The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG.

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette-Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment.

Correlation between prognosis and peripheral blood levels of NLRP3 and triglyceride-glucose index after myocardial ischemia-reperfusion injury.

OBJECTIVE: We aim to investigate the association between prognosis and outcomes following myocardial ischemia-reperfusion injury, as well as peripheral blood levels of NLRP3 and the triglyceride-glucose index (TyG). METHODS: A total of 100 patients who underwent emergency coronary intervention following myocardial infarction confirmed by coronary angiography at our hospital between October 2021 and May 2023 were included in this study. Patients were stratified into two groups based on their prognoses: the control group (n = 73), which did not experience new myocardial infarctions or require hospitalization for heart failure or suffer sudden cardiac death post-interventional treatment; and the observation group (n = 27), which experienced one or more cardiovascular events post-treatment. Patient demographics were obtained from clinical records while biochemical analyses assessed peripheral blood triglycerides, blood glucose levels, and TyG index. Additionally, ELISA measurements determined levels of NLRP3 as well as inflammatory factors IL-6, TNF-α, and CRP in peripheral blood samples. Cardiac function was evaluated according to NYHA standards. Univariable Cox regression analysis identified factors influencing patient prognosis while Pearson correlation analysis examined relationships among prognosis, outcomes following myocardial ischemia-reperfusion injury, TyG index, and peripheral blood NLRP3. RESULTS: No significant differences were observed in the general characteristics between the two patient groups (P > 0.05). However, the observation group exhibited higher levels of peripheral blood triglycerides, blood glucose, and TyG index compared to the control group (P < 0.05). Additionally, levels of NLRP3 and inflammatory factors IL-6, TNF-α, and CRP were elevated in the observation group compared to the control group (P < 0.05). Cardiac function impairment was more pronounced in the observation group (P < 0.05). Notably, TyG index and peripheral blood NLRP3 demonstrated higher risk ratios compared to other biomarkers (P < 0.05), indicating their significance in prognosis and outcomes. Elevated levels of NLRP3 and TyG index were associated with poorer recovery of cardiac function, increased rehospitalization rates, and higher mortality (P < 0.05). CONCLUSION: Elevated NLRP3 levels and an increased TyG index are strongly associated with impaired cardiac function and heightened risk of cardiovascular events. These findings suggest that these biomarkers may serve as crucial prognostic indicators following myocardial ischemia-reperfusion injury.

Petaloid technique and prognostic significance of macular hole shapes by optical coherence tomography for full thickness macular hole.

Surgical advancements for full-thickness macular hole (FTMH) treatment include vitrectomy, membrane peeling, and the inverted flap technique (IFT). IFT, which involves inverting the internal limiting membrane (ILM) flap over the macular hole (MH) or into the MH, improves success rates and visual recovery. However, issues like mis-aspiration during flap handling have been problematic. We introduce the petaloid technique, to position the ILM flap under air during FTMH surgery to evaluate its outcomes. This retrospective study included 28 eyes, with a mean minimum linear diameter (MLD) 472.04 ± 199.7 µm and basal diameter (BD) of 834.95 ± 593.54 µm. Primary closure of MH was achieved in 96.42% of patients, with 3.57% showing persistent MH during the 6-month follow-up. The VA improved significantly from preoperative levels at each postoperative stage, with notable increases at 3 months (0.86 ± 0.49 logMAR; p = 0.0132) and 6 months (0.77 ± 0.41 logMAR; p = 0.000081). The new closure patterns showed Type A in 28.6%, B in 14.3%, C in 28.6%, and D in 25%. Among different types of closure patterns, although VA improved in all types, significant improvement in VA was noted for type A and type C, with notable improvements at the 6-month follow-up for Type A (0.60 ± 0.23 logMAR; p = 0.02) and at the 1-month follow-up for Type C (0.62 ± 0.28 logMAR; p = 0.02). For macular hole retinal detachment in 5 eyes, the average preoperative VA was 1.86 ± 0.19 logMAR, while the final mean postoperative VA showed a significant improvement to 1.1 ± 0.40 logMAR (p = 0.021, paired t-tests). Retinal reattachment was achieved in all cases (5/5) without recurrent detachment post-silicone oil removal. For the prognostic significance of MH shapes identified by OCT, it can be concluded that the shape of macular holes significantly influences visual acuity outcomes at 6 months post-surgery (p = 0.037). The shape of macular holes, particularly Flask-shaped, significantly impacts visual acuity compared to other shape. The modified petaloid technique for treating FTMH proved safe and effective, with no significant complications noted.

