Machine learning and new insights for breast cancer diagnosis.

Breast cancer (BC) is the most prominent form of cancer among females all over the world. The current methods of BC detection include X-ray mammography, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and breast thermographic techniques. More recently, machine learning (ML) tools have been increasingly employed in diagnostic medicine for its high efficiency in detection and intervention. The subsequent imaging features and mathematical analyses can then be used to generate ML models, which stratify, differentiate and detect benign and malignant breast lesions. Given its marked advantages, radiomics is a frequently used tool in recent research and clinics. Artificial neural networks and deep learning (DL) are novel forms of ML that evaluate data using computer simulation of the human brain. DL directly processes unstructured information, such as images, sounds and language, and performs precise clinical image stratification, medical record analyses and tumour diagnosis. Herein, this review thoroughly summarizes prior investigations on the application of medical images for the detection and intervention of BC using radiomics, namely DL and ML. The aim was to provide guidance to scientists regarding the use of artificial intelligence and ML in research and the clinic.

NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction.

AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.

Combined miRNA and mRNA sequencing reveals the defensive strategies of resistant YHY15 rice against differentially virulent brown planthoppers.

Introduction: The brown planthopper (BPH) poses a significant threat to rice production in Asia. The use of resistant rice varieties has been effective in managing this pest. However, the adaptability of BPH to resistant rice varieties has led to the emergence of virulent populations, such as biotype Y BPH. YHY15 rice, which carries the BPH resistance gene Bph15, exhibits notable resistance to biotype 1 BPH but is susceptible to biotype Y BPH. Limited information exists regarding how resistant rice plants defend against BPH populations with varying levels of virulence. Methods: In this study, we integrated miRNA and mRNA expression profiling analyses to study the differential responses of YHY15 rice to both avirulent (biotype 1) and virulent (biotype Y) BPH. Results: YHY15 rice demonstrated a rapid response to biotype Y BPH infestation, with significant transcriptional changes occurring within 6 hours. The biotype Y-responsive genes were notably enriched in photosynthetic processes. Accordingly, biotype Y BPH infestation induced more intense transcriptional responses, affecting miRNA expression, defenserelated metabolic pathways, phytohormone signaling, and multiple transcription factors. Additionally, callose deposition was enhanced in biotype Y BPH-infested rice seedlings. Discussion: These findings provide comprehensive insights into the defense mechanisms of resistant rice plants against virulent BPH, and may potentially guide the development of insect-resistant rice varieties.

Pre-rigor salting improves gel strength and water-holding of surimi gel made from snakehead fish (Channa argus): The role of protein oxidation.

The purpose of this study was to determine the effect of pre-rigor salting on the quality characteristics of surimi gels prepared from snakehead fish muscle. Pre-rigor and post-rigor muscle were mixed with 0.3% or 3% NaCl (w/w) and made into surimi gels, respectively. Results showed that pre-rigor muscle had a higher content of ATP, longer sarcomere, higher pH and greater protein solubility. Metabolic profile suggested that pre-rigor muscle had higher content (a 28-fold increase) of antioxidants such as butyryl-l-carnitine. Transmission electron microscopy showed more damage of mitochondria in post-rigor muscle. Surimi paste from pre-rigor meat chopped with 3% NaCl generally showed greater radical scavenging ability and had higher content of free sulfhydryl. Surimi gel made from pre-rigor muscle salted with 3% NaCl showed a larger gel strength (3.18 kg*mm vs. 2.22 kg*mm) and better water-holding (86% vs. 80%) than that of post-rigor group. Based on these findings, we hypothesized that: In addition to other factors such as pH, degree of denaturation, etc., less protein oxidation in pre-rigor salted surimi also contributes to the improved gel properties.

The long-term efficacy of intra-cervical lymphatic immunotherapy on adults with allergic rhinitis: A randomized controlled study.

