areas with frequent low-intensity rainfall, optimized GIs and GRs should be selected based on local cost or benefit requirements for drainage reconstruction. In high-intensity storm-prone areas, the optimized GI-GR combination should be selected for drainage reconstruction. The proposed method can compensate for the shortcomings of existing optimization methods in controlling WWDP for the reconstruction of old storm drainages.

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems have revolutionized traditional gene-editing tools and are a significant tool for ameliorating gene defects. Characterized by high target specificity, extraordinary efficiency, and cost-effectiveness, CRISPR/Cas systems have displayed tremendous potential for genetic manipulation in almost any organism and cell type. Despite their numerous advantages, however, CRISPR/Cas systems have some inherent limitations, such as off-target effects, unsatisfactory efficiency of delivery, and unwanted adverse effects, thereby resulting in a desire to explore approaches to address these issues. Strategies for improving the efficiency of CRISPR/Cas-induced mutations, such as reducing off-target effects, improving the design and modification of sgRNA, optimizing the editing time and the temperature, choice of delivery system, and enrichment of sgRNA, are comprehensively described in this review. Additionally, several newly emerging approaches, including the use of Cas variants, anti-CRISPR proteins, and mutant enrichment, are discussed in detail. Furthermore, the authors provide a deep analysis of the current challenges in the utilization of CRISPR/Cas systems and the future applications of CRISPR/Cas systems in various scenarios. This review not only serves as a reference for improving the maturity of CRISPR/Cas systems but also supplies practical guidance for expanding the applicability of this technology.

Concise Review: Optimized Strategies for Stem Cell-Based Therapy in Myocardial Repair: Clinical Translatability and Potential Limitation.

Ischemic heart diseases (IHDs) remain major public health problems with high rates of morbidity and mortality worldwide. Despite significant advances, current therapeutic approaches are unable to rescue the extensive and irreversible loss of cardiomyocytes caused by severe ischemia. Over the past 16 years, stem cell-based therapy has been recognized as an innovative strategy for cardiac repair/regeneration and functional recovery after IHDs. Although substantial preclinical animal studies using a variety of stem/progenitor cells have shown promising results, there is a tremendous degree of skepticism in the clinical community as many stem cell trials do not confer any beneficial effects. How to accelerate stem cell-based therapy toward successful clinical application attracts considerate attention. However, many important issues need to be fully addressed. In this Review, we have described and compared the effects of different types of stem cells with their dose, delivery routes, and timing that have been routinely tested in recent preclinical and clinical findings. We have also discussed the potential mechanisms of action of stem cells, and explored the role and underlying regulatory components of stem cell-derived secretomes/exosomes in myocardial repair. Furthermore, we have critically reviewed the different strategies for optimizing both donor stem cells and the target cardiac microenvironments to enhance the engraftment and efficacy of stem cells, highlighting their clinical translatability and potential limitation. Stem Cells 2018;36:482-500.