Residual inflammatory risk and vulnerable plaque in the carotid artery in patients with ischemic stroke.

Objective: Inflammation is a central driver of atherogenesis and eventual plaque rupture. This study aimed to evaluate the association between residual inflammatory risk (RIR) and vulnerable plaques in the carotid artery in patients with ischemic stroke. Methods: Patients with acute ischemic stroke were enrolled from January 2021 to July 2022. They were divided into four groups: RIR only (LDL-C <2.6 mmol/L and hsCRP ≥2 mg/L), residual cholesterol risk (RCR) only (LDL-C ≥2.6 mmol/L and hsCRP <2 mg/L), both risk or residual cholesterol and inflammatory risk (RCIR) (LDL-C ≥2.6 mmol/L and hsCRP ≥2 mg/L), and neither risk (LDL-C <2.6 mmol/L and hsCRP <2 mg/L). Vulnerable plaques were determined if it had a low attenuated plaque CT value of <35 Hounsfield Units (HU) and a remodeling index of >1.1, which indicated a positive remodeling. Results: Out of the 468 enrolled patients, 157 (33.5%) were detected to have vulnerable plaques. The proportion of patients with neither risk, RIR, RCR, and RCIR were 32.9%, 28.6%, 18.8%, and 19.7%, respectively. Patients with vulnerable plaques exhibited a higher prevalence of hyperlipidemia (P = 0.026), higher proportion of RIR (P = 0.015), a higher ratio of stroke subtypes of large artery atherosclerosis (P = 0.012), and high leukocyte counts (P < 0.001). The logistic regression analysis detected that RIR was associated with vulnerable plaques after adjusted for major confounding factors (OR 1.98, 95% CI 1.13-3.45, P = 0.016), especially in the large artery atherosclerosis subtype (OR 2.71, 95% CI 1.08-6.77, P = 0.034). Conclusions: In patients with ischemic stroke, RIR is associated with the vulnerability of carotid plaques, especially for those with the large artery atherosclerosis subtype. Therefore, further studies investigating the interventions to modulate inflammation in these patients may be warranted.

Comparative genomic analysis provides insights into the genetic diversity and pathogenicity of the genus Brucella.

Some Brucella spp. are important pathogens. According to the latest prokaryotic taxonomy, the Brucella genus consists of facultative intracellular parasitic Brucella species and extracellular opportunistic or environmental Brucella species. Intracellular Brucella species include classical and nonclassical types, with different species generally exhibiting host preferences. Some classical intracellular Brucella species can cause zoonotic brucellosis, including B. melitensis, B. abortus, B. suis, and B. canis. Extracellular Brucella species comprise opportunistic or environmental species which belonged formerly to the genus Ochrobactrum and thus nowadays renamed as for example Brucella intermedia or Brucella anthropi, which are the most frequent opportunistic human pathogens within the recently expanded genus Brucella. The cause of the diverse phenotypic characteristics of different Brucella species is still unclear. To further investigate the genetic evolutionary characteristics of the Brucella genus and elucidate the relationship between its genomic composition and prediction of phenotypic traits, we collected the genomic data of Brucella from the NCBI Genome database and conducted a comparative genomics study. We found that classical and nonclassical intracellular Brucella species and extracellular Brucella species exhibited differences in phylogenetic relationships, horizontal gene transfer and distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes, showing the close relationship between the genetic variations and prediction of phenotypic traits of different Brucella species. Furthermore, we found significant differences in horizontal gene transfer and the distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes between the two chromosomes of Brucella, indicating that the two chromosomes had distinct dynamics and plasticity and played different roles in the survival and evolution of Brucella. These findings provide new directions for exploring the genetic evolutionary characteristics of the Brucella genus and could offer new clues to elucidate the factors influencing the phenotypic diversity of the Brucella genus.

The Resource Utilization of Poplar Leaves for CO2 Adsorption.

