An Antibacterial Hemostasis Sponge of Gelatin/ε-Poly-L-Lysine Composite.

Massive bleeding and bacterial infection of wounds may be life-threatening or even lead to death. Nowadays, gelatin-based hemostatic sponges have been widely used, but gelatin is not antibacterial and has poor structural stability. In this study, we mixed an antibacterial polypeptide, ε-poly-L-lysine (EPL), into gelatin.

Trojan-Horse Strategy Targeting the Gut-Liver Axis Modulates Gut Microbiome and Reshapes Microenvironment for Orthotopic Hepatocellular Carcinoma Therapy.

Reversing the hepatic inflammatory and immunosuppressive microenvironment caused by gut microbiota-derived lipopolysaccharides (LPS), accumulating to the liver through the gut-liver axis, is crucial for suppressing hepatocellular carcinoma (HCC) and metastasis. However, synergistically manipulating LPS-induced inflammation and gut microbiota remains a daunting task. Herein, a Trojan-horse strategy is proposed using an oral dextran-carbenoxolone (DEX-CBX) conjugate, which combines prebiotic and glycyrrhetinic acid (GA) homologs, to targeted delivery GA to HCC through the gut-liver axis for simultaneous modulation of hepatic inflammation and gut microbiota.

In-situ activation of biomimetic single-site bioorthogonal nanozyme for tumor-specific combination therapy.

Copper-catalyzed click chemistry offers creative strategies for activation of therapeutics without disrupting biological processes. Despite tremendous efforts, current copper catalysts face fundamental challenges in achieving high efficiency, atom economy, and tissue-specific selectivity. Herein, we develop a facile "mix-and-match synthetic strategy" to fabricate a biomimetic single-site copper-bipyridine-based cerium metal-organic framework (Cu/Ce-MOF@M) for efficient and tumor cell-specific bioorthogonal catalysis.

Antioxidative, Anti-Inflammatory, Antibacterial, Photo-Cross-Linkable Hydrogel of Gallic Acid-Chitosan Methacrylate: Synthesis, , and Assessments.

Chitosan (CS)-based photo-cross-linkable hydrogels have gained increasing attention in biomedical applications. In this study, we grafted CS with gallic acid (GA) by carbodiimide chemistry to prepare the GA-CS conjugate, which was subsequently modified with methacrylic anhydride (MA) modification to obtain the methacrylated GA-CS conjugate (GA-CS-MA). Our results demonstrated that the GA-CS-MA hydrogel not only exhibited improved physicochemical properties but also showed antibacterial, antioxidative, and anti-inflammatory capacity.

Photocrosslinkable hydrogel of ibuprofen-chitosan methacrylate modulates inflammatory response.

Methacrylated biopolymers are unique and attractive in preparing photocrosslinkable hydrogels in biomedical applications. Here we report a novel chitosan (CS) derivative-based injectable hydrogel with anti-inflammatory capacity via methacrylation modification. First, ibuprofen (IBU) was conjugated to the backbone of CS by carbodiimide chemistry to obtain IBU-CS conjugate, which converts water-insoluble unmodified CS into water-soluble IBU-CS conjugate.

Orally available dextran-aspirin nanomedicine modulates gut inflammation and microbiota homeostasis for primary colorectal cancer therapy.

Reversing the aggravated immunosuppression hence overgrowth of colorectal cancer (CRC) caused by the gut inflammation and microbiota dysbiosis is pivotal for effective CRC therapy and metastasis inhibition. However, the low delivery efficiency and severe dose-limiting off-target toxicities caused by unsatisfied drug delivery systems remain the major obstacles in precisely modulating gut inflammation and microbiota in CRC therapy. Herein, a multifunctional oral dextran-aspirin nanomedicine (P3C-Asp) was utilized for oral treatment of primary CRC, as it could release salicylic acid (SA) while scavenging reactive oxygen species (ROS) and held great potential in modulating gut microbiota with prebiotic (dextran).

Radiation-Activated Resiquimod Prodrug Nanomaterials for Enhancing Immune Checkpoint Inhibitor Therapy.

