GNE-317 Reverses MSN-Mediated Proneural-to-Mesenchymal Transition and Suppresses Chemoradiotherapy Resistance in Glioblastoma via PI3K/mTOR.

Glioblastoma (GBM) resistance to chemoradiotherapy is a major factor contributing to poor treatment outcomes. This resistance markedly affects the effectiveness of surgery combined with chemoradiotherapy and leads to post-surgical tumor recurrence. Therefore, exploring the mechanisms underlying chemoradiotherapy resistance in GBM is crucial for understanding its progression and improving therapeutic options.

Titanium Alloy Ti-6Al-4V Electrochemical Dissolution Behavior in NaNO and NaCl Solutions at Low Current Density.

Jet electrochemical micromilling (JEMM) exhibits significant potential for high-efficiency and high-quality machining of titanium alloy microstructures. However, during the JEMM process, the machined surface of the workpiece inevitably experiences stray current attacks at low current levels. Due to the formation of a dense passive film on the surface of the titanium alloy under electrochemical action, stray corrosion occurs on the machined surface.

Electrochemical Machining of Micro-Pit Arrays on a GH4169 Alloy with a Roll-Print Mask Using a CHNaO-Containing NaNO Mixed Electrolyte.

GH4169 alloy, a nickel-based superalloy known for its excellent high temperature resistance, corrosion resistance, mechanical properties, and high-temperature tribological properties, is widely used in industrial applications, such as in gas turbines for space shuttles and rocket engines. This study addresses the issue of electrolyte product residue in the electrochemical machining process of a GH4169 alloy by utilizing a CHNaO-containing NaNO new mixed electrolyte. Comparative investigations of the electrochemical behavior and electrolyte product removal mechanisms at different concentrations of CHNaO additive in NaNO solutions were conducted.

Electrochemical Properties and Jet Electrochemical Micromilling of (TiB+TiC)/Ti6Al4V Composites in NaCl+NaNO Mixed Electrolyte.

Difficult-to-cut titanium matrix composites (TiB+TiC)/Ti6Al4V have extensive application prospects in the fields of biomedical and aerospace metal microcomponents due to their excellent mechanical properties. Jet electrochemical micromilling (JEMM) technology is an ideal method for machining microstructures that leverages the principle of electrochemical anodic dissolution. However, the matrix Ti6Al4V is susceptible to passivation during electrochemical milling, and the inclusion of high-strength TiB whiskers and TiC particles as reinforcing phases further increases the machining difficulty of (TiB+TiC)/Ti6Al4V.

High-Entropy Sulfide (FeCoNiCrMn)S for Room Temperature NO Sensors.

Metal sulfides have been extensively studied in the field of chemical sensors working at room temperature (RT). However, compared to metal oxides, metal sulfides often suffer from incomplete recovery and unsatisfactory selectivity. In this work, we for the first time report the high-entropy sulfide (HES) (FeCoNiCrMn)S, prepared by the solvothermal method, is a promising candidate for utilization as the sensitive layer in gas sensors.

Polypropylene Blends with Durable Hydrophobicity and Enhanced Mechanical Properties Based on POSS and Alkane Modified Polypentafluorophenyl Methacrylate.

Durable functionalization on polypropylene (PP) surfaces is always a key problem to besolved. Coatings with low surface energy peel off easily especially under extreme conditions, owing to their weak adhesion. In this paper, side groups of both polyhedral oligomeric silsesquioxane (POSS) and alkane are grafted to polypentafluorophenyl methacrylate (PFP), and then PP blends with these side-group modified PFP are obtained through a melt-blending process.

Jet Electroforming of High-Aspect-Ratio Microcomponents by Periodically Lifting a Necked-Entrance Through-Mask.

High-aspect-ratio micro- and mesoscale metallic components (HAR-MMMCs) can play some unique roles in quite a few application fields, but their cost-efficient fabrication is significantly difficult to accomplish. To address this issue, this study proposes a necked-entrance through-mask (NTM) periodically lifting electroforming technology with an impinging jet electrolyte supply. The effects of the size of the necked entrance of the through-mask and the jet speed of the electrolyte on electrodeposition behaviors, including the thickness distribution of the growing top surface, deposition defect formation, geometrical accuracy, and electrodeposition rate, are investigated numerically and experimentally.