Every late autumn, fluttering poplar leaves scatter throughout the campus and city streets. In this work, poplar leaves were used as the raw material, while H3PO4 and KOH were used as activators and urea was used as the nitrogen source to prepare biomass based-activated carbons (ACs) to capture CO2. The pore structures, functional groups and morphology, and desorption performance of the prepared ACs were characterized; the CO2 adsorption, regeneration, and kinetics were also evaluated. The results showed that H3PO4 and urea obviously promoted the development of pore structures and pyrrole nitrogen (N-5), while KOH and urea were more conductive to the formation of hydroxyl (-OH) and ether (C-O) functional groups. At optimal operating conditions, the CO2 adsorption capacity of H3PO4- and KOH-activated poplar leaves after urea treatment reached 4.07 and 3.85 mmol/g, respectively, at room temperature; both showed stable regenerative behaviour after ten adsorption-desorption cycles.

Predominance of A2063G mutant strains in the Mycoplasma pneumoniae epidemic in children-a clinical and epidemiological study in 2023 in Wuhan, China.

OBJECTIVES: The prevalence of respiratory infectious diseases has changed in the post Covid-19 epidemic era, and mycoplasma pneumoniae (MP) infection in children has attracted wide attention. METHODS: Children hospitalized for pneumonia in Wuhan, China, in 2023 were enrolled. Respiratory secretions were obtained for the targeted next-generation sequencing (tNGS) including mutation of MP. Pulmonary inflammation was divided into bronchopneumonia and pulmonary consolidation/atelectasis according to lung CT imaging. RESULTS: Of the 667 pediatric pneumonia, 478 were MP positive (72%). The positive rate of MP detected by tNGS increased from April, and MP had become the primary pathogen of pneumonia in children in year 2023. The 23S rRNA mutations were all A2063G, accounting for 85% of detected MP. The clinical symptoms of the mutant and wild type strains were similar, with half of them experiencing atelectasis and lung consolidation. Early bronchoscopic lavage combined with azithromycin in pediatric pulmonary consolidation was an effective therapy strategy, which could be an alternative selection to MPP treatment. CONCLUSION: A2063G mutant strain MP was the primary pathogen of mycoplasma pneumoniae in children recently, which was often complicated by extra-pulmonary symptoms and complications.

Freeprotmap: waiting-free prediction method for protein distance map.

BACKGROUND: Protein residue-residue distance maps are used for remote homology detection, protein information estimation, and protein structure research. However, existing prediction approaches are time-consuming, and hundreds of millions of proteins are discovered each year, necessitating the development of a rapid and reliable prediction method for protein residue-residue distances. Moreover, because many proteins lack known homologous sequences, a waiting-free and alignment-free deep learning method is needed. RESULT: In this study, we propose a learning framework named FreeProtMap. In terms of protein representation processing, the proposed group pooling in FreeProtMap effectively mitigates issues arising from high-dimensional sparseness in protein representation. In terms of model structure, we have made several careful designs. Firstly, it is designed based on the locality of protein structures and triangular inequality distance constraints to improve prediction accuracy. Secondly, inference speed is improved by using additive attention and lightweight design. Besides, the generalization ability is improved by using bottlenecks and a neural network block named local microformer. As a result, FreeProtMap can predict protein residue-residue distances in tens of milliseconds and has higher precision than the best structure prediction method. CONCLUSION: Several groups of comparative experiments and ablation experiments verify the effectiveness of the designs. The results demonstrate that FreeProtMap significantly outperforms other state-of-the-art methods in accurate protein residue-residue distance prediction, which is beneficial for lots of protein research works. It is worth mentioning that we could scan all proteins discovered each year based on FreeProtMap to find structurally similar proteins in a short time because the fact that the structure similarity calculation method based on distance maps is much less time-consuming than algorithms based on 3D structures.

The impact of continuous cultivation of Ganoderma lucidum on soil nutrients, enzyme activity, and fruiting body metabolites.

