The role of TMEM163 protein in thyroid microcarcinoma: expression pattern and clinical implications.

BACKGROUND: TMEM163 protein is a new zinc ion transporter whose regulatory role in tumors has yet to be discovered. This study aimed to analyze the expression pattern of TMEM163 in thyroid microcarcinoma and explore its potential molecular function and clinical value. METHODS: Differential analysis was performed to detect the expression pattern of TMEM163 in papillary thyroid carcinoma. Functional analysis was performed to explore the biological function of TMEM163. Logistic regression was performed to detect the relationship between TMEM163 expression and lymph node metastasis. A correlation analysis of the relationship between 163 and anoikis was performed. qRT-PCR and western blot were used to verify its expression in PTC tissues. The effect of TMEM163 on PTC cell function was studied by a series of in vitro cell experiments. The prediction model of lymph node metastasis was constructed based on the ultrasonic characteristics of PTMC and the expression of TMEM163. RESULTS: The expression of TMEM163 in PTC tissue was higher than in normal thyroid tissue. In vitro, silencing TMEM163 inhibited PTC cells' proliferation, migration, and invasion, while TMEM163 overexpression exhibited the opposite effect. In addition, down-regulating its expression can inhibit the cell cycle process and induce the apoptosis of tumor cells. In pathway analysis, we demonstrated that knockout of TMEM163 significantly increased p21 expression and inhibited BCL-2 expression. Logistic regression results suggested that the expression of TMEM163 combined with PTMC ultrasound characteristics helped predict lymph node metastasis. CONCLUSION: TMEM163 is highly expressed in PTC, which may be involved in the mechanism of anoikis, and can be used as a molecular marker to predict PTMC lymph node metastasis.

Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy with chemotherapy improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Given its immunomodulating effect, we investigated whether stereotactic body radiotherapy (SBRT) enhances the effect of immunochemotherapy. METHODS: The SACTION01 study was a single-arm, open-label, phase 2 trial that recruited patients who were 18 years or older and had resectable stage IIA-IIIB NSCLC from the Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients received SBRT (24 Gy in three fractions) to the primary tumour followed by two cycles of 200 mg intravenous PD-1 inhibitor, tislelizumab, plus platinum-based chemotherapy. Surgical resection was performed 4-6 weeks after neoadjuvant treatment. The primary endpoint was major pathological response (MPR), defined as no more than 10% residual viable tumour in the resected tumour. All analyses were conducted on an intention-to-treat basis, including all patients who were scheduled for neoadjuvant treatment. The trial was registered with ClinicalTrials.gov (NCT05319574) and is ongoing but closed to recruitment. FINDINGS: Between May 18, 2022, and June 20, 2023, 46 patients (42 men and four women) were enrolled and scheduled for neoadjuvant treatment. MPR was observed in 35 (76%, 95% CI 61-87) of 46 patients. The second cycle of immunochemotherapy was withheld in four (9%) patients due to pneumonia (n=2), colitis (n=1), and increased creatinine (n=1). Grade 3 or worse adverse events related to neoadjuvant treatment occurred in 12 (26%, 95% CI 14-41) patients. The most frequent treatment-related adverse event (TRAE) was alopecia (16 [35%] patients), and the most frequent grade 3 or worse TRAE was neutropenia (six [13%]). There was one treatment-related death, caused by neutropenia. No deaths within 90 days of surgery were reported. INTERPRETATION: Preoperative SBRT followed by immunochemotherapy is well tolerated, feasible, and leads to a clinically significant MPR rate. Future randomised trials are warranted to support these findings. FUNDING: BeiGene.

Integrative analysis of transcriptome and metabolome reveals how ethylene increases natural rubber yield in Hevea brasiliensis.