BACKGROUND: The efficacy and safety of the novel immunotherapy method, intra-cervical lymphatic immunotherapy (ICLIT), need to be investigated. Comparing it with subcutaneous immunotherapy (SCIT), we clarified the long-term efficacy and safety of intra-cervical lymphatic immunotherapy on allergic rhinitis (AR), and investigated the improvement of clinical efficacy of the booster injection at 1 year after ICLIT treatment. METHODS: Ninety adult patients with dust mite allergy were randomly divided into 3 groups: 30 in the SCIT group, 30 in the ILCLIT group, and 30 in ICLIT booster group. Changes in total symptom score (TSS), nasal symptom score (TNSS), ocular symptom score (TOSS) and total medication score (TMS) were evaluated in the three groups. Adverse reactions were recorded, and serum dust mite specific IgE (sIgE) and specific IgG4 were assessed in the ICLIT group and ICLIT booster group. RESULTS: TSS, TNSS, TOSS, and TMS scores were significantly lower in the three groups at 36 months after treatment (p < 0. 05). And at 36 months the ICLIT-booster group showed results similar to SCIT and superior to ICLIT (p < 0. 05). Serum specific IgE decreased in all three groups at 12 and 36 months after treatment, p < 0.01. The ICLIT group and the ICLIT booster group showed a significant increase in sIgG4, p < 0.01. None of the patients in the three groups had any serious systemic adverse effects during the 3-year follow-up. CONCLUSION: The ICLIT treatment is effective and safe on AR. One booster injection of allergens at 1 year can greatly improve its long-term efficacy. TRIAL REGISTRY: Clinical trial registration number: ChiCTR1800017130.

Salinity-dependent top-down effect of rotifer Brachionus plicatilis on removing harmful alga Phaeocystis globosa.

Using appropriate zooplankton to transfer the primary productivity of harmful algae to higher trophic levels through food chain is an eco-friendly mode to remove harmful algae. To assess the top-down efficiency of rotifer removing Phaeocystis and the salinity effect, we adopted a series of salinities to carry out Phaeocystis-rotifer population dynamics and rotifer life-history experiments. Results showed that the time for rotifers to remove Phaeocystis population was the shortest when the salinity was ≤20 ‰. With salinity rising to above 25 ‰, although the clearance time of Phaeocystis population by rotifer was significantly prolonged, ultimately the Phaeocystis population were almost completely eliminated at all salinities. Additionally, rotifer matured and reproduced earlier at low salinity, while high salinity significantly delayed first reproductive time and decreased the total offspring. The above findings are helpful to assess the impacts of external environmental factors on the application of zooplankton to control harmful algae.

Single-cell RNA sequencing reveals the landscape of biomarker in allergic rhinitis patient undergoing intracervical lymphatic immunotherapy and related pan-cancer analysis.

INTRODUCTION: Allergic rhinitis (AR) is one of the leading allergic diseases worldwide. Allergen immunotherapy (AIT) induces persistent specific allergen tolerance to achieve remission of the symptoms in AR patients. We creatively conducted the intra-cervical lymphatic immunotherapy (ICLIT) for AR patients. However, the underlying molecular mechanism of immune cell response of AIT in AR remains elusive. METHOD: To investigate the transcriptome profile in AR patients who underwent ICLIT, we comprehensively investigated the transcriptional changes in B cells from peripheral blood mononuclear cells of AR patient by single-cell RNA sequencing. Immunoglobulins and relative key gene, which influences the B cell differentiation, was demonstrated. The biomarkers' association with different types of tumors was investigated. RESULTS: Naive B cells, germinal center B cells, activated memory B cells, and memory B cells constituted the B cells subsets. The expression of IGHE, IGHGs, IGHA, IGHD, and IGHM from memory B cells was validated. Pseudotime analysis further indicated the dynamic change from the expression of the immunoglobulins in the memory B cells, suggesting that ITGB1 may contribute to the differentiation procedure of memory B cells. The cell-cell communication among these immune cells demonstrated the significantly enhanced CD23, BTLA signaling after ICLIT in AR patient. ITGB1 was upregulated in 13 tumors and downregulated in six others. High ITGB1 expression was linked to poor prognosis in eight types of tumors. ITGB1 expression showed correlations with tumor mutation burden, tissue purity, and microsatellite instability in different types of tumors. DISCUSSION: ITGB1 was demonstrated as a potential biomarker for AR patients after ICLIT and is significant in identifying immune infiltration in tumor tissue and predicting tumor prognosis.