Nitrogen oxides emissions from coastal wetland sediments: Experimental assessment of the influence of vegetation and nitrogen input.

Nitrogen oxides (NOx = NO + NO2) have essential impacts on global climate and the environment, making it essential to study the contribution of wetland-generated NOx to environmental problems. With exogenous nitrogen input from anthropogenic activities, wetland sediments become active emission hotspots for NOx. In this study, we conducted field experiments in a typical salt marsh wetland to measure nitric oxide (NO, the primary component of NOx from sediments) exchange fluxes in both mudflat and vegetated sediments. We found that NO fluxes in vegetated sediments (0.40 ± 0.15 × 10-12 kg N m-2 s-1) were relatively higher than in mudflat sediments (-1.31 ± 1.39 × 10-12 kg N m-2 s-1), with this difference occurring only during the vegetation-dying season (autumn). Correlations between sediment NO fluxes and environmental parameters revealed that NO flux variation during the observation period was primarily influenced by sediment respiration, temperature, water content, and substrate availability. However, the influence of these factors on NO fluxes differed between mudflat and vegetated sediments. In-situ data analysis also suggested that tidal horizontal migration, which affects sediment substrate and salinity, may regulate sediment NO emissions. Furthermore, in-situ incubations with nitrogen addition (ammonia, nitrite, and nitrate) were conducted to study the response of sediment NO emissions to exogenous nitrogen. We observed that nitrogen addition caused a 259.7 % increase in NO emissions from vegetated sediments compared to the control during the effective period of nitrogen addition (days 1-3). However, although nitrogen addition markedly stimulated sediment NO emissions, the overall NO production capacity constrained the extent of this increase.

Antiferromagnetism and Phase Stability of CrMnFeCoNi High-Entropy Alloy.

It has long been suspected that magnetism could play a vital role in the phase stability of multicomponent high-entropy alloys. However, the nature of the magnetic order, if any, has remained elusive. Here, by using elastic and inelastic neutron scattering, we demonstrate evidence of antiferromagnetic order below ∼80 K and strong spin fluctuations persisting to room temperature in a single-phase face-centered cubic (fcc) CrMnFeCoNi high-entropy alloy. Despite the chemical complexity, the magnetic structure in CrMnFeCoNi can be described as γ-Mn-like, with the magnetic moments confined in alternating (001) planes and pointing toward the ⟨111⟩ direction. Combined with first-principles calculation results, it is shown that the antiferromagnetic order and spin fluctuations help stabilized the fcc phase in CrMnFeCoNi high-entropy alloy.

Biological conversion of lignin-derived ferulic acid from wheat bran into vanillin.

Lignin is a promising feedstock for producing vanillin, one of the most extensively used flavor enhancers. However, the biotransformation performance of lignin derivatives into vanillin is still unsatisfactory. In this study, an efficient conversion strategy of lignin into vanillin was established by employing engineered Saccharomyces cerevisiae as a whole-cell biocatalyst. Optimization of cell culture media and whole-cell bioconversion improved the production efficiency of vanillin. The vanillin titer reached 15.3 mM with a molar yield of 71 % in fed-batch fermentation mode, while incorporating in-situ product separation, demonstrated a remarkable 2.6-fold increase. The whole-cell bioconversion, coupled with in-situ separation, successfully converted real lignin hydrolysate into a record vanillin titer of 21.1 mM, equivalent to 1.8 mg of vanillin per gram of wheat bran biomass. The whole-cell bioconversion process integrated in-situ product separation, represents a sustainable approach for vanillin production and offers a promising pathway for lignin valorization.

Multimodal evidence for cerebellar influence on cortical development in autism: structural growth amidst functional disruption.

