The benefits of oral glucose-lowering agents: GLP-1 receptor agonists, DPP-4 and SGLT-2 inhibitors on myocardial ischaemia/reperfusion injury.

Myocardial infarction (MI) is a life-threatening cardiovascular disease that, on average, results in 8.5 million deaths worldwide each year. Timely revascularization of occluded vessels is a critical method of myocardial salvage. However, reperfusion paradoxically leads to the worsening of myocardial damage known as myocardial ischaemia/reperfusion injury (MI/RI). Therefore, reducing the size of myocardial infarction after reperfusion is critical and remains an important therapeutic goal. The susceptibility of the myocardium to MI/RI may be increased by diabetes. Currently, some traditional antidiabetic agents such as metformin reduce MI/RI by decreasing inflammation, inhibiting oxidative stress, and improving vascular endothelial function. This appears to be a new direction for the treatment of MI/RI. Recent cardiovascular outcome trials have shown that several oral antidiabetic agents, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4is), and sodium-glucose-linked transporter-2 inhibitors (SGLT-2is), not only have good antidiabetic effects but also have a protective effect on myocardial protection. This article aims to discuss the mechanisms and effects of oral antidiabetic agents, including GLP-1RAs, DPP-4is, and SGLT-2is, on MI/RI to facilitate their clinical application.

A portable solid sampling visualization nano-sensor for soil Cd based on "three-phase transforming" technique.

Direct analysis of solid samples is always challenging for ionic sensors due to solidified elemental presence and matrix interference. In this work, a "three-phase transforming" technique was first established to make solid sampling elemental sensors and visual detection possible in the future. For Cd transforming from soil samples, a metal ceramic heater (MCH) electrothermal vaporizer (ETV) coupled with a dielectric barrier discharge quartz trap (DBD-QT) was first utilized to fulfill the solid sampling and preconcentration of Cd in soil; for on-site analysis, a colorimetric sensor based on the trithiocyanuric acid (TMT) functionalized gold nanoparticles (AuNPs) was chosen as a chromogenic analysis model. The portable and miniature ETV-DBD apparatus directly introduced Cd from soil and then captured Cd, consuming only <130 W and 4.5 kg weight; finally, only 200 µL water was injected as eluent to dissolve Cd for the following colorimetric detection. Herein, the Cd analyte underwent a "three-phase transforming" from solid (Cd compounds in soil), to aerosol (vaporization and transportation), to solid (Cd oxides trapped on quartz surface) and to liquid (Cd2+ in eluate). Under optimized conditions, the method limit of detection (LOD) reached 0.04 mg/kg Cd (50 mg sample), fulfilling fast monitoring of Cd contamination in soil, with <20 % relative standard deviations (RSDs). The analysis time was <10 min excluding sample digestion and acid application, as well as the interference of Pb2+ on the AuNPs sensor can be eliminated via the "three-phase transforming" process, proving an excellent anti-interference for solid analysis. This "three-phase transforming" processing technique coupled with colorimetric sensor holds a great potential for direct and on-site analysis in solid samples without complicated handling, providing a fantastic methodology for the application of ionic sensors and making solid sampling elemental sensor and visual detection possible.

QDPR deficiency drives immune suppression in pancreatic cancer.

The relevance of biopterin metabolism in resistance to immune checkpoint blockade (ICB) therapy remains unknown. We demonstrate that the deficiency of quinoid dihydropteridine reductase (QDPR), a critical enzyme regulating biopterin metabolism, causes metabolite dihydrobiopterin (BH2) accumulation and decreases the ratio of tetrahydrobiopterin (BH4) to BH2 in pancreatic ductal adenocarcinomas (PDACs). The reduced BH4/BH2 ratio leads to an increase in reactive oxygen species (ROS) generation and a decrease in the distribution of H3K27me3 at CXCL1 promoter. Consequently, myeloid-derived suppressor cells are recruited to tumor microenvironment via CXCR2 causing resistance to ICB therapy. We discovered that BH4 supplementation is capable to restore the BH4/BH2 ratio, enhance anti-tumor immunity, and overcome ICB resistance in QDPR-deficient PDACs. Tumors with lower QDPR expression show decreased responsiveness to ICB therapy. These findings offer a novel strategy for selecting patient and combining therapies to improve the effectiveness of ICB therapy in PDAC.

Prognostic Evaluation for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Patients Treated with Transarterial Chemoembolization Plus Molecular Targeted Therapies-Development and Validation of the ABPS Score.