Reversing cancer immunoediting phases with a tumor-activated and optically reinforced immunoscaffold.

vaccine (ISV) is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire. However, its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity scarcity. To break this plight, a tumor-activated and optically reinforced immunoscaffold (TURN) is exploited to trigger cancer immunoediting phases regression, thus levering potent systemic antitumor immune responses.

A programmable releasing versatile hydrogel platform boosts systemic immune responses via sculpting tumor immunogenicity and reversing tolerogenic dendritic cells.

Immunogenicity improvement is a valuable strategy for tumor immunotherapy. However, immunosuppressive factors bestow tolerogenic phenotype on tumor-infiltrating DCs, which exhibit weak antigen presentation and strong anti-inflammatory cytokines secretion abilities, limiting the effectiveness of tumor immunotherapy even if the tumor has adequate immunogenicity. Herein, we designed a programmable releasing versatile hydrogel platform (PIVOT) to sculpt tumor immunogenicity, increase intratumoral DCs and cDC1s abundance, and reverse the tolerogenic phenotype of DCs, thus promoting their maturation for boosting innate and adaptive immune responses.

Tumor Environment Regression Therapy Implemented by Switchable Prune-to-Essence Nanoplatform Unleashed Systemic Immune Responses.

Coevolution of tumor cells and surrounding stroma results in protective protumoral environment, in which abundant vessel, stiff structure and immunosuppression promote each other, cooperatively incurring deterioration and treatment compromise. Reversing suchenvironment may transform tumors from treatment-resistant to treatment-vulnerable. However, effective reversion requires synergistic comprehensive regression of such environment under precise control.

Artificial Intelligence Aided Lipase Production and Engineering for Enzymatic Performance Improvement.

With the development of artificial intelligence (AI), tailoring methods for enzyme engineering have been widely expanded. Additional protocols based on optimized network models have been used to predict and optimize lipase production as well as properties, namely, catalytic activity, stability, and substrate specificity. Here, different network models and algorithms for the prediction and reforming of lipase, focusing on its modification methods and cases based on AI, are reviewed in terms of both their advantages and disadvantages.

Effects of probiotics in patients with morbid obesity undergoing bariatric surgery: a systematic review and meta-analysis.

Background: Probiotics are commonly used after bariatric surgery. However, uncertainty remains regarding their effects. The purpose of this systematic review was to assess the effect of probiotics in patients with morbid obesity undergoing bariatric surgery.

Antigenicity and adjuvanticity co-reinforced personalized cell vaccines based on self-adjuvanted hydrogel for post-surgical cancer vaccination.

Cancer vaccine-based postsurgical immunotherapy is emerging as a promising approach in patients following surgical resection for inhibition of tumor recurrence. However, low immunogenicity and insufficient cancer antigens limit the widespread application of postoperative cancer vaccines. Here, we propose a "trash to treasure" cancer vaccine strategy to enhance postsurgical personalized immunotherapy, in which antigenicity and adjuvanticity of purified surgically exfoliated autologous tumors (with whole antigen repertoire) were co-reinforced.

A Multivalent Personalized Vaccine Orchestrating Two-Signal Activation Rebuilds the Bridge Between Innate and Adaptive Antitumor Immunity.

Personalized vaccines capable of circumventing tumor heterogeneity have exhibited compelling prospects. However, their therapeutic benefit is greatly hindered by the limited antigen repertoire and poor response of CD8 T-cell immunity. Here, a double-signal coregulated cross-linking hydrogel-based vaccine (Bridge-Vax) is engineered to rebuild the bridge between innate and adaptive immunity for activating CD8 T-cells against full repertoire of tumor antigens.

A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence.

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system.

The effect of students' online learning experience on their satisfaction during the COVID-19 pandemic: The mediating role of preference.

Introduction: During the peak of the COVID-19 pandemic, nearly all educational institutions globally had to eventually embrace the maneuver of transferring to nearly 100% online learning as a new routine for different curricula. Although many students in developing countries such as Kenya are only experiencing the exclusive online learning approach for the first time, research on students' experience and satisfaction with COVID-19-imposed online learning is largely lacking. Thus, this study examined the effect of online-learning experiences on satisfaction in the setting of the COVID-19 pandemic in Kenya.

New insights into the characteristics of DRAK2 and its role in apoptosis: From molecular mechanisms to clinically applied potential.