Oxidation affects pH buffering capacity of myofibrillar proteins via modification of histidine residue and structure of myofibrillar proteins.

The pH buffering capacity is an important functionality of muscle proteins, and muscle foods are susceptible to being oxidized during storage and processing. In order to study the effect of oxidation on the pH buffering capacity of myofibrillar proteins, myofibrils extracted from snakehead fish (Channa argus) were oxidized with H2O2. Results showed that increased oxidation led to loss of free sulfhydryl groups, formation of carbonyl groups, increased surface hydrophobicity, and aggregation of myofibrillar proteins. In addition, there was a significant reduction in the content of histidine in oxidized myofibrillar proteins. The pH buffering capacity of myofibrillar proteins significantly decreased from 3.14 ± 0.03 mM H+/(mL × ΔpH) down to 2.55 ± 0.03 mM H+/(mL × ΔpH) after oxidation with 50 mM H2O2. Both oxidized myofibrillar proteins and histidine showed a high pH buffering capacity at pH near 5.8, which is the histidine pKa value. Here, we hypothesize that oxidation-induced changes in the pH buffering capacity of myofibrillar proteins were driven by oxidative modification of histidine and structural changes of myofibrillar proteins. The significance of this study to food industry may be the awareness that protein oxidation may affect pH through changes in buffering capacity. And the use of antioxidants, especially those targeting at histidine will be promising in addressing this issue.

Association between type 1 diabetes and systemic lupus erythematosus: a Mendelian randomization study.

OBJECTIVES: Observational studies have shown that there is a bidirectional relationship between type 1 diabetes (T1D) and systemic lupus erythematosus (SLE); the causality of this association remains elusive and may be affected by confusion and reverse causality. There is also a lack of large-scale randomized controlled trials to verify. Therefore, this Mendelian randomization (MR) study aimed to investigate the causal association between T1D and SLE. METHODS: We aggregated data using publicly available genome-wide association studies (GWAS), all from European populations. Select independent (R2 < 0.001) and closely related to exposure (P < 5 × 10-8) as instrumental variables (IVs). The inverse-variance weighted (IVW) method was used as the primary method. We also used MR-Egger, the weighted median method, MR-Robust, MR-Lasso, and other methods leveraged as supplements. RESULTS: T1D had a positive causal association with SLE (IVW, odds ratio [OR] = 1.358, 95% confidence interval [CI], 1.205 - 1.530; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.137, 95% CI, 1.033 - 1.251; P = 0.001). SLE had a positive causal association with T1D (IVW, OR = 1.108, 95% CI, 1.074 - 1.144; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.085, 95% CI, 1.046 - 1.127; P < 0.001). These results have also been verified by sensitivity analysis. CONCLUSION: The MR analysis results indicated a causal association between T1D and SLE. Therefore, further research is needed to clarify the potential biological mechanism between T1D and SLE. Key Points • Observational studies have shown that there is a bidirectional relationship between T1D and SLE. • We evaluated causal effects between T1D and SLE by Mendelian randomization analyses. • The MR analysis results indicated a causal association between T1D and SLE.

Oncostatin M Induces IFITM1 Expression to Inhibit Hepatitis B Virus Replication Via JAK-STAT Signaling.