RATIONALE AND OBJECTIVES: Transarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: A retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score. Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study. RESULTS: The ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1: 0 score; grade 2: 1 score), PVTT(I-II type: 0 score; III-IV type: 1 score), and systemic-immune inflammation index (SII,<550 × 1012: 0 score; ≥550 × 1012: 1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1-2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6-12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P < 0.05). These research findings were further validated in the external validation cohorts. CONCLUSION: The ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients.

Efficient Fabrication of Self-Assembled Polylactic Acid Colloidosomes for Pesticide Encapsulation.

Colloidosomes are microcapsules whose shells are composed of cumulated or fused colloidal particles. When colloidosomes are used for in situ encapsulation, it is still a challenge to achieve a high encapsulation efficiency and controllable release by an effective fabrication method. Herein, we present a highly efficient route for the large-scale preparation of colloidosomes. The biodegradable polylactic acid (PLA) nanoparticles (NPs) as shell materials can be synthesized using an antisolvent precipitation method, and the possible formation mechanism was given through the molecular dynamics (MD) simulation. The theoretical values are basically consistent with the experimental results. Through the use of the modified and unmodified PLA NPs, the colloidosomes with controllable shell porosities can be easily constructed using spray drying technology. We also investigate the mechanism of colloidosomes successfully self-assembled by PLA NPs with various factors of inlet temperature, feed rate, and flow rates of compressed air. Furthermore, avermectin (AVM) was used as a model for in situ encapsulation and a controllable release. The spherical modified colloidosomes encapsulating AVM not only achieve a small mean diameter of 1.57 µm but also realize a high encapsulation efficiency of 89.7% and impermeability, which can be further verified by the MD simulation. AVM molecules gather around and clog the shell pores during the evaporation of water molecules. More importantly, the PLA colloidosomes also reveal excellent UV-shielding properties, which can protect AVM from photodegradation.

Association between Postmenopausal Osteoporosis and IL-6、TNF-α: A Systematic Review and A Meta-analysis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) greatly increases the risk of bone fracture in postmenopausal women, seriously affects the quality of life of patients, and is an important global public health problem. Persistent chronic systemic inflammation may be involved in the change process of PMOP, and many cytokines, such as TNF-alpha and Interleukin-6, play an important role in the inflammatory response. Therefore, This study takes commonly representative inflammatory factors as indicators to better determine their role in PMOP patients by means of databases from multiple studies for use in Meta-analysis. METHOD: Systematic review of studies on the relationship between PMOP and markers of inflammation: interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Each effect size was expressed with a 95% confidence interval (CI), and I2 quantified the heterogeneity. The final results were aggregated and evaluated using random or fixed effects models. RESULTS: Twenty-one original studies were identified. There were twenty studies involving IL-6 and eleven involving TNF-α. Overall, The levels of IL-6[MD=23.93, 95%CI (19.65, 28.21)] and TNF-α[MD=2.9, 95%CI (2.37, 3.44)] were increased in PMOP patients compared with postmenopausal women without osteoporosis; The levels of IL-6[MD=42.4, 95%CI (38.62, 46.19)] and TNF-α[MD=0.40, 95%CI (0.36, 0.44)] were significantly higher than those of premenopausal healthy women. CONCLUSIONS: The levels of inflammatory cytokines IL-6 and TNF-α were significantly increased in PMOP patients compared with controls, suggesting that persistent chronic inflammatory reaction exists in PMOP patients, which may be an important cause of aggravated osteoporosis in postmenopausal women. Therefore, the level of IL-6 and TNF-α indexes may be of great significance for the early prevention, diagnosis, treatment and prognosis assessment of PMOP.

Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis.

OBJECTIVE: Metastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered. DESIGN: We performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). We also conducted immunofluorescence staining and functional experiments to examine the mechanism. RESULTS: Integrative analyses of epithelial cells reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O (PTPRO) and achaete scute-like 2 (ASCL2) expression as the metastatic culprit. This cell cluster comprising distinct subpopulations shows distinct liver or ovary metastatic preference. Population 1 (P1) cells with high delta-like ligand 4 (DLL4) and MAF bZIP transcription factor A (MAFA) expression are enriched in primary CRC and oCRC, thus may be associated with ovarian metastasis. P3 cells having a similar expression pattern as cholangiocytes are found mainly in primary CRC and lCRC, presuming to be likely the culprits that specifically metastasise to the liver. Stem-like cells interacted with cancer-associated fibroblasts and endothelial cells via the DLL4-NOTCH signalling pathway to metastasise from primary CRC to the ovary. In the oCRC microenvironment, myofibroblasts provide cancer cells with glutamine and perform a metabolic reprogramming, which may be essential for cancer cells to localise and develop in the ovary. CONCLUSION: We uncover a mechanism for organ-specific CRC metastasis.