Hevea brasiliensis is an important cash crop with the product named natural rubber (NR) for markets. Ethylene (ET) is the most effective yield stimulant in NR production but the molecular mechanism remains incomplete. Here, latex properties analysis, transcriptome analysis, and metabolic profiling were performed to investigate the mechanism of NR yield increase in four consecutive tappings after ET stimulation. The results revealed that sucrose and inorganic phosphate content correlated positively with dry-rubber yield and were induced upon ET stimulation. Stimulation with ET also led to significant changes in gene expression and metabolite content. Genes involved in phytohormone biosynthesis and general signal transduction as well as 51 transcription factors potentially involved in the ET response were also identified. Additionally, KEGG annotation of differentially accumulated metabolites suggested that metabolites involved in secondary metabolites, amino-acid biosynthesis, ABC transporters, and galactose metabolism were accumulated in response to ET. Integrative analysis of the data collected by transcriptomics and metabolomics identified those differentially expressed genes and differentially accumulated metabolites are mainly involved in amino-acid biosynthesis and carbohydrate metabolism. Correlation analysis of genes and metabolites showed a strong correlation between amino-acid biosynthesis during ET stimulation. These findings provide new insights into the molecular mechanism underlying the ET-induced increase in rubber yield and further our understanding of the regulatory mechanism of ethylene signaling in rubber biosynthesis.

Intestinal deguelin drives resistance to acetaminophen-induced hepatotoxicity in female mice.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI), with gender-specific differences in susceptibility. However, the mechanism underlying this phenomenon remains unclear. Our study reveals that the gender-specific differences in susceptibility to APAP-induced hepatotoxicity are due to differences in the gut microbiota. Through microbial multi-omics and cultivation, we observed increased gut microbiota-derived deguelin content in both women and female mice. Administration of deguelin was capable of alleviating hepatotoxicity in APAP-treated male mice, and this protective effect was associated with the inhibition of hepatocyte oxidative stress. Mechanistically, deguelin reduced the expression of thyrotropin receptor (TSHR) in hepatocytes with APAP treatment through direct interaction. Pharmacologic suppression of TSHR expression using ML224 significantly increased hepatic glutathione (GSH) in APAP-treated male mice. These findings suggest that gut microbiota-derived deguelin plays a crucial role in reducing APAP-induced hepatotoxicity in female mice, offering new insights into therapeutic strategies for DILI.

A Meta-Analysis and Meta-Regression of the Efficacy, Toxicity, and Quality of Life Outcomes Following Prostate-Specific Membrane Antigen Radioligand Therapy Utilising Lutetium-177 and Actinium-225 in Metastatic Prostate Cancer.

BACKGROUND AND OBJECTIVE: Management of metastatic prostate cancer (mPCa) presents significant challenges. In this systematic review, meta-analysis, and meta-regression, the efficacy, safety, and quality of life (QoL) outcomes of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) utilising lutetium-177 ([177Lu]Lu-PSMA) and actinium-225 ([225Ac]Ac-PSMA) were assessed. METHODS: A detailed literature search across PubMed/Medline, EMBASE, Web of Science, Scopus, and Cochrane Library was conducted, culminating in the inclusion of 100 studies involving 8711 patients. Data on prostate-specific antigen (PSA) responses, toxicity profiles, and QoL and survival outcomes were analysed. Proportional meta-analyses and meta-regression analyses were performed. KEY FINDINGS AND LIMITATIONS: The estimated proportion of patients with PSA decline ≥50% was 0.49 for [177Lu]Lu-PSMA and 0.60 for [225Ac]Ac-PSMA in mPCa, particularly metastatic castration-resistant prostate cancer. A meta-regression analysis indicated an association between the cumulative amount of administered activity and the proportion of PSA ≥50% decline. Positive PSA responses were observed alongside improved overall survival across both therapies. Our analyses also identified the key factors associated with PSA responses and survival outcomes, including baseline haemoglobin level, and the presence of visceral metastases. Although anaemia was commonly observed, with [177Lu]Lu-PSMA, severe toxicities were infrequent. Improved QoL was observed following [177Lu]Lu-PSMA therapy, whereas it remained stable following the second cycle of [225Ac]Ac-PSMA treatment. Heterogeneity across studies for PSA responses and toxicity profiles is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our findings suggest an association between PRLT and reductions in PSA levels, as well as associations with enhanced survival outcomes in mPCa. Furthermore, our analysis shows a low incidence of severe toxicity associated with this treatment. These observations highlight the important role of PRLT in the management of mPCa.

