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An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed. Outer membrane vesicles (OMVs) can strongly activate the innate immune system and are qualified as immunoadjuvants. Here, we describe a versatile OMV-based vaccine platform to elicit a specific anti-tumor immune response via specifically presenting antigens onto OMV surface. We first display tumor antigens on the OMVs surface by fusing with ClyA protein, and then simplify the antigen display process by employing a Plug-and-Display system comprising the tag/catcher protein pairs. OMVs decorated with different protein catchers can simultaneously display multiple, distinct tumor antigens to elicit a synergistic antitumour immune response. In addition, the bioengineered OMVs loaded with different tumor antigens can abrogate lung melanoma metastasis and inhibit subcutaneous colorectal cancer growth. The ability of the bioengineered OMV-based platform to rapidly and simultaneously display antigens may facilitate the development of these agents for personalized tumour vaccines. Outer membrane vesicles (OMVs), non-replicative particles secreted by Gram-negative bacteria, are known for their immunostimulatory and adjuvant properties. Here, by employing a Plug-and-Display technology, the authors engineer OMVs to display tumor antigens on the surface, a platform that promotes anti-tumor immune responses in preclinical cancer models.

Chemotherapy remains one of the irreplaceable treatments for cancer therapy. The use of immunogenic cell death (ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells, simultaneously eliciting an antitumor immune response by promoting the recruitment of cytotoxic immune cells and production of granzyme B (GrB). However, numerous malignant cancers adaptively acquired the capacity of secreting serpinb9 (Sb9), a physiological inhibitor of GrB, which can reversibly inhibit the biological activity of GrB. To circumvent this dilemma, in this study, an integrated tailor-made nanomedicine composed of tumor-targeting peptide (Arg-Gly-Asp, RGD) decorated liposome, doxorubicin (DOX, an effective ICD inducer), and the compound 3034 (an inhibitor of Sb9), is developed (termed as D3RL) for breast cancer chemo-immunotherapy. In vitro and in vivo studies show that D3RL can directly kill tumor cells and trigger the host immune response by inducing ICD. Meanwhile, D3RL can competitively relieve the inhibition of Sb9 to GrB. The restored GrB can not only effectively induce tumor immunotherapy, but also degrade matrix components in the tumor microenvironment, consequently improving the infiltration of immune cells and the penetration of nanomedicines, which in return enhance the combined antitumor effect. Taken together, this work develops an integrated therapeutic solution for targeted production and restoration of GrB to achieve a combined chemoimmunotherapy for breast cancer.

Breast cancer remains a leading cause of morbidity and mortality among women worldwide, emphasizing the urgent need for enhanced diagnostic and therapeutic approaches. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has emerged as a notable target due to its markedly elevated expression in breast tumors, suggesting the viability of LRG1 as a theranostic target. In our study, we employed phage display technology to identify a peptide, termed ET, that binds to LRG1 with a dissociation constant of 48.4 µM. After modified with fluorescent cyanine dye, the ET peptide showcased effective tumor-targeting imaging across three different primary breast tumor models and a metastatic breast tumor model. We also undertook a comprehensive safety evaluation, which verified the good biosafety credentials of ET peptide. In summary, the ET peptide identified in this study shows effective LRG1-targeting ability both in vitro and in vivo , thus exhibiting immense potential for clinical translation.

Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas (ESCC), and postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis. Since surgical resection promotes the local angiogenesis at the tumor site, further exacerbating the proliferation and invasion of residual tumor cells, it is urgent to inhibit angiogenesis after surgery. Here, a functional peptide-based nanomedicine was obtained from peptide—drug conjugates, which are composed of a hydrophilic targeting motif (vascular endothelial growth factor family and their receptors (VEGFR) targeting peptide for anti-angiogenesis), and an ester-linked hydrophobic oridonin (ORI). The nanomedicine exhibits esterase-catalyzed disassembly and drug release, and significantly enhanced the anti-tumor efficacy of chemotherapeutics in a postoperative tumor recurrence model through synergistic anti-angiogenic strategies. This study provides an integrated solution for anti-angiogenesis-augmented chemotherapy and demonstrates the encouraging potential for postoperative treatment.

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Liquid–liquid phase separation is considered a generic approach to organize membrane-less compartments, enabling the dynamic regulation of phase-separated assemblies to be investigated and pivotal roles of protein posttranslational modifications to be demonstrated. By surveying the subcellular localizations of human deubiquitylases, USP42 was identified to form nuclear punctate structures that are associated with phase separation properties. Bioinformatic analysis demonstrated that the USP42 C-terminal sequence was intrinsically disordered, which was further experimentally confirmed to confer phase separation features. USP42 is distributed to SC35-positive nuclear speckles in a positively charged C-terminal residue- and enzymatic activity-dependent manner. Notably, USP42 directs the integration of the spliceosome component PLRG1 into nuclear speckles, and its depletion interferes with the conformation of SC35 foci. Functionally, USP42 downregulation deregulates multiple mRNA splicing events and leads to deterred cancer cell growth, which is consistent with the impact of PLRG1 repression. Finally, USP42 expression is strongly correlated with that of PLRG1 in non-small-cell lung cancer samples and predicts adverse prognosis in overall survival. As a deubiquitylase capable of dynamically guiding nuclear speckle phase separation and mRNA splicing, USP42 inhibition presents a novel anticancer strategy by targeting phase separation.

