MDM2-p53 mediate a miR-181c-3p/LIF axis to regulate low dose-rate radiation-induced DNA damage in human B lymphocytes.

PURPOSE: Prolonged exposure to low dose-rate radiation (LDRR) is of growing concern to public health. Recent evidences indicates that LDRR causes deleterious health effects and is closely related to miRNAs. The aim of our study is to investigate the relationship between miRNAs and DNA damage caused by LDRR. MATERIALS AND METHODS: In this study, we irradiated C57BL/6J mice with 12.5µGy/h dose of γ ray emitted from uranium ore for 8 h a day for 120 days at a total dose of 12 mGy, and identified differentially expressed miRNAs from the mice long-term exposed to LDRR through isolating serum RNAs, constructing small RNA library, Illumina sequencing. To further investigate the role of differential miRNA under LDRR，we first built DNA damage model in Immortal B cells irradiated with 12.5µGy/h dose of γ ray for 28 days at a total dose of 9.4 mGy. Then, we chose the highly conserved miR-181c-3p among 12 miRNA and its mechanism in alleviating DNA damage induced by LDRR was studied by transfection, quantitative PCR, luciferase assay, and Western blot. RESULTS AND CONCLUSIONS: We have found that 12 differentially expressed miRNAs including miR-181c-3p in serum isolated from irradiated mice. Analysis of GO and KEGG indicated that target genes of theses 12 miRNA enriched in pathways related to membrane, protein binding and cancer. Long-term exposure to LDRR induced upregulation of gamma-H2A histone family member X (γ-H2AX) expression, a classical biomarker for DNA damage in B cells. miR-181c-3p inhibited Leukemia inhibitory factor (LIF) expression via combining its 3'UTR. LIF, MDM2, p53, and p-p53-s6 were upregulated after exposure to LDRR. In irradiated B cells, Transfection of miR-181c-3p reduced γ-H2AX expression and suppressed LIF and MDM2 protein levels, whereas p-p53-s6 expression was increased. As expected, the effect of LIF inhibition on irradiated B cells was similar to miR-181c-3p overexpression. Our results suggest that LDRR alters miRNA expression and induces DNA damage. Furthermore, miR-181c-3p can alleviate LDRR-induced DNA damage via the LIF/MDM2/p-p53-s6 pathway in human B lymphocytes. This could provide the basis for prevention and treatment of LDRR injury.

Recent insights into glucans biosynthesis and engineering strategies in edible fungi.

Fungal α/ß-glucans have significant importance in cellular functions including cell wall structure, host-pathogen interactions and energy storage, and wide application in high-profile fields, including food, nutrition, and pharmaceuticals. Fungal species and their growth/developmental stages result in a diversity of glucan contents, structures and bioactivities. Substantial progresses have been made to elucidate the fine structures and functions, and reveal the potential molecular synthesis pathway of fungal α/ß-glucans. Herein, we review the current knowledge about the biosynthetic machineries, including: precursor UDP-glucose synthesis, initiation, elongation/termination and remodeling of α/ß-glucan chains, and molecular regulation to maximally produce glucans in edible fungi. This review would provide future perspectives to biosynthesize the targeted glucans and reveal the catalytic mechanism of enzymes associated with glucan synthesis, including: UDP-glucose pyrophosphate phosphorylases (UGP), glucan synthases, and glucanosyltransferases in edible fungi.

Theoretical Exploration on the Role of Magnetic States to the N2 Fixation behaviors of 2D Transition Metal Tri-borides (TMB3 s).

Fixing nitrogen (N2 ) by electrosynthesis method has become a promising way to ammonia (NH3 ) production, nevertheless, developing electrocatalysts combining long-term stable and low-cost feathers are still a great challenge to date. Using comprehensive first-principles calculations, we herein investigate the potential of a new class of two-dimensional (2D) transition metal tri-borides (TMB3 s) as nitrogen reduction reaction (NRR) electrocatalysts, and explore the effect of magnetic orders on the NRR. Our results show that the TMB3 s can sufficiently activate N2 and convert it to NH3 . Particularly, TiB3 is identified as a high-efficiency catalyst for NRR because of its low limiting potential (-0.24 V) and good suppression of the competitive hydrogen evolution reaction (HER). For the first time, we present that these TMB3 s with various magnetic states exhibit different performances in the adsorption of N2 and NRR intermediates, and minor effect on activation of N2 . Besides, VB3 , CrB3 , MnB3 , and FeB3 monolayers possess the superior capacity to suppress surface oxidation via the self-activating process, which reduces * O/* OH into * H2 O under NRR electrochemical conditions, thus favoring the N2 electroreduction. This work paves the way for finding high-performance NRR catalysts for transition metal borides and pioneering the research of magnetic states effects in NRR.

