Nanoplatform based on carbon nanoparticles loaded with doxorubicin enhances apoptosis by generating reactive oxygen species for effective cancer therapy.

At present, due to its wide application and relatively low cost, chemotherapy remains a clinically important cancer treatment option; however, a number of chemotherapeutic drugs have important limitations, such as lack of specificity, high toxicity and side effects, and multi-drug resistance. The emergence of nanocarriers has removed numerous clinical application limitations of certain antitumor chemotherapy drugs and has been widely used in the treatment of tumors with nanodrugs. The present study used carbon nanoparticles (CNPs) as a nanocarrier for doxorubicin (DOX) to form the novel nanomedicine delivery system (CNPs@DOX)was demonstrated by UV-vis and fluorescence spectrophotometry, ζ potential and TEM characterization experiments. The results confirmed the successful preparation of CNPs@DOX nanoparticles with a particle size of 96±17 nm, a wide range of absorption and a negatively charged surface. Furthermore, CNPs@DOX produced more reactive oxygen species and induced apoptosis, and thus exhibited higher cytotoxicity than DOX, which is a small molecule anticancer drug without a nanocarrier delivery system.. The present study provides a strategy for the treatment of tumors with nanomedicine.

Zwitterion-Modified MXene Quantum Dot as a Nanocarrier for Traditional Chinese Medicine Sanguinarine Delivery and Its Application for Photothermal-Chemotherapy Synergistic Antibacterial and Wound Healing.

The nanomaterialization of traditional Chinese medicine (TCM) has aroused widespread interest among researchers. Sanguinarine (SAN) is a kind of TCM with good antibacterial properties, which has important applications in anti-infection of wounds. Additionally, the combination of photothermal therapy and chemotherapy can overcome bacterial resistance, further improving bactericidal and wound healing efficiency. In this paper, we prepared an antibacterial agent by loading SAN on the zwitterion-modified MXene quantum dot nanocarrier (SAN@AHEP@Ta4C3), realizing pH/NIR controlled drug release and photothermal/chemotherapy synergistic antibacterial and wound healing. The particle size of SAN@AHEP@Ta4C3 is about 120 nm, and it has a good water solubility and stability. In addition, it also has excellent photothermal conversion performance (η = 39.2%), which can effectively convert light energy into heat energy under near-infrared (NIR) laser irradiation, further promoting drug release and achieving bactericidal effects by synergistic chemotherapy and photothermal therapy. The in vitro and in vivo experiments show that SAN@AHEP@Ta4C3 exhibits an excellent antibacterial effect against Staphylococcus aureus and Escherichia coli, and it can effectively promote the wound healing of mice. Moreover, the SAN@AHEP@Ta4C3 also has good biocompatibility and has no side effects on normal tissue and organs. This work introduces a multifunctional antibacterial agent based on TCM and hot-spot material MXene, which will have considerable application prospects in biomedical fields.

From Polyester Plastics to Diverse Monomers via Low-Energy Upcycling.

Polyester plastics, constituting over 10% of the total plastic production, are widely used in packaging, fiber, single-use beverage bottles, etc. However, their current depolymerization processes face challenges such as non-broad spectrum recyclability, lack of diversified high-value-added depolymerization products, and crucially high energy consumption. Herein, an efficient strategy is developed for dismantling the compact structure of polyester plastics to achieve diverse monomer recovery. Polyester plastics undergo swelling and decrystallization with a low depolymerization energy barrier via synergistic effects of polyfluorine/hydrogen bonding, which is further demonstrated via density functional theory calculations. The swelling process is elucidated through scanning electron microscopy analysis. Obvious destruction of the crystalline region is demonstrated through X-ray crystal diffractometry curves. PET undergoes different aminolysis efficiently, yielding nine corresponding high-value-added monomers via low-energy upcycling. Furthermore, four types of polyester plastics and five types of blended polyester plastics are closed-loop recycled, affording diverse monomers with exceeding 90% yields. Kilogram-scale depolymerization of real polyethylene terephthalate (PET) waste plastics is successfully achieved with a 96% yield.

