PROTACs in Antivirals: Current Advancements and Future Perspectives.

Proteolysis-targeting chimera (PROTAC) technology has demonstrated remarkable progress in tumor therapy, attributed to its unique capability of catalytically degrading "undruggable" targets. In the context of the ongoing global health threat posed by the Coronavirus Disease 2019 (COVID-19) pandemic, the application scope of PROTAC technology has been gradually extended to the field of antiviral research. Unlike traditional small molecule inhibitors, PROTAC employs an "event-driven" mechanism to achieve ubiquitination-mediated degradation of target proteins.

Biomimetic Chitosan Nanogels Codeliver Drug/Small Activating RNA for Metastasis-Inhibited Necroptosis Therapy of Ovarian Cancer.

Ovarian cancer remains the leading cause of gynecologic malignancy-related deaths. Developing novel nanoplatforms to overcome the low efficacy of chemotherapy and advanced metastasis in ovarian cancer is crucial. Here, we report biomimetic chitosan nanogels (CH NGs) designed to codeliver gambogic acid (GA) and MAS1 small activating RNA (saMAS1).

A biomimetic nanoplatform mediates hypoxia-adenosine axis disruption and PD-L1 knockout for enhanced MRI-guided chemodynamic-immunotherapy.

Malignant melanoma is an extremely aggressive and fatal form of skin cancer due to the limited efficacy of conventional therapies. While immune checkpoint blockade therapy and chemodynamic therapy (CDT) have emerged as promising strategies for melanoma treatment, their effectiveness is compromised by the immunosuppressive and complex tumor microenvironment (TME). Here, cancer cell membrane-camouflaged nanoplatforms (PPMC@CM) were developed to co-deliver the CRISPR/Cas9-PD-L1 system and manganese dioxide nanoparticles (MnO NPs) for magnetic resonance imaging (MRI)-guided CDT and enhanced immunotherapy.

Efficacy and tolerability of perampanel as add-on therapy in Dravet syndrome: A prospective real-world study.

Objective: To investigate the efficacy and tolerability of perampanel (PER) on Dravet syndrome in China by a prospective real-world study.

Methods: We prospectively enrolled children with Dravet syndrome from the neurology clinic of Shenzhen Children's Hospital from September 2020 to October 2021. The average monthly seizure frequency within 2 months before enrollment was recorded as the baseline.

Mesenchymal Stem-Cell-Derived Exosomes Loaded with Phosphorus Dendrimers and Quercetin Treat Parkinson's Disease by Modulating Inflammatory Immune Microenvironment.

The intricate pathologic features of Parkinson's disease (PD) coupled with the obstacle posed by the blood-brain barrier (BBB) significantly limit the efficacy of most medications, leading to difficulties in PD treatments. Herein, we have developed a nanomedicine based on stem-cell-derived exosomes coloaded with hydroxyl-terminated phosphorus dendrimers (AK76) and quercetin (Que) for combined therapeutic intervention of PD. The engineered nanocomplexes (for short, QAE NPs) exhibit an optimal size of 269.

Dendrimer-Entrapped CuPt Bimetallic Nanozymes for Tumor Microenvironment-Regulated Photothermal/Catalytic Therapy.

Noble metal nanozymes have attracted extensive attention in tumor therapy due to their multiple enzyme-like activities for catalytic therapy and unique optical properties for photothermal therapy (PTT). However, their therapeutic efficiency may be compromised by the intricate tumor microenvironment (TME). Herein, copper-platinum (CuPt) bimetallic nanozymes were synthesized and entrapped by poly(amidoamine) dendrimers, with -carboxybenzenesulfonamide (BS, a carbonic anhydrase IX (CA IX) inhibitor) modified on the surface and lonidamine (Lon) loaded inside to regulate TME for enhanced catalytic therapy and PTT.

Controllable Preparation of Hollow Spheroidal Nickel-Based Metal-Organic Frameworks Microparticles for Aqueous Nickel-Zinc Batteries.

Metal-organic frameworks (MOFs) have garnered increasing interest due to their porous structure, high surface area, and rich redox active metal ions that can be exploited as good electrode materials for electrochemical energy storage. Herein, nickel-based MOFs materials with different morphological structures of solid spheres (Ni-BTC-0), hollow spheroidal microparticles (Ni-BTC-5), and hollow spheres (Ni-BTC-10) have been facilely synthesized by using water as a regulator. Among them, the unique structure of hollow spheroidal Ni-BTC-5 microparticles with the largest surface area can provide abundant channels for fast electron and electrolyte transport as well as expose more active sites.

Surgical outcomes of drug-refractory infantile epileptic spasms syndrome and related prognostic factors: a retrospective study.

Background: In this study, we aimed to assess the efficacy of surgical treatment in children with drug-refractory infantile epileptic spasms syndrome (IESS) and examine the factors influencing the post-surgical outcomes.

Methods: The clinical data of 30 children (18 males and 12 females) with epileptic spasms (ES) who underwent surgery at the Epilepsy Center of Shenzhen Children's Hospital between June 2018 and June 2020 were retrospectively analyzed. Post-surgical outcomes were evaluated using the Engel Epilepsy Surgery Outcome Scale.

Novel insights into differences in the whey proteome of porcine and human colostrum and mature milk.

Many mothers are unable to exclusively breastfeed for several reasons. Other mammalian milks should be explored as human milk supplements. Pigs and humans are physiologically similar.

How Does Disgust Affect Mpox Prevention? Examining the Underlying Mechanisms of Perceived Severity and Perceived Susceptibility Moderated by Stigma.

