The advent of soft robotics represents a paradigm shift, incepting an era defined by unparalleled flexibility, adaptability, and a profound embrace of biomimicry. This highlight celebrates one such recent study conducted by Dr. Tadesse and his team, which aims to delve deeper into jellyfish-like self-deployable actuators, thereby bridging the gap between theoretical concepts and pragmatic applications.

The advent of soft robotics represents a paradigm shift, incepting an era defined by unparalleled flexibility, adaptability, and a profound embrace of biomimicry. This highlight celebrates one such recent study conducted by Dr. Tadesse and his team, which aims to delve deeper into jellyfish-like self-deployable actuators, thereby bridging the gap between theoretical concepts and pragmatic applications.

Shape memory polymers (SMPs) circumscribe materials exhibiting responsive behavior to diverse external stimuli, ranging from heat and light to electric and magnetic fields. Originating in mid-20th-century studies, the realm of SMPs has expanded swiftly, tapping into the domains of biomedical applications, revolutionizing biomaterials, and finding applications from medical devices to regenerative medicine. Evolving beyond biocompatibility, the emphasis shifted to cytocompatible SMPs for cell mechanobiology, paving the way for direct cell-responsive SMPs. Recent breakthroughs in enzymatically triggered SMPs, particularly those influenced by cellular enzymatic activity, signify a transformative leap. This opens avenues for precision drug delivery and biosensors, merging SMPs with biomedical applications. This commentary celebrates the discovery of polymers responding to cells, unfolding the promising future of SMPs in personalized medicine, and seamlessly integrating advanced materials with cellular therapies for groundbreaking medical solutions.

Science, technology, engineering, mathematics, and medicine (STEMM) fields change rapidly and are increasingly interdisciplinary. Commonly, STEMM practitioners use short-format training (SFT) such as workshops and short courses for upskilling and reskilling, but unaddressed challenges limit SFT's effectiveness and inclusiveness. Education researchers, students in SFT courses, and organizations have called for research and strategies that can strengthen SFT in terms of effectiveness, inclusiveness, and accessibility across multiple dimensions. This paper describes the project that resulted in a consensus set of 14 actionable recommendations to systematically strengthen SFT. A diverse international group of 30 experts in education, accessibility, and life sciences came together from 10 countries to develop recommendations that can help strengthen SFT globally. Participants, including representation from some of the largest life science training programs globally, assembled findings in the educational sciences and encompassed the experiences of several of the largest life science SFT programs. The 14 recommendations were derived through a Delphi method, where consensus was achieved in real time as the group completed a series of meetings and tasks designed to elicit specific recommendations. Recommendations cover the breadth of SFT contexts and stakeholder groups and include actions for instructors (e.g., make equity and inclusion an ethical obligation), programs (e.g., centralize infrastructure for assessment and evaluation), as well as organizations and funders (e.g., professionalize training SFT instructors; deploy SFT to counter inequity). Recommendations are aligned with a purpose-built framework-"The Bicycle Principles"-that prioritizes evidenced-based teaching, inclusiveness, and equity, as well as the ability to scale, share, and sustain SFT. We also describe how the Bicycle Principles and recommendations are consistent with educational change theories and can overcome systemic barriers to delivering consistently effective, inclusive, and career-spanning SFT.

The rising global prevalence of diabetes and increasing demand for insulin, calls for an increase in accessibility and affordability of insulin drugs through efficient and cost-effective manufacturing processes. Often downstream operations become manufacturing bottlenecks while processing a high volume of product. Thus, process integration and intensification play an important role in reducing process steps and time, volume reduction, and lower equipment footprints, which brings additional process efficiencies and lowers the production cost. Manufacturers thrive to optimize existing unit operation to maximize its benefit replacing with simple but different efficient technologies. In this manuscript, the typical property of insulin in forming the pH-dependent zinc-insulin complex is explored. The benefit of zinc chloride precipitation/crystallization has been shown to increase the in-process product purity by reducing the product and process-related impurities. Incorporation of such unit operation in the insulin process has also a clear potential for replacing the high cost involved capture chromatography step. Same time, the reduction in volume of operation, buffer consumption, equipment footprint, and capabilities of product long time storage brings manufacturing flexibility and efficiencies. The data and capabilities of simple operation captured here would be significantly helpful for insulins and other biosimilar manufacturer to make progresses on cost-effective productions.