Despite perinatal damage to the cerebellum being one of the highest risk factors for later being diagnosed with autism spectrum disorder (ASD), it is not yet clear how the cerebellum might influence the development of cerebral cortex and whether this co-developmental process is distinct between neurotypical and ASD children. Leveraging a large structural brain MRI dataset of neurotypical children and those diagnosed with ASD, we examined whether structural variation in cerebellar tissue across individuals was correlated with neocortical variation during development, including the thalamus as a coupling factor. We found that the thalamus plays a distinct role in moderating cerebro-cerebellar structural coordination in ASD. Notably, structural coupling between cerebellum, thalamus, and neocortex was strongest in younger childhood and waned by early adolescence, mirroring a previously undescribed trajectory of behavioral development between ASD and neurotypical children. Complementary functional connectivity analyses likewise revealed atypical connectivity between cerebellum and neocortex in ASD. This relationship was particularly prominent in a model of cerebellar structure predicting functional connectivity, where ASD and neurotypical children showed divergent patterns. Interestingly, these functional-structural relationships became more prominent with age, while structural effects were most prominent earlier in childhood, and showed significant lateralization. This pattern may suggest a developmental sequence where early uncoordinated structural growth amongst regions is followed by increasingly atypical functional synchronization. These findings provide multimodal evidence in the living brain for a cerebellar diaschisis model of autism, where both increased cerebellar-cerebral structural coupling and altered functional connectivity in cerebro-cerebellar pathways contribute to the ontogeny of this neurodevelopmental disorder.

Emerging insights into the application of metal-organic framework (MOF)-based materials for electrochemical heavy metal ion detection.

Heavy metal ions are one of the main sources of water pollution, which has become a major global problem. Given the growing need for heavy metal ion detection, electrochemical sensor stands out for its high sensitivity and efficiency. Metal-organic frameworks (MOFs) have garnered much interest as electrode modifiers for electrochemical detection of heavy metal ions owing to their significant specific surface area, tailored pore size, and catalytic activity. This review summarizes the progress of MOF-based materials, including pristine MOFs and MOF composites, in the electrochemical detection of various heavy metal ions. The synthetic methods of pristine MOFs, the detection mechanisms of heavy metal ions and the modification strategies of MOFs are introduced. Besides, the diverse applications of MOF-based materials in detecting both single and multiple heavy metal ions are presented. Furthermore, we present the current challenges and prospects for MOF-based materials in electrochemical heavy metal ion detection.

Pyrrolic-Nitrogen Chemistry in 1-(2-hydroxyethyl)imidazole Electrolyte Additives toward a 50,000-Cycle-Life Aqueous Zinc-Iodine Battery.

Rechargeable aqueous zinc iodine (Zn-I2) batteries offer benefits such as low cost and high safety. Nevertheless, their commercial application is hindered by hydrogen evolution reaction (HER) and polyiodide shuttle, which result in a short lifespan. In this study, 1-(2-hydroxyethyl)imidazole (HEI) organic molecules featuring pyrrole-N groups are introduced as dually-functional electrolyte additives to simultaneously stabilize Zn anode and confine polyiodide through ion-dipole interactions. The pyrrole-N groups in HEI can preserve the interfacial pH equilibrium at Zn anode by reversibly capturing H+ ions and dynamically neutralizing OH- ions, thereby suppressing the HER. Notably, the H2 evolution rate at the Zn anode is reduced to a mere 2.20 µmol h-1 cm-2. Furthermore, the pyrrole-N moieties in HEI effectively curtail the polyiodide shuttle at I2 cathode, which show adsorption energies of -0.174 eV for I2, -0.521 eV for I3-, and -0.768 eV for I-, as indicated by density functional theory calculations. Electrochemical testing demonstrates that the Zn//Zn symmetric cell maintains stable cycling for up to 4,200 hours at 1 mA cm-2. Most strikingly, at a high I2 mass loading of 9.7 mg cm-2, the Zn-I2 battery achieves an extraordinary cycle life of 50,000 cycles.

Effect of thermal pretreatments on the quality attributes and irradiation markers of sesame oil extracted from sesame seeds without and with gamma irradiation.