Does surgeon-performed intraoperative wire localization allow for lower margin positivity rates compared to radiologist-performed preoperative localization in early breast cancer?

BACKGROUND: This study compares positive margin rates in breast conserving surgery (BCS) for early breast cancer using two localization techniques: surgeon-performed intraoperative ultrasound-guided wire localization (IOWL) versus radiologist-performed preoperative wire localization (POWL). METHODS: Patients with unifocal breast cancer undergoing BCS with follow-up at a single institution were retrospectively identified. Factors associated with positive margins were identified. RESULTS: 177 patients underwent IOWL (N â€‹= â€‹85) or POWL (N â€‹= â€‹92). There was a significantly lower rate of positive margins for IOWL vs. POWL (7.1 â€‹% vs. 23.9 â€‹%, p â€‹= â€‹0.002) and a corresponding lower rate of re-excision for IOWL vs. POWL (5.9 â€‹% vs. 18.5 â€‹%, p â€‹= â€‹0.011). Presence of DCIS was associated with positive margins (p â€‹= â€‹0.015). After adjusting for presence of DCIS, tumor size, and volume of tissue removed, the positive margin rate was significantly lower in the IOWL group compared to the POWL group (aOR 0.34, 95 â€‹% CI 0.13-0.93). CONCLUSIONS: In this study, adjusted analysis favored IOWL in achieving negative tumor margins. Prospective studies are needed to further explore the impact of IOWL on quality, cost-effectiveness, and patient experience.

Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.

Mitochondrial-nuclear communication plays a vital role in maintaining cellular homeostasis. MOTS-c, a short peptide derived from the 12S rRNA of mitochondrial DNA, has been suggested as a retrograde mitochondrial signal. Although recent clinical studies have suggested a possible link between MOTS-c and human cancer, the role of MOTS-c in tumorigenesis has yet to be investigated. Here, MOTS-c levels are found to be reduced in both serum and tumor tissues from ovarian cancer (OC) patients, which are associated with poor patients' prognosis. Exogenous MOTS-c inhibits the proliferation, migration and invasion of OC cells, and induces cell cycle arrest and apoptosis. Mechanistically, MOTS-c interacts with LARS1 and promotes its ubiquitination and proteasomal degradation. In addition, USP7 was identified as a deubiquitinase of LARS1, and MOTS-c can attenuates USP7-mediated LARS1 deubiquitination by competing with USP7 for binding to LARS1. Besides, LARS1 was found to be increased and play an important oncogenic function in OC. More importantly, MOTS-c displays a marked anti-tumor effect on OC growth without systemic toxicity in vivo. In conclusion, this study reveals a crucial role of MOTS-c in OC and provides a possibility for MOTS-c as a therapeutic target for the treatment of this manlignacy.

Effect of tibia-first, restricted functional alignment technique on gap width changes, and component positioning in robotic arm-assisted total knee arthroplasty.

PURPOSE: This study aims to quantitatively assess the predictability of post-resection gap dimensions and the attainment of balanced gaps using robotic arm-assisted total knee arthroplasty (TKA). METHODS: This retrospective cohort study included 100 consecutive patients who underwent robotic arm-assisted TKA for knee osteoarthritis using a restricted functional alignment (FA) technique. Tibial cuts were performed based on preoperative tibial anatomy within predefined boundaries, followed by femoral component adjustments according to tensioned soft tissues to optimise gap balance. The primary outcome was the proportion of balanced gaps, defined as differential laxities of ≤2 mm, across extension, flexion, lateral, and medial gap measurements. Ligament balancing in lateral and medial compartments was assessed using a robotic system at 10° and 90° flexion to evaluate if restricted FA facilitated a balanced knee. Secondary outcomes included implant alignment, resection depth, and patient-reported outcome measures (PROMs). RESULTS: Significant increases in both lateral and medial gaps at 10° and 90° flexion were observed following tibial and femoral bone resections (p < 0.001). At extension, average gap changes were 0.9 mm (lateral) and 1.6 mm (medial) after tibial cuts, and 0.5 mm (lateral) and 1.2 mm (medial) after femoral cuts. At 90° flexion, changes were 0.3 mm (lateral) and 1.7 mm (medial) following tibial cuts, and 1.0 mm (lateral) and 1.4 mm (medial) after femoral cuts. Despite these variations, the tibia-first, gap-balancing technique achieved overall balance in 98% of gap measurements. The tibial component was placed at an average of 2.1° varus, while the femoral component was positioned at 0.3° varus and 1.3° external rotation relative to the surgical transepicondylar axis. Significant improvements in PROMs were noted between preoperative and one-year postoperative evaluations (all p < 0.05). CONCLUSIONS: The tibia-first, restricted FA technique achieved a well-balanced knee in 98% of cases, despite inconsistent gap increments observed between initial assessments and post-resection. LEVEL OF EVIDENCE: Therapeutic Level IV.