Background: Multiple Myeloma (MM) is an incurable hematological malignancy with current treatments comprising combination regimens, typically featuring immunomodulatory agents (IMiDs) due to their potent anti-tumor activity and immunomodulatory effects. Clinical studies utilizing the combination of IMiD agents and daratumumab (DARA), an anti-CD38 monoclonal antibody, have shown improved patient outcomes for MM. However, patients ultimately relapse demonstrating the need for novel therapies. Iberdomide (IBER) is a novel cereblon E3 ligase modulator. It promotes faster and deeper degradation of the substrate targets compared to IMiDs, resulting in enhanced anti-proliferative, pro-apoptotic and immune stimulatory activity. In early clinical studies, IBER has been shown to overcome resistance to IMiDs and in the ongoing Phase 3 EXCALIBER study (NCT04975997) is being explored for treatment of newly diagnosed (ND) and relapsed/refractory (RR) MM in combination with DARA and dexamethasone. Here, we investigate the potential mechanisms of synergy between IBER and DARA in preclinical models. Methods: Complement dependent cytotoxicity (CDC) of DARA was assessed with 15% human serum for human complement components and assays were performed by titrating either single agent or combinations in a tritiated thymidine assay. Antibody dependent cellular cytotoxicity (ADCC) was performed by co-culturing MM cells with varying expression levels of CD38 and effector cells and assessing target cell viability with annexin-v/topro-3 flow. A humanized PBMC adoptive transfer mouse model, utilizing human PBMC engraftment 14 days prior to implantation, was used to assess in vivo activity of IBER, DARA and IBER + DARA. Results: In CDC assays, we observed variable sensitivity of MM cells to complement-specific CDC in the presence of DARA (0.1-1 µg/ml), regardless of cell surface CD38 expression. Notably, IBER treatment resulted in upregulation of CD38 surface expression in 60% of MM cell lines tested. LP1 and MOLP8 displayed susceptibility to DARA-mediated CDC. DARA showed a dose-dependent increase in CDC activity in both cell lines. Notably, IBER+DARA also showed ~35% more synergistic CDC activity in both cell lines, than the single agents. In ADCC assays, we observed pretreatment of PBMC with IBER (vs. DMSO) significantly increased DARA mediated ADCC in H929 and LP-1 cells. To confirm that this effect was directed by NK cells, we cultured NK cells for 24 hr in supernatants from stimulated PBMC in presence of IBER prior to co-culture with MM cells. We noted that IBER-treated PBMC supernatant significantly enhanced the NK ADCC activity of DARA suggesting that IBER enhancement of cytokine secretion from PBMC increases NK cell mediated ADCC. Orthogonally, we pre-treated MM cells with IBER or DMSO prior to co-culture in ADCC assay. Notably, IBER treatment of MM cells, without treating immune cells, also increased DARA-mediated ADCC, indicating that IBER directly increases sensitivity to DARA-directed ADCC. To investigate the MOA of IBER-DARA synergy in ADCC, we analyzed gene expression and cell surface changes of a panel of NK-specific receptor ligands on MM cells following treatment with IBER. We observed IBER-induced upregulation of MICA mRNA levels (~2x) and surface expression (~40%) in MM target cells. We used RNAi to knock down Ikaros, an IBER substrate, which resulted in increased MICA expression (~3x) in MM cells. Furthermore, we observed that RNAi knock down of MICA in MM cells resulted in a significant decrease (60%, p<0.0001) in MM cell killing by NK cells, suggesting IBER-enhanced sensitivity of MM cells to NK-cell killing was in part, due to the upregulation of MICA through degradation of Ikaros. Lastly, we examined the anti-MM effects of IBER in a humanized xenograft model with a lenalidomide resistant cell line. Longitudinal analysis identified persistence of human PBMC engraftment and activation of immune subsets (NK cells and T-cells) that were increased upon IBER treatments, consistent with clinical observations. The combination of IBER/DARA resulted in ~22% tumor growth inhibition (TGI) in comparison to single agents, DARA and IBER and ~37% TGI in comparison to vehicle. Conclusion: Taken together, these data demonstrate that IBER and DARA work synergistically in preclinical models primarily through enhancement of both ADCC and CDC. This combination has the potential to improve outcomes in MM.

Oligonychus coffeae (Acari: Tetranychidae), popularly known as red spider mite (RSM) is one of the major pests of commercial tea (Camellia sinensis (L.) O. Kuntze) plantation world over. Many attempts have been made in the past to control this devastating pest using a variety of microbial bioagents, however, area-wise field success is very limited. We carried out an in vitro study to explore the potential of rhizospheric Bacillus spp. (B. amyloliquefaciens BAC1, B. subtilis LB22, and B. velezensis AB22) against O. coffeae through adulticidal and ovicidal activity. The 100% adult and egg mortality was observed with bacterial suspension (1 × 109 CFU/mL) by B. velezensis AB22, showing the lowest LC50 values for both adults and eggs of O. coffeae, i.e., 0.28 × 105 and 0.29 × 105, respectively. The study also throws some insights into the underlying mechanism through electron microscopy study and identification of some putative pesticidal metabolites from all the species. The three Bacillus species were observed to have four commonly secreted putative bioactive secondary metabolites, brevianamide A, heptadecanoic acid, thiolutin, and versimide responsible for their bio-efficacy against O. coffeae. The outcome of our study provides a strong possibility of introducing Bacillus spp. as a biological miticide and developing synthetic metabolites mimicking the mechanistic pathway involved in microbial bioefficacy.