The effect of switchable electronic polarization states on the electronic properties of two-dimensional multiferroic TMBr2/Ga2SSe2 (TM = V-Ni) heterostructures.

Multiferroic van der Waals (vdW) heterostructures (HSs) prepared by combining different ferroic materials offer an exciting platform for next-generation nanoelectronic devices. In this work, we investigate the magnetoelectric coupling properties of multiferroic vdW HSs consisting of a magnetic TMBr2 (TM = V-Ni) monolayer and a ferroelectric Ga2SSe2 monolayer using first-principles theory calculations. It is found that the magnetic orderings in the magnetic TMBr2 layers are robust and the band alignment of these TMBr2/Ga2SSe2 HSs can be altered by reversing the polarization direction of the ferroelectric layer. Among them, VBr2/Ga2SSe2 and FeBr2/Ga2SSe2 HSs can be switched from a type-I to a type-II semiconductor, which allows the generation of spin-polarized and unpolarized photocurrent. Besides, CrBr2/Ga2SSe2, CoBr2/Ga2SSe2 and NiBr2/Ga2SSe2 exhibit a type-II band alignment in reverse ferroelectric polarization states. Moreover, the magnetic configuration and band alignment of these TMBr2/Ga2SSe2 HSs can be further modulated by applying an external strain. Our findings suggest the potential of TMBr2/Ga2SSe2 HSs in 2D multiferroic and spintronic applications.

Identification of a metabolism-related gene signature predicting overall survival for bladder cancer.

Reprogramming of metabolism is becoming a novel hallmark of cancer. This study aims to perform bioinformatics analysis of metabolism-related genes in bladder cancer, and to construct a signature of metabolism-related genes for predicting the prognosis. A total of 373 differentially expressed metabolism-related genes were identified from TCGA database. Taking survival time and clinical information into consideration, we constructed a risk score to predict clinical prognosis. Low-risk patients had a better prognosis than high-risk patients. Multivariate analysis showed that risk score was an independent prognostic indicator in bladder cancer. ROC curve also proved that risk score had better ability to predict prognosis than other individual indicators. Nomogram also showed a clinical net benefit to evaluate the prognosis of bladder cancer patients. GSEA revealed several metabolism-related pathways that were differentially enriched in the high-risk and low-risk groups, which might help to explain the underlying mechanisms. This signature was confirmed to be an effective prognostic biomarker in bladder cancer.

Effect of 3d Transition Metal Atom Intercalation Concentration on the Electronic and Magnetic Properties of Graphene/MoS2 Heterostructure: A First-Principles Study.

The electronic and magnetic properties of graphene/MoS2 heterostructures intercalated with 3d transition metal (TM) atoms at different concentrations have been systematically investigated by first principles calculations. The results showed that all the studied systems are thermodynamically stable with large binding energies of about 3.72 eV-6.86 eV. Interestingly, all the TM-intercalated graphene/MoS2 heterostructures are ferromagnetic and their total magnetic moments increase with TM concentration. Furthermore, TM concentration-dependent spin polarization is obtained for the graphene layer and MoS2 layer due to the charge transfer between TM atoms and the layers. A significant band gap is opened for graphene in these TM-intercalated graphene/MoS2 heterostructures (around 0.094 eV-0.37 eV). With the TM concentration increasing, the band gap of graphene is reduced due to the enhanced spin polarization of graphene. Our study suggests a research direction for the manipulation of the properties of 2D materials through control of the intercalation concentration of TM atoms.

Graphene adlayer growth between nonepitaxial graphene and the Ni(111) substrate: a theoretical study.

Understanding the fundamentals of chemical vapor deposition bilayer graphene growth is crucial for its synthesis. By employing density functional theory calculations and classical molecular dynamics simulations, we have investigated the evolution of carbon structures and the kinetics of the adlayer graphene nucleation between the graphene top layer (GTL) and the Ni(111) substrate. Compared to the epitaxial GTL, the weaker interaction between the nonepitaxial GTL and the Ni(111) substrate makes the nucleation of the adlayer more favorable. Furthermore, the defects involving in the adlayer graphene are easier to be healed by adopting the nonepitaxial GTL. Our results agree well with the experimental observation and demonstrate that the adlayer graphene with a high quality can be grown underneath the nonepitaxial GTL on Ni-like substrates.