BACKGROUND & AIMS: Functional cure is achieved by a limited number of patients with chronic hepatitis B (CHB) after nucleotide analogue(s) and interferon treatment. It is urgent to develop therapies that can help a larger proportion of patients achieve functional cure. The present study was designed to explore the anti-hepatitis B virus (HBV) potency of interleukin-6 family cytokines and to characterize the underlying mechanisms of the cytokine displaying the highest anti-HBV potency. METHODS: HBV-infected cells were used to screened the anti-HBV potency of interleukin-6 family cytokines. The concentration of oncostatin M (OSM) in patients with chronic HBV infection was examined by enzyme-linked immunosorbent assay. The underlying mechanism of OSM anti-HBV was explored through RNA-seq. C57BL/6 mice injected with rAAV8-1.3HBV were used to explore the suppression effect of OSM on HBV in vivo. RESULTS: OSM is the most effective of the interleukin-6 family cytokines for suppression of HBV replication (percentage of average inhibition: hepatitis B surface antigen, 34.44%; hepatitis B e antigen, 32.52%; HBV DNA, 61.57%). Hepatitis B e antigen-positive CHB patients with high OSM levels had lower hepatitis B surface antigen and hepatitis B e antigen than those with low levels. OSM activated JAK-STAT signaling pathway promoting the formation of STAT1-IRF9 transcription factor complex. Following this, OSM increased the expression of various genes with known functions in innate and adaptive immunity, which was higher expression in patients with CHB in immune clearance phase than in immune tolerance phase (data from GEO: GSE65359). Interferon-induced transmembrane protein 1, one of the most differentially expressed genes, was identified as an HBV restriction factor involved in OSM-mediated anti-HBV effect. In vivo, we also found OSM significantly inhibited HBV replication and induced expression of antiviral effector interferon-induced transmembrane protein 1. CONCLUSIONS: Our study shows that OSM remodels the immune response against HBV and exerts potent anti-HBV activity, supporting its further development as a potential therapy for treating CHB.

The relationship between air pollution and depression and anxiety disorders - A systematic evaluation and meta-analysis of a cohort-based study.

OBJECTIVE: To explore the correlation between air pollution and the onset of depression and anxiety disorders, to draw more comprehensive and integrated conclusions, and to provide recommendations for maintaining mental health and developing policies to reduce mental health risks caused by air pollution. METHODS: Meta-analysis of cohort study articles exploring the relationship between air pollution and depression or anxiety disorders included in Pubmed, Web Of Science, CNKI, and Wan Fang database before October 31, 2022, and subgroup analysis of the association between air pollution and depression and anxiety disorders regarding the air pollutants studied, the study population, and Publication bias analysis and sensitivity analysis. RESULTS: A total of 25 articles meeting the criteria were included in this study, including 23 articles examining the relationship between air pollution and depression and 5 articles examining the relationship between air pollution and anxiety disorders. The results of the meta-analysis were based on the type of pollutant and showed that there was a high degree of heterogeneity among the studies on the relationship between air pollution and depression and a significant heterogeneity among the studies on PM2.5 and the risk of anxiety disorders (I2 = 71%, p < .01), so a random-effects model was selected for the analysis. CO, O3, and SO2 and depression onset had combined RR values of 1.10 (1.00, 1.20), 1.06 (0.87, 1.29), 1.17 (1.06, 1.31), 1.19 (0.90, 1.58), 1.03 (0.99, 1.07), and 1.09 (0.97, 1.24), respectively, and PM2.5 and anxiety The combined RR value for morbidity was 1.10 (0.99, 1.22). The results of sensitivity analysis showed that the combined results were stable and reliable. The results of Egger regression method test showed that none of them had significant publication bias (p > .05). LIMITATION: Combined exposure to air pollutants on depression and anxiety, further studies by other researchers are needed in the future. CONCLUSIONS: PM2.5 and NO2 exposure, especially long-term exposure, may be associated with the onset of depression, and no association was found for the time being between PM10, CO, O3, SO2 exposure and depression and PM2.5 exposure and anxiety disorders.