This study comparatively studied the effects of three thermal pretreatment methods, i.e., wet-heat (WT), roasting (RT) and microwave (MT), on the quality attributes and irradiation markers of sesame oil obtained from sesame seeds without and with gamma irradiation. Results showed that gamma irradiation had negligible effect on the quality of sesame seeds and their extracted oils. The effects of thermal pretreatments on irradiated and non-irradiated sesame seeds and their oils were similar, little synergistic effects were observed. The RT-treated oils had more carotenoids, chlorophyll, total phenols, tocopherols, and heterocyclic volatiles content, as well as longer oxidation induction time, but darker color compared with their WT- and MT-treated counterparts. All oil samples had identical FTIR spectra. Eight radiolytic hydrocarbons were identified in the irradiated sesame oils. Thermal pretreatments reduced the content of radiolytic hydrocarbons, but did not significantly change their composition. Our study helps to identify products from irradiated sesame seeds.

New Meroterpenes from South China Sea Soft Coral Litophyton brassicum.

A chemical investigation of the extracts from the soft coral Litophyton brassicum led to the isolation and identification of four new meroterpenes, brassihydroxybenzoquinone A and B (1 and 2) and brassinaphthoquinone A and B (3 and 4), along with two known related meroterpenes (5 and 6). Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR) spectroscopy, and a comparison with the literature data. All compounds were evaluated for antibacterial activity against six pathogenic bacterial strains and for cytotoxic activity against three cancer cell lines. In the cytotoxic assay, all compounds were inactive at 10 µM against the A549, HeLa, and MDA-MB-231 cell lines. In the antibacterial assay, compounds 1 and 2 exhibited moderate inhibitory activity with minimum inhibitory concentrations (MIC) ranging from 8 to 64 µg/mL.

A necroptosis-regulated model from single-cell analysis that predicts survival and identifies the Pivotal role of MAGEA6 in hepatocellular carcinoma.

Objective: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths, constituting 75%-85 % of all primary liver cancers. The objective of this study was to develop a necroptosis-related gene signature using single-cell and bulk RNA sequencing to predict HCC patient prognoses. Methods: A total of 25 key necroptosis regulators were identified from previous literature. We evaluated the necroptosis scores of different cell types using single-cell sequencing data from HCC and analyzed 168 necroptosis-related genes. The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset served as the training set for establishing a novel necroptosis-related gene risk signature, employing univariate and multivariate Cox regression analyses. Additionally, the study examined the model's relevance in immunity and immunotherapy, and predicted chemosensitivity in HCC patients based on the gene signature. The key genes were validated by the biological experiments. Results: Compared to other cell types, hepatoma cells displayed the lowest necroptosis scores. A new six-gene necroptosis-related signature (S100A11, MAGEC2, MAGEA6, CTP2C9, SOX4, AKR1B10) was developed using the TCGA database and validated in the ICGC database. Patients in the high-risk category had poorer prognoses, with the risk score serving as an independent prognostic indicator beyond other clinical factors. These high-risk patients also exhibited greater immune infiltration but demonstrated a weaker anti-tumor response due to elevated expression of immune checkpoints. Pathways involving hypoxia, glycolysis, and P53, as well as the frequency of P53 somatic mutations, were notably heightened in the high-risk group. Additionally, the six genes in the model showed significantly different mRNA expression in hepatoma cell lines compared to normal hepatocytes, with the role of MAGEA6 in liver cancer being elucidated through critical experiments. Conclusions: This study successfully developed a six-gene necroptosis-related signature to predict prognoses in HCC patients. It further explored the roles of necroptosis in hepatoma cells and the tumor microenvironment.

Preparation and characterization of biochar from four different solid wastes and its ampicillin adsorption performance.

