Supramolecular Channels Assembled within Intercellular Gaps.

Tubular structures exist broadly in biological systems and exhibit important functions including mediating cellular communications. The construction of artificial analogues in living cells would provide a new strategy for chemotherapy. In this report, a kind of supramolecular channel has been constructed within intercellular gaps by mimicking the assembly process and structure of natural gap junctional channels, which consist of hydrophobic tubular modules located in the adjacent cell membranes and hydrophilic modules within the extracellular space. The assembly of the channels was driven by electrostatic interactions. The channels could inhibit tumor cell invasion by preventing cell migration.

[Determination of 13 perfluorinated and polyfluoroalkyl substances in fishes by QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry].

Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 µg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 µg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 µg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.

Study on the occurrence and influencing factors of gastrointestinal symptoms in hemodialysis patients with uremia.

BACKGROUND: Gastrointestinal symptoms are common in patients with uremia undergoing hemodialysis, and these symptoms seriously affect patients' prognosis. AIM: To assess the occurrence and factors influencing gastrointestinal symptoms in patients with uremia undergoing hemodialysis. METHODS: We retrospectively selected 98 patients with uremia who underwent regular hemodialysis treatment in the blood purification center of our hospital from December 2022 to December 2023. The gastrointestinal symptoms and scores of each dimension were evaluated using the Gastrointestinal Symptom Grading Scale (GSRS). Patients were divided into gastrointestinal symptoms and no gastrointestinal symptom groups according to whether they had gastrointestinal symptoms. The factors that may affect gastrointestinal symptoms were identified by single-factor analysis. Multiple logistic regression analysis was performed to identify independent risk factors for gastrointestinal symptoms. RESULTS: Gastrointestinal symptoms included indigestion, constipation, reflux, diarrhea, abdominal pain, and eating disorders, and the total average GSRS score was 1.35 ± 0.47. This study showed that age, number of tablets, dialysis time, glucocorticoid, parathyroid hormone (PTH), combined diabetes mellitus and C-reactive protein (CRP) were independent risk factors for gastrointestinal symptoms in patients with uremia undergoing hemodialysis, whereas body mass index (BMI), hemoglobin (Hb), and urea clearance index were independent protective factors (P < 0.05). CONCLUSION: Gastrointestinal symptoms are mostly mild in patients with uremia undergoing hemodialysis, most commonly including dyspepsia, eating disorders, and gastroesophageal reflux. The independent influencing factors mainly include the BMI, age, number of pills taken, dialysis time, urea clearance index, Hb, use of glucocorticoids, and thyroid hormone level. PTH, CRP, and diabetes are clinically related factors influencing the occurrence of gastrointestinal symptoms, and targeted prevention can be performed.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

[Genome-wide screening and bioinformatics analysis of Cannabis sativa LecRLK gene family].

Lectin receptor-like kinase(LecRLK) is a class of phytokinase with lectin conserved domain, which plays an important role in plant resistance to biological and abiotic stresses, as well as plant growth and development. Cannabis sativa is an important multi-purpose plant, widely used in food, textile, medicine, and other fields. Genome-wide screening and expression analysis of the LecRLK family of C. sativa were performed in this paper, so as to provide scientific reference for functional analysis of the LecRLK family of C. sativa. Based on BLAST and HMM methods, 93 LecRLKs were identified in the whole genome of C. sativa, including 69 G types, 23 L types, and one C types. Subsequently, a series of bioinformatics analyses were performed on the LecRLK family members, and the physicochemical properties of the protein of the LecRLK family members were initially revealed. The prediction of cis-acting elements of promoters in family members showed that family members were regulated by hormones and stress response. The expression analysis showed that some family members were highly expressed in the roots, which may participate in the process of stress resistance. Several members were highly expressed in female flowers and may be involved in female flower development. This study provides a theoretical basis for further study of LecRLK gene function. Meanwhile, the expression analysis screens candidate LecRLK members who may participate in the resistance of C. sativa, which provides a theoretical basis for the subsequent selection of C. sativa varieties against resistance.