Diabetic status aggravates atherosclerosis in aged ApoE-/- mice.

Streptozocin (STZ) aggravates diabetic atherosclerosis in aged ApoE-/- mice. (A). Study design: ApoE-/- mice were given STZ (50 mg/kg/day) or vehicle by intraperitoneal injection for five days consecutively to induce diabetes. (B). Body weight and blood glucose levels were measured in mice on the baseline, 16th, and 32nd weeks. (C). Representative oil red O staining of en face aorta and quantifications of the lesional area of the whole aortic tree (D). Representative micrographs stained by H&E and Oil red O (left), and quantifications of microscopic atherosclerotic area. All data are expressed as mean ± SEM; All data were tested for normality and equal variance. For analysis of body weight and blood glucose, two-way ANOVA analysis was used (B). For normally or approximately normally distributed data, a Student's t-test was performed (C, D). n = 6 mice/group. *p<0.05 and **p<0.01 vs vehicle group.

The role of the purinergic ligand-gated ion channel 7 receptor in common digestive system cancers.

The incidence of digestive malignancies has increased in recent years, including colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic cancer. Advanced stages of these cancers are prone to metastasis, which seriously reduce the standard of living of patients and lead to decline in the survival rate of patients. So far there are no good specific drugs to stop this phenomenon. It is very important and urgent to find new biomarkers and therapeutic targets. Purinergic ligand-gated ion channel 7 receptor (P2X7R) is ATP-gated and nonselective ion channel receptor involved in many inflammatory processes and cancer progression. P2X7R is present in many cancer cells and promotes or inhibits cancer development through signal transduction. Studies have presented that P2X7R plays a role in the proliferation and migration of digestive system cancers, such as CRC, HCC and pancreatic cancer. Therefore, P2X7R may serve as a biomarker or therapeutic target for digestive system cancers. This paper describes the structure and function of P2X7R, and mainly reviews the research progress on the role of P2X7R in CRC, HCC and pancreatic cancer.

Maresin1 ameliorates MSU crystal-induced inflammation by upregulating Prdx5 expression.

BACKGROUND: Maresin1 (MaR1) is a potent lipid mediator that exhibits significant anti-inflammatory activity in the context of several inflammatory diseases. A previous study reported that MaR1 could suppress MSU crystal-induced peritonitis in mice. To date, the molecular mechanism by which MaR1 inhibits MSU crystal-induced inflammation remains poorly understood. METHODS: Mousebone marrow-derived macrophages (BMDMs) were pretreated with MaR1 and then stimulated with FAs (palmitic, C16:0 and stearic, C18:0) plus MSU crystals (FAs + MSUc). In vivo, the effects of MaR1 treatment or Prdx5 deficiency on MSUc induced peritonitis and arthritis mouse models were evaluated. RESULTS: The current study indicated that MaR1 effectively suppressed MSUc induced inflammation in vitro and in vivo. MaR1 reversed the decrease in Prdx5 mRNA and protein levels induced by FAs + MSUc. Further assays demonstrated that MaR1 acceleratedPrdx5 expression by regulating the Keap1-Nrf2 signaling axis. Activation of AMPK by Prdx5 improved homeostasis of the TXNIP and TRX proteins and alleviated mitochondrial fragmentation. In addition, Prdx5 overexpression inhibited the expression of CPT1A, a key enzyme for fatty acid oxidation (FAO). Prdx5 protected against defects in FA + MSUc induced FAO and the urea cycle. CONCLUSION: MaR1 treatment effectively attenuated MSUc induced inflammation by upregulating Prdx5 expression. Our study provides a new strategy by which Prdx5 may help prevent acute gout attacks.

Formononetin attenuates high glucose-induced neurotoxicity by negatively regulating oxidative stress and mitochondrial dysfunction in Schwann cells via activation of SIRT3.