Immune checkpoint inhibitor (ICI) therapy is effectively employed in treating various malignancies. However, the response rate is constrained to 5-30%, which is attributed to differences in immune responses across different tumors. Overcoming all obstacles of multistep immune activation with monotherapy is difficult.

Orchestrating Precision within the Tumor Microenvironment by Biomimetic Nanoprodrugs for Effective Tumor Therapy.

Malignant tumors are still one of the most deadly diseases that threaten human life and health. However, developing new drugs is challenging due to lengthy trials, funding constraints, and regulatory approval procedures. Consequently, researchers have devoted themselves to transforming some clinically approved old drugs into antitumor drugs with certain active ingredients, which have become an attractive alternative.

Emerging nanoparticle platforms for CpG oligonucleotide delivery.

Unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), which were therapeutic DNA with high immunostimulatory activity, have been applied in widespread applications from basic research to clinics as therapeutic agents for cancer immunotherapy, viral infection, allergic diseases and asthma since their discovery in 1995. The major factors to consider for clinical translation using CpG motifs are the protection of CpG ODNs from DNase degradation and the delivery of CpG ODNs to the Toll-like receptor-9 expressed human B-cells and plasmacytoid dendritic cells. Therefore, great efforts have been devoted to the advances of efficient delivery systems for CpG ODNs.

Electrospun membranes chelated by metal magnesium ions enhance pro-angiogenic activity and promote diabetic wound healing.

Diabetic wounds, resulting from skin atrophy due to localized ischemia and hypoxia in diabetic patients, lead to chronic pathological inflammation and delayed healing. Using electrospinning technology, we developed magnesium ion-chelated nanofiber membranes to explore their efficacy in antibacterial, anti-inflammatory, and angiogenic applications for wound healing. These membranes are flexible and elastic, resembling native skin tissue, and possess good hydrophilicity for comfortable wound bed contact.

An Fc Binding Peptide-Based Facile and Versatile Build Platform for Multispecific Antibodies.

Multispecific antibodies (MsAbs) maintain the specificity of versatile antibodies while simultaneously addressing different epitopes for a cumulative, collaborative effect. They could be an alternative treatment to chimeric antigen receptor-T cell therapy by helping to redirect T cells to tumors . However, one major limitation of their development is their relatively complex production process, which involves performance of a massive screen with low yield, inconsistent quality, and nonnegligible impurities.

Azide-Masked Resiquimod Activated by Hypoxia for Selective Tumor Therapy.

Resiquimod (R848) is an immunomodulator that causes a severe systemic inflammatory reaction due to low tumor selectivity, thus hindering its use in cancer therapy. Therefore, an azide-masked prodrug (R848-N ) of R848 is developed, which is selectively activated to R848 in hypoxic tumors. R848-N significantly reduces pro-inflammatory cytokines in treated mice to 1/12 compared to R848 at the same dose.

Cisplatin Nanoparticles Promote Intratumoral CD8 T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk.

Nanomedicines are highly promising for cancer therapy due to their minimal side effects. However, little is known regarding their host immune response, which may limit their clinical efficacy and applications. Here, we find that cisplatin (CDDP)-loaded poly(l-glutamic acid)--methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) elicit a strong antitumor CD8 T cell-mediated immune response in a tumor-bearing mouse model compared to free CDDP.

A Minimalist Binary Vaccine Carrier for Personalized Postoperative Cancer Vaccine Therapy.

In recent years, significant evolutions have been made in applying nanotechnologies for prophylactic and therapeutic cancer vaccine design. However, the clinical translation of nanovaccines is still limited owing to their complicated compositions and difficulties in the spatiotemporal coordination of antigen-presenting cell activation and antigen cross-presentation. Herein, a minimalist binary nanovaccine (BiVax) is designed that integrates innate stimulating activity into the carrier to elicit robust antitumor immunity.

A simple and general strategy for postsurgical personalized cancer vaccine therapy based on an injectable dynamic covalent hydrogel.