As a member of the death-associated protein kinase (DAPK) family, DAP kinase-associated apoptosis-inducing kinase 2 (DRAK2) performs apoptosis-related functions. Compelling evidence suggests that DRAK2 is involved in regulating the activation of T lymphocytes as well as pancreatic β-cell apoptosis in type I diabetes. In addition, DRAK2 has been shown to be involved in the development of related tumor and non-tumor diseases through a variety of mechanisms, including exacerbation of alcoholic fatty liver disease (NAFLD) through SRSF6-associated RNA selective splicing mechanism, regulation of chronic lymphocytic leukemia and acute myeloid leukemia, and progression of colorectal cancer.

Tumor Microenvironment-Activated Hydrogel Platform with Programmed Release Property Evokes a Cascade-Amplified Immune Response against Tumor Growth, Metastasis and Recurrence.

In situ tumor vaccines (ITV) have been recognized as a promising antitumor strategy since they contain the entire tumor-specific antigens, avoiding tumor cells from evading immune surveillance due to antigen loss. However, the therapeutic benefits of ITV are limited by obstacles such as insufficient antigen loading, inadequate immune system activation, and immunosuppressive tumor microenvironments (TME). Herein, a tumor microenvironment-activated hydrogel platform (TED-Gel) with programmed drug release property is constructed for cascaded amplification of the anti-tumor immune response elicited by ITV.

Multifunctional light-activatable nanocomplex conducting temperate-heat photothermal therapy to avert excessive inflammation and trigger augmented immunotherapy.

Photothermal therapy (PTT) has been known as an effective weapon against cancer. However, the necrosis induced by hyperthermia post PTT can trigger excessive inflammation response and arouse tumor self-protection resulting in tumor immunosuppression, metastasis and recurrence. To settle this issue, we here reported a multifunctional light-activatable nanocomplex (MILAN) to avoid hyperthermia and achieve temperate-heat PTT for extensive apoptosis, but not necrosis, and further antitumor immune response augmentation to inhibit metastasis and recurrence.

Lanthanide-Nucleotide Coordination Nanoparticles for STING Activation.

Activation of the stimulator of interferon genes (STING) is essential for blocking viral infections and eliciting antitumor immune responses. Local injection of synthetic STING agonists, such as 2'3'-cGAMP [cGAMP = cyclic 5'-guanosine monophosphate (cGMP)-adenosine monophosphate (AMP)], is a promising approach to enhance antiviral functions and cancer immunotherapy. However, the application of such agonists has been hindered by complicated synthetic procedures, high doses, and unsatisfactory systemic immune responses.

An spontaneously forming micelle-hydrogel system with programmable release for the sequential therapy of anaplastic thyroid cancer.

Anaplastic thyroid carcinoma (ATC) is a lethal malignancy with a 1 year survival rate of less than 20%. Combination chemotherapy with cisplatin and paclitaxel is recommended as a critical therapeutic approach toward ATC. However, harsh side-effects on patients and unsatisfactory intratumoral concentrations hamper the effectiveness of systemic chemotherapy.

An Acidity-Initiated Self-Assembly/Disassembly Nanoprobe to Switch on Fluorescence for Tumor-Targeted Near-Infrared Imaging.

The deep penetration, real-time monitoring ability, and high resolution of near-infrared (NIR) fluorescence imaging make it suitable for tumor diagnosis. However, the lack of specificity and selectivity restricts its further application. Here, for the first time, we applied a CBT-Cys click condensation reaction to synthesize an acidity-initiated molecular probe (AIM-Probe, Cys(StBu)-Lys(Cy 5.

A spontaneous multifunctional hydrogel vaccine amplifies the innate immune response to launch a powerful antitumor adaptive immune response.

Substantial progress has been made with cancer immunotherapeutic strategies in recent years, most of which mainly rely on enhancing the T cell response. However, sufficient tumor antigen information often cannot be presented to T cells, resulting in a failed effector T cell response. The innate immune system can effectively recognize tumor antigens and then initiate an adaptive immune response.

Numerical Analysis and Experimental Study on Fabrication of High Aspect Ratio Tapered Ultrafine Holes by Over-Growth Electroforming Process.

High aspect ratio (HAR) ultrafine tapered holes (diameter ≤5 μm; AR ≥5) are the most important elements for some high-tech perforated metallic products, but they are very difficult to manufacture. Therefore, this paper proposes a nontraditional over-growth electroforming process. The formation mechanism of the HAR ultrafine tapered holes is investigated, and the factors controlling the geometric shape evolution are analyzed numerically.