To explore the impacts of continuous Ganoderma lucidum cultivation on soil physicochemical factors, soil enzyme activity, and the metabolome of Ganoderma lucidum fruiting bodies, this study conducted two consecutive years of cultivation on the same plot of land. Soil physicochemical factors and enzyme activity were assessed, alongside non-targeted metabolomic analysis of the Ganoderma lucidum fruiting bodies under continuous cultivation. The findings unveiled that in the surface soil layer (0-15 cm), there was a declining trend in organic matter, ammonium nitrogen, available phosphorus, available potassium, pH, polyphenol oxidase, peroxidase, alkaline phosphatase, and sucrase, whereas nitrate nitrogen, electrical conductivity (EC), and salt content exhibited an upward trend. Conversely, in the deeper soil layer (15-30 cm), organic matter, ammonium nitrogen, available potassium, alkaline phosphatase, and sucrase demonstrated a decreasing trend, while nitrate nitrogen, available phosphorus, pH, EC, salt content, polyphenol oxidase, and soil peroxidase showed an increasing trend. Metabolomic analysis of Ganoderma lucidum fruiting bodies distinguished 64 significantly different metabolites between the GCK and GT groups, with 39 components having markedly higher relative contents in GCK and 25 components having significantly lower relative contents in GCK compared to GT. Moreover, among these metabolites, there were more types with higher contents in the fruiting bodies harvested in the first year (GCK) compared to those harvested in the second year (GT), with pronounced differences. KEGG pathway analysis revealed that GCK exhibited more complex metabolic pathways compared to GT. The metabolites of Ganoderma lucidum fruiting bodies were predominantly influenced by soil physicochemical factors and soil enzyme activity. In the surface soil layer (0-15 cm), the metabolome was significantly affected by soil pH, soil organic matter, available phosphorus, and soil alkaline phosphatase, while in the deeper soil layer (15-30 cm), differences in the Ganoderma lucidum metabolome were more influenced by soil alkaline phosphatase, soil catalase, pH, nitrate nitrogen, and soil sucrase.

Small-diameter acellular porcine corneal stroma for peripheral corneal ulceration treatment.

AIM: To evaluate the clinical efficacy of small-diameter acellular porcine corneal stroma (SAPS) for the treatment of peripheral corneal ulceration (PCU). METHODS: This retrospective clinical study included 18 patients (18 eyes) with PCU between April 2018 and December 2020. All patients had PCU and underwent lamellar keratoplasty with SAPS. Observation indicators included preoperative and postoperative best-corrected visual acuity (BCVA) and transparency of SAPS. The infection control rate in the surgical eye-lesion area was also calculated. RESULTS: Eighteen patients underwent lamellar keratoplasty with SAPS to treat PCU. None of the patients experienced rejection after 6mo (18/18) and 12mo (16/16) of follow-up. The BCVA (0.47±0.30) at the 6mo follow-up after operation was significantly improved compared with the baseline (0.99±0.80), and the difference was statistically significant (Z=-3.415, P<0.05). The BCVA at the 12mo follow-up after operation was not statistically significant compared to the 6mo (Z=0, P=1). With time, the SAPS graft gradually became transparent. At the 6mo (18/18) and 12mo (16/16) follow-up, none of the patients had recurrent corneal infection. CONCLUSION: SAPS is clinically effective in the treatment of PCU, improving the patient's BCVA and reducing the incidence of rejection after keratoplasty.

Association of Oral Anticoagulant Therapy with the Prevalence and Severity of Vascular Calcification among Patients with Atrial Fibrillation: A Cohort Study.

