Pyrolytic Depolymerization of Polyolefins Catalyzed by Zirconium-based UiO-66 Metal-Organic Frameworks.

Polyolefins such as polyethylenes and polypropylenes are the most-produced plastic waste globally, yet are difficult to convert into useful products due to their unreactivity. Pyrolysis is a practical method for large-scale treatment of mixed, contaminated plastic, allowing for their conversion into industrially-relevant petrochemicals. Metal-organic frameworks (MOFs), despite their tremendous utility in heterogenous catalysis, have been overlooked for polyolefin depolymerization due to their perceived thermal instabilities and inability of polyethylenes and polypropylenes to penetrate their pores. Herein, we demonstrate the viability of UiO-66 MOFs containing coordinatively-unsaturated zirconia nodes, as effective catalysts for pyrolysis that significantly enhances the yields of valuable liquid and gas hydrocarbons, whilst halving the amounts of residual solids produced. Reactions occur on the Lewis-acidic UiO-66 zirconia nodes, without the need for noble metals, and yields aliphatic product distributions distinctly different from the aromatic-rich hydrocarbons from zeolite catalysis. We also demonstrate the first unambiguous characterization of polyolefin penetration into UiO-66 pores at pyrolytic temperatures, allowing access to the abundant Zr-oxo nodes within the MOF interior for efficient C-C cleavage. Our work highlights the potential of MOFs as highly-designable heterogeneous catalysts for depolymerization of plastics which can complement conventional catalysts in reactivity.

Treatments and prognostic outcomes of combined hepatocellular-cholangiocarcinoma with distant metastasis: an analysis based on SEER data.

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare liver cancer with a poor prognosis, often diagnosed at an advanced stage. The management of cHCC-CCA with distant metastasis remains challenging, and prognostic factors are not well-defined. This study aimed to investigate prognostic factors and treatment outcomes for cHCC-CCA patients with distant metastasis. Methods: Retrospective analysis was conducted using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. Patients with distant metastasis [stage M1, according to the American Joint Committee on Cancer (AJCC) 7th edition] between January 2010 and December 2020 were included. Their characteristics, clinical profiles, and prognostic information were evaluated. Cox multifactorial survival analysis and Kaplan-Meier survival curves were used for statistical analysis. Results: A total of 130 patients were included, with 78 (60%) receiving chemotherapy. Cox multivariate survival analysis revealed worse prognosis for Black individuals compared to White individuals (P<0.05). The median overall survival was 2 months for Black patients and 5 months for White patients. Chemotherapy significantly improved patient prognosis (P<0.05), while lung metastasis emerged as an independent risk factor (P<0.05). Kaplan-Meier survival curves confirmed the impact of lung metastasis and chemotherapy on overall survival. Patients with lung metastasis had lower survival rates (P<0.05), and those receiving chemotherapy had higher survival rates (P<0.05). Subgroup analysis based on age showed lower survival rates in patients aged 75 years or older compared to those below 75 years. Chemotherapy showed significant beneficial effects on the prognosis of patients below 75 years old, but no significant difference was observed in patients aged 75 years or above. Conclusions: Chemotherapy improves the prognosis of cHCC-CCA patients with distant metastasis, especially for those under 75 years old. Black race and lung metastasis are poor prognostic factors.

Antibiotics improve reproductive outcomes after frozen-thaw embryo transfer for chronic endometritis treatment, especially in those with repeated implantation failure.

PURPOSE: To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. METHODS: A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. RESULTS: Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05). CONCLUSION: Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

Nrf2 affects DNA damage repair and cell apoptosis through regulating HR and the intrinsic Caspase-dependent apoptosis pathway in TK6 cells exposed to hydroquinone.

Hydroquinone (HQ) is one of benzene metabolites that can cause oxidative stress damage and Homologous recombination repair (HR). A good deal of reactive oxygen species (ROS) generated by oxidative stress can trigger apoptotic signaling pathways. The nuclear factor erythroid 2-related factor 2 (Nrf2) can regulate the cell response to oxidative stress damage. The aim of this study was to explore whether Nrf2 participate in HQ-induced apoptosis and its mechanism. The findings displayed that HQ triggered HR, promoted Nrf2 transfer into the cell nucleus and induced cell apoptosis, while Nrf2 deficient elevated cell apoptosis, attenuated the expression of PARP1 and RAD51. We also observed that Nrf2 deficient triggered Caspase-9. Thus, we speculated that Nrf2 might participate in HQ-induced cell apoptosis through Caspase-9 dependent pathways. Meanwhile, Nrf2 participated in HQ-induced DNA damage repair by regulating the level of PARP1 and RAD51.

LASSO-Based Machine Learning Algorithm for Prediction of PICS Associated with Sepsis.

Introduction: This study aims to establish a comprehensive, multi-level approach for tackling tropical diseases by proactively anticipating and managing Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) within the initial 14 days of Intensive Care Unit (ICU) admission. The primary objective is to amalgamate a diverse array of indicators and pathogenic microbial data to pinpoint pivotal predictive variables, enabling effective intervention specifically tailored to the context of tropical diseases. Methods: A focused analysis was conducted on 1733 patients admitted to the ICU between December 2016 and July 2019. Utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression, disease severity and laboratory indices were scrutinized. The identified variables served as the foundation for constructing a predictive model designed to forecast the occurrence of PICS. Results: Among the subjects, 13.79% met the diagnostic criteria for PICS, correlating with a mortality rate of 38.08%. Key variables, including red-cell distribution width coefficient of variation (RDW-CV), hemofiltration (HF), mechanical ventilation (MV), Norepinephrine (NE), lactic acidosis, and multiple-drug resistant bacteria (MDR) infection, were identified through LASSO regression. The resulting predictive model exhibited a robust performance with an Area Under the Curve (AUC) of 0.828, an accuracy of 0.862, and a specificity of 0.977. Subsequent validation in an independent cohort yielded an AUC of 0.848. Discussion: The acquisition of RDW-CV, HF requirement, MV requirement, NE requirement, lactic acidosis, and MDR upon ICU admission emerges as a pivotal factor for prognosticating PICS onset in the context of tropical diseases. This study highlights the potential for significant improvements in clinical outcomes through the implementation of timely and targeted interventions tailored specifically to the challenges posed by tropical diseases.

Ca2+-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy upon glucose starvation.

Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to glucose starvation to induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal that connects environmental sensing to the formation of the autophagy initiation complex during glucose starvation. Mechanistically, glucose starvation instigates the release of vacuolar calcium into the cytoplasm, thus triggering the activation of Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances Atg11 interactions with Bmh1/2 bound to the Snf1-Sip1-Snf4 complex, leading to recruitment of vacuolar membrane-localized Snf1 to the PAS and subsequent Atg1 activation, thereby initiating autophagy. We also identified Glc7, a protein phosphatase-1, as a critical regulator of the association between Bmh1/2 and the Snf1 complex. We thus propose that calcium-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy by controlling Snf1-mediated Atg1 activation in response to glucose starvation.

A LAMP-CRISPR/Cas12b rapid detection platform for canine parvovirus detection.

Canine parvovirus (CPV) is one of the main pathogens causing toxic diarrhea in Chinese dogs, is the cause of large-scale epidemic of dogs, and poses a great threat to the dog industry in China. Rapid, sensitive, and specific CPV testing facilitates the timely diagnosis and treatment of sick dogs. The aim of this study was to build a LAMP-CRISPR/Cas12b platform for CPV detection. The loop mediated isothermal amplification (LAMP) technique was combined with CRISPR-Cas12b analysis to establish a "two-step" and "one-tube" CRISPR/Cas12b rapid CPV method, respectively. The detection system was constructed with specific LAMP primers and single guide RNA (sgRNA) for the highly conserved short fragment of the CPV gene, which could be detected within 1 h without cross-reaction with the other viruses causing canine diarrhea. The detection limits of both "two-step" and "one-tube" CRISPR/Cas12b reactions were 10-1 copies per µL, which was 100 times more sensitive than qPCR and LAMP. In order to achieve point-of-care testing (POCT) of CPV, a one-tube LAMP-CRISPR/Cas12b nucleic acid extraction and detection platform based on magnetic nanoparticle enrichment technology was established to achieve "sample in-result out". The results of this method for simulated samples were compared with those of quantitative real-time PCR; the results showed 100% consistency, and the time was shorter, which could be used to detect the diseased dogs earlier and provide a basis for clinical diagnosis. The LAMP-CRISPR/Cas12b method established in this study provides a sensitive and specific method for rapid detection of CPV, and provides technical support for rapid diagnosis of CPV.