The integration of biochar (BC) production from organic waste with ampicillin (AMP), an emerging pollutant, adsorption is a novel and promising treatment approach. In this study, peanut shells, coffee grounds, digestates, and oyster shells were used for BC production. Among these, the use of anaerobic digestate from food waste fermentation to produce extracts for antibiotic adsorption is relatively unexplored. The pyrolysis temperature was determined using thermogravimetric analysis (TGA) and the materials were characterized with BET, SEM, FTIR, and XRD. The TGA results indicate that PSB, CRB, and DSB underwent pyrolysis involving cellulose, hemicellulose, and lignin, whereas OSB underwent crystal formation. Characterization revealed that DSB has more functional groups, a superior mesoporous structure, appropriate O/C ratio, and trace amounts of calcite crystals, which are favorable for AMP adsorption. Adsorption experiments demonstrate that all four materials adhere to the Freundlich and Langmuir isotherm and Elovich kinetic models, indicating predominant physical adsorption, with some chemical adsorption also present. Thermodynamic studies demonstrate that BC is spontaneous during adsorption and is a heat-absorbing reaction. DSB exhibits the strongest AMP adsorption. A 53.81 mg g-1 adsorbance was obtained at a dosage of 150 mg, pH = 2, and 60 °C. This study introduces innovative approaches for managing waste types and provides data to support the selection of suitable solid wastes for the preparation of BC with excellent adsorption properties. Furthermore, it lays the groundwork for future studies aimed at enhancing the AMP treatment efficacy.

New Insights into Mitochondria in Health and Diseases.

Mitochondria are a unique type of semi-autonomous organelle within the cell that carry out essential functions crucial for the cell's survival and well-being. They are the location where eukaryotic cells carry out energy metabolism. Aside from producing the majority of ATP through oxidative phosphorylation, which provides essential energy for cellular functions, mitochondria also participate in other metabolic processes within the cell, such as the electron transport chain, citric acid cycle, and ß-oxidation of fatty acids. Furthermore, mitochondria regulate the production and elimination of ROS, the synthesis of nucleotides and amino acids, the balance of calcium ions, and the process of cell death. Therefore, it is widely accepted that mitochondrial dysfunction is a factor that causes or contributes to the development and advancement of various diseases. These include common systemic diseases, such as aging, diabetes, Parkinson's disease, and cancer, as well as rare metabolic disorders, like Kearns-Sayre syndrome, Leigh disease, and mitochondrial myopathy. This overview outlines the various mechanisms by which mitochondria are involved in numerous illnesses and cellular physiological activities. Additionally, it provides new discoveries regarding the involvement of mitochondria in both disorders and the maintenance of good health.

Syn-COM: A Multi-Level Predictive Synergy Framework for Innovative Drug Combinations.

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations and interactions by integrating molecular virtuality, similarity clustering, overlap area, and network distance. It uniquely combines the characteristics of Chinese herbal medicine with clinical experience and innovatively assesses drug interaction and correlation through a synergy matrix. Gouty arthritis (GA) was used as a case study to validate the framework's reliability, leading to the identification of an effective drug combination for GA treatment, comprising Tamaricis Cacumen (Si = 0.73), Cuscutae Semen (Si = 0.68), Artemisiae Annuae Herba (Si = 0.62), Schizonepetae Herba (Si = 0.73), Gleditsiae Spina (Si = 0.89), Prunellae Spica (Si = 0.75), and Achyranthis Bidentatae Radix (Si = 0.62). The efficacy of the identified drug combination was confirmed through animal experiments and traditional Chinese medicine (TCM) component analysis. Results demonstrated significant reductions in the blood inflammatory factors IL1A, IL6, and uric acid, as well as downregulation of TGFB1, PTGS2, and MMP3 expression (p < 0.05), along with improvements in ankle joint swelling in GA mice. This drug combination notably enhances therapeutic outcomes in GA by targeting key genes, underscoring the potential of integrating traditional medicine with modern bioinformatics for effective disease treatment.

Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial.