The study aims to examine the influencing mechanism of incidental exposure to Disgusting Graphics Information (DGI) about Monkeypox (Mpox) on the intention of prevention behavior. This study first investigates the components of disgust and then examines the mechanism of disgust's influence. The study uses a cross-sectional survey design among respondents who have been incidentally exposed to DGI about Mpox ( = 368).

Dual drug-loaded metal-phenolic networks for targeted magnetic resonance imaging and synergistic chemo-chemodynamic therapy of breast cancer.

The development of nanomedicines with simplified compositions and synergistic theranostic functionalities remains a great challenge. Herein, we develop a simple method to integrate both atovaquone (ATO, a mitochondrial inhibitor) and cisplatin within tannic acid (TA)-iron (Fe) networks coated with hyaluronic acid (HA) for targeted magnetic resonance (MR) imaging-guided chemo-chemodynamic synergistic therapy. The formed TFP@ATO-HA displayed good colloidal stability with a mean size of 95.

Proteomic and phosphoproteomic reveal immune-related function of milk fat globule membrane in bovine milk of different lactation periods.

Information regarding protein expression and phosphorylation modifications in the bovine milk fat globule membrane is scarce, particularly throughout various lactation periods. This study employed a complete proteome and phosphoproteome between bovine colostrum and mature milk. A total of 11 proteins were seen in both protein expression and phosphorylation levels.

Cell Membrane-Camouflaged Chitosan-Polypyrrole Nanogels Co-Deliver Drug and Gene for Targeted Chemotherapy and Bone Metastasis Inhibition of Prostate Cancer.

The development of functional nanoplatforms to improve the chemotherapy outcome and inhibit distal cancer cell metastasis remains an extreme challenge in cancer management. In this work, a human-derived PC-3 cancer cell membrane-camouflaged chitosan-polypyrrole nanogel (CH-PPy NG) platform, which can be loaded with chemotherapeutic drug docetaxel (DTX) and RANK siRNA for targeted chemotherapy and gene silencing-mediated metastasis inhibition of late-stage prostate cancer in a mouse model, is reported. The prepared NGs with a size of 155.

Neurokinin-1 receptor antagonist aprepitant regulates autophagy and apoptosis via ROS/JNK in intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis and limited treatment options. Aprepitant, a selective NK-1R antagonist, can inhibit the growth of various tumours in vitro and in vivo. However, it remains unclear whether aprepitant has cytotoxic effects on iCCA.

Underwater versus conventional endoscopic mucosal resection for ≥10 mm sessile or flat colorectal polyps: A systematic review and meta-analysis.

Background And Aim: Underwater endoscopic mucosal resection (UEMR) has been an emerging substitute for conventional EMR (CEMR). This systematic review and meta-analysis aimed at comparing the efficiency and safety of the two techniques for removing ≥10 mm sessile or flat colorectal polyps.

Methods: PubMed, Cochrane Library and Embase databases were searched up to February 2023 to identify eligible studies that compared the outcomes of UEMR and CEMR.

Characterization and Comparison Analysis of Milk Fat Globule Membrane Proteins between Human and Porcine Milk.

This study aimed to explore the differences in milk fat globule membrane (MFGM) proteins between human milk (HM) and porcine milk (PM) using a label-free quantitative proteomic approach. A total of 3920 and 4001 MFGM proteins were identified between PM and HM, respectively. Among them, 3520 common MFGM proteins were detected, including 956 significant differentially expressed MFGM proteins (DEPs).

Label-free-based proteomic analysis reveals differential whey proteins of porcine milk during lactation.

In this study, label-free proteomic technology was applied to analyze and compare the whey proteomes of porcine colostrum and mature milk. In total, 2993 and 2906 whey proteins were detected in porcine colostrum and mature milk, respectively. A total of 2745 common proteins were identified in the two milk samples, and 280 proteins were found to be significantly differentially expressed whey proteins in porcine milk.

Comparative Site-Specific -Glycosylation Analysis of the Milk Fat Globule Membrane Proteome in Donkey Colostrum and Mature Milk.

Donkey milk fat globule membrane (MFGM) proteins are a class of membrane-bound secreted proteins with broad-spectrum biofunctional activities; however, their site-specific -glycosylation landscapes have not been systematically mapped. In this study, an in-depth MFGM -glycoproteome profile of donkey milk during lactation was constructed based on an intact glycopeptide-centered, label-free glycoproteomics pipeline, with 2137 site-specific -glycans from 1121 MFGM glycoproteins and 619 site-specific -glycans from 217 MFGM glycoproteins identified in donkey colostrum and donkey mature milk, respectively. As lactation progressed, the number of site-specific -glycans from three glycoproteins significantly increased, whereas that of 11 site-specific -glycans from five glycoproteins significantly decreased.

Analysis of the mediating role of BMI in associations of different folate forms with hepatic steatosis and liver fibrosis in adolescents in the USA: results from the NHANES 2017-2018.

Background: Most studies have explored the relationship between serum total folate and nonalcoholic fatty liver disease (NAFLD) in adults, but there has been no study on the relationship between different folate forms and hepatic steatosis or liver stiffness in adolescents.

Objective: To investigate the association of different folate forms with hepatic steatosis or liver stiffness in adolescents, and further explore the intermediary role of BMI in this relationship.

Methods: The cross-sectional study included 549 participants from the 2017-2018 National Health and Nutrition Inspection Survey (NHANES) survey cycle who had complete data.

Phenotypes in children with encephalopathy in China.

Background: The gene encodes the α-subunit (Gαo) of the heterotrimeric guanine nucleotide-binding protein (G protein). The aim of this study was to explore the clinical characteristics of patients with pathogenic variations.

Methods: Ten patients with pathogenic variations in were enrolled from the Shenzhen Children's Hospital.