Dental Pulp Stem Cell Lysate-Based Hydrogel Improves Diabetic Wound Healing via the Regulation of Anti-Inflammatory Macrophages and Keratinocytes.

The prolonged existence of chronic wounds heightens the risk of patients experiencing chronic pain, necrosis, and amputation. Dental pulp stem cells (DPSCs) have garnered attention due to their potential immunomodulatory and tissue repair regenerative effects in the management of chronic wounds. However, stem-cell-based therapy faces challenges such as malignant differentiation, immune rejection, and long-term effectiveness.

Hepatic FXR-FGF4 is required for bile acid homeostasis via an FGFR4-LRH-1 signal node under cholestatic stress.

Bile acid (BA) homeostasis is vital for various physiological processes, whereas its disruption underlies cholestasis. The farnesoid X receptor (FXR) is a master regulator of BA homeostasis via the ileal fibroblast growth factor (FGF)15/19 endocrine pathway, responding to postprandial or abnormal transintestinal BA flux. However, the de novo paracrine signal mediator of hepatic FXR, which governs the extent of BA synthesis within the liver in non-postprandial or intrahepatic cholestatic conditions, remains unknown.

The evolution of small-molecule Akt inhibitors from hit to clinical candidate.

Akt, a key regulator of cell survival, proliferation, and metabolism, has become a prominent target for treatment of cancer and inflammatory diseases. The journey of small-molecule Akt inhibitors from discovery to the clinic has faced numerous challenges, with a significant emphasis on optimization throughout the development process. Early discovery efforts identified various classes of inhibitors, including ATP-competitive and allosteric modulators.

Causal relationship between thyroid function and multiple sclerosis: A bidirectional Mendelian randomization study.

An association between thyroid function and multiple sclerosis (MS) has been reported in several observational studies, but the causal relationship between them is still unclear. Thus, this study used a bidirectional Mendelian randomization (MR) to investigate the associations between thyroid function and MS. Bidirectional MR was used to explore the causal relationship between thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [FT4], hyperthyroidism, and hypothyroidism) and MS.

Sequential Regulation of Local Reactive Oxygen Species by Ir@Cu/Zn-MOF Nanoparticles for Promoting Infected Wound Healing.

Most antimicrobials treat wound infections by an oxidation effect, which is induced by the generation of reactive oxygen species (ROS). However, the potential harm of the prolonged high level of ROS should not be ignored. In this study, we presented a novel cascade-reaction nanoparticle, Ir@Cu/Zn-MOF, to effectively regulate the ROS level throughout the healing progress of the infected wound.

A supramolecular hydrogel dressing with antibacterial, immunoregulation, and pro-regeneration ability for biofilm-associated wound healing.

Chronic wound treatment has emerged as a significant healthcare concern worldwide due to its substantial economic burden and the limited effectiveness of current treatments. Effective management of biofilm infections, regulation of excessive oxidative stress, and promotion of tissue regeneration are crucial for addressing chronic wounds. Hydrogel stands out as a promising candidate for chronic wound treatment.

Construction of Selective Ion Transport Polymer at Anode-Electrolyte Interface for Stable Aqueous Zinc-Ion Batteries.

Rampant dendrite formation and serious adverse parasitic reactions induced by migration of dissolved V/Mn cathode ions on Zn anode have hampered the high performance of aqueous zinc-ion batteries (AZIBs). Inspired by the coordination chemistry between functional groups of polymer and electrolyte ions, a freestanding layer consisting of dopamine-functionalized polypyrrole (DA-PPy) nanowires served as a selective ion transport layer at the anode-electrolyte interface to address these two issues, which could simultaneously avoid polarization caused by the introduction of an additional interface. On the one hand, the DA-PPy layer displays excellent zinc ion and charge transfer ability, as well as provides chemical homochanneling for zinc ions at the interface, which endow the DA-PPy layer with properties as a chemical guider and physical barrier for dendrite inhibition.

Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG.

The identification of mechanisms to store glucose carbon in the form of glycogen rather than fat in hepatocytes has important implications for the prevention of nonalcoholic fatty liver disease (NAFLD) and other chronic metabolic diseases. In this work, we show that glycogenesis uses its intermediate metabolite uridine diphosphate glucose (UDPG) to antagonize lipogenesis, thus steering both mouse and human hepatocytes toward storing glucose carbon as glycogen. The underlying mechanism involves transport of UDPG to the Golgi apparatus, where it binds to site-1 protease (S1P) and inhibits S1P-mediated cleavage of sterol regulatory element-binding proteins (SREBPs), thereby inhibiting lipogenesis in hepatocytes.

Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Background: Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients.

Methods: A total of 276 patients with HBV-ACLF were retrospectively recruited.

Pancreatic cancer pathology image segmentation with channel and spatial long-range dependencies.

Based on deep learning, pancreatic cancer pathology image segmentation technology effectively assists pathologists in achieving improved treatment outcomes. However, compared to traditional image segmentation tasks, the large size of tissues in pathology images requires a larger receptive field. While methods based on dilated convolutions or attention mechanisms can enhance the receptive field, they cannot capture long-range feature dependencies.

Human Adipose Tissue Lysate-Based Hydrogel for Lasting Immunomodulation to Effectively Improve Spinal Cord Injury Repair.

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel.

Self-Induced Dual-Layered Solid Electrolyte Interphase with High Toughness and High Ionic Conductivity for Ultra-Stable Lithium Metal Batteries.

Lithium (Li) metal is considered as one of the most promising candidates of anode material for high-specific-energy batteries, while irreversible chemical reactions always occur on the Li surface to continuously consume active Li, electrolyte. Solid electrolyte interphase (SEI) layer has been regarded as the key component in protecting Li metal anode. Herein, a controllable dual-layered SEI for Li metal anode in a scalable, low-loss manner is constructed.

An inflammation-responsive double-layer microneedle patch for recurrent atopic dermatitis therapy.

Seeking a potent therapeutic strategy for alleviating atopic dermatitis (AD) attack and preventing its recurrence is highly desired but remains challenging in clinical practice. Here, we propose an inflammation-responsive double-layer microneedle (IDMN) patch in situ delivering VD for recurrent AD therapy. IDMN comprises the backing layer part and the double-layer microneedle part, in which the inner layer is gelatin methacryloyl (GelMA) loaded with VD while the outer layer is composed of hyaluronic acid (HA).

Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine.

Translational medicine aims to improve human health by exploring potential treatment methods developed during basic scientific research and applying them to the treatment of patients in clinical settings. The advanced perceptions of gene functions have remarkably revolutionized clinical treatment strategies for target agents. However, the progress in gene editing therapy has been hindered due to the severe off-target effects and limited editing sites.

GOx-Powered Janus Platelet Nanomotors for Targeted Delivery of Thrombolytic Drugs in Treating Thrombotic Diseases.

Low efficiency of targeting and delivery toward the thrombus site poses challenges to using thrombolytic drugs. Inspired by the biomimetic system of platelet membranes (PMs) and glucose oxidase (GOx) modification technologies, we develop a novel GOx-powered Janus nanomotor by asymmetrically attaching the GOx to polymeric nanomotors coated with the PMs. Then the PM-coated nanomotors were conjugated with urokinase plasminogen activators (uPAs) on their surfaces.

Dynamic covalent nano-networks comprising antibiotics and polyphenols orchestrate bacterial drug resistance reversal and inflammation alleviation.

New antimicrobial strategies are urgently needed to meet the challenges posed by the emergence of drug-resistant bacteria and bacterial biofilms. This work reports the facile synthesis of antimicrobial dynamic covalent nano-networks (aDCNs) composing antibiotics bearing multiple primary amines, polyphenols, and a cross-linker acylphenylboronic acid. Mechanistically, the iminoboronate bond drives the formation of aDCNs, facilitates their stability, and renders them highly responsive to stimuli, such as low pH and high HO levels.

PI3K/ c-Myc/AFF4 axis promotes pancreatic tumorigenesis through fueling nucleotide metabolism.

MLL-AFF4 fusion gene has been discovered in acute leukemia, whether AFF4 alone plays a role in tumor, especially pancreatic tumorigenesis, is still elusive. Increasing evidence suggests that cancer cells altered nucleotide metabolism during tumorigenesis. In present study, we observed AFF4 overexpression promoted cell proliferation, colony formation and cell cycle progression while loss of AFF4 impairs above phenotypes of pancreatic ductal carcinoma (PDAC) cells.

Robust Acute Pancreatitis Identification and Diagnosis: RAPIDx.

The occurrence of acute pancreatitis (AP) is increasing significantly worldwide. However, current diagnostic methods of AP do not provide a clear clinical stratification of severity, and the prediction of complications in AP is still limited. Here, we present a robust AP identification and diagnosis (RAPIDx) method by the proteomic fingerprinting of intact nanoscale extracellular vesicles (EVs) from clinical samples.

Cell Membranes from Tumor-Tropic MSCs Screened by a Microfluidic Chip for Drug Nanoparticles Encapsulation and Cancer Targeted Therapy.

Nanoparticles (NPs)-based drug carriers are effective in reducing systemic toxicity and drug resistance for chemotherapy, and an emerging trend focuses on integrating cell membranes with nanomedicines for tumor targeting. Mesenchymal stem cells (MSCs) are promising candidates due to their unique tropism toward cancer cells, yet the tumor-tropic abilities can differ for MSCs sourced from different tissues. Here, a multichannel microfluidic chip to screen different sourced MSCs with the greatest tropism toward cervical cancer cells is developed.

Engineered Apoptosis-Bioinspired Nanoparticles Initiate Immune Cascade for Cancer Immunotherapy of Malignant Ascites.

Malignant ascites (MA) is a common symptom of peritoneal metastasis in liver cancer. Cancer immunotherapy can modulate immune cells to induce antitumor immune efficiency. Reprogramming tumor immune microenvironment (TIME) is a momentous strategy to overcome immunosuppression and achieve immune functional normalization.

Tumor Cell-Derived Microparticles Induced by Methotrexate Augment T-cell Antitumor Responses by Downregulating Expression of PD-1 in Neutrophils.

Neutrophils act as a "double-edged sword" in the tumor microenvironment by either supporting or suppressing tumor progression. Thus, eliciting a neutrophil antitumor response remains challenging. Here, we showed that tumor cell-derived microparticles induced by methotrexate (MTX-MP) acts as an immunotherapeutic agent to activate neutrophils, increasing the tumor-killing effect of the cells and augmenting T-cell antitumor responses.

Rapid, label-free histopathological diagnosis of liver cancer based on Raman spectroscopy and deep learning.

Biopsy is the recommended standard for pathological diagnosis of liver carcinoma. However, this method usually requires sectioning and staining, and well-trained pathologists to interpret tissue images. Here, we utilize Raman spectroscopy to study human hepatic tissue samples, developing and validating a workflow for in vitro and intraoperative pathological diagnosis of liver cancer.

Aligned electrospun fiber film loaded with multi-enzyme mimetic iridium nanozymes for wound healing.

A film with elaborate microstructures that offers biomimetic properties and multi functionalities is highly desired in wound healing. Here, we develop an aligned hydrogel fiber film integrated with multi-active constituents to promote wound healing. Such fiber films are designed and constructed by photo-crosslinking the methacrylate gelatin (GelMA) doped with silver nanoparticles (Ag NPs) and iridium nanoparticles coated with polyvinylpyrrolidone (PVP-Ir NPs) in the precursor solution using electrospinning.