SMALL PLANT AND ORGAN 1 (SPO1) Encoding a Cellulose Synthase-like Protein D4 (OsCSLD4) Is an Important Regulator for Plant Architecture and Organ Size in Rice.

Plant architecture and organ size are considered as important traits in crop breeding and germplasm improvement. Although several factors affecting plant architecture and organ size have been identified in rice, the genetic and regulatory mechanisms remain to be elucidated. Here, we identified and characterized the small plant and organ 1 (spo1) mutant in rice (Oryza sativa), which exhibits narrow and rolled leaf, reductions in plant height, root length, and grain width, and other morphological defects. Map-based cloning revealed that SPO1 is allelic with OsCSLD4, a gene encoding the cellulose synthase-like protein D4, and is highly expressed in the roots at the seedling and tillering stages. Microscopic observation revealed the spo1 mutant had reduced number and width in leaf veins, smaller size of leaf bulliform cells, reduced cell length and cell area in the culm, and decreased width of epidermal cells in the outer glume of the grain. These results indicate the role of SPO1 in modulating cell division and cell expansion, which modulates plant architecture and organ size. It is showed that the contents of endogenous hormones including auxin, abscisic acid, gibberellin, and zeatin tested in the spo1 mutant were significantly altered, compared to the wild type. Furthermore, the transcriptome analysis revealed that the differentially expressed genes (DEGs) are significantly enriched in the pathways associated with plant hormone signal transduction, cell cycle progression, and cell wall formation. These results indicated that the loss of SPO1/OsCSLD4 function disrupted cell wall cellulose synthase and hormones homeostasis and signaling, thus leading to smaller plant and organ size in spo1. Taken together, we suggest the functional role of SPO1/OsCSLD4 in the control of rice plant and organ size by modulating cell division and expansion, likely through the effects of multiple hormonal pathways on cell wall formation.

Super-enhancer RNA m6A promotes local chromatin accessibility and oncogene transcription in pancreatic ductal adenocarcinoma.

The biological functions of noncoding RNA N6-methyladenosine (m6A) modification remain poorly understood. In the present study, we depict the landscape of super-enhancer RNA (seRNA) m6A modification in pancreatic ductal adenocarcinoma (PDAC) and reveal a regulatory axis of m6A seRNA, H3K4me3 modification, chromatin accessibility and oncogene transcription. We demonstrate the cofilin family protein CFL1, overexpressed in PDAC, as a METTL3 cofactor that helps seRNA m6A methylation formation. The increased seRNA m6As are recognized by the reader YTHDC2, which recruits H3K4 methyltransferase MLL1 to promote H3K4me3 modification cotranscriptionally. Super-enhancers with a high level of H3K4me3 augment chromatin accessibility and facilitate oncogene transcription. Collectively, these results shed light on a CFL1-METTL3-seRNA m6A-YTHDC2/MLL1 axis that plays a role in the epigenetic regulation of local chromatin state and gene expression, which strengthens our knowledge about the functions of super-enhancers and their transcripts.

CSTF2 mediated mRNA N6-methyladenosine modification drives pancreatic ductal adenocarcinoma m6A subtypes.

N6-methyladenosine (m6A) modification of gene transcripts plays critical roles in cancer. Here we report transcriptomic m6A profiling in 98 tissue samples from 65 individuals with pancreatic ductal adenocarcinoma (PDAC). We identify 17,996 m6A peaks with 195 hyper-methylated and 93 hypo-methylated in PDAC compared with adjacent normal tissues. The differential m6A modifications distinguish two PDAC subtypes with different prognosis outcomes. The formation of the two subtypes is driven by a newly identified m6A regulator CSTF2 that co-transcriptionally regulates m6A installation through slowing the RNA Pol II elongation rate during gene transcription. We find that most of the CSTF2-regulated m6As have positive effects on the RNA level of host genes, and CSTF2-regulated m6As are mainly recognized by IGF2BP2, an m6A reader that stabilizes mRNAs. These results provide a promising PDAC subtyping strategy and potential therapeutic targets for precision medicine of PDAC.