Molecular Cloning and Functional Identification of a Pericarp- and Testa-Abundant Gene's (AhN8DT-2) Promoter from Arachis hypogaea.

Cultivated peanut (Arachis hypogaea L.) is a key oil- and protein-providing legume crop of the world. It is full of nutrients, and its nutrient profile is comparable to that of other nuts. Peanut is a unique plant as it showcases a pegging phenomenon, producing flowers above ground, and after fertilization, the developing peg enters the soil and produces seeds underground. This geocarpic nature of peanut exposes its seeds to soil pathogens. Peanut seeds are protected by an inedible pericarp and testa. The pericarp- and testa-specific promoters can be effectively used to improve the seed defense. We identified a pericarp- and testa-abundant expression gene (AhN8DT-2) from available transcriptome expression data, whose tissue-specific expression was further confirmed by the qRT-PCR. The 1827bp promoter sequence was used to construct the expression vector using the pMDC164 vector for further analysis. Quantitative expression of the GUS gene in transgenic Arabidopsis plants showed its high expression in the pericarp. GUS staining showed a deep blue color in the pericarp and testa. Cryostat sectioning of stained Arabidopsis seeds showed that expression is only limited to seed coat (testa), and staining was not present in cotyledons and embryos. GUS staining was not detected in any other tissues, including seedlings, leaves, stems, and roots, except for some staining in flowers. Under different phytohormones, this promoter did not show an increase in expression level. These results indicated that the AhN8DT-2 promoter drives GUS gene expression in a pericarp- and testa-specific manner. The identified promoter can be utilized to drive disease resistance genes, specifically in the pericarp and testa, enhancing peanut seed defense against soil-borne pathogens. This approach has broader implications for improving the resilience of peanut crops and other legumes, contributing to sustainable agricultural practices and food security.

3D Porous Fibers with Spatial Traps and Excellent Zn2+ Transport Kinetics Enable Stable Zn-Based Aqueous Battery.

Adverse side reactions and uncontrolled Zn dendrites growth are the dominant factors that have restricted the application of Zn ion batteries. Herein, a 3D self-supporting porous carbon fibers (denoted as PCFs) host is developed with "trap" effect to adjust the Zn deposition. The unique open structural design of N-doped carbon can act as the zincophilic sites to induce uniform deposition and inhibit adverse side reactions. More importantly, the porous hollow PCFs host with "trap" effect can induce Zn deposition in the fiber by adjusting the local electric field and current density, thereby increasing the specific energy density of the battery and inhibiting dendrite growth. In addition, the 3D open frameworks can regulate Zn2+ flux to enable outstanding cycling performance at ultra-high current densities. As expected, the PCFs framework guarantees the uniform Zn plating and stripping with an outstanding stability over 6000 cycles at the current density of 40 mA cm-2. And the Zn@PCFs||MnO2 full battery shows an excellent lifespan over 1300 cycles at 2000 mA g-1.

Investigating optimal compression approach following radial artery puncture: a retrospective study.