Photouranium-Catalyzed C-F Activation Hydroxylation via Water Splitting.

The C-F bond is the strongest covalent single bond (126 kcal/mol) in carbon-centered bonds, in which the highest electronegativity of fluorine (χ = 4) gives rise to the shortest bond length (1.38 Å) and the smallest van der Waals radius (rw = 1.47 Å), resulting in enormous challenges for activation and transformation. Herein, C-F conversion was realized via photouranium-catalyzed hydroxylation of unactivated aryl fluorides using water as a hydroxyl source to deliver multifunctional phenols under ambient conditions. The activation featured cascade sequences of single electron transfer (SET)/hydrogen atom transfer (HAT)/oxygen atom transfer (OAT), highly integrated from the excited uranyl cation. The *UO22+ prompted water splitting under mild photoexcitation, caging the active oxygen in a peroxo-bridged manner for the critical OAT process and releasing hydrogen via the HAT process.

Epidemiological changes and molecular characteristics of Brucella strains in Ningxia, China.

Objective: Human brucellosis causes serious public health concerns in Ningxia, China. Methods: This study employed epidemiological, bacteriological, and multiple-locus variable-number tandem repeat analysis (MLVA) methods to conduct an epidemiological investigation, which is necessary for devising tailored control strategies. Results: Between 1958 and 2022, 29,892 cases were reported, with an average annual number of cases and incidence of 467 and 7.1/100,000, respectively. The epidemic situation gradually worsened, with cases escalating from 26 cases in 2005 to 6,292 in 2022, with the incidence rate rising from 0.441 in 2005 to 86.83 in 2022. Geographically, the disease spread from a single affected county in 2004 to encompass all 22 counties in 2022. Yanchi County had the highest incidence, followed by the Hongsibao and Tongxin counties. These data suggest that Brucella infection has become a rampant regional concern in human brucellosis. Between 1958 and 2019, a total of 230 Brucella strains were identified across four studied hosts. These strains comprised four species with 12 biovars, including B. melitensis bv. 1, bv. 2, bv. 3, B. abortus bv. 1, bv. 3, bv. 4, bv. 5, bv. 6, bv. 7, B. suis bv. 1 and bv. 3, and B. canis. These data highlight the high species/biovars and host diversity of the Brucella population, posing a substantial challenge to brucellosis surveillance. There was an apparent transition from multiple species/biovars historically to the current dominance of a single species, B. melitensis, emphasizing the requirement for strengthening surveillance of B. melitensis. Genotypes 42 and 116, constituting 96.2% of the total number of genotypes, predominated in panel 1 and MLVA-11, indicating that all strains belong to the East Mediterranean lineage. MLVA cluster analysis revealed persistent transmission of dominant circulating genotypes, presenting an epidemic pattern characterized primarily by epidemiologically related cases with a few sporadic cases. Strains in this study exhibited high genetic homogeneity with strains from the Northwest, and those from Kazakhstan and Mongolia. Conclusion: The epidemic situation of human brucellosis has gradually worsened; the rampant epidemic of the disease has become a regional concern. The present study highlights that implementing the of targeted surveillance and intervention strategies is urge.

Exploring the substrate stereoselectivity and catalytic mechanism of nonribosomal peptide macrocyclization in surugamides biosynthesis.

SurE, the first reported penicillin-binding protein-like thioesterase (PBP-like TE), is known as a new off-loading cyclase, which catalyzes heterochiral coupling in nonribosomal peptides (NRPs). However, the structural rationale for substrate stereoselectivity and enzymatic mechanism remains mysterious. Here, computational models, integrating MD simulations and QM/MM methods, unveiled SurE's substrate recognition and catalytic process. An oxyanion hole stabilized the C-terminal D-residue during recognition. Residue R446 anchored the substrate for macrocyclization. A vital hydrogen-bonding network (Y154, K66, N156), verified by mutation results, was responsible for the recognition of N-terminal L-residue and involvement in catalytic process with a calculated 19.4 kcal/mol energy barrier. Four novel-designed peptide precursors were effectively cyclized into cyclopeptides by SurE based on computational analysis. Our results provide a comprehensive understanding of SurE's catalytic mechanism and guiding design of versatile PBP-like TEs for novel macrocyclic NRPs.

XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression.

Background: Osteoarthritis (OA) is the most common age-related musculoskeletal disease. However, there is still a lack of therapy that can modify OA progression due to the complex pathogenic mechanisms. The aim of the study was to explore the role and mechanism of XJB-5-131 inhibiting chondrocytes ferroptosis to alleviate OA progression. Methods: We treated tert-butyl hydroperoxide (TBHP)-induced ferroptosis of mouse primary chondrocytes with XJB-5-131 in vitro. The intracellular ferroptotic hallmarks, cartilage anabolic and catabolic markers, ferroptosis regulatory genes and proteins were detected. Then we established a mouse OA model via destabilization of the medial meniscus (DMM) surgery. The OA mice were treated with intra-articular injection of XJB-5-131 regularly (2 µM, 3 times per week). After 4 and 8 weeks, we performed micro-CT and histological examination to evaluate the protection role of XJB-5-131 in mouse OA subjects. RNA sequencing analysis was performed to unveil the key downstream gene of XJB-5-131 exerting the anti-ferroptotic effect in OA. Results: XJB-5-131 significantly suppressed TBHP-induced increases of ferroptotic hallmarks (ROS, lipid peroxidation, and Fe2+ accumulation), ferroptotic drivers (Ptgs2, Pgd, Tfrc, Atf3, Cdo1), while restored the expression of ferroptotic suppressors (Gpx4, Fth1). XJB-5-131 evidently promoted the expression of cartilage anabolic and decreased the expression of cartilage catabolic markers. Moreover, intra-articular injection of XJB-5-131 significantly inhibited the expression of Cox2 and Mmp13, while promoted the expression of Col2a1, Gpx4 and Fth1 in DMM-induced mouse articular cartilage. Further, we identified Pebp1 as a potential target of XJB-5-131 by RNA sequencing analysis. The anti-ferroptosis and chondroprotective effects of XJB-5-131 were significantly diminished by Locostatin, a specific antagonist of Pebp1. Conclusion: XJB-5-131 significantly protects chondrocytes from ferroptosis in TBHP-induced mouse primary chondrocytes and DMM surgery-induced OA mice model via restoring the expression of Pebp1. XJB-5-131 is a potential therapeutic drug in the management of OA progression.

Integrated single-cell and bulk characterization of branched chain amino acid metabolism-related key gene BCAT1 and association with prognosis and immunogenicity of clear cell renal cell carcinoma.

BACKGROUND: The relationship between clear cell renal cell carcinoma (ccRCC) and branched-chain amino acids (BCAA) metabolism has yet to be thoroughly explored. METHODS: The BCAA metabolism-related clusters were constructed using non-negative matrix factorization (NMF). The features of BCAA metabolism in ccRCC were evaluated by building a prognostic model using least absolute shrinkage and selection operator (LASSO) regression algorithm. Real-time quantitative PCR (RT-qPCR) was employed to analyze differential expression of branched-chain amino acid transaminase 1 (BCAT1) between cancer and paracancer tissues and between different cell lines. Cell counting kit-8, wound healing and Transwell chamber assays were conducted to determine changes in proliferative and metastatic abilities of A498 and 786-O cells. RESULTS: Two BCAA metabolism-related clusters with distinct prognostic and immune infiltration characteristics were identified in ccRCC. The BCAA metabolic signature (BMS) was capable of distinguishing immune features, tumor mutation burden, responses to immunotherapy, and drug sensitivity among ccRCC patients. RT-qPCR revealed overexpression of BCAT1 in ccRCC tissues and cell lines. Additionally, single-gene RNA sequencing analysis demonstrated significant enrichment of BCAT1 in macrophages and tumor cells. BCAT1 played tumor-promoting role in ccRCC and was closely associated with immunosuppressive cells and checkpoints. BCAT1 promoted ccRCC cell proliferation and metastasis. CONCLUSIONS: The BMS played a crucial role in determining the prognosis, tumor mutation burden, responses to immunotherapy and drug sensitivity of ccRCC patients, as well as the immune cell infiltration features. BCAT1 was linked to immunosuppressive microenvironments and may offer new sights into ccRCC immunotherapeutic targets.