Achieving Ultralow Lattice Thermal Conductivity and High Thermoelectric Performance in SnTe by Alloying with MnSb2Se4.

The manipulation of defect chemistry is crucial in the design of high-performance thermoelectric materials. Studies have demonstrated that alloying compounds within the I-V-VI2 family, such as AgSbTe2, NaSbTe2, etc., can effectively enhance the thermoelectric performance of SnTe by controlling the hole concentration and reducing the lattice thermal conductivity. In this paper, samples of SnTe alloyed with MnSb2Se4 were prepared, and the microstructure, electrical properties, and thermal properties were thoroughly investigated. Based on SEM and TEM analysis, it was observed that MnSb2Se4 can dissolve into SnTe during the preparation of the samples, which leads to the formation of various secondary phases with different compositions and point defects. Consequently, the lattice thermal conductivity is reduced to 0.44 W m-1 K-1 at 800 K, approaching the amorphous limit. Furthermore, the diffusion of the Mn and Sb elements leads to a significant improvement in the Seebeck coefficient through valence band convergence. The vacancy concentration in SnTe can also be modulated by alloying with MnSb2Se4. The findings indicated that MnSb2Se4 alloying can enhance the thermoelectric performance of SnTe through increasing the vacancy concentration, promoting valence band convergence, and introducing secondary phases. Consequently, a ZT value of 1.36 at 800 K for Sn1.03Te-5%MnSb2Se4 can be achieved.

LncRNA BCAN-AS1 stabilizes c-Myc via N6-methyladenosine-mediated binding with SNIP1 to promote pancreatic cancer.

C-Myc overexpression contributes to multiple hallmarks of human cancer but directly targeting c-Myc is challenging. Identification of key factors involved in c-Myc dysregulation is of great significance to develop potential indirect targets for c-Myc. Herein, a collection of long non-coding RNAs (lncRNAs) interacted with c-Myc is detected in pancreatic ductal adenocarcinoma (PDAC) cells. Among them, lncRNA BCAN-AS1 is identified as the one with highest c-Myc binding enrichment. BCAN-AS1 was abnormally elevated in PDAC tumors and high BCAN-AS1 level was significantly associated with poor prognosis. Mechanistically, Smad nuclear-interacting protein 1 (SNIP1) was characterized as a new N6-methyladenosine (m6A) mediator binding to BCAN-AS1 via recognizing its m6A modification. m6A-modified BCAN-AS1 acts as a scaffold to facilitate the formation of a ternary complex together with c-Myc and SNIP1, thereby blocking S phase kinase-associated protein 2 (SKP2)-mediated c-Myc ubiquitination and degradation. Biologically, BCAN-AS1 promotes malignant phenotypes of PDAC in vitro and in vivo. Treatment of metastasis xenograft and patient-derived xenograft mouse models with in vivo-optimized antisense oligonucleotide of BCAN-AS1 effectively represses tumor growth and metastasis. These findings shed light on the pro-tumorigenic role of BCAN-AS1 and provide an innovant insight into c-Myc-interacted lncRNA in PDAC.

A Brief Review on the Potential of Psychedelics for Treating Alzheimer's Disease and Related Depression.

Alzheimer's disease (AD), the most common form of senile dementia, is poised to place an even greater societal and healthcare burden as the population ages. With few treatment options for the symptomatic relief of the disease and its unknown etiopathology, more research into AD is urgently needed. Psychedelic drugs target AD-related psychological pathology and symptoms such as depression. Using microdosing, psychedelic drugs may prove to help combat this devastating disease by eliciting psychiatric benefits via acting through various mechanisms of action such as serotonin and dopamine pathways. Herein, we review the studied benefits of a few psychedelic compounds that may show promise in treating AD and attenuating its related depressive symptoms. We used the listed keywords to search through PubMed for relevant preclinical, clinical research, and review articles. The putative mechanism of action (MOA) for psychedelics is that they act mainly as serotonin receptor agonists and induce potential beneficial effects for treating AD and related depression.

Clinical efficacy and tendon integrity of patients with subscapularis tear by the technique of arthroscopic single external row repair.