Comparative analysis of large language models in medical counseling: A focus on Helicobacter pylori infection.

BACKGROUND: Large language models (LLMs) are promising medical counseling tools, but the reliability of responses remains unclear. We aimed to assess the feasibility of three popular LLMs as counseling tools for Helicobacter pylori infection in different counseling languages. MATERIALS AND METHODS: This study was conducted between November 20 and December 1, 2023. Three large language models (ChatGPT 4.0 [LLM1], ChatGPT 3.5 [LLM2], and ERNIE Bot 4.0 [LLM3]) were input 15 H. pylori related questions each, once in English and once in Chinese. Each chat was conducted using the "New Chat" function to avoid bias from correlation interference. Responses were recorded and blindly assigned to three reviewers for scoring on three established Likert scales: accuracy (ranged 1-6 point), completeness (ranged 1-3 point), and comprehensibility (ranged 1-3 point). The acceptable thresholds for the scales were set at a minimum of 4, 2, and 2, respectively. Final various source and interlanguage comparisons were made. RESULTS: The overall mean (SD) accuracy score was 4.80 (1.02), while 1.82 (0.78) for completeness score and 2.90 (0.36) for comprehensibility score. The acceptable proportions for the accuracy, completeness, and comprehensibility of the responses were 90%, 45.6%, and 100%, respectively. The acceptable proportion of overall completeness score for English responses was better than for Chinese responses (p = 0.034). For accuracy, the English responses of LLM3 were better than the Chinese responses (p = 0.0055). As for completeness, the English responses of LLM1 was better than the Chinese responses (p = 0.0257). For comprehensibility, the English responses of LLM1 was better than the Chinese responses (p = 0.0496). No differences were found between the various LLMs. CONCLUSIONS: The LLMs responded satisfactorily to questions related to H. pylori infection. But further improving completeness and reliability, along with considering language nuances, is crucial for optimizing overall performance.

Role of Cardiolipin in regulating and treating atherosclerotic cardiovascular diseases.

Cardiovascular diseases, mainly caused by atherosclerosis, are the leading causes of morbidity and mortality worldwide. Despite the discrepancies in clinical manifestations between different abnormalities, atherosclerosis shares similar pathophysiological processes, such as mitochondrial dysfunction. Cardiolipin (CL) is a conserved mitochondria-specific lipid that contributes to the cristae structure of the inner mitochondrial membrane (IMM). Alterations in the CL, including oxidative modification, reduced quantity, and abnormal localization, contribute to the onset and progression of atherosclerosis. In this review, we summarize the knowledge that CL is involved in the pathogenesis of atherosclerosis. On the one hand, CL and its oxidative modification promote the progression of atherosclerosis via several mechanisms, including oxidative stress, apoptosis, and inflammation in response to stress. On the other hand, CL externalizes to the outer mitochondrial membrane (OMM) and acts as the pivotal "eat-me" signal in mitophagy, removing dysfunctional mitochondria and safeguarding against the progression of atherosclerosis. Given the imbalance between proatherogenic and antiatherogenic effects, we provide our understanding of the roles of the CL and its oxidative modification in atherosclerotic cardiovascular diseases, in addition to potential therapeutic strategies aimed at restoring the CL. Briefly, CL is far more than a structural IMM lipid; broader significances of the evolutionarily conserved lipid need to be explored.

Alstomaphylines A-K, monoterpenoid bisindole alkaloids from Alstonia macrophylla with AChE inhibitory activity and cytotoxicity.

Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.

Esketamine mitigates mechanical ventilation-induced lung injury in chronic obstructive pulmonary disease rats via inhibition of the MAPK/NF-κB signaling pathway and reduction of oxidative stress.

PURPOSE: To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms. METHODS: Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays. RESULTS: Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue. CONCLUSION: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.

Engineered small extracellular vesicle-mediated ferroptosis: A new frontier in cancer immunotherapy.