BACKGROUND: The method for compressing hemorrhagic sites after transradial access has been a topic of interest, yet definitive guidelines remain elusive. This study aims to address this gap by optimizing the mechanical compression hemostasis protocol after transradial access. METHODS: This retrospective analysis included 300 patients from the Department of Cerebrovascular Diseases, Shanghai Fourth People's Hospital affiliated to Tongji University, who underwent transradial access for cerebrovascular angiography. Following the procedure, patients received radial artery compression hemostasis using a balloon compressor. They were divided into group A (n=100, continuous deflation) and group B (n=200, intermittent deflation) according to different hemostasis methods. The incidence of bleeding at the puncture site and complications were compared between the two groups. RESULTS: The rate of bleeding at the puncture site was significantly lower in group B (20 out of 200 patients) compared to group A (20 out of 100 patients) (P=0.032). Similarly, the incidence of puncture site complications, such as edema, congestion, and wound infection was lower in group B (5 out of 200 patients) compared to group A (10 out of 100 patients) (P=0.006). CONCLUSION: Four hours of compression with intermittent deflation (group B) emerged as the optimal compression method after transradial access, demonstrating fewer complications at the patient's puncture site.

Structural modification strategies of triazoles in anticancer drug development.

The triazole functional group plays a pivotal role in the composition of biomolecules with potent anticancer activities, including numerous clinically approved drugs. The strategic utilization of the triazole fragment in the rational modification of lead compounds has demonstrated its ability to improve anticancer activities, enhance selectivity, optimize pharmacokinetic properties, and overcome resistance. There has been significant interest in triazole-containing hybrids in recent years due to their remarkable anticancer potential. However, previous reviews on triazoles in cancer treatment have failed to provide tailored design strategies specific to these compounds. Herein, we present an overview of design strategies encompassing a structure-modification approach for incorporating triazoles into hybrid molecules. This review offers valuable references and briefly introduces the synthesis of triazole derivatives, thereby paving the way for further research and advancements in the field of effective and targeted anticancer therapies.

Quantitative mapping of the mammalian epitranscriptome.

The epitranscriptome encompasses a diverse array of dynamic and reversible RNA modifications, affecting both coding and noncoding RNAs. Over 170 types of RNA chemical modifications have been identified, underscoring the need for innovative detection methods to deepen our understanding of RNA modification roles and mechanisms. In particular, the base resolution and quantitative information on RNA modifications are critical for understanding the regulation and functions of RNA modifications. Based on detection throughput and principles, existing quantitative RNA modification detection methods can be categorized into two groups, including next-generation sequencing and nanopore direct RNA sequencing. In this review, we focus on methodologies for elucidating the base resolution and stoichiometric information of RNA modifications. In addition, we further discuss the challenges and the potential prospects of the quantitative RNA modification detection methods.

Engineering of Aromatic Naphthalene and Solvent Molecules to Optimize Chemical Prelithiation for Lithium-Ion Batteries.

A cost-effective chemical prelithiation solution, which consists of Li+, polyaromatic hydrocarbon (PAH), and solvent, is developed for a model hard carbon (HC) electrode. Naphthalene and methyl-substituted naphthalene PAHs, namely 2-methylnaphthalene and 1-methylnaphthalene, are first compared. Grafting an electron-donating methyl group onto the benzene ring can decrease electron affinity and thus reduce the redox potential, which is validated by density functional theory calculations. Ethylene glycol dimethyl ether (G1), diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether solvents are then compared. The G1 solution has the highest conductivity and least steric hindrance, and thus the 1-methylnaphthalene/G1 solution shows superior prelithiation capability. In addition, the effects of the interaction time between Li+ and 1-methylnaphthalene in G1 solvent on the electrochemical properties of a prelithiated HC electrode are investigated. Nuclear magnetic resonance data confirm that 10-h aging is needed to achieve a stable solution coordination state and thus optimal prelithiation efficacy. It is also found that appropriate prelithiation creates a more Li+-conducing and robust solid-electrolyte interphase, improving the rate capability and cycling stability of the HC electrode.

Role of the PARP1/NF-κB Pathway in DNA Damage and Apoptosis of TK6 Cells Induced by Hydroquinone.