Discovery of a Highly Potent and Selective Inhibitor Targeting Protein Lysine Methyltransferase NSD2.

The histone lysine methyltransferase NSD2 has been recognized as an attractive target for cancer treatment, due to the functional implication of its dysregulation in the initiation and progression of many cancers. Although considerable efforts have been made to develop NSD2 small-molecule inhibitors, highly potent and selective ones are still rarely available till now. Here, we report the discovery of a series of novel NSD2 inhibitors via an extensive SAR exploration of the privileged quinazoline scaffold within compound 8. The most promising compound 42 showed excellent NSD2 enzymatic inhibitory activity and good antiproliferative activity in cells. In addition, it demonstrated favorable pharmacokinetic properties and significantly inhibited the tumor growth in a RS411 tumor xenograft model with good safety. Taken together, compound 42 could be a promising NSD2 inhibitor and deserves further investigation.

Polysialic acid driving cardiovascular targeting co-delivery 1,8-cineole and miR-126 to synergistically alleviate lipopolysaccharide-induced acute cardiovascular injury.

Infection-induced cardiovascular damage is the primary pathological mechanism underlying septic cardiac dysfunction. This condition affects the majority of patients in intensive care unit and has an unfavorable prognosis due to the lack of effective therapies available. Vascular cell adhesion molecule-1 (VCAM-1) plays a vital role in coordinating the inflammatory response and recruitment of leukocytes in cardiac tissue, making it a potential target for developing novel therapies. MicroRNA-126 (miR-126) has been shown to downregulate VCAM-1 expression in endothelial cells, reducing leukocyte adhesion and exerting anti-inflammatory effects. Therefore, this work described a polysialic acid (PSA) modified ROS-responsive nanosystem to targeted co-delivery 1,8-Cineole and miR-126 for mitigating septic cardiac dysfunction. The nanosystem consists of 1,8-Cineole nanoemulsion (CNE) conjugated with PEI/miR126 complex by a ROS-sensitive linker, with PSA on its surface to facilitate targeted delivery via specific interactions with selectins on endothelial cells. CNE has demonstrated protective effects against inflammation in the cardiovascular system and synergistic anti-inflammatory effects when combined with miR-126. The targeted nanosystem successfully delivered miR-126 and 1,8-Cineole to the injured heart tissues and vessels, reducing inflammatory responses and improving cardiac function. In summary, this work provides a promising therapy for alleviating the inflammatory response in sepsis while boosting cardiovascular protection.

A bibliometric analysis of studies on death anxiety in patients with cancer.

Purpose: This study evaluates the evolution and focal points of research on death anxiety among cancer patients over the last three decades, utilizing bibliometric analyses.Methods: We analyzed publications related to death anxiety among cancer patients from January 1994 to January 2024 using data from the Web of Science Core Collection. Bibliometric indicators such as the number of publications, leading countries, institutions, and research themes were examined.Results: A total of 2,602 papers from 286 institutions across 97 countries were identified. There has been a significant increase in research interest, particularly between 2014 and 2023, with a peak in 2022. The United States and Harvard University were found to be the most prolific contributors. Major research themes include quality of life, palliative care, mental health, and cancer-specific concerns.Conclusion: The results highlight the rapid development in the field of death anxiety research among cancer patients, with an increase in publications and emerging research themes. However, there is limited international and institutional collaboration. The study underscores the need for enhanced cooperative efforts to advance understanding and research in this area, suggesting directions for future research.

