Regulated Photocatalytic CO2-to-CH3OH Pathway by Synergetic Dual Active Sites of Interlayer.

Herein, composites of nanosheets with van der Waals contacts are employed to disclose how the interlayer-microenvironment affects the product selectivity of carbon dioxide (CO2) photoreduction. The concept of composites of nanosheets with dual active sites is introduced to manipulate the bonding configuration and promote the thermodynamic formation of methanol (CH3OH). As a prototype, the CoNi2S4-In2O3 composites of nanosheets are prepared, in which high-resolution transmission electron microscopy imaging, X-ray photoelectron spectroscopy spectra, and zeta potential tests confirm the presence of van der Waals contacts rather than chemical bonding between the In2O3 nanosheets and the CoNi2S4 nanosheets within the composite. The fabricated CoNi2S4-In2O3 composites of nanosheets exhibit the detection of the key intermediate *CH3O during CO2 photoreduction through in situ Fourier transform infrared spectra, while the In2O3 nanosheets and CoNi2S4 nanosheets alone do not show this capability, further verified by the density functional theory calculations. Accordingly, the CoNi2S4-In2O3 composites of nanosheets show the ability to produce CH3OH, whereas the CoNi2S4 and In2O3 nanosheets solely generate carbon monoxide products from CO2 photoreduction.

Effectiveness of Core Excision Technique for Keloids: A Systematic Review.

BACKGROUND: The keloid core excision technique mitigates the risk of wound tension and promotes favorable morphological outcomes. However, whether residual keloid tissue or other factors increase the risk of recurrence remains unclear. This systematic review aimed to evaluate the therapeutic outcomes of core excision techniques for keloids. METHODS: A systematic literature review was conducted by searching PubMed, Embase, Web of Science Core Collection, and Cochrane Library databases on July 30, 2023. The search terms employed were "keloid," "core excision," "intralesional excision," "intramarginal excision," "rind flap," and "fillet flap." The inclusion criteria for the studies were established in advance and evaluated by multiple investigators. RESULTS: Overall, 20 studies involving 926 keloid cases managed through core excision were included. Adjuvant therapies were used in 19 studies, with radiotherapies and steroid injections emerging as the predominant methods. The recurrence rates ranged from 0% to 28.6%. Residual scar tissue after core excision and complications, such as flap necrosis and hematoma, are the major factors contributing to recurrence. CONCLUSION: The core excision technique is a surgical treatment of keloids with a low recurrence rate when combined with adjuvant therapies. However, randomized controlled trials and conclusive quantitative studies are necessary to further investigate the effects of the core excision technique on keloids.

Rare-Earth Metal Complexes Bearing Electrophilic Carbon and Strongly Polarized Metallacyclopropane Moiety: Synthesis and Diverse Reactivity toward Small Molecules.

Metallacyclopropanes are highly strained and very reactive organometallics; the rare-earth metal complexes bearing both highly reactive electrophilic carbon and strongly polarized metallacyclopropanes are extremely rare. This type of rare-earth metal complexes (κ2-L)RE(η2-C2B10H10)·(THF)3 [L = 1-(2-N-C5H10NCH2CH2)-3-(2,6-iPr2C6H3N═CH)-C8H4N, RE = Lu(1a), Yb(1b), Er(1c), Y(1d), Dy(1e)] bearing the indol-2-yl electrophilic carbon and carboryne-based strongly polarized metallacyclopropanes have been synthesized. Structures of complexes 1 are further confirmed by single-crystal X-ray diffraction and DFT theoretical calculations. It is found that complexes 1 have remarkable reactivity toward different polar unsaturated small molecules, elemental sulfur, and selenium to provide different products (2-15) through the selective reactions of the RE-Ccage, and RE-C2-ind bonds with the given small molecules, respectively. The reactivities of these complexes are different from those of the reported rare-earth metallacyclopropenes and d-block metal-carborynes.

Development and validation of a diagnostic and prognostic model for bone metastasis of intrahepatic cholangiocarcinoma: a population-based analysis.