High glucose induces Schwann cells death and neurotoxicity. Formononetin was originally found in Astragalus membranaceus and showed anti-tumor and anti-neuroinflammation properties. The aim of this study is to explore the molecular mechanism underlying the neuroprotective effects of formononetin and identify its direct protein target. The effects of formononetin on oxidative stress and mitochondrial dysfunction in Schwann cells induced by high glucose were investigated. High glucose treatment significantly induced oxidative stress, mitochondrial dysfunction and apoptosis in Schwann cells, while these effects were partially or completely prevented by co-treatment with formononetin. Mechanistically, we found that SIRT3/PGC-1α/SOD2 pathway was activated by formononetin under high glucose conditions as evidenced by western blotting. Knockdown of SIRT3 by siRNA delivery reversed the protective effects of formononetin on high glucose-induced Schwann cells injury and changes in expression profile of SIRT3 downstream target genes. Molecular docking, thermal shift assay and surface plasmon resonance assay revealed a direct binding between formononetin and SIRT3. Taken together, we identified a novel SIRT3 activator formononetin and revealed its beneficial effects on high glucose-induced neurotoxicity, suggesting that targeting SIRT3 in Schwann cells may be a new approach for treatment of peripheral nerve regeneration related diseases such as diabetic peripheral neuropathy.

Unveiling the molecular interactions between alkyl imidazolium ionic liquids and human serum albumin: Implications for toxicological significance.

Alkyl imidazolium-based ionic liquids (ILs) are promising for diverse industrial applications; however, their growing prevalence has raised concerns regarding human exposure and potential health implications. A critical aspect to be clarified to address the adverse health effects associated with ILs exposure is their binding mode to human serum albumin (HSA). In this study, we delved into the binding interactions between three alkyl imidazolium ILs (1-hexyl-3-methyl-imidazolium (C6[MIM]), 1-ethyl-3-methyl-imidazolium chloride (C8[MIM]) and 1-decyl-3-methyl-imidazolium (C10[MIM]) and human serum albumins (HSAs) using a comprehensive approach encompassing molecular docking and multi-spectroscopy (UV-visible, Fluorescence, Circular Dichroism, FTIR). Furthermore, for the first time, we developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach time to quantify plasma protein binding rates. Our results revealed that the ILs primarily bind to the hydrophobic cavity of HSA through hydrogen bonding and van der Waals forces, forming stable complexes via static quenching. This affected HSA's secondary structure, reducing α-helical content, particularly around specific residues. Equilibrium dialysis and ultrafiltration coupled with UPLC-MS/MS analysis showed modest plasma protein binding rates (17.84%-31.85%) for the three ILs, with no significant influence from alkyl chain effects or concentration relationship. Lower plasma protein binding rates can affect bioavailability and distribution of ILs, potentially influencing their toxicity. These findings provide critical insights into the potential toxicological implications at the molecular level, thereby contributing to continuous efforts to evaluate the risk profiles and ensure the safe utilization of these compounds.

The function of MSP-activated γδT cells in hepatocellular carcinoma.

Immunotherapeutic strategies targeting γδT cells are now recognized as a promising treatment method for hepatocellular carcinoma (HCC). To date, no specific antigen or antigenic epitope recognized by γδT cells has been identified, limiting their application in the field of HCC treatment. Previously, we used an established screening strategy to identify a novel HCC protein antigen recognized by γδT cells called MSP. In this study, we explored the function of MSP activated-γδT cells in HCC. Results demonstrated that the proportions of γδT cells in the peripheral blood of HCC patients and the level of IFN-γ in the serum were higher than in healthy controls. We also determined that γδT cells can bind MSP protein. MSP-activated γδT cells were shown to contain a specific CDR3δ2 sequence that supports the recognition of MSP by γδT cells. We determined that MSP is highly expressed in HCC, MSP-activated γδT cells in the peripheral blood of HCC patients express co-stimulatory molecules, and MSP-activated γδT cells directly killed HCC cells. In conclusion, we demonstrated that the novel protein ligand MSP activated γδT cells, leading to the killing of HCC cells through direct and indirect mechanisms. These findings could provide a potential new target for the clinical diagnosis and treatment of HCC and a foundation for clinical treatment strategies in HCC.