Background: With the development of arthroscopic technology and equipment, arthroscopy can effectively repair the tear of the subscapular muscle. However, it is difficult to expose the subscapular muscle and operate it under a microscope. In this study, the SwiveLock® C external row anchor under arthroscopy was applied to repair the tear of the subscapular muscle in a single row, which is relatively easy to operate with reliable suture and fixation, and its efficacy was evaluated. Purpose: This study aimed to assess the clinical efficacy and the tendon integrity of patients who had subscapularis tears by adopting the single-row repair technique with a SwiveLock® C external row anchor. Methods: Patients who had the subscapular muscle tear either with or without retraction were included, and their follow-up time was at least 1 year. The degree of tendon injury was examined by magnetic resonance imaging (MRI) and confirmed by arthroscopy. The tendon was repaired in an arthroscopic manner by utilizing the single-row technique at the medial margin of the lesser tuberosity. One double-loaded suture SwiveLock® C anchor was applied to achieve a strong fixation between the footprint and tendon. The range of motion, pain visual simulation score, American Shoulder and Elbow Surgeons (ASES) score, and Constant score of shoulder joint were evaluated for each patient before the operation, 3 months after the operation, and at least 1 year after the operation. Results: In total, 110 patients, including 31 males and 79 females, with an average age of 68.28 ± 8.73 years were included. Arthroscopic repair of the subscapular tendon with SwiveLock® C external anchor can effectively improve the range of motion of the shoulder joint. At the last follow-up, the forward flexion of the shoulder joint increased from 88.97 ± 26.33° to 138.38 ± 26.48° (P < 0.05), the abduction range increased from 88.86 ± 25.27° to 137.78 ± 25.64° (P < 0.05), the external rotation range increased from 46.37 ± 14.48° to 66.49 ± 14.15° (P < 0.05), and the internal rotation range increased from 40.03 ± 9.01° to 57.55 ± 7.43° (P < 0.05). The clinical effect is obvious. The constant shoulder joint score increased from 40.14 ± 15.07 to 81.75 ± 11.00 (P < 0.05), the ASES score increased from 37.88 ± 13.24 to 82.01 ± 9.65 (P < 0.05), and the visual analog scale score decreased from 5.05 ± 2.11 to 1.01 ± 0.85 (P < 0.05). In the 6th month after the operation, two cases (1.81%) were confirmed to have re-tears via MRI. Conclusion: In this study, we repaired the subscapularis muscle with a single-row technique fixed by SwiveLock® C anchor and FiberWire® sutures and evaluated its efficacy. The results showed that the clinical effect of single-row arthroscopic repair was satisfactory and that reliable tendon healing could be achieved.

A Concise Review on Oxidative Stress-Mediated Ferroptosis and Cuproptosis in Alzheimer's Disease.

Alzheimer's disease (AD), which was first identified more than a century ago, has become a pandemic that exacts enormous social burden and economic tolls as no measure of combating devastated AD is currently available. Growing etiopathological, genetic, and biochemical data indicate that AD is a heterogeneous, polygenic, multifactorial, and complex disease. However, its exact etiopathology remains to be determined. Numerous experimental data show that cerebral iron and copper dyshomeostasis contribute to Aß amyloidosis and tauopathy, two neuropathological hallmarks of AD. Moreover, increasing experimental evidence suggests ferroptosis, an iron-dependent and nonapoptotic form of cell death, may be involved in the neurodegenerative process in the AD brain. Thus, the anti-ferroptosis approach may be an efficacious therapeutic strategy for AD patients. Furthermore, it remains to be further determined whether cuproptosis, a copper-dependent and distinct form of regulated cell death, also plays a contributing role in AD neurodegeneration. We hope this concise review of recent experimental studies of oxidative stress-mediated ferroptosis and cuproptosis in AD may spur further investigations on this timely and essential line of research.

N 6-methyladenosine Modification of FZR1 mRNA Promotes Gemcitabine Resistance in Pancreatic Cancer.

The therapeutic options for treating pancreatic ductal adenocarcinoma (PDAC) are limited, and resistance to gemcitabine, a cornerstone of PDAC chemotherapy regimens, remains a major challenge. N6-methyladenosine (m6A) is a prevalent modification in mRNA that has been linked to diverse biological processes in human diseases. Herein, by characterizing the global m6A profile in a panel of gemcitabine-sensitive and gemcitabine-insensitive PDAC cells, we identified a key role for elevated m6A modification of the master G0-G1 regulator FZR1 in regulating gemcitabine sensitivity. Targeting FZR1 m6A modification augmented the response to gemcitabine treatment in gemcitabine-resistant PDAC cells both in vitro and in vivo. Mechanistically, GEMIN5 was identified as a novel m6A mediator that specifically bound to m6A-modified FZR1 and recruited the eIF3 translation initiation complex to accelerate FZR1 translation. FZR1 upregulation maintained the G0-G1 quiescent state and suppressed gemcitabine sensitivity in PDAC cells. Clinical analysis further demonstrated that both high levels of FZR1 m6A modification and FZR1 protein corresponded to poor response to gemcitabine. These findings reveal the critical function of m6A modification in regulating gemcitabine sensitivity in PDAC and identify the FZR1-GEMIN5 axis as a potential target to enhance gemcitabine response. SIGNIFICANCE: Increased FZR1 translation induced by m6A modification engenders a gemcitabine-resistant phenotype by inducing a quiescent state and confers a targetable vulnerability to improve treatment response in PDAC.

Roles and implications of mRNA N6 -methyladenosine in cancer.

RNA N6 -methyladenosine modification is the most prevalent internal modification of eukaryotic RNAs and has emerged as a novel field of RNA epigenetics, garnering increased attention. To date, m6 A modification has been shown to impact multiple RNA metabolic processes and play a vital role in numerous biological processes. Recent evidence suggests that aberrant m6 A modification is a hallmark of cancer, and it plays a critical role in cancer development and progression through multiple mechanisms. Here, we review the biological functions of mRNA m6 A modification in various types of cancers, with a particular focus on metabolic reprogramming, programmed cell death and tumor metastasis. Furthermore, we discuss the potential of targeting m6 A modification or its regulatory proteins as a novel approach of cancer therapy and the progress of research on m6 A modification in tumor immunity and immunotherapy. Finally, we summarize the development of different m6 A detection methods and their advantages and disadvantages.

Loganin reduces neuroinflammation and promotes functional recovery after spinal cord injury through inhibiting NF-κB/NLRP3 signalling.

The highly disabling nature of spinal cord injuries (SCI) and high cost of treatment and rehabilitation impose a burden on families and society. Loganin has potential medicinal value in alleviating neuroinflammation. This study aimed to explore whether loganin can be used to reduce SCI-induced neuroinflammation and elucidate the molecular mechanisms underlying its action. An SCI rat model was developed to assess whether loganin promotes motor recovery after SCI. The anti-inflammatory effects of loganin on the dorsal horn of the spinal cord were identified by haematoxylin-eosin and immunohistochemical staining. The inflammatory effects of loganin were characterised using a lipopolysaccharide (LPS)-induced neuroinflammatory model in BV2 cells. For mechanistic exploration, the signalling pathways and target proteins of loganin action were predicted using bioinformatics and computational biology and then validated in cellular inflammation models. Loganin promoted animal motor recovery after SCI at the behavioural level, and it inhibited M1 differentiation of microglia and reduced NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated inflammatory responses at the tissue level. Loganin inhibited LPS-induced inflammation in BV2 cells, and bioinformatics and computational biology suggested that loganin acts on the p65 protein through the nuclear factor kappa-B (NF-κB)/NLRP3 signalling pathway. This was validated in a cellular model in which p65 trans-overexpression eliminated the downregulation of inflammatory factors by loganin. In conclusion, loganin reduces neuroinflammatory responses and promotes motor recovery after SCI. Loganin inhibits the NF-κB/NLRP3 signalling pathway by targeting the p65 protein to achieve repair.

A Preliminary Study of Mild Heat Stress on Inflammasome Activation in Murine Macrophages.

Inflammation and mitochondrial-dependent oxidative stress are interrelated processes implicated in multiple neuroinflammatory disorders, including Alzheimer's disease (AD) and depression. Exposure to elevated temperature (hyperthermia) is proposed as a non-pharmacological, anti-inflammatory treatment for these disorders; however, the underlying mechanisms are not fully understood. Here we asked if the inflammasome, a protein complex essential for orchestrating the inflammatory response and linked to mitochondrial stress, might be modulated by elevated temperatures. To test this, in preliminary studies, immortalized bone-marrow-derived murine macrophages (iBMM) were primed with inflammatory stimuli, exposed to a range of temperatures (37-41.5 °C), and examined for markers of inflammasome and mitochondrial activity. We found that exposure to mild heat stress (39 °C for 15 min) rapidly inhibited iBMM inflammasome activity. Furthermore, heat exposure led to decreased ASC speck formation and increased numbers of polarized mitochondria. These results suggest that mild hyperthermia inhibits inflammasome activity in the iBMM, limiting potentially harmful inflammation and mitigating mitochondrial stress. Our findings suggest an additional potential mechanism by which hyperthermia may exert its beneficial effects on inflammatory diseases.