Background: Bone metastasis (BM) is a common site of metastasis in patients with intrahepatic cholangiocarcinoma (ICC), significantly impacting the quality of life and prognosis of affected individuals. This investigation aimed to assess the risk of BM development in ICC patients and to prognosticate for patients with ICC-associated BM (ICCBM) through the construction of two nomograms. Methods: We conducted a retrospective analysis of data from 2,651 ICC patients, including 148 cases of BM, documented in the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. Independent predictors for the occurrence of BM in ICC patients were identified via univariate and multivariate logistic regression analyses; simultaneously, independent prognostic indicators for ICCBM patients were ascertained through univariate and multivariate Cox regression analyses. The utility of the nomograms was evaluated through calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and Kaplan-Meier (KM) analysis. Results: Independent risk factors for BM in ICC included sex, tumor size, lung metastasis, brain metastasis, and intrahepatic metastasis. For ICCBM patients, independent prognostic factors comprised age, chemotherapy, and radiotherapy. The prognostic nomogram exhibited C-indexes of 0.737 [95% confidential interval (CI): 0.682-0.792] for the training cohort and 0.696 (95% CI: 0.623-0.769) for the validation cohort. Calibration curves demonstrated strong concordance between predicted outcomes and observed events. The areas under the curve (AUC) for 3-, 6-, and 12-month cancer-specific survival (CSS) were 0.853, 0.781, and 0.739, respectively, in the training cohort, and 0.794, 0.822, and 0.780 in the validation cohort. DCA illustrated significant net benefits across a broad spectrum of threshold probabilities. KM analysis revealed 1-, 2-, and 3-year CSS rates of 23.91%, 7.55%, and 2.35%, respectively, with a median CSS of 6 months, underscoring the nomograms' capacity to distinctly stratify patients according to survival risk. Conclusions: The development of these nomograms offers substantial clinical utility in forecasting BM risk among ICC patients and prognosticating for those with ICCBM, thereby facilitating the formulation of more efficacious treatment modalities.

Recombinant fibrous protein biomaterials meet skin tissue engineering.

Natural biomaterials, particularly fibrous proteins, are extensively utilized in skin tissue engineering. However, their application is impeded by batch-to-batch variance, limited chemical or physical versatility, and environmental concerns. Recent advancements in gene editing and fermentation technology have catalyzed the emergence of recombinant fibrous protein biomaterials, which are gaining traction in skin tissue engineering. The modular and highly customizable nature of recombinant synthesis enables precise control over biomaterial design, facilitating the incorporation of multiple functional motifs. Additionally, recombinant synthesis allows for a transition from animal-derived sources to microbial sources, thereby reducing endotoxin content and rendering recombinant fibrous protein biomaterials more amenable to scalable production and clinical use. In this review, we provide an overview of prevalent recombinant fibrous protein biomaterials (collagens, elastin, silk proteins and their chimeric derivatives) used in skin tissue engineering (STE) and compare them with their animal-derived counterparts. Furthermore, we discuss their applications in STE, along with the associated challenges and future prospects.

Angiosome-Guided Perfusion Decellularization of Fasciocutaneous Flaps.

Background Tissue engineering based on whole-organ perfusion decellularization has successfully generated small-animal organs, including the heart and limbs. Herein, we aimed to use angiosome-guided perfusion decellularization to generate an acellular fasciocutaneous flap matrix with an intact vascular network. Method Abdominal flaps of rats were harvested, and the vascular pedicle (iliac artery and vein) was dissected and injected with methylene blue to identify the angiosome region and determine the flap dimension for harvesting. To decellularize flaps, the iliac artery was perfused sequentially with 1% sodium dodecyl sulfate, deionized water, and 1% Triton-X100. Gross morphology, histology, and DNA quantity of flaps were then obtained. Flaps were also subjected to glycosaminoglycan and hydroxyproline content assays, as well as computer tomography angiography. Results Histological assessment indicated that cellular content was completely removed in all flap layers following 10-h perfusion in sodium dodecyl sulfate. DNA quantification confirmed 81% DNA removal. Based on biochemical assays, decellularized flaps had hydroxyproline content comparable with that of native flaps, although significantly fewer glycosaminoglycans (p = 0.0019). Histology and computed tomography angiography illustrated the integrity and perfusability of the vascular system. Conclusion The proposed angiosome-guided perfusion decellularization protocol could effectively remove cellular content from rat fasciocutaneous flaps and preserve the integrity of innate vascular networks.

Determinants of parental demand of human papillomavirus vaccination for adolescent daughters in China: Contingent valuation survey.