Hydroquinone(HQ) is a widely used industrial raw material and is a topical lightening product found in over-the-counter products. However, inappropriate exposure to HQ can pose certain health hazards. This study aims to explore the mechanisms of DNA damage and cell apoptosis caused by HQ, with a focus on whether HQ activates the nuclear factor-κB (NF-κB) pathway to participate in this process and to investigate the correlation between the NF-κB pathway activation and poly(ADP-ribose) polymerase 1(PARP1). Through various experimental techniques, such as DNA damage detection, cell apoptosis assessment, cell survival rate analysis, immunofluorescence, and nuclear-cytoplasmic separation, the cytotoxic effects of HQ were verified, and the activation of the NF-κB pathway was observed. Simultaneously, the relationship between the NF-κB pathway and PARP1 was verified by shRNA interference experiments. The results showed that HQ could significantly activate the NF-κB pathway, leading to a decreased cell survival rate, increased DNA damage, and cell apoptosis. Inhibiting the NF-κB pathway could significantly reduce HQ-induced DNA damage and cell apoptosis and restore cell proliferation and survival rate. shRNA interference experiments further indicated that the activation of the NF-κB pathway was regulated by PARP1. This study confirmed the important role of the NF-κB pathway in HQ-induced DNA damage and cell apoptosis and revealed that the activation of the NF-κB pathway was mediated by PARP1. This research provides important clues for a deeper understanding of the toxic mechanism of HQ.

Prenatal triphenyl phosphate exposure impairs placentation and induces preeclampsia-like symptoms in mice.

Triphenyl phosphate (TPhP) is an organophosphate flame retardant that is widely used in many commercial products. The United States Environmental Protection Agency has listed TPhP as a priority compound that requires health risk assessment. We previously found that TPhP could accumulate in the placentae of mice and impair birth outcomes by activating peroxisome proliferator-activated receptor gamma (PPARγ) in the placental trophoblast. However, the underlying mechanism remains unknown. In this study, we used a mouse intrauterine exposure model and found that TPhP induced preeclampsia (PE)-like symptoms, including new on-set gestational hypertension and proteinuria. Immunofluorescence analysis showed that during placentation, PPARγ was mainly expressed in the labyrinth layer and decidua of the placenta. TPhP significantly decreased placental implantation depth and impeded uterine spiral artery remodeling by activating PPARγ. The results of the in vitro experiments confirmed that TPhP inhibited extravillous trophoblast (EVT) cell migration and invasion by activating PPARγ and inhibiting the PI3K-AKT signaling pathway. Overall, our data demonstrated that TPhP could activate PPARγ in EVT cells, inhibit cell migration and invasion, impede placental implantation and uterine spiral artery remodeling, then induce PE-like symptom and impair birth outcomes. Although the exposure doses used in this study was several orders of magnitude higher than human daily intake, our study highlights the placenta as a potential target organ of TPhP worthy of further research.

Identification of the immune repertoire of γδ T-cell receptors in psoriasis.

The γδ T cells are a subpopulation of T cells that are abundantly found in the skin and mucous membranes. Their reactivity to self-antigens and ability to secrete various cytokines make them a key component in psoriasis development. Although the correlation between the immune repertoire (IR) of γδ T-cell receptors and the occurrence and severity of psoriasis remains incompletely explored, high-throughput sequencing of γδ T cells has led to a deeper understanding of IR in psoriasis. This study investigated the differences between γδ T cells in patients with psoriasis and healthy controls. The γδ T cells were identified via immunofluorescence staining and a correlation analysis was performed according to the psoriasis area and severity index (PASI) scores. The IR sequencing method was used to detect IR in the γδ T-cell receptors. The findings demonstrated more skin γδ T cells in patients with psoriasis, which were positively correlated with the PASI score. There were subtle differences in most variable (V), diversity (D) and joining (J) gene segments and VJ/VDJ combination segments between patients with psoriasis and healthy controls. However, a higher diversity of complementarity-determining region 3 (CDR3) was observed in patients with psoriasis. In summary, the IR of skin γδ T cells was significantly altered in patients with psoriasis, and the diversity in the cell's CDR3 population is a promising biomarker for assessment of psoriasis severity.

TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.