N-Acetylcysteine Inhibits Coxsackievirus B3 Replication by Downregulating Eukaryotic Translation Elongation Factor 1 Alpha 1.

Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1.

Development of a bioluminescent immunoassay based on Fc-specific conjugated antibody-nanoluciferase immunoreagents for determining aflatoxin B1.

Aflatoxin B1 (AFB1) is a potent carcinogen, and is among the most hazardous mycotoxins in agricultural products. Therefore, the development of sensitive and convenient detection methods for AFB1 is significant for food safety against mycotoxins. Herein, a bioluminescent enzyme immunoassay (BLEIA) was developed for ultrasensitive detection of AFB1, based on the novel Fc-specific antibody-nanoluciferase (Ab-Nluc) conjugates which were fabricated using an IgG-binding protein-assisted photo-conjugation strategy. In indirect competitive immunoassay format, the proposed BLEIA exhibited the detection limit of 0.0232 ng mL-1, which was 37.4-fold lower than that obtained using the classical enzyme-linked immunosorbent assay (ELISA) based on Ab-horseradish peroxidase (Ab-HRP) chemical conjugates (0.868 ng mL-1). Meanwhile, the BLEIA exhibited high accuracy and precision. Thus, the proposed Fc-specific Ab-Nluc conjugates-based BLEIA provides an ultrasensitive and reliable method for detecting toxins and has potential for use in food safety monitoring.

Progress of Nanomaterials Based on Manganese Dioxide in the Field of Tumor Diagnosis and Therapy.

As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.

Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts.

BACKGROUND: This study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China. METHODS: From February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1-6 and the second for cases 7-9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test. RESULTS: The second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76-0.81; mean Hmean = 2.11-3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63-0.64; mean Hmean = 5.66-7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature. CONCLUSIONS: We have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.

Impaired TGF-ß signaling via AHNAK family mutations elicits an esophageal cancer subtype with sensitivities to genotoxic therapy and immunotherapy.

BACKGROUND: Genome instability (GI) is a hallmark of esophageal squamous cell carcinoma (ESCC) while factors affecting GI remain unclear. METHODS: Here, we aimed to characterize genomic events representing specific mechanisms of GI based on 201 ESCC samples and validated our findings at the patient, single-cell and cancer cell-line levels, including a newly generated multi-omics dataset of the trial NCT04006041. RESULTS: A two-gene (AHNAK and AHNAK2) mutation signature was identified to define the "AHNAK1/2-mutant" cancer subtype. Single-cell-assisted multi-omics analysis showed that this subtype had a higher neoantigen load, active antigen presentation, and proficient CD8 + T cell infiltrations, which were validated at pan-cancer levels. Mechanistically, AHNAK1/2-mutant ESCC was characterized by impaired response of TGF-ß and the inefficient alternative end-join repair (Alt-EJ) that might promote GI. Knockdown of AHNAK in ESCC cell lines resulted in more Alt-EJ events and increased sensitivities to cisplatin. Furthermore, this two-gene signature accurately predicted better responses to DNA-damaging therapy in various clinical settings (HR ≈ 0.25). The two-gene signature predicted higher pCR rates in ESCCs receiving neoadjuvant immunotherapy-involved treatment. Finally, a molecular classification scheme was built and outperformed established molecular typing models in the prognosis stratification of ESCC patients. CONCLUSION: Our study extended our understanding of the AHNAK family in promoting GI and selecting treatment responders of ESCC.

HuR/miR-124-3p/VDR complex bridges lipid metabolism and tumor development in colorectal cancer.

Maintaining a balanced lipid status to prevent lipotoxicity is of paramount importance in various tumors, including colorectal cancer (CRC). HuR, an RNA-binding protein family member, exhibits high expression in many cancers possibly because it regulates cell proliferation, migration, invasion, and lipid metabolism. However, the role of HuR in the regulation of abnormal lipid metabolism in CRC remains unknown. We found that HuR promotes vitamin D receptor (VDR) expression to ensure lipid homeostasis by increasing Triglyceride (TG) and Total Cholesterol (TC) levels in CRC, thus confirming the direct binding of an overexpressed HuR to the CDS and 3'-UTR of Vdr, enhancing its expression. Concurrently, HuR can indirectly affect VDR expression by inhibiting miR-124-3p. HuR can suppress the expression of miR-124-3p, which binds to the 3'-UTR of Vdr, thereby reducing VDR expression. Additionally, a xenograft model demonstrated that targeting HuR inhibits VDR expression, blocking TG and TC formation, and hence mitigating CRC growth. Our findings suggest a regulatory relationship among HuR, miR-124-3p, and VDR in CRC. We propose that the HuR/miR-124-3p/VDR complex governs lipid homeostasis by impacting TG and TC formation in CRC, offering a potential therapeutic target for CRC prevention and treatment.

CEUS LI-RADS in Combination With the Serum Biomarker-Based ASAP Model Improves the Diagnostic Performance of HCC in High-Risk Patients.

OBJECTIVE: To assess the diagnostic efficacy of the CEUS LI-RADS combined with a model constructed on the basis of age, sex, AFP, and PIVKA-II (ASAP) for the diagnosis of HCC in high-risk patients. METHODS: This retrospective study included 366 liver lesions from 366 patients who underwent liver CEUS. All liver lesions were characterized and categorized according to CEUS LI-RADS v2017. Two modified methods were applied: LR-3/4/M nodules accompanied by AFP > 200 ng/mL (Criterion 2) or ASAP model score > 0.5256 and CA 19-9 in the normal range (Criterion 3) were recategorized as LR-5. The reference criteria included histopathological or comprehensive imaging and the clinical follow-up results. The diagnostic performance was evaluated and compared by the sensitivity, specificity, PPV, and NPV. RESULTS: The incidence of HCC in LR-3, LR-4, LR-5, and LR-M was 33.3% (4/12), 86.4% (38/44), 98.5% (191/194) and 82.7% (81/98), respectively. After using Criterion 2 compared to CEUS LI-RADS v2017, the sensitivity of the modified LR-5 for diagnosing HCC increased from 60.8% to 70.7% (p < 0.01) with little effect on its specificity (94.2% vs. 92.3%, p = 1.00) or PPV (98.5% vs. 98.2%, p = 0.86). After using Criterion 3, the sensitivity of the modified LR-5 for the diagnosis of HCC was further improved to 86.9% (p < 0.01), and its specificity and PPV were not significantly changed (92.3% and 98.6%, both p > 0.05). CONCLUSION: CEUS LI-RADS combined with the serum biomarker-based ASAP model improved the sensitivity of LR-5 in diagnosing HCC with little effect on its specificity and PPV.

TRIM103 activates the RLRs pathway to enhance antiviral response by targeting VP5 and VP7.

Grass carp (Ctenopharyngodon idella), crucial to global inland aquaculture with a production of 5.8 million tones in 2020, faces significant challenges from hemorrhagic disease caused by grass carp reovirus (GCRV). Rapid mutations compromise current vaccines, underscoring the need for a deeper understanding of antiviral mechanisms to enhance molecular marker-assisted selection. This study investigates the role of Tripartite Motif (TRIM) family in the innate immune response of grass carp, focusing on TRIM103 from Ctenopharyngodon Idella (CiTRIM103), a member of the TRIM-B30.2 family, which includes proteins with the B30.2 domain at the N-terminus, known for antiviral properties in teleosts. CiTRIM103 bind to the outer coat proteins VP5 and VP7 of GCRV. This binding is theorized to strengthen the function of the RIG-I-like Receptor (RLR) signaling pathway, crucial for antiviral responses. Demonstrations using overexpression and RNA interference (RNAi) techniques have shown that CiTRIM103 effectively inhibits GCRV replication. Moreover, molecular docking and pulldown assays suggest potential binding interactions of CiTRIM103's B30.2 domain with GCRV outer coat proteins VP5 and VP7. These interactions impede viral replication, enhance RLR receptor expression, and activate key transcription factors to induce type I interferons (IFNs). These findings elucidate the antiviral mechanisms of CiTRIM103, provide a foundation for future Molecular genetic breeding in grass carp.