BACKGROUND: Several types of human papillomavirus (HPV) vaccines have been approved for use in adolescent girls in China. These vaccines are regulated as non-National Immunisation Program vaccines and are optional and generally fully self-paid by vaccinees. OBJECTIVE: To assess parents' demand for HPV vaccination by eliciting their willingness-to-pay for their adolescent daughters to be vaccinated against HPV and to examine the determinants of demand for HPV vaccination in China. METHODS: A contingent valuation survey was conducted across three cities in Shandong Province in eastern China. We selected 11 junior middle schools with different socioeconomic features and randomly selected 6 classes in each school, and questionnaires were distributed to all girls aged 12-16 in the 66 classes for their parents to complete. A payment card approach was used to elicit parental willingness-to-pay for HPV vaccination for their daughters. We also collected a wide array of socioeconomic and psychological variables and interval regressions were applied to examine the determinants of parental willingness-to-pay. RESULTS: A total of 1074 eligible parents who completed valid questions were included in analyses. Over 85% of parents believed HPV vaccines were, in general, necessary and beneficiary. However, only around 10% believed that their daughters would be infected by HPV. About 8% of parents would not accept HPV vaccine even if the vaccine were free mainly due to concerns about the potential side effects and vaccine safety and quality issues, and 27.37% would only accept the vaccine if it were free. The median willingness-to-pay was 300 CNY (42 USD). Several factors were positively correlated with higher willingness-to-pay: income, urban residence (relative to rural residence), mothers (relative to fathers), parents' beliefs about vaccine benefits, whether they should make decisions for their daughters, and whether their daughters would be susceptible to HPV. Though education-level was not significantly correlated with willingness-to-pay in the main regressions, a subgroup analysis revealed interesting dynamics in the relation between education and willingness-to-pay across different income-levels. CONCLUSIONS: There is a large gap between parents' willingness-to-pay and the market price of HPV vaccine for girls in China. Parents generally believed the HPV vaccines were beneficial and necessary but when asked for their daughters, most parents did not believe their daughters would be infected by HPV despite the high prevalence in China. Future focus should be on ensuring the provision of accurate health information about HPV prevalence, vaccine quality, and safety to promote vaccine uptake, and promotional efforts tailored to different income groups might yield better effects. Government involvement in negotiating more widely acceptable and affordable prices or subsidising may be necessary for protecting high-risk population groups.

Intracapsular Enucleation of Cervical Sympathetic Chain Schwannoma: Improved Strategy of Intraoperative Hemostasis and Better Outcome.

Objective: Intracapsular enucleation (ICE) of cervical sympathetic chain schwannoma (CSCS) is associated with technical difficulties, with diffuse hemorrhage being the main challenge in our previous attempts. This article presents our new strategy for achieving better hemostasis during ICE procedures in CSCS cases. Methods: A retrospective review of CSCS cases treated at our tertiary medical institution was undertaken between April 2018 and February 2024. Only cases with successful ICE were included. Results: A total of 8 cases were included, with 4 male and 4 female patients and an age range of 23 to 77 (average and median ages were 48.5 and 49.5 years, respectively). The presenting symptom was a neck mass for all the patients, with 4 masses on the left and 4 on the right sides. Enucleation was first undertaken for the first 3 cases (before March 2022), followed by hemostasis; this strategy was quite difficult and time-consuming. For the remaining 5 cases, a new strategy was developed to preemptively manage any potential nourishing vessel between the capsule and tumor parenchyma, which significantly decreased operation time (P = .0155) and facilitated hemorrhage control. First bite syndrome (FBS) was avoided in all cases. Postoperative Horner's syndrome (HS) was avoided in 1 patient (Case 6, new strategy) but occurred in 7 patients, taking 8 days to 1 month to recover with the new strategy (4 patients), significantly shorter (P = .0364) than before (3 patients, 1-3 months). The median duration of follow-up was 20 months. No recurrence was documented. Conclusions: ICE was achieved for CSCS cases, especially with our newly developed strategy, by preemptively and securely managing potential nourishing vessels. Operation time and duration of recovery of postoperative HS could both be shortened. Moreover, FBS could be avoided.

KLF13 Attenuates Lipopolysaccharide-Induced Alveolar Epithelial Cell Damage by Regulating Mitochondrial Quality Control via Binding PGC-1α.