Single-layer ZnMN2 (M = Si, Ge, Sn) zinc nitrides as promising photocatalysts.

Searching for two-dimensional semiconductor materials that are suitable for visible-light photocatalytic water splitting provides a sustainable solution to deal with the future energy crisis and environmental problems. Herein, based on first-principles calculations, single-layer ZnMN2 (M = Si, Ge, Sn) zinc nitrides are proposed as efficient photocatalysts for water splitting. Stability analyses show that the single-layer ZnMN2 zinc nitrides exhibit energetic and dynamical stability. The electronic properties reveal that all of the single-layer ZnMN2 zinc nitrides are semiconductors. Interestingly, single-layer ZnSnN2 is a direct band gap semiconductor with a desirable band gap (1.74 eV), and the optical adsorption spectrum confirms its optical absorption in the visible light region. The hydrogen evolution reaction (HER) calculations show that the catalytic activity for single-layer ZnMN2 (M = Ge, Sn) is better than that of single-layer ZnSiN2. Furthermore, the band gaps and band edge positions for the single-layer ZnMN2 zinc nitrides can be effectively tuned by biaxial strain. Especially, single-layer ZnGeN2 can be effectively tuned to match better with the redox potentials of water and enhance the light absorption in the visible light region at a tensile strain of 5%, which is confirmed by the corresponding optical absorption spectrum. Our results provide guidance for experimental synthesis efforts and future searches for single-layer materials suitable for photocatalytic water splitting.

Raman mapping investigation of chemical vapor deposition-fabricated twisted bilayer graphene with irregular grains.

Bilayer graphene as a prototype of two-dimensional stacked material has recently attracted great attention. The twist angle between graphene layers adds another dimension to control its properties. In this study, we used Raman mapping to investigate the twist angle dependence of properties of twisted bilayer graphene (TBG) with irregular grains that was fabricated by chemical vapor deposition (CVD). Different Raman parameters including intensity, width, and position of G and 2D peaks were used to distinguish TBG with different twist angles. The statistical results from Raman imaging on the distribution of twist angle are consistent with the results from selected area election diffraction (SAED). Finally, the Raman peak at approximately 1347 cm(-1) for TBG with a large twist angle was assigned to the D-like peak, although it has similar excitation energy dependence of frequency as the defect-induced D peak. Theoretical calculation further confirmed that vacancy-like defect is not favored in the formation energy for TBG with a large twist angle as compared to monolayer graphene or TBG with other twist angles. These results will help to advance the understanding of TBG properties, especially for CVD samples with irregular grains.

Explorative case control study on the associations of serum vitamin D3, folic acid and vitamin B12 levels on Kawasaki disease and coronary artery lesions.

Background: Kawasaki Disease (KD) is a pediatric vasculitic disorder characterized by systemic small vasculitis, notably coronary arteritis, with unclear pathogenesis. This explorative case-control study investigated the association between folic acid (FA), vitamin D3 (VD3), and vitamin B12 (VB12) levels and the different types of Kawasaki Disease, as well as the incidence of coronary artery lesions (CALs). Methods: In this explorative case control study, 365 KD children admitted to our hospital from January 1, 2022 to June 30, 2023 were included as the KD group. Simultaneously, 365 healthy children who received physical examination during the same period were included as the control group. The KD group was divided into typical KD group and incomplete KD group (IKD group), CALs group and non-CALS group, and IVIG sensitive group and IVIG resistant group. The children with CALs were divided into small tumor group, medium tumor group and large tumor group. Serum levels of FA, VB12, and VD3 were compared across all groups. Results: Serum levels of FA and VD3 were significantly decreased in both the KD and CALs groups (p < 0.05), and both factors were identified as independent risk factors for KD and CALs. Similarly, reduced serum VD3 levels were observed in the IKD and IVIG-resistant groups (p < 0.05), with VD3 also being an independent risk factor for both IKD and IVIG resistance. Additionally, lower serum FA levels were noted in the group with large aneurysms (p < 0.05), establishing FA as an independent risk factor for aneurysm size. Conclusion: Serum levels of folic FA and vitamin VD3 were significantly reduced in children with KD. Furthermore, these reductions were more pronounced in children with IKD and CALs. This pattern suggests that lower FA and VD3 levels may increase the risk of more severe coronary lesions in KD patients. Therefore, monitoring these biomarkers could provide valuable insights for early clinical diagnosis and intervention.