Ferroptosis is a novel iron-dependent form of cell death discovered in recent years, characterized by the accumulation of ferrous iron, the production of reactive oxygen species (ROS) through the Fenton reaction, and lipid peroxidation, ultimately leading to the disruption of the antioxidant system and cell membrane damage. Extensive research has found that ferroptosis plays a significant role in regulating tumor cell immune evasion, tumor development, and remodeling the tumor microenvironment. Small Extracellular vesicles (sEVs), carrying various bioactive molecules (ncRNA, DNA, proteins), are key nanoscale mediators of intercellular communication. Increasing evidence confirms that EVs can regulate the ferroptosis pathway in tumors, promoting tumor cell immune evasion and reshaping the tumor microenvironment. This article aims to comprehensively review the key mechanisms by which sEVs mediate ferroptosis in cancer and provide new insights into targeting tumor immunotherapy.

An Unusual Crystalline Porous Framework Constructed from Multitypes of Cages with Proton Conduction Property and Heterogeneous Catalytic Activity for Pyrazole Synthesis.

An unusual crystalline porous framework constructed from four types of cages, including all-inorganic Keggin-type polyoxometalate (POM) cages [H3W12O40]5-, organic hexamethylenetetramine (Hmt) cages, nanosized silver-Hmt coordination cages, and giant POM-silver-Hmt cages, was hydrothermally synthesized and structurally characterized. The framework features a highly symmetrical structure with one-dimensional nanoscale channels and holds good thermal/solvent stability, which endow it with proton conduction properties and heterogeneous catalytic activity for pyrazole. This paper not only contributes to broadening the structural diversity of cage-based crystalline porous framework materials but also sheds new light on the design of new functional framework materials.

CRISPR-array-mediated imaging of non-repetitive and multiplex genomic loci in living cells.

Dynamic imaging of genomic loci is key for understanding gene regulation, but methods for imaging genomes, in particular non-repetitive DNAs, are limited. We developed CRISPRdelight, a DNA-labeling system based on endonuclease-deficient CRISPR-Cas12a (dCas12a), with an engineered CRISPR array to track DNA location and motion. CRISPRdelight enables robust imaging of all examined 12 non-repetitive genomic loci in different cell lines. We revealed the confined movement of the CCAT1 locus (chr8q24) at the nuclear periphery for repressed expression and active motion in the interior nucleus for transcription. We uncovered the selective repositioning of HSP gene loci to nuclear speckles, including a remarkable relocation of HSPH1 (chr13q12) for elevated transcription during stresses. Combining CRISPR-dCas12a and RNA aptamers allowed multiplex imaging of four types of satellite DNA loci with a single array, revealing their spatial proximity to the nucleolus-associated domain. CRISPRdelight is a user-friendly and robust system for imaging and tracking genomic dynamics and regulation.

Melatonin attenuates scopolamine-induced cognitive dysfunction through SIRT1/IRE1α/XBP1 pathway.

BACKGROUND: The prevalence of dementia around the world is increasing, and these patients are more likely to have cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorders over their lifetime. Previous studies have proven that melatonin could improve memory loss, but its specific mechanism is still confused. METHODS: In this study, we used in vivo and in vitro models to examine the neuroprotective effect of melatonin on scopolamine (SCOP)-induced cognitive dysfunction. The behavioral tests were performed. 18F-FDG PET imaging was used to assess the metabolism of the brain. Protein expressions were determined through kit detection, Western blot, and immunofluorescence. Nissl staining was conducted to reflect neurodegeneration. MTT assay and RNAi transfection were applied to perform the in vitro experiments. RESULTS: We found that melatonin could ameliorate SCOP-induced cognitive dysfunction and relieve anxious-like behaviors or HT22 cell damage. 18F-FDG PET-CT results showed that melatonin could improve cerebral glucose uptake in SCOP-treated mice. Melatonin restored the cholinergic function, increased the expressions of neurotrophic factors, and ameliorated oxidative stress in the brain of SCOP-treated mice. In addition, melatonin upregulated the expression of silent information regulator 1 (SIRT1), which further relieved endoplasmic reticulum (ER) stress by decreasing the expression of phosphorylate inositol-requiring enzyme (p-IRE1α) and its downstream, X-box binding protein 1 (XBP1). CONCLUSIONS: These results indicated that melatonin could ameliorate SCOP-induced cognitive dysfunction through the SIRT1/IRE1α/XBP1 pathway. SIRT1 might be the critical target of melatonin in the treatment of dementia.