Sepsis is a clinically life-threatening syndrome, and acute lung injury is the earliest and most serious complication. We aimed to assess the role of kruppel-like factor 13 (KLF13) in lipopolysaccharide (LPS)-induced human alveolar type II epithelial cell damage and to reveal the possible mechanism related to peroxisome proliferator-activated receptor-γ co-activator 1-α (PGC-1α). In LPS-treated A549 cells with or without KLF13 overexpression or PGC-1α knockdown, cell viability was measured by a cell counting kit-8 assay. Enzyme-linked immunosorbent assay kits detected the levels of inflammatory factors, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining measured cell apoptosis. Besides, mitochondrial reactive oxygen species (MitoSOX) and mitochondrial membrane potential were detected using MitoSOX red- and JC-1 staining. Expression of proteins related to mitochondrial quality control (MQC) was evaluated by western blot. Co-immunoprecipitation (Co-IP) assay was used to analyze the interaction between KLF13 and PGC-1α. Results indicated that KLF13 was highly expressed in LPS-treated A549 cells. KLF13 upregulation elevated the viability and reduced the levels of inflammatory factors in A549 cells exposed to LPS. Moreover, KLF13 gain-of-function inhibited LPS-induced apoptosis of A549 cells, accompanied by upregulated BCL2 expression and downregulated Bax and cleaved caspase3 expression. Furthermore, MQC was improved by KLF13 overexpression, as evidenced by decreased MitoSOX, JC-1 monomers and increased JC-1 aggregates, coupled with the changes of proteins related to MQC. In addition, Co-IP assay confirmed the interaction between KLF13 and PGC-1α. PGC-1α deficiency restored the impacts of KLF13 upregulation on the inflammation, apoptosis, and MQC in LPS-treated A549 cells. In conclusion, KLF13 attenuated LPS-induced alveolar epithelial cell inflammation and apoptosis by regulating MQC via binding PGC-1α.

Heterogeneity of lymphocyte subsets in predicting immune checkpoint inhibitor treatment response in advanced lung cancer: an analysis across different pathological types, therapeutic drugs, and age groups.

Background: Immune checkpoint inhibitor (ICI) has become pivotal in the treatment of advanced lung cancer, yet the absence of reliable biomarkers for assessing treatment response poses a significant challenge. This study aims to explore the predictive value of various lymphocyte subsets in different lung cancer subtypes, thus potentially identifying novel biomarkers to improve ICI treatment stratification and outcomes. Methods: We conducted a retrospective analysis of 146 stage III or IV lung cancer patients undergoing ICI treatment. The study focused on exploring the relationship between various lymphocyte subsets and the efficacy of ICIs, aiming to determine their predictive value for post-treatment outcomes. Results: Subgroup analysis revealed a positive correlation (P=0.01) between lower CD3+CD8+ T lymphocyte levels and treatment response in squamous cell carcinoma patients. However, no significance was observed in lung adenocarcinoma patients. Additionally, the predictive ability of lymphocyte subsets for different immunotherapy drugs varies. In individuals receiving anti-programmed cell death ligand 1 (PD-L1) treatment, a lower CD3+CD8+ T lymphocyte levels is significantly associated with a positive treatment outcome (P=0.002), while there is no difference for programmed death 1 (PD-1) drugs. Among patients under 60, higher expression of CD3+CD4+ T lymphocytes (P=0.03) combined with lower CD3+CD8+ T lymphocyte levels (P=0.006) showed a statistically significant association with improved treatment response. However, in patients aged over 60, no discernible correlation was ascertained between lymphocyte subsets and therapeutic response. Through prognostic analysis, two distinct lymphocyte subsets were identified, both exerting considerable impact on progression-free survival subsequent to ICIs treatment: CD3+CD4+ T lymphocytes [hazard ratio (HR) =0.50, P=0.006] and CD3+CD8+ T lymphocytes (HR =1.78, P=0.02). Conclusions: Our findings underscore the significant heterogeneity in the predictive value of distinct lymphocyte subsets for lung cancer patients undergoing ICI treatment. These findings are particularly salient when considering various pathological types, immunotherapeutic agents, and patient age groups.

Synthesis and Reactivity of the Rare-Earth Metal Complexes Bearing the Indol-2-yl-Based NCN Pincer Ligand.

The pincer rare-earth dialkyl complexes [κ3-LRE(CH2SiMe3)2 (RE = Lu(1a), Yb(1b), Er(1c), Y(1d), Dy(1e))] with the indol-2-yl-based NCN pincer ligand were synthesized by the reactions of the proligand HL (L = 1-Me2NCH2CH2-3-(2-iPrC6H5N═CH)C8H4N) with RE(CH2SiMe3)3(THF)2. These complexes exhibited a variety of reactivities toward organic compounds such as amines, triphenylphosphine ylide, N-phenylimidazole, pyridine derivatives, and o-carborane leading to σ-bond metathesis, migration insertion, and redox reaction products. The reactions of the dialkyl rare-earth metal complexes with o-carborane afforded the novel NCN pincer-ligated carboryne-based metallacyclopropanes which reacted with diphenyl ketone to give insertion products of the RE-C2-ind and one of the RE-Ccage bonds, while the reaction of the carboryne-based metallacyclopropanes with diphenyldiazomethane produced the di-aza-metallacyclopentanes via the insertions of the N═N bond of the diphenyldiazomethane into two RE-Ccage bonds and the RE-C2-ind bond. The reactions of the dialkyl complexes with 2 equiv of 2,2'-bipyridine afforded the pincer-ligated bis(2,2'-bipyridyl monoanionic radical) complexes via the homolytic redox reaction.

The RNA helicase DHX35 functions as a co-sensor for RIG-I-mediated innate immunity.

RNA helicases are involved in the innate immune response against pathogens, including bacteria and viruses; however, their mechanism in the human airway epithelial cells is still not fully understood. Here, we demonstrated that DEAH (Asp-Glu-Ala-His) box polypeptide 35 (DHX35), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family, boosts antiviral innate immunity in human airway epithelial cells. DHX35 knockdown attenuated the production of interferon-ß (IFN-ß), IL6, and CXCL10, whereas DHX35 overexpression increased their production. Upon stimulation, DHX35 was constitutively expressed, but it translocated from the nucleus into the cytosol, where it recognized cytosolic poly(I:C) and poly(dA:dT) via its HELICc domain. Mitochondrial antiviral signaling protein (MAVS) acted as an adaptor for DHX35 and interacted with the HELICc domain of DHX35 using amino acids 360-510. Interestingly, DHX35 interacted with retinoic acid-inducible gene 1 (RIG-I), enhanced the binding affinity of RIG-I with poly(I:C) and poly(dA:dT), and formed a signalsome with MAVS to activate interferon regulatory factor 3 (IRF3), NF-κB-p65, and MAPK signaling pathways. These results indicate that DHX35 not only acted as a cytosolic nucleic acid sensor but also synergized with RIG-I to enhance antiviral immunity in human airway epithelial cells. Our results demonstrate a novel molecular mechanism for DHX35 in RIG-I-mediated innate immunity and provide a novel candidate for drug and vaccine design to control viral infections in the human airway.

Identification of risk factors and construction of a nomogram predictive model for post-stroke infection in patients with acute ischemic stroke.

BACKGROUND: Post-stroke infection is the most common complication of stroke and poses a huge threat to patients. In addition to prolonging the hospitalization time and increasing the medical burden, post-stroke infection also significantly increases the risk of disease and death. Clarifying the risk factors for post-stroke infection in patients with acute ischemic stroke (AIS) is of great significance. It can guide clinical practice to perform corresponding prevention and control work early, minimizing the risk of stroke-related infections and ensuring favorable disease outcomes. AIM: To explore the risk factors for post-stroke infection in patients with AIS and to construct a nomogram predictive model. METHODS: The clinical data of 206 patients with AIS admitted to our hospital between April 2020 and April 2023 were retrospectively collected. Baseline data and post-stroke infection status of all study subjects were assessed, and the risk factors for post-stroke infection in patients with AIS were analyzed. RESULTS: Totally, 48 patients with AIS developed stroke, with an infection rate of 23.3%. Age, diabetes, disturbance of consciousness, high National Institutes of Health Stroke Scale (NIHSS) score at admission, invasive operation, and chronic obstructive pulmonary disease (COPD) were risk factors for post-stroke infection in patients with AIS (P < 0.05). A nomogram prediction model was constructed with a C-index of 0.891, reflecting the good potential clinical efficacy of the nomogram prediction model. The calibration curve also showed good consistency between the actual observations and nomogram predictions. The area under the receiver operating characteristic curve was 0.891 (95% confidence interval: 0.839-0.942), showing predictive value for post-stroke infection. When the optimal cutoff value was selected, the sensitivity and specificity were 87.5% and 79.7%, respectively. CONCLUSION: Age, diabetes, disturbance of consciousness, NIHSS score at admission, invasive surgery, and COPD are risk factors for post-stroke infection following AIS. The nomogram prediction model established based on these factors exhibits high discrimination and accuracy.

Highly Reversible Sodium-ion Storage in A Bifunctional Nanoreactor Based on Single-atom Mn Supported on N-doped Carbon over MoS2 Nanosheets.

Conversion-type electrode materials have gained massive research attention in sodium-ion batteries (SIBs), but their limited reversibility hampers practical use. Herein, we report a bifunctional nanoreactor to boost highly reversible sodium-ion storage, wherein a record-high reversible degree of 85.65 % is achieved for MoS2 anodes. Composed of nitrogen-doped carbon-supported single atom Mn (NC-SAMn), this bifunctional nanoreactor concurrently confines active materials spatially and catalyzes reaction kinetics. In situ/ex situ characterizations including spectroscopy, microscopy, and electrochemistry, combined with theoretical simulations containing density functional theory and molecular dynamics, confirm that the NC-SAMn nanoreactors facilitate the electron/ion transfer, promote the distribution and interconnection of discharging products (Na2S/Mo), and reduce the Na2S decomposition barrier. As a result, the nanoreactor-promoted MoS2 anodes exhibit ultra-stable cycling with a capacity retention of 99.86 % after 200 cycles in the full cell. This work demonstrates the superiority of bifunctional nanoreactors with two-dimensional confined and catalytic effects, providing a feasible approach to improve the reversibility for a wide range of conversion-type electrode materials, thereby enhancing the application potential for long-cycled SIBs.

Sequential Inhibition of PARP and BET as a Rational Therapeutic Strategy for Glioblastoma.

PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient-derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.

Process optimization and mechanism for the selective extraction of copper(ii) from polymetallic acidic solutions using a polymer inclusion membrane (PIM) with Mextral®5640H as the carrier.

This study introduces a novel approach by integrating solvent extraction and polymer inclusion membrane (PIM) separation technologies to engineer an innovative PIM membrane material for the selective separation and enrichment of strategic metals, particularly copper, from polymetallic acidic solutions. The primary objectives were to streamline the technological process, reduce production costs, and enhance separation coefficients between copper and other metals. The optimal extraction conditions were determined as a mass fraction of Mextral®5640H : PVC : NPOE = 3 : 3 : 4, extraction temperature of 35 °C, and 0.9 mol L-1 H2SO4 in the stripping solution. Under these conditions, we achieved remarkable extraction efficiencies, with copper reaching 100%, and the separation coefficients between Cu2+ and Ni2+, Co2+, and Zn2+ exceeding 106. To elucidate the substantial differences in extraction performance between Cu2+ and the other metals (Ni2+, Co2+, and Zn2+), we employed an integrative analytical approach that combines FT-IR spectroscopy, BET analysis, and theoretical calculations. All extracted complexes demonstrated molecular sizes compatible with PIMs, underscoring the critical role of stability and back-extraction performance in the selective extraction of these metal ions.

USP36 inhibits apoptosis by deubiquitinating cIAP1 and survivin in colorectal cancer cells.

Chemotherapeutic agents for treating colorectal cancer (CRC) primarily induce apoptosis in tumor cells. The ubiquitin-proteasome system is critical for apoptosis regulation. Deubiquitinating enzymes (DUBs) remove ubiquitin from substrates to reverse ubiquitination. Although over 100 DUB members have been discovered, the biological functions of only a small proportion of DUBs have been characterized. Here, we aimed to systematically identify the DUBs that contribute to the development of CRC. Among the DUBs, ubiquitin-specific protease 36 (USP36) is upregulated in CRC. We showed that the knockdown of USP36 induces intrinsic and extrinsic apoptosis. Through gene silencing and coimmunoprecipitation techniques, we identified survivin and cIAP1 as USP36 targets. Mechanistically, USP36 binds and removes lysine-11-linked ubiquitin chains from cIAP1 and lysine-48-linked ubiquitin chains from survivin to abolish protein degradation. Overexpression of USP36 disrupts the formation of the XIAP-second mitochondria-derived activator of caspase complex and promotes receptor-interacting protein kinase 1 ubiquitination, validating USP36 as an inhibitor to intrinsic and extrinsic apoptosis through deubiquitinating survivin and cIAP1. Therefore, our results suggest that USP36 is involved in CRC progression and is a potential therapeutic target.

Gold(III) Porphyrin-Metal-Polyphenolic Nanocomplexes: Breaking Intracellular Redox Environment for Enhancing Mild-Temperature Photothermal Therapy.

Photothermal therapy (PTT) is a promising clinical antitumor strategy. However, local hyperthermia inevitably induces heat damage to adjacent normal tissues, while alternative mild-temperature therapy (MPTT, T < 45 °C) is also inefficient due to the overexpressed hyperthermia-induced heat shock proteins (HSPs) by cancer cells. Therefore, developing PTT strategies with minimizing damage to healthy tissues with improved cellular temperature sensitivity is extremely valuable for clinical application. Herein, we proposed the strategy of disrupting the intracellular redox environment via destroying the ROS-defending systems to promote MPTT. The gold(III) porphyrin-Fe3+-tannic acid nanocomplexes (AuTPP@TA-Fe NPs) were achieved via interfacial cohesion and supramolecular assembly of bioadhesive species, which could trigger the Fenton reaction to produce ·OH radicals and downregulation of reductive TrxR enzyme and mitochondrial chaperone protein Hsp60. The aggravation of oxides and the inactivation of Hsp60 provide favorable pathways for impeding the heat shock-induced self-repair mechanism of cancer cells, which strengthens AuTPP@TA-Fe NPs mediated MPTT.

GDF11 OVEREXPRESSION ALLEVIATES SEPSIS-INDUCED LUNG MICROVASCULAR ENDOTHELIAL BARRIER DAMAGE BY ACTIVATING SIRT1/NOX4 SIGNALING TO INHIBIT FERROPTOSIS.

ABSTRACT: Sepsis is a lethal clinical syndrome, and acute lung injury (ALI) is the earliest and most serious complication. We aimed to explore the role of growth differentiation factor 11 (GDF11) in sepsis-induced dysfunction of lung microvascular endothelial barrier in vivo and in vitro to elucidate its potential mechanism related to sirtuin 1 (SIRT1)/NADPH oxidase 4 (NOX4) signaling. Cecal ligation and puncture (CLP)-induced sepsis mice and lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial cells (PMECs) were used in this study. Histopathological changes in lung tissues were tested by hematoxylin-eosin staining. Lung wet-to-dry weight ratio and inflammatory factors contents in bronchoalveolar lavage fluid were assessed. Evens blue index, trans-epithelial electrical resistance, and expression of zona occludens 1 (ZO-1), occludin-1, and claudin-1 were used to evaluate alveolar barrier integrity. Reactive oxygen species, lipid peroxidation, and ferroptosis markers were analyzed. Iron deposition in the lung tissues was assessed using Prussian blue staining. Intracellular Fe 2+ level was detected using FerroOrange staining. Additionally, expression of GDF11, SIRT1, and NOX4 was estimated with western blot. Then, EX527, a SIRT1 inhibitor, was employed to treat GDF11-overexpressed PMECs with LPS stimulation to clarify the regulatory mechanism. Results showed that GDF11 overexpression attenuated sepsis-induced pathological changes and inflammation and maintained alveolar barrier integrity. Moreover, GDF11 overexpression inhibited ferroptosis, upregulated SIRT1 expression and downregulated NOX4 expression. Additionally, EX527 treatment relieved the impacts of GDF11 overexpression on ferroptosis and destruction of integrity of human pulmonary microvascular endothelial cells exposed to LPS. Taken together, GDF11 overexpression could alleviate sepsis-induced lung microvascular endothelial barrier damage by activating SIRT1/NOX4 signaling to inhibit ferroptosis. Our findings potentially provide new molecular target for clinical therapy of ALI.