Many patients with atrial fibrillation (AF) requiring long-term use of oral anticoagulants (OACs) are at high risk for vascular calcification and anticoagulation therapy with warfarin exacerbate vascular calcification. However, the effect of nonvitamin K agonists on vascular calcification has not been clearly investigated. This study explored the effects of dabigatran etexilate, rivaroxaban, and warfarin on vascular calcification among 1527 patients with AF. Demographics, comorbidities, laboratory test data, medications, and the prevalence and severity of vascular calcification in different vascular beds were compared. After propensity score matching, the incidence of vascular calcification in the rivaroxaban and warfarin group was significantly higher than that in the nonanticoagulant group, while there was no difference between the dabigatran etexilate group and the nonanticoagulant group. Similarly, we found that the rivaroxaban group had more severe calcification in the overall vascular level (P < 0.001), thoracic aorta (P < 0.001), aortic arch (P = 0.001), and left common carotid artery (P = 0.005) than the nonanticoagulant group. In addition, in the left common carotid artery, there was more severe calcification in the rivaroxaban group than that in the dabigatran group (P = 0.005). Our results suggest that rivaroxaban can significantly increase both the incidence and severity of vascular calcification among patients with AF, while dabigatran etexilate has no such effect. Many patients with AF requiring long-term use of OACs are at high risk for vascular calcification. This is the first study to conduct a head-to-head comparison of the effects of dabigatran etexilate and rivaroxaban on vascular calcification. Rivaroxaban, rather than dabigatran etexilate, promotes vascular calcification in patients with AF, providing important implications to aid clinicians in their choice for OAC selection, especially those at high risk for vascular calcification.

Dysregulation of Gut Microbiota-Derived Neuromodulatory Amino Acid Metabolism in Human Immunodeficiency Virus-Associated Neurocognitive Disorder: An Integrative Metagenomic and Metabolomic Analysis.

OBJECTIVE: Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear. METHODS: Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND. RESULTS: The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria. INTERPRETATION: Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024.

Layered BaV6O16·3H2O@GO as a high performance cathode material for calcium ion batteries.

The lack of suitable cathode materials has hampered the further development of calcium-ion batteries (CIBs). A novel composite cathode material, namely BaV6O16·3H2O@GO, was fabricated, which delivers a high specific capacity of 285.72 mA h g-1 at 50 mA g-1 after 50 cycles and a long cycle life, benefiting from a large layer spacing and robust structure. This study provides guidance for the development of vanadium-based cathode materials for CIBs.

Low-dose cadmium induces lymphangiogenesis through activation of the STAT3 signaling pathway.

Cadmium (Cd) is a widespread environmental toxicant that poses significant threat to public health. After intake, Cd is distributed throughout the body via blood and lymphatic circulation. However, the effect of Cd on lymphatic vessels has not been revealed. In this study, mice were exposed to 10 µM cadmium chloride through drinking water immediately after corneal alkali burn. In vivo analyses showed that Cd treatment enhances the alkali burn-induced corneal lymphangiogenesis, which is characterized by increased expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), prospero-related homeobox 1 (PROX-1) and vascular endothelial growth factor receptor 3 (VEGFR3). In vitro, the proliferation and migration of human dermal lymphatic endothelial cells (HDLECs) are increased by 1 µM Cd treatment, while inhibited by 10 µM Cd treatment. At a concentration of 1 µM, Cd specifically induces phosphorylation of signal transducer and activator of transcription 3 (STAT3), but has no effect on the MAPK, AKT, or NF-κB signaling pathway. In the presence of the STAT3 inhibitor STATTIC, Cd fails to induce HDLECs proliferation and migration. In addition, Cd upregulates VEGFR3 expression and its gene promoter activity in a STAT3-dependent manner. Our study suggests that low-dose Cd promotes lymphangiogenesis through activation of the STAT3 signaling pathway.

Predictors of early versus delayed neurological deterioration after thrombolysis for ischemic stroke: ENCHANTED study.

BACKGROUND AND PURPOSE: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: END and DND were defined as scores of a ≥2 point increase on the National Institutes of Health Stroke Scale (NIHSS) or ≥1 point decrease on Glasgow coma scale, or death, from baseline to 24 hours and 24 hours to 72 hours, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs 0-1 and 3-6 vs 0-2, and death). RESULTS: Of 4496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 hours, were all independent predictors for both END (all P ≤0.01) and DND (all P ≤0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 hours (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 hours were the key predictor of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all P<0.001). CONCLUSIONS: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for acute ischemic stroke. Both END and DND predict unfavorable outcomes at 90 days.