Construction of Near-Infrared Probes with Remarkable Large Stokes Shift Based on a Novel Purine Platform for the Visualization of mtG4 Upregulation during Mitochondrial Disorder in Somatic Cells and Human Sperms.

G-quadruplex structures within the nuclear genome (nG4) is an important regulatory factor, while the function of G4 in the mitochondrial genome (mtG4) still needs to be explored, especially in human sperms. To gain a better understanding of the relationship between mtG4 and mitochondrial function, it is crucial to develop excellent probes that can selectively visualize and track mtG4 in both somatic cells and sperms. Herein, based on our previous research on purine frameworks, we attempted for the first time to extend the conjugated structure from the C-8 site of purine skeleton and discovered that the purine derivative modified by the C-8 aldehyde group is an ideal platform for constructing near-infrared probes with extremely large Stokes shift (>220 nm). Compared with the compound substituted with methylpyridine (PAP), the molecule substituted with methylthiazole orange (PATO) showed better G4 recognition ability, including longer emission (∼720 nm), more significant fluorescent enhancement (∼67-fold), lower background, and excellent photostability. PATO exhibited a sensitive response to mtG4 variation in both somatic cells and human sperms. Most importantly, PATO helped us to discover that mtG4 was significantly increased in cells with mitochondrial respiratory chain damage caused by complex I inhibitors (6-OHDA and rotenone), as well as in human sperms that suffer from oxidative stress. Altogether, our study not only provides a novel ideal molecular platform for constructing high-performance probes but also develops an effective tool for studying the relationship between mtG4 and mitochondrial function in both somatic cells and human sperms.

Ginkgetin Pretreatment Reduces Inflammatory Response in DCD Donor Liver via JAK2/STAT3 Signaling Pathway.

BACKGROUND Ginkgetin inhibits growth of tumor cells, reducing blood lipids, and improving atherosclerosis, but the protective effect of ginkgetin in donation after cardiac death (DCD) livers is still unknown. The aim of this study was to determine whether pretreatment of DCD donor livers with ginkgetin can reduce inflammatory response through the JAK2/STAT3 signaling pathway. MATERIAL AND METHODS Twenty male Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: Sham, DCD, Ginkgetin (0.6 mg/kg) pretreatment 1 h before surgery, and Ginkgetin (0.6 mg/kg) plus broussonin E (0.3 mg/kg) (JAK2/STAT3 signaling agonist) pretreatment 1 h before surgery. Rat livers were subjected to 30 min warm ischemia and 24 h cold storage to simulate the preservation process of DCD donor livers, followed by normothermic machine perfusion for 1 h to simulate liver reperfusion in vivo. Liver tissues and perfusate samples were collected for further studies. RESULTS Ginkgetin pretreatment significantly decreased the values of ALT and AST (P<0.05), and improved histological alterations according to improved Suzuki's Score (P<0.05). Ginkgetin also inhibited the protein expression levels of p-JAK2/JAK2 and p-STAT3/STAT3 (P<0.05). Furthermore, ginkgetin pretreatment inhibited levels of interleukin-1ß, interleukin-6 and tumor necrosis factor a (P<0.05) to suppress inflammatory response. In addition, broussonin E reversed the improvement of ginkgetin on DCD donor livers. CONCLUSIONS Ginkgetin can inhibit the inflammatory response through the JAK2/STAT3 signaling pathway to improve the quality of DCD donor livers.

New Cytotoxic γ-Lactam Alkaloids from the Mangrove-Derived Fungus Talaromyces hainanensis sp. nov. Guided by Molecular Networking Strategy.