Honokiol attenuates high glucose-induced peripheral neuropathy via inhibiting ferroptosis and activating AMPK/SIRT1/PGC-1α pathway in Schwann cells.

Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.

Genetic diversity analysis and molecular characteristics of wild centipedegrass using sequence-related amplified polymorphism (SRAP) markers.

Centipedegrass (Eremochloa ophiuroides (Munro) Hack.) is commonly used as a low-maintenance warm-season turfgrass owing to its excellent adaptation to various soil types. A better understanding of the genetic diversity pattern of centipedegrass is essential for the efficient development and utilization of accessions. This study used fifty-five pairs of primers to detect the genetic variation and genetic structure of twenty-three wild centipedegrass accessions by Sequence-related amplified polymorphism (SRAP) markers. A total of 919 reliable bands were amplified, among which 606 (65.80%) were polymorphic and 160 (2.91%) were the monomorphic loci. The average polymorphic information content (PIC) value was 0.228. The unweighted pair group method with arithmetic mean (UPGMA) clustering analysis grouped the twenty-three accessions into two clusters. Meanwhile, the structure analysis showed that the tested accessions possessed two main genetic memberships (K = 2). The Mantel test significantly correlated the genetic and geographic distance matrices (r = 0.3854, p = 0.000140). Furthermore, geographical groups showed moderate genetic differentiation, and the highest intragroup genetic diversity was found in the Sichuan group (He = 0.201). Overall, the present research findings could promote the protection and collection of centipedegrass and provide comprehensive information to develop novel breeding strategies.

Intra-cervical lymphatic immunotherapy for dust mite-induced allergic rhinoconjunctivitis in children: a 3-year prospective randomized controlled trial.

Background: Pediatric allergic rhinoconjunctivitis has become a public concern with an increasing incidence year by year. Conventional subcutaneous immunotherapy (SCIT) has long treatment time, high cost and poor compliance. The novel immunotherapy significantly shortens the course of treatment by directly injecting allergens into cervical lymph nodes, which can perform faster clinical benefits to children. Objective: By comparing with SCIT, this study aimed to evaluate the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT). Methods: This is a prospective randomized controlled study. A total of 50 allergic rhinoconjunctivitis children with dust mite allergy was randomly divided into ICLIT group and SCIT group, receiving three cervical intralymphatic injections of dust mite allergen or three years of subcutaneous injection, separately. Primary outcomes included total nasal symptom scores (TNSS), total ocular symptom scores (TOSS), total symptom scores (TSS), total medication scores (TMS), and total quality of life score. Secondary outcomes included pain perception and adverse reactions during treatment. Other secondary outcome was change in Dermatophagoides pteronyssinus (Derp) and Dermatophagoides farina (Derf) -specific IgE level. Results: Both groups had significantly decreased TNSS, TOSS, TSS, TMS, and total quality of life score after 36 months of treatment (p<0.0001). Compared with SCIT, ICLIT could rapidly improve allergic symptoms (p<0.0001). The short-term efficacy was consistent between the two groups (p=0.07), while the long-term efficacy was better in SCIT group (p<0.0001). The pain perception in ICLIT group was lower than that in SCIT group (p<0.0001). ICLIT group was safer. Specifically, the children had only 3 mild local adverse reactions without systemic adverse reactions. The SCIT group had 14 systemic adverse reactions. At last, the serum Derp and Derf-specific IgE levels in ICLIT and SCIT groups decreased 3 years later (p<0.0001). Conclusion: ICLIT could ameliorate significantly the allergic symptoms in pediatric patients with an advantage in effectiveness and safety, besides an improved life quality including shortened period of treatment, frequency of drug use and pain perception. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR1800017130.