Fabrication of hyaluronic acid-inulin coated Enterococcus faecium for colon-targeted delivery to fight Fusobacterium nucleatum.

The abundance of Fusobacterium nucleatum (F. nucleatum) is highly associated with the development and poor prognosis of colorectal cancer (CRC), which is regarded as a promising target for CRC. However, until now, the novel strategy to clear F. nucleatum in the colon and CRC has not been well proposed. Herein, a probiotic strain Enterococcus faecium (E. faecium, EF47) is verified to secrete various organic acids and bacteriocins to exert superior antimicrobial activity towards F. nucleatum. However, the oral delivery of EF47 is affected by the complex digestive tract environment, so we design the hyaluronic acid-inulin (HA-IN) coated EF47 for colon-targeted delivery to fight F. nucleatum. IN can protect EF47 from the harsh gastrointestinal tract environment and is degraded specifically in the colon, acting as prebiotics to further promote the proliferation of EF47. The exposed HA can also enhance the targeting effect to the tumor area via the interaction with the CD44 receptor on the tumor cells, which is confirmed to increase the adhesive ability in tumor tissues and inhibit the growth of F. nucleatum. Therefore, this colon-targeted delivery system provides a novel platform to realize high-activity and adhesive delivery of probiotics to assist the therapeutic efficiency of CRC.

SNX10 promoted liver IR injury by facilitating macrophage M1 polarization via NLRP3 inflammasome activation.

BACKGROUND: Liver ischemia reperfusion (IR) injury is a common cause of liver dysfunction in patients post liver partial resection and liver transplantation. However, the cellular defense mechanisms underlying IR are not well understood. Macrophage mediated sterile inflammation plays critical roles in liver IR injury. Sorting nexin (SNX) 10, a member of the SNX family which functions in regulation of endosomal sorting. This study aimed to explore the role of sorting nexin 10 (SNX10) during liver IR injury with a focus on regulating macrophage function. METHODS: Both the gene and protein expression levels of SNX10 were analyzed in human specimens from 10 patients undergoing liver partial resection with ischemic insult and in a mouse model of liver IR. The in vivo effects of SNX10 in liver IR injury and sterile inflammation in mice were investigated. Bone marrow derived macrophages (BMDMs) were used to determine the role of SNX10 in modulating macrophage function in vitro. RESULTS: Increased expression of SNX10 was observed both in human specimens and mice livers post IR. SNX10 knockdown alleviated IR induced sterile inflammation and liver damage in mice. SNX10 promoted M1 polarization of macrophage treated with LPS and facilitated inflammatory response by activating NLRP3 inflammasome. CONCLUSIONS: We report for the first time that SNX10 is upregulated in IR-stressed livers. SNX10 activation aggravates liver IR injury and sterile inflammation by facilitating macrophage M1 polarization and inflammatory response suggesting SNX10 as a potential therapeutic target for liver IR injury.

First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE): a phase 1 study.

Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).

[Correlation between the methylation of SULF2 and WRN promoter and chemosensitivity to irinotecan in gastric cancer].

OBJECTIVE: To explore the relationship between SULF2 and WRN promoter methylation and chemosensitivity to irinotecan, and also the clinicopathological features in patients with gastric cancer. METHODS: The chemosensitivity to irinotecan was tested by MTT assay. The methylation of SULF2 and WRN promoter in the fresh gastric cancer tissues was detected by methylation specific PCR. The differences of chemosensitivity and clinicopathological features of the methylation group were compared with that of the non-methylation group. The tumor growth in nude mice bearing human gastric cancer xenografts treated with CPT-11was also observed. RESULTS: The methylation rates of SULF2 and WRN were 28.4% (29/102) and 23.5% (24/102), respectively. There were no significant association between promoter methylation and clinicopathological features of patients including age, gender, histologic type, lymphatic invasion, and TNM Stage. In all the 102 cases, there were 30 cases of irrinotecan-sensitive group, and 72 cases of the irrinotecan-resistant group. The SULF2 methylation rate was 46.7% (14/30)in the sensitive group, and 20.8% (15/72) in the resistant group (P = 0.008),The WRN methylation rate was 33.3% (10/30) in the sensitive group, and 19.4% (14/72) in the resistant group (P = 0.214). Gastric cancer tissues were more sensitive to irrinotecan when both the genes were methylated. The nude mice bearing human gastric cancer xenografts with SULF2 methylation were more sensitive to irrinotecan. CONCLUSIONS: The detection of SULF2 and WRN promoter methylation may provide evidence for screening and targeting the most sensitive gastric cancer subpopulation suitable for personalized irrinotecan chemotherapy.

Ferroptosis, a new form of cell death: mechanisms, biology and role in gynecological malignant tumor.

Ferroptosis, a term coined by Dixon et al. in 2012, refers to an iron-dependent form of regulated cell death driven by an overload of lipid peroxides on cellular membranes. It is morphologically and mechanistically distinct from apoptosis and other types of regulated cell death. Many studies have confirmed that ferroptosis is involved in the occurrence and development of many diseases, such as neurodegenerative diseases, chronic cardiovascular diseases, respiratory diseases and even tumors. While in the systemic diseases of obstetrics and gynecology, the related researches are still limited. In this article, we retrieved PubMed and WEB OF SCI databases for articles and reviews published before May 6, 2022, using "ferroptosis, ferroptosis regulator, gynecological tumors" as keywords, and comprehensively reviewed on their basis. Here, we systematically summarize the studies on the mechanism and characteristics of ferroptosis, investigate the role of ferroptosis in clinical systemic diseases of obstetrics and gynecology, evaluate the research status, unsolved problems and further research directions of ferroptosis, so as to let people learn more about ferroptosis and establish a research foundation for the exploration of the treatment strategies for ferroptosis-mediated diseases.

The Ninj1/Dusp1 Axis Contributes to Liver Ischemia Reperfusion Injury by Regulating Macrophage Activation and Neutrophil Infiltration.

BACKGROUND & AIMS: Liver ischemia-reperfusion (IR) injury represents a major risk factor in both partial hepatectomy and liver transplantation. Nerve injury-induced protein 1 (Ninj1) is widely recognized as an adhesion molecule in leukocyte trafficking under inflammatory conditions, but its role in regulating sterile inflammation during liver IR injury remains unclear. METHODS: Myeloid Ninj1-deficient mice were generated by bone marrow chimeric models using Ninj1 knockout mice and wild-type mice. In vivo, a liver partial warm ischemia model was applied. Liver injury and hepatic inflammation were investigated. In vitro, primary Kupffer cells (KCs) isolated from Ninj1 knockout and wild-type mice were used to explore the function and mechanism of Ninj1 in modulating KC inflammation upon lipopolysaccharide stimulation. RESULTS: Ninj1 deficiency in KCs protected mice against liver IR injury during the later phase of reperfusion, especially in neutrophil infiltration, intrahepatic inflammation, and hepatocyte apoptosis. This prompted ischemia-primed KCs to decrease proinflammatory cytokine production. In vitro and in vivo, using small-interfering RNA against dual-specificity phosphatase 1 (DUSP1), we found that Ninj1 deficiency diminished the inflammatory response in KCs and neutrophil infiltration through DUSP1-dependent deactivation of the c-Jun-N-terminal kinase and p38 pathways. Sivelestat, a neutrophil elastase inhibitor, functioned similarly to Ninj1 deficiency, resulting in both mitigated hepatic IR injury in mice and a more rapid recovery of liver function in patients undergoing liver resection. CONCLUSIONS: The Ninj1/Dusp1 axis contributes to liver IR injury by regulating the proinflammatory response of KCs, and influences neutrophil infiltration, partly by subsequent regulation of C-X-C motif chemokine ligand 1 (CXCL1) production after IR.

Whole-exome sequencing analysis identifies novel variants associated with Kawasaki disease susceptibility.