Cancer vaccines artificially stimulate the immune system against cancer and are considered the most promising treatment of cancer. However, the current progress in vaccine research against cancer is still limited and slow, partially due to the difficulties in identifying and obtaining tumor-specific antigens. Considering surgery as the first choice for tumor treatment in most cases, the authors evaluated whether the resected tumor can be directly used as a source of tumor antigens for designing personalized cancer vaccines.

[The potential role of mirnas in the pathogenesis of hemorrhagic fever with renal syndrome].

Hemorrhagic fever with renal syndrome (HFRS) is an acute natural focal viral disease caused by viruses of the genus hantavirus, characterized by damage to small blood vessels, kidneys, lungs and other organs of a person. MicroRNAs (miRNAs) are 18-22 nucleotide endogenously expressed RNA molecules that inhibit gene expression at the post-transcriptional level by binding to the 3-untranslated region of the target mRNA. It has been proven that miRNAs play a significant role in various biological processes, including the cell cycle, apoptosis, cell proliferation and differentiation.

miR-186 Inhibits Liver Cancer Stem Cells Expansion Targeting PTPN11.

MicroRNAs (miRNAs) participated in the regulation of tumorigenesis, progression, metastasis, recurrence and chemo-resistance of cancers. However, the potential function of miRNAs in cancer stem cells (CSCs) or tumor-initiating cells (T-ICs) was not clearly elucidated. In the present study, we found that miR-186 expression was reduced in liver CSCs.

Precise delivery of obeticholic acid nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy.

Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy.

Biopolymer Immune Implants' Sequential Activation of Innate and Adaptive Immunity for Colorectal Cancer Postoperative Immunotherapy.

Surgical resection is the first-line therapy for colorectal cancer (CRC). However, for advanced CRC, the curative effect of surgical resection is limited due to either local recurrence or distal metastasis. Postoperative in situ immunotherapy, presents a promising option for preventing tumor recurrence and metastasis, owing to the fact that surgeons have unique opportunities and direct access to the surgical site.

In situ activation of STING pathway with polymeric SN38 for cancer chemoimmunotherapy.

STING (stimulator of interferon genes) signaling pathway has attracted considerable attention in cancer immunotherapy due to its capacity to boost vigorous antitumor immunity. However, the shortage of effective STING agonists limits the promotion of STING pathway in cancer treatment. Herein, we present an approach for in situ activation of STING pathway with nanoparticles delivered DNA-targeting chemo agents, based on the understanding that cytosol DNA is a pre-requisite for STING pathway activation.

Severity Detection for the Coronavirus Disease 2019 (COVID-19) Patients Using a Machine Learning Model Based on the Blood and Urine Tests.

The recent outbreak of the coronavirus disease-2019 (COVID-19) caused serious challenges to the human society in China and across the world. COVID-19 induced pneumonia in human hosts and carried a highly inter-person contagiousness. The COVID-19 patients may carry severe symptoms, and some of them may even die of major organ failures.

Epidemiologic and clinical characteristics of 42 deaths caused by SARS-CoV-2 infection in Wuhan, China: A retrospective study.

This study described the epidemiologic and clinical characteristics of patients who died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and pointed out the potential risk factors associated with fatal outcomes. Retrospective data from 42 death cases due to SARS-CoV-2 infection at Tongji Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, China was analyzed. Demographics, clinical detection, laboratory findings, and treatments of the deceased were collected and analyzed.

Non-coding RNA in bladder cancer.

Bladder cancer is the tenth most common cancer worldwide and has been associated with high mortality and morbidity. Although the treatment of bladder cancer is based on well-defined tumor classifications and gradings, patients still experience different clinical response. The heterogeneity of this disease calls for substantial research with more in-depth molecular characterization, with the hope of identifying new diagnostic and treatment options.

Prognostic value of platelet to lymphocyte ratio in hepatocellular carcinoma: a meta-analysis.

This study was designed to evaluate the prognostic value of platelet to lymphocyte ratio (PLR) in hepatocellular carcinoma (HCC). A comprehensive literature search for relevant studies was performed in Web of science, Embase and Pubmed. A total of nine studies with 2017 patients were included in this meta-analysis, and combined hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95%CIs) were served as effect measures.