Background: The incidence of multiple myeloma (MM) with t(4;14) translocation is ~15% of newly diagnosed MM (NDMM), and is associated with poor prognosis and high-risk disease. Recent analysis of t(4;14) genomics indicate that the location of the chromosome 4 (chr4) breakpoint can significantly segregate patient outcome regardless of therapeutic intervention. Translocation of IGH regulatory elements from chr14, drive the expression of NSD2 (chr4), a histone (H3) methyltransferase responsible for di-methylation of H3 lysine 36 (H3K36me2), a mark of active chromatin. Depending upon the location of the chr4 breakpoint, different isoforms of NSD2 are expressed, including full-length (NSD2-FL) and various N-terminus truncations (NSD2-TR). The mechanisms of how the location of the chr4 breakpoint and the functionalities of NSD2 isoforms may contribute to a higher risk biology in t(4;14) MM patients is not known. Here we compare and contrast the 3D chromosomal organization of t(4;14)-NSD2-FL, t(4;14)-NSD2-TR and non-t(4;14) in pre-clinical MM models. Results: Comparative analysis of chromosome conformation capture (Hi-C) indicates that there is a decrease in medium-to-long range chromosomal looping interactions accompanied by an increase in short-range interactions from t(4;14) vs. non-t(4;14) models (Figure A). Accordingly, relative quantification of chromosomal contact probabilities of intra-chromosomal (cis) contacts increase in frequency from non-t(4;14) (77%) vs. t(4;14)-NSD2-FL (87%) vs. t(4;14)-NSD2-TR (89%). Evaluation of active/inactive (A/B) 3D genomic compartments between non-t(4;14) and t(4;14) models suggest significant compartment switches (~30% genome; combined A-to-B and B-to-A). Analysis of gene neighborhoods through topologically associated domains (TADs) suggests that there are decreases in contacts at the TAD boundary regions in t(4;14)-NSD2-TR vs. t(4;14)-NSD2-FL vs. non-t(4;14) models. TAD sizes are also generally smaller in size, from t(4;14)-NSD2-TR vs. t(4;14)-NSD2-FL vs. non-t(4;14). Complimentary analysis of activity by contact (ABC) to assess the potential influence of proximal and distal enhancers on gene activity confirms there is a decrease in ABC scores when comparing t(4;14) vs. non-t(4;14). Assessment of global chromatin accessibility (ATAC-Seq) indicate significant consensus open peaks (~135k), differentially accessible (DA) peaks (~2.6k), and differential closed peaks (~8.8k) in t(4;14) vs. non-t(4;14). Principal component (PC) analysis demonstrated a unique grouping of t(4;14) models compared to a very heterogenous distribution of non-t(4;14) models. DA regions in t(4;14) were found to be primarily more enriched in both intronic and intergenic regions, and within proximal and distal promoters. Analysis of histone marks was used to assess differences in global active enhancers (H3K4me1, H3K27ac), repressive chromatin (H3K9me3, H3K27me3), and active transcription (H3K36me2/3, H3K4me3) between non-t(4;14) and t(4;14). Active marks were shown to be increased, and repressive marks decreased in t(4;14) vs. non-t(4;14) models that also correlated with DA peaks. Enhancer ranking suggests the frequency of potentially poised superenhancers increase in t(4;14) vs. non-t(4;14). Differential expression (DE) analysis between t(4;14) and non-t(4;14) was highly correlative with DA peaks (Figure B). In addition, distinctive transcriptional signatures between non-t(4;14), t(4;14)-NSD2-FL, and t(4;14)-NSD2-TR were identified. Conservative (DA+DE) pathway enrichment suggests multiple and distinct biological processes including cell adhesion through adherens junctions, cell-cycle regulation through mitotic checkpoints, chromosomal reorganization through depolymerization of the nuclear lamina, and epithelial to mesenchymal transition. Conclusions: Systematic chromosomal re-arrangement and accessibility driven by differential epigenetic deposition of histone regulatory marks, differentiates t(4;14) from non-t(4;14) MM biology. These analyses suggest that given the nature of the translocation, and additionally the location of the chr4 breakpoint, result in major 3D chromosomal structural rearrangement, mediating biological programs that may explain the differences between successful and poor interventional therapies for this subset of MM disease.