The fungus Talaromyces hainanensis, isolated from the mangrove soil, was characterized as a novel species by morphology observation and phylogenetic analyses. Four new γ-lactam alkaloids talaroilactams A-D (1-4) and two reported compounds harzianic acid (5) and isoharzianic acid (6) were identified from the fungus T. hainanensis WHUF0341, assisted by OSMAC along with molecular networking approaches. Their structures were determined through ECD calculations and spectroscopic analyses. Moreover, the biosynthetic route of 1-4 was also proposed. Compound 1 displayed potent cytotoxicity against HepG2 cell lines, with an IC50 value of 10.75 ± 1.11 µM. In addition, network pharmacology was employed to dissect the probable mechanisms contributing to the antihepatocellular carcinoma effects of compound 1, revealing that cytotoxicity was mainly associated with proteolysis, negative regulation of autophagy, inflammatory response, and the renin-angiotensin system. These results not only expanded the chemical space of natural products from the mangrove associated fungi but also afforded promising lead compounds for developing the antihepatocellular carcinoma agents.

The influence of near-infrared carbon dots on the conformational variation and enzymatic activity of glucose oxidase: A multi-spectroscopic and biochemical study with molecular docking.

In recent years, the exceptional biocatalytic properties of glucose oxidase (GOx) have spurred the development of various GOx-functionalized nanocatalysts for cancer diagnosis and treatment. Carbon dots, renowned for their excellent biocompatibility and distinctive fluorescence properties, effectively incorporate GOx. Given the paramount importance of GOx's enzymatic activity in therapeutic efficacy, this study conducts a thorough exploration of the molecular-level binding dynamics between GOx and near-infrared carbon dots (NIR-CDs). Utilizing various spectrometric and molecular simulation techniques, we reveal that NIR-CDs form a ground-state complex with GOx primarily via hydrogen bonds and van der Waals forces, interacting directly with amino acid residues in GOx's active site. This binding leads to conformational change and reduces thermal stability of GOx, slightly inhibiting its enzymatic activity and demonstrating a competitive inhibition effect. In vitro experiments demonstrate that NIR-CDs attenuate the GOx's capacity to produce H2O2 in HeLa cells, mitigating enzyme-induced cytotoxicity and cellular damage. This comprehensive elucidation of the intricate binding mechanisms between NIR-CDs and GOx provides critical insights for the design of NIR-CD-based nanotherapeutic platforms to augment cancer therapy. Such advancements lay the groundwork for innovative and efficacious cancer treatment strategies.

The burden of cardiovascular disease attributable to high fasting plasma glucose：Findings from the global burden of disease study 2019.

AIM: High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. METHODS: We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. RESULTS: Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of -0.22 and -0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio-demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. CONCLUSION: The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.

A dual responsive nitric oxide / ß-lapachone co-delivery platform for redox imbalance-enhanced tumor therapy.

Nitric oxide (NO) / ß-Lapachone (Lap) combined therapy by causing oxidative stress is an effective tumor therapy strategy. Herein, a dual-responsive lipid nanoparticles (LNPs) LSNO for NO / Lap co-delivery were constructed from the zinc-coordinated lipid (DSNO(Zn)) and the hydrophobic drug Lap in the presence of helper lipids (DOPE and DSPE-PEG2000). The zinc-coordinated structure in LSNO might elevate the Zn2+ content in tumor cells, contributing to antioxidant imbalance. The fluorescent assays proved the light-triggered NO release and fluorescent self-reporting abilities of LSNO. In addition, the LNPs had good drug release behavior under high concentration of GSH, indicating the NO / drug co-delivery capacity. In vitro antitumor assays showed that the NO / Lap combination treatment group could induce more significant tumor cell growth inhibition and cell apoptosis than individual NO or Lap treatment. The following mechanism studies revealed that NO / Lap combination treatment led to distinct oxidative stress by producing reactive oxygen species (ROS) and peroxynitrite anion (ONOO-). On the other hand, the intracellular redox balance could be further disrupted by Lap-induced NADPH consumption and Zn2+ / NO-induced reductase activities downregulation, thus promoting the degree of cell damage. Besides, it was also found that NO and Lap could directly damage nuclear DNA and induce mitochondrial dysfunction, thereby leading to caspase-3 activation and tumor cell death. These results proved that LSNO could serve as a promising multifunctional tumor therapy platform.