BACKGROUND: Kawasaki disease (KD) is an acute pediatric vasculitis affecting genetically susceptible infants and children. Although the pathogenesis of KD remains unclear, growing evidence links genetic susceptibility to the disease. METHODS: To explore the genes associated with susceptibility in KD, we applied whole-exome sequencing to KD and control subjects from Yunnan province, China. We conducted association study analysis on the two groups. RESULTS: In this study, we successfully identified 11 significant rare variants in two genes (MYH14 and RBP3) through the genotype/allele frequency analysis. A heterozygous variant (c.2650G > A, p.V884M) of the RBP3 gene was identified in 12 KD cases, while eight heterozygous variants (c.566G > A, p.R189H; c.1109 C > T, p.S370L; c.3917T > G, p.L1306R; c.4301G > A, p.R1434Q; c.5026 C > T, p.R1676W; c.5329 C > T, p.R1777C; c.5393 C > A, p.A1798D and c.5476 C > T, p.R1826C) of the MYH14 gene were identified in 8 KD cases respectively. CONCLUSION: This study suggested that nine variants in MYH14 and RBP3 gene may be associated with KD susceptibility in the population from Yunnan province.

Advances in immunotherapy and molecular targeted therapy of gestational trophoblastic tumor: current practice and future perspectives.

Gestational trophoblastic neoplasia (GTN) is a rare pregnancy-related gynecological malignancy caused by abnormal proliferation of placental trophoblastic cells. It can invade the uterine muscle layer and metastasize early, more common in women of childbearing age. GTN is invasive and can destroy surrounding tissues and blood vessels, causing massive bleeding in uterus and metastatic sites (such as lung, liver, brain, etc.) through blood transfer. Chemotherapy is the main treatment for GTN, and the disease is extremely sensitive to chemotherapy and can be cured by chemotherapy. However, in clinical practice, a large number of patients have failed chemotherapy or even multiple treatments due to drug resistance, recurrence or metastasis of special sites. Therefore, how to individually select the initial chemotherapy regimen and reduce the occurrence of drug resistance is the key to the treatment of high-risk GTN. With the remarkable efficacy of immunotherapy in endometrial cancer, cervical cancer and other diseases, the research on GTN has been further deepened. Therefore, this review discusses the mechanism, methods and efficacy of GTN immunotherapy and molecular targeted therapy, in order to provide new ideas for the diagnosis and treatment of GTN.

Development an Immune-Related MicroRNA Risk Index in Hepatocellular Carcinoma.

Purpose: Hepatocellular carcinoma (HC) has emerged as one of the most prevalent malignancies on a global scale. Recently, immunotherapy has achieved favorable effectiveness in the management of multiple cancers. However, there are limited therapeutic options for advanced HC. As the liver is a special immune organ, we intend to uncover potential and effective immunotherapeutic modalities for HC. Our study was designed to develop specific immune-related miRNAs (IRMs) for outcome assessment and individualized strategies for the management of HC. Methods: The miRNA-seq and survival data of TCGA-LIHC dataset was enrolled into this program. We first collected IRMs from Immune-miR website. Differentially expression analysis was applied to screen aberrantly expressed IRMs. In order to set up an IRM-related index (IRMRI) in HC, we conducted the Cox relevant methods. Next, the statistical approaches (survival curve and ROC curve analyses) were utilized to detect the evaluation capacity of our IRMRI. Subsequently, we obtained the target genes of hub miRNAs from IRMRI through three miRNA-related predictive online tools (miRDB, miRTarBase, and TargetScan websites). Results: Five IRMs were determined to develop the IRMRI. It can effectively segregate all HC cases from two different risk subgroups. We identified a marked discrepancy in survival outcome between the two groups by survival analysis and confirmed the reliability of IRMRI in two testing sets. Moreover, we collected 10 hub target genes (ESR1, IGF1, PDGFRB, JUN, MYC, ZWINT, MAD2L1, TOP2A, KIF11, and CDCA8) which were strongly linked to HC progression and malignant behavior. Conclusion: We screened out five hub IRMs with clinical value and constructed a risk index model in HC, which can precisely assess the risk status and outcome of patients to a certain extent.

New Developments and Opportunities of Microbiota in Treating Breast Cancers.

Despite the prevalence of breast cancer (BC), over half of BC cases are unrelated to known risk factors, which highlights the importance of uncovering more cancer-related factors. Currently, the microbiota has been proven to be a potent modulator of the tumor environment in BC, which regulates the immune balance in tumor-related networks. Through a large amount of data accumulation, the microbiota has shown many possibilities to reveal more insights into the development or control of BC. To expand the potential benefits of patients with BC, this study discusses the distribution profile and the effect mechanism of BC-related microbiota on tumors and further discusses its impact on different tumor therapies. Finally, we summarize the possibility of targeting microbiological therapies to improve BC treatment or in combination with other therapies.