C-SuFEx linkage of sulfonimidoyl fluorides and organotrifluoroborates.

Sulfur(VI) fluoride exchange, a new type of linkage reaction, has excellent potential for application in functional molecule linkage to prepare pharmaceuticals, biomolecules, and polymers. Herein, a C-SuFEx reaction is established to achieve fast (in minutes) linkage between sulfonimidoyl fluorides and aryl/alkyl organotrifluoroborates. Potassium organotrifluoroborates are instantaneously activated via a substoichiometric amount of trimethylsilyl triflate to afford organodifluoroboranes, releasing BF3 as an activating reagent in situ. This sulfur(VI) fluoride exchange technique is capable of forming S(VI)-C(alkyl), S(VI)-C(alkenyl) and S(VI)-C(aryl) bonds, demonstrating its broad scope. Natural products and pharmaceuticals with sensitive functional groups, such as valdecoxib, celecoxib and diacetonefructose, are compatible with this protocol, allowing the formation of diverse sulfoximines.

Epidemiology, clinical manifestations, and laboratory findings of 1,590 human brucellosis cases in Ningxia, China.

Introduction: Epidemiological and clinical analyses of brucellosis are vital for public health leaders to reinforce disease surveillance and case management strategies. Methods: In this study, we aimed to analyse the epidemiology and clinical features of 1,590 cases of human brucellosis. Results: Approximately 72.08% (1,146) of the patients were male and 27.92% (444) were female. At least 88.18% (1,402/1,590) of the patients had a history of contact with sheep/goats and cattle, which was identified as the main risk factor for infection. The most common age group affected was 30-69 years, comprising 83.90% of all cases, with a median age of 47.3 years. Meanwhile, 75.03% (1,193/1,590) of the patients were farmers, followed by workers (10.50%, 167/1,590). The spectrum of clinical manifestations varied, and the major symptoms were fatigue (42.96%), joint pain (37.30%), and fever (23.33%). Arthritis was diagnosed in 989 patients, spondylitis was diagnosed in 469 patients, and external genital complications were found in at least 53.96% (858/1,590) of patients. In addition, approximately 41.25% (625/1,515) and 24.53% (390/1,590) of cases exhibited elevated CRP and D-dimer levels, respectively. Conversely, a significant decrease was observed in fibrinogen, total protein, and albumin levels, affecting 48.36% (769/1,590), 77.30% (1,226/1,586), and 91.80% (1,456/1,586) of the patients, respectively. These data demonstrate that brucellosis is a severe wasting disease that leads to an imbalance in nutritional metabolism and a decline in immunity. In total, 86.73% (1,379/1,590) of patients showed improvement with antibiotic therapy, while 13.27% (211/1,590) of patients experienced relapses or treatment failure. Conclusion: Brucellosis often presents with non-specific symptoms and laboratory findings, accompanied by multiple organ invasions, as well as being a vital challenge for diagnosis and treatment; thus, it is essential for a high degree of suspicion to be placed on brucellosis for a timely diagnosis and treatment. This study provides basic data and resources for developing tailored countermeasures to curb its further spread.

Identification of Crotonylation Metabolism Signature Predicting Overall Survival for Clear Cell Renal Cell Carcinoma.