Background: Sports fatigue in soccer athletes has been shown to decrease neural activity, impairing cognitive function and negatively affecting motor performance. Transcranial direct current stimulation (tDCS) can alter cortical excitability, augment synaptic plasticity, and enhance cognitive function. However, its potential to ameliorate cognitive impairment during sports fatigue remains largely unexplored. This study investigated the effect of dual-site tDCS targeting the dorsolateral prefrontal cortex (DLPFC) or primary motor cortex (M1) on attention, decision-making, and working memory in elite soccer athletes during sports fatigue. Methods: Sports fatigue was induced in 23 (non-goalkeeper) elite soccer athletes, who then participated in three counterbalanced intervention sessions: dual-site tDCS over the M1, dual-site tDCS over the DLPFC, and sham tDCS. Following tDCS, participants completed the Stroop, Iowa Gambling, and 2-back tasks. Results: We found a significant improvement in Stroop task accuracy following dual-site anodal tDCS over the M1 compared with the sham intervention in the incongruent condition (p = 0.036). Net scores in the Iowa Gambling task during blocks 4 (p = 0.019) and 5 (p = 0.014) significantly decreased under dual-site tDCS targeting the DLPFC compared with the sham intervention. No differences in 2-back task performance were observed between sessions (all p > 0.05). Conclusions: We conclude that dual-site anodal tDCS applied to the M1 enhanced attention performance while tDCS targeting the DLPFC increased risk propensity in a decision-making task during sports fatigue in elite soccer athletes. However, dual-site anodal tDCS targeting either the M1 or DLPFC did not significantly influence working memory performance during sports fatigue in this population. These preliminary findings suggest that dual-site tDCS targeting the M1 has beneficial effects on attention performance, potentially informing future research on sports fatigue in athletes. Clinical Trial Registration: No: NCT06594978. Registered 09 September, 2024; https://clinicaltrials.gov/search?cond=NCT06594978.

Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes. In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting. To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

Gastroduodenal ulcers are associated with infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the causal relationship between gastroduodenal ulcers and gut microbiota, especially specific gut microbiota, remains unclear. We conducted an analysis of published data on the gut microbiota and Gastroduodenal ulcer using genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was performed to determine the causal relationship between gut microbiota and Gastroduodenal ulcer. Sensitivity, heterogeneity, and pleiotropy analyses were conducted to confirm the accuracy of the research findings. Our study showed that the abundance of , , , , , and was negatively correlated with the risk of Gastroduodenal ulcer. Conversely, the abundance of , , , , , , and was positively correlated with the risk of Gastroduodenal ulcer. MR analysis revealed causal relationships between 13 bacterial genera and Gastroduodenal ulcer. This study represents a groundbreaking endeavor by furnishing preliminary evidence regarding the potentially advantageous or detrimental causal link between the gut microbiota and Gastroduodenal ulcer, employing Mendelian Randomization (MR) analysis for the first time. These discoveries have the potential to yield fresh perspectives on the prevention and therapeutic approaches concerning Gastroduodenal ulcer, with a specific focus on the modulation of the gut microbiota.

Shape memory hydrogels (SMHs) have emerged as transformative materials in tissue engineering, owing to their unique ability to recover their original shape after deformation. These hydrogels combine hydrophilicity and elasticity with shape memory capabilities, making them ideal candidates for various biomedical applications. This review examines their innovative design and synthesis, highlighting the physical and biological characteristics that make them well-suited for tissue engineering, such as mechanical properties, biocompatibility, and biodegradability. SMHs have diverse applications in tissue engineering, including bone regeneration, soft tissue reconstruction, and the engineering of vascular and neural tissues. Additionally, they are utilized in smart drug delivery systems and the fabrication of 3D-printed customized implants. Despite these advancements, challenges such as production scalability, optimization of mechanical properties, shape recovery and fixation, controlled degradation, and long-term stability persist. Interdisciplinary approaches are crucial for overcoming these challenges and enhancing their clinical potential. In conclusion, SMHs offer innovative solutions to complex biomedical problems, making them valuable tools for advancing regenerative medicine and improving patient outcomes. [Display omitted] •Comprehensiveness: Reviews shape memory hydrogels from design to biomedical applications.•Clarity and accessibility: Summarizes key material properties for functional tissue scaffolds.•Advancement: Highlights emerging uses in 3D printing, drug delivery, and regenerative therapy.•Insightfulness: Discusses unresolved challenges in shape fixation, degradation, and scaling.•Relevance: Provides a foundational guide for designing next-generation bioactive hydrogels.