Purification of Photorhabdus Virulence Cassette (PVC) Protein Complexes from Escherichia coli for Artificial Translocation of Heterologous Cargo Proteins.

Contractile injection systems (CISs), one of the most important bacterial secretion systems that transport substrates across the membrane, are a collection of diverse but evolutionarily related macromolecular devices. Numerous effector proteins can be loaded and injected by this secretion complex to their specific destinations. One group of CISs called extracellular CIS (eCIS) has been proposed as secretory molecules that can be released from the bacterial cytoplasm and attack neighboring target cells from the extracellular environment. This makes them a potential delivery vector for the transportation of various cargos without the inclusion of bacterial cells, which might elicit certain immunological responses from hosts. We have demonstrated that the Photorhabdus virulence cassette (PVC), which is a typical eCIS, could be applied as an ideal vector for the translocation of proteinaceous cargos with different physical or chemical properties. Here, we describe the in-depth purification protocol of this mega complex from Escherichia coli. The protocol provided is a simpler, faster, and more productive way of generating the eCIS complexes than available methodologies reported previously, which can facilitate the subsequent applications of these nanodevices and other eCIS in different backgrounds.

Application Value of CYFRA21-1 Combined with NSE, CEA, and SCC-Ag in Lung Cancer.

BACKGROUND: This study aims to investigate the application value of serum cytokeratin 19 fragment (CYFRA21-1) combined with nerve-specific enolase (NSE), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-Ag) in the diagnosis of lung cancer (LC). METHODS: A total of 831 cases of LC, 360 cases of benign lung disease (BLD) and 102 healthy controls, were enrolled. The data were processed using SPSS, GraphPad Prism, and MedCalc software. RESULTS: The tumor marker (TM) levels in the LC and BLD groups were significantly higher than those in the control group; the CYFRA21-1, NSE, and CEA levels in the patients with LC were higher than in those with BLD. In particular, the increase was predominantly observed for the levels of CEA and CYFRA21-1 in adenocarcinoma (LUAD), CYFRA21-1 and SCC-Ag in squamous cell carcinoma (LUSC), and NSE in small cell carcinoma (SCLC). The CYFRA21-1, NSE, and CEA levels were significantly higher in stage IV than in other stages in LC. Univariate binary logistic analysis showed that increased levels of all four TMs were risk factors for BLD and LC. The area under the curve (AUC) of CYFRA21-1 was most effective in distinguishing patients with BLD or LC from the controls and in distinguishing patients with BLD and LC. The AUCs of combined CYFRA21-1, NSE, and CEA were increased to 0.755, 0.922, and 0.783, respectively, with no significant difference with the AUC of the four combined tests. In the histological classification, the best predictors were CEA, for LUAD, CYFRA21-1 for LUSC, and NSE for SCLC. Moreover, the expression levels of CYFRA21-1, NSE, and CEA significantly decreased after each treatment course. CONCLUSIONS: The combined assay of CYFRA21-1, NSE, and CEA addresses the aspects of accuracy, sensitivity, specificity, and economic cost and should be considered as a potential diagnostic test in LC.

The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.

N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.

Systematic investigation of TetR-family transcriptional regulators and their roles on lignocellulosic inhibitor acetate tolerance in Zymomonas mobilis.

TetR-family transcriptional regulators are widely distributed among bacteria and involved in various cellular processes such as multidrug and inhibitor resistance. Zymomonas mobilis is a industrial bacterium for lignocellulosic ethanol production. Although TetR-family regulators and their associated RND-family efflux pumps in Z. mobilis have been identified to be differentially expressed under various inhibitors and stressful conditions, there are no systematic investigation yet. In this study, bioinformatic analyses indicated that there are three TetR-family transcriptional regulators (ZMO0281, ZMO0963, ZMO1547) and two RND-family efflux pumps (ZMO0282-0285, ZMO0964-0966) adjacent to corresponding TetR-family regulators of ZMO0281 and ZMO0963 in Z. mobilis. Genetics studies were then carried out with various mutants of TetR-family regulators constructed, and ZMO0281 was characterized to be related to acetate tolerance. Combining transcriptomics and dual-reporter gene system, this study demonstrated that three TetR-family regulators repressed their adjacent genes specifically. Moreover, TetR-family regulator ZMO0281 might also be involved in other cellular processes in the presence of acetate. In addition, the upregulation of RND-family efflux pumps due to ZMO0281 deletion might lead to an energy imbalance and decreased cell growth in Z. mobilis under acetate stress. The systematic investigation of all three TetR-family regulators and their roles on a major lignocellulosic inhibitor acetate tolerance in Z. mobilis thus not only unravels the molecular mechanisms of TetR-family regulators and their potential cross-talks on regulating RND-family efflux pumps and other genes in Z. mobilis, but also provides guidance on understanding the roles of multiple regulators of same family in Z. mobilis and other microorganisms for efficient lignocellulosic biochemical production.

Preclinical and phase I studies of an antisense oligonucleotide drug targeting IGF-1R in liver cancer.

Aim: To evaluate a novel antisense oligonucleotide drug targeting human IGF-1R in preclinical and phase I studies of liver cancer. Materials & methods: The tolerability and safety of an investigational new drug were evaluated in a dose-escalation trial involving 17 patients with advanced liver cancer after preclinical assessment of pharmacokinetics and pharmacodynamics. Results: The drug exposure levels in the phase I trial were determined by the in vivo efficacy with pharmacokinetics evaluation in rats and rhesus monkeys. This clinical study showed that the maximum tolerated dose was 3.96 mg/kg, and the dose-limiting toxicity dose was 4.4 mg/kg. Conclusion: The drug was safe and tolerable in patients with advanced liver cancer. Clinical Trial Registration: ChiCTR2100044235 (www.chictr.org.cn).

CT102 is a potential new drug for liver cancer treatment. It belongs to a new form of medicine using gene therapy technology called antisense oligonucleotides. There are some antisense oligonucleotides approved for treating rare diseases. This study evaluated the antitumor effect, metabolism and safety of CT102 in preclinical and clinical trials. The results showed that CT102 could inhibit tumor growth in mice with liver cancer and maintain high levels in the liver. It was found that CT102 was safe and tolerable in patients with advanced liver cancer. This suggests that CT102 has therapeutic potential for liver cancer treatment. The good tolerability and safety of CT102 in patients supports further studies on liver cancer treatment.

Cadmium aggravates liver injury by activating ferroptosis and neutrophil extracellular traps formation in Nile tilapia (Oreochromis niloticus).

Cadmium (Cd) is a pervasive environmental contaminant and a significant risk factor for liver injury. The present study was undertaken to evaluate the involvement of ferroptosis and neutrophil extracellular traps (NETs) in Cd-induced liver injury in Nile tilapia (Oreochromis niloticus), and to explore its underlying mechanism. Cd-induced liver injury was associated with increased total iron, malondialdehyde (MDA), and Acyl-CoA synthetase long-chain family member 4 (ACSL4), together with reduced levels of glutathione, glutathione peroxidase-4a (Gpx4a), and solute carrier family 7 member 11 (SLC7A11), which are all hallmarks of ferroptosis. Moreover, liver hyperemia, neutrophil infiltration, increased inflammatory factors and myeloperoxidase, as well as elevated serum DNA content in Cd-stimulated Nile tilapia suggested that a considerable number of neutrophils were recruited to the liver. Furtherly, in vitro experiments demonstrated that Cd induced the formation of NETs, and the possible mechanism was related to the generation of reactive oxygen species and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, along with the P38 and extracellular regulated protein kinase (ERK) signaling pathways. We concluded that ferroptosis and NETs are the critical mechanisms contributing to Cd-induced liver injury in Nile tilapia. These findings will contribute to Cd toxicological studies in aquatic animals.