Background: Immunotherapy shows promise in treating cancer by leveraging the immune system to combat cancer cells. However, the influence of crotonylation metabolism on the prognosis and tumor environment in ccRCC patients is not fully understood. Methods: We conducted various systematic analyses, including prognosis and cluster analyses, to investigate the role of KAT2A in immunotherapy. We used qRT-PCR to compare KAT2A expression in cancer and adjacent tissues and among different cell lines. Additionally, we employed Cell Counting Kit-8, wound healing, and Transwell chamber assays to assess changes in the proliferative and metastatic ability of A498 and 786-O cells. Results: We identified three clusters related to crotonylation metabolism, each with distinct prognosis and immune characteristics in ccRCC. We categorized CT1 as immune-inflamed, CT2 as immune-excluded, and CR3 as immune-desert. A new system, CRS, emerged as an effective predictor of patient outcomes with differing immune characteristics. Moreover, qRT-PCR revealed elevated KAT2A levels in ccRCC tissues and cell lines. KAT2A was found to promote ccRCC and correlate significantly with immunosuppressive elements and checkpoints. Reducing KAT2A expression hindered ccRCC cell growth and metastasis. Conclusion: Our study highlights the critical role of crotonylation metabolism in cancer development and progression, particularly its link to poor prognosis. CRS proves to be an accurate predictor of patient outcomes and immune features in ccRCC. KAT2A shows strong associations with clinical factors and the immunosuppressive environment, suggesting potential for innovative immunotherapies in ccRCC treatment.

Disulfide Click Reaction for Stapling of S-terminal Peptides.

A disulfide click strategy is disclosed for stapling to enhance the metabolic stability and cellular permeability of therapeutic peptides. A 17-membered library of stapling reagents with adjustable lengths and angles was established for rapid double/triple click reactions, bridging S-terminal peptides from 3 to 18 amino acid residues to provide 18- to 48-membered macrocyclic peptides under biocompatible conditions. The constrained peptides exhibited enhanced anti-HCT-116 activity with a locked α-helical conformation (IC50 =6.81 µM vs. biological incompetence for acyclic linear peptides), which could be unstapled for rehabilitation of the native peptides under the assistance of tris(2-carboxyethyl)phosphine (TCEP). This protocol assembles linear peptides into cyclic peptides controllably to retain the diverse three-dimensional conformations, enabling their cellular uptake followed by release of the disulfides for peptide delivery.

Biomedical Application of Decellularized Scaffolds.

Tissue loss and end-stage organ failure are serious health problems across the world. Natural and synthetic polymer scaffold material based artificial organs play an important role in the field of tissue engineering and organ regeneration, but they are not from the body and may cause side effects such as rejection. In recent years, the biomimetic decellularized scaffold based materials have drawn great attention in the tissue engineering field for their good biocompatibility, easy modification, and excellent organism adaptability. Therefore, in this review, we comprehensively summarize the application of decellularized scaffolds in tissue engineering and biomedicine in recent years. The preparation methods, modification strategies, construction of artificial tissues, and application in biomedical applications are discussed. We hope that this review will provide a useful reference for research on decellularized scaffolds and promote their application tissue engineering.

Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation.

Background and aim: Diabetic Kidney Disease (DKD) is a common microvascular complication of diabetes mellitus. Multi-center, randomized controlled trials have shown that Qidan Dihuang Granule (QDDHG) reduces the levels of albuminuria of DKD. However, the specific mechanisms of QDDHG on DKD are not clarified. Thus, this study utilized network pharmacology, UHPLC-MS/MS (Ultra-High Performance Liquid Chromatography - Mass Spectrometry) and animal experiments to reveal the mechanisms of QDDHG on DKD. Experimental procedure: Screening and retrieving active ingredients and corresponding targets of QDDHG on DKD through the TCMSP, ETCM, Disgenet, GeneCards, Omim and DrugBank databases. The PPI were performed with BioGrid, STRING, OmniPath, InWeb-IM. AutoDock Vina molecular docking module to estimate the validation from the compounds and target proteins. Free energy to estimate the binding affinity for identified compounds and target proteins. The ingredients of QDDHG were analyzed utilizing UHPLC-MS/MS. In vivo experiment with db/db mice were used to verify the targets and pathway predicted by network pharmacology. Results and conclusion: The results demonstrated that QDDHG has 18 active compounds and 13 target proteins of QDDHG exerted a crucial role in treatment of DKD. QDDHG affect the multiple biological processes included cellular response to lipid, response to oxidative stress, and various pathways, such as AGE-RAGE, PI3K-Akt, MAPK, TNF, EGFR, STAT3. The results of UHPLC-MS/MS showed that six ingredients predicted by network pharmacology were also verified in experiment. In vivo experiment verified the effects of QDDHG on protecting the renal function mainly through inhibited the expression of EGFR, STAT3 and pERK in the db/db mice.

Rh(I)-Catalyzed Cascade Carbonylative Cyclization of Propargyl α-Diazoindolacetates for Construction of Carbazoles.

A Rh(I)-catalyzed carbene migration/carbonylation/cyclization (MCC) strategy has been established for the construction of diverse functionalized carbazoles from propargyl α-diazoindolacetates. Rh(I)-stabilized carbene with different electrophilic properties displays specific reactivity toward alkyne and CO during the transformation, ensuring the smooth progress of the tandem cyclization. Other heteroaryl scaffolds were achieved simultaneously through this cascade protocol, thus offering a straightforward pathway toward functionalized polycyclic aromatic molecule synthesis.

A whispering-gallery scanning microprobe for Raman spectroscopy and imaging.

Optical whispering-gallery-mode microsensors are a promising platform for many applications, such as biomedical monitoring, magnetic sensing, and vibration detection. However, like many other micro/nanosensors, they cannot simultaneously have two critical properties - ultrahigh sensitivity and large detection area, which are desired for most sensing applications. Here, we report a novel scanning whispering-gallery-mode microprobe optimized for both features and demonstrate enhanced Raman spectroscopy, providing high-specificity information on molecular fingerprints that are important for numerous sensing applications. Combining the superiorities of whispering-gallery modes and nanoplasmonics, the microprobe exhibits a two-orders-of-magnitude sensitivity improvement over traditional plasmonics-only enhancement; this leads to molecular detection demonstrated with stronger target signals but less optical power required than surface-enhanced-Raman-spectroscopy substrates. Furthermore, the scanning microprobe greatly expands the effective detection area and realizes two-dimensional micron-resolution Raman imaging of molecular distribution. The versatile and ultrasensitive scanning microprobe configuration will thus benefit material characterization, chemical imaging, and quantum-enhanced sensing.

Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy.

Ovarian cancer (OC) stands as the second most prominent factor leading to cancer-related fatalities, characterized by a notably low five-year survival rate. The insidious onset of OC combined with its resistance to chemotherapy poses significant challenges in terms of treatment, emphasizing the utmost importance of developing innovative therapeutic agents. Despite its remarkable anti-tumor efficacy, celastrol (CEL) faces challenges regarding its clinical utilization in OC due to its restricted water solubility and notable side effects. In this study, celastrol (CEL) was encapsulated into Zeolitic imidazolate framework-8(ZIF-8) nanoparticle and grafted with biotin-conjugated polyethylene glycol (CEL@ZIF-8@PEG-BIO). Comprehensive comparisons of the physicochemical properties and anticancer activities of CEL and CEL@ZIF-8@PEG-BIO were conducted. Our findings revealed that CEL@ZIF-8@PEG-BIO exhibited favorable characteristics, including hydrodynamic diameters of 234.5 nm, excellent water solubility, high drug loading (31.60% ± 2.85), encapsulation efficiency (60.52% ± 2.79), and minimal side effects. Furthermore, CEL@ZIF-8@PEG-BIO can release chemicals in response to an acidic micro-environment, which is more likely a tumor micro-environment. In vitro, studies showed that CEL@ZIF-8@BIO inhibited cell proliferation, led to mitochondrial membrane potential (MMP) decline, and generated reactive oxygen species in OC cells. Both in vitro and in vivo experiments indicated that CEL@ZIF-8@PEG-BIO enhanced anti-tumor activity against OC via up-regulated apoptosis-promoting biomarkers and rendered cancer cell apoptosis via the P38/JNK MAPK signaling pathway. In conclusion, we have successfully developed a novel drug delivery system (CEL@ZIF-8@PEG-BIO), resulting in significant improvements in both water solubility and anti-tumor efficacy thereby providing valuable insights for future clinical drug development.

Assessing the effect of powder characteristics of infant milk on the compressibility of milk powder compression molding.

Infant formula is an important food for those infants who are deprived of breast milk. However, infant formula powder is prone to fly apart, moisture absorption, sticky spoon, and inaccurate measurement. Block infant formula can solve these problems well. In this study, the characteristics (including particle structure morphology, moisture content, particle size, etc.) of infant formula powder were investigated on the compressive strength and solubility of block infant formula after compression molding with infant formula powder as the object. The results showed that the compressive strength and solubility of the block infant formula made from milk powder with a moisture content of 4.75%, particle size larger than 80 mesh, and morphology of compact grape structure appendages were the best. Therefore, milk powder with this characteristic is the most suitable for the preparation of block infant formula. This study provides referenceable experimental data and theoretical basis for the preparation and application of block infant formula.

Tumor necrosis factor-like cytokine 1A plays a role in inflammatory bowel disease pathogenesis.

The binding of tumor necrosis factor-like cytokine 1A (TL1A) to death receptor 3 (DR3) plays an important role in the interaction between dendritic cells (DCs) and T cells and contributes to intestinal inflammation development. However, the mechanism by which DCs expressing TL1A mediate helper T (Th) cell differentiation in the intestinal lamina propria (LP) during the pathogenesis of inflammatory bowel disease remains unclear. In this study, we found that TL1A/DR3 promoted Th1 and Th17 cell differentiation in T-T and DC-T cell interaction-dependent manners. TL1A-deficient CD4+ T cells failed to polarize into Th1/Th17 cells and did not cause colonic inflammation in a T cell transfer colitis model. Notably, TL1A was located in the cytoplasm and nuclei of DCs, positively regulated the DC-specific ICAM-grabbing nonintegrin/RAF1/nuclear factor κB signaling pathway, enhanced the antigen uptake ability of DCs, and promoted TLR4-mediated DC activation, inducing naive CD4+ T cell differentiation into Th1 and Th17 cells. Our work reveals that TL1A plays a regulatory role in inflammatory bowel disease pathogenesis.

Degradation of plastic wastes to commercial chemicals and monomers under visible light.

Plastics are playing an incrementally extensive and irreplaceable role in human life, but with alarming cyclic unsustainability. Numerous attempts have been undertaken to recycle plastics, among which chemical recycling from waste plastics back to chemicals and monomers has attracted great attention. Herein, the depolymerization of nine types of plastics to commercial chemicals and monomers was achieved under ambient conditions via synergetic integrated uranyl-photocatalysis, which contains a process for converting five kinds of mixed plastics into a value-added product. The degradation processes were depicted in terms of variation in scanning electron microscopy imaging, distinction in the X-ray diffraction pattern, alteration in water contact angle, and dynamic in molecular weight distribution. Single electron transfer, hydrogen atom transfer, and oxygen atom transfer were synergistically involved in uranyl-photocatalysis, which were substantiated by mechanistic studies. Relying on flow system design, the chemical recycling of plastics was feasible for kilogram-scale degradation of post-consumer-waste polyethylene terephthalate bottles to commercial chemicals, displaying a promising practical application potential in the future.