Background: The clinical utility of Bacteroides fragilis in treating autism spectrum disorder (ASD) remains unclear. Therefore, this randomized, double-blind, placebo-controlled study aimed to explore the therapeutic effects and safety of B. fragilis BF839 in the treatment of pediatric ASD. Methods: We examined 60 children aged 2-10 years diagnosed with ASD, and participants received either BF839 powder (10 g/bar with ≥106 CFU/bar of viable bacteria, two bars/day) or placebo for 16 weeks. The primary outcomes was Autism Behavior Checklist (ABC) score. The secondary outcomes were Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Normal Development of Social Skills from Infants to Junior High School Children (S-M), Gastrointestinal Symptom Rating Scale (GSRS) scores, and fecal microbiome composition. Assessments were performed on day 0 and at weeks 8 and 16. Results: Compared with the placebo group, the BF839 group showed significant improvement in the ABC body and object use scores at week 16, which was more pronounced in children with ASD aged <4 years. Among children with a baseline CARS score ≥30, the BF839 group showed significant improvements at week 16 in the ABC total score, ABC body and object use score, CARS score, and GSRS score compared to the placebo group. Only two patients (6.67%) in the BF839 group experienced mild diarrhea. Compared with baseline and placebo group levels, the BF839 group showed a significant post-intervention increase in abundance of bifidobacteria and change in the metabolic function of neuroactive compounds encoded by intestinal microorganisms. Conclusion: BF839 significantly and safely improved abnormal behavior and gastrointestinal symptoms in children with ASD.

A comprehensive review of artificial intelligence for pharmacology research.

With the innovation and advancement of artificial intelligence, more and more artificial intelligence techniques are employed in drug research, biomedical frontier research, and clinical medicine practice, especially, in the field of pharmacology research. Thus, this review focuses on the applications of artificial intelligence in drug discovery, compound pharmacokinetic prediction, and clinical pharmacology. We briefly introduced the basic knowledge and development of artificial intelligence, presented a comprehensive review, and then summarized the latest studies and discussed the strengths and limitations of artificial intelligence models. Additionally, we highlighted several important studies and pointed out possible research directions.

Progressive failure processes and mechanisms of disasters caused by interrelated failure of residual coal pillars and rock strata.

The increasing number of closed/abandoned mines being reused has become a concern for people. However, a large number of coal pillars were left behind in the closed/abandoned mines. Before effectively utilizing the underground space of mines (CO2 goaf storage, etc.), it is necessary to study the stability of the residual pillars and rock strata. However, limited laboratory experiments and numerical simulation tests have been carried out to understand the relationship between residual pillars and strata in the context of their failure process and mechanism. In this study, the progressive failure and movement of the pillars and strata during the multi-seam mining is simulated using a physical model and numerical simulation. In addition, the failure mechanism was analyzed. The results suggest that the failure process of the pillar is strongly related to the rock strata. The mining of the below seam will bring about not only the collapse of the above strata, but also penetrate the gob of the overlying seam, and then cause the roof of the overlying seam to further collapse. The damage zone acting on the pillar increases accordingly, and the pillars are also gradually damaged. When the pillar is completely destroyed, it will further cause the stable strata to fracture, collapse and become unstable, and a rock burst may be formed. It is also found that under the effect of the stress concentration of the pillar, the floor rock will be damaged to a certain depth. When the collapse height of the overlying strata overlaps with the failure depth of the floor due to the stress concentration, it is more likely to bring about the occurrence of rock burst. The mechanisms of progressive failure of the residual pillars and rock strata revealed by this study offers guidance for the control of disasters, and also provides a reference for the stability research during goaf utilization in the later stage.

METTL protein family: focusing on the occurrence, progression and treatment of cancer.

Methyltransferase-like protein is a ubiquitous enzyme-like protein in the human body, with binding domains for nucleic acids, proteins and other small molecules, and plays an important role in a variety of biological behaviours in normal organisms and diseases, characterised by the presence of a methyltransferase-like structural domain and a structurally conserved SAM-binding domain formed by the seven-stranded ß-fold structure in the center of the protein. With the deepening of research, the METTL protein family has been found to be abnormally expressed in a variety of tumor diseases, and the clarification of its relationship with tumor diseases can be used as a molecular therapeutic target and has an important role in the prognosis of tumors. In this paper, we review the structure, biological process, immunotherapy, drug-targeted therapy, and markers of the METTL protein family to provide new ideas for the diagnosis and treatment of tumors.

Lanthanum chloride exerts therapeutic potential for chronic kidney disease by suppressing nanohydroxyapatite-induced mitophagy and mitochondria-mediated apoptosis.

OBJECTIVE: To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism. METHODS: 1. Patients with CKD stage 2-5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected. RESULTS: 1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride. CONCLUSION: Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively.