Molecular characterization, expression and antibacterial function of a macin, HdMac, from Haliotis discus hannai.

Macins are a family of antimicrobial peptides, which play multiple roles in the elimination of invading pathogens. In the present study, a macin was cloned and characterized from Pacific abalone Haliotis discus hannai (Designated as HdMac). Analysis of the conserved domain suggested that HdMac was a new member of the macin family. In non-stimulated abalones, HdMac transcripts were constitutively expressed in all five tested tissues, especially in hemocytes. After Vibrio harveyi stimulation, the expression of HdMac mRNA in hemocytes was significantly up-regulated at 12 hr (P < 0.01). RNAi-mediated knockdown of HdMac transcripts affected the survival rates of abalone against V. harveyi. Moreover, recombinant protein of HdMac (rHdMac) exhibited high antibacterial activities against invading bacteria, especially for Vibrio anguillarum. In addition, rHdMac possessed binding activities towards glucan, lipopolysaccharides (LPS), and peptidoglycan (PGN), but not chitin in vitro. Membrane integrity analysis revealed that rHdMac could increase the membrane permeability of bacteria. Meanwhile, both the phagocytosis and chemotaxis ability of hemocytes could be significantly enhanced by rHdMac. Overall, the results showed that HdMac could function as a versatile molecule involved in immune responses of H. discus hannai.

Dual-branch feature encoding framework for infrared images super-resolution reconstruction.

Infrared thermal imaging is a passive non-contact detection and identification technology, which is not subject to electromagnetic infection and good concealment, is widely used in military and commercial fields. However, due to the limitations of the existing infrared imaging system mechanisms, the spatial resolution of the acquired infrared images is low and the edge details are blurred, which in turn leads to poor performance in downstream missions based on infrared images. In this paper, in order to better solve the above problems, we propose a new super-resolution reconstruction framework for infrared images, called DBFE, which extracts and retains abundant structure and textual information for robust infrared image high-resolution reconstruction with a novel structure-textual encoder module. Extensive experiment demonstrates that our proposed method achieves significantly superior contraband high-resolution reconstruction results on the multiple dataset compared to progressive methods for high resolution infrared image reconstruction, effectively proving the practicability of the method proposed in this paper.

Magnetic solid-phase extraction based on polydopamine-coated magnetic nanoparticles for rapid and sensitive analysis of eleven illicit drugs and metabolites in wastewater with the aid of UHPLC-MS/MS.

The quantification of illicit drugs in wastewater has become a valuable tool for monitoring illicit drug abuse. The commonly utilized methods for detecting drugs in wastewater require a substantial sample volume, extended pretreatment durations, and intricate procedures. This study first employed polydopamine-coated magnetic nanocomposites as adsorbents for magnetic solid-phase extraction, combined with UPLC-MS/MS, to simultaneously determine the concentrations of eleven common illicit drugs in wastewater. The synthesis process for Fe3O4@PDA is straightforward and high-yield. Benefiting from the strong magnetic response, good dispersibility, and abundant binding sites of the prepared nanocomposites, the extraction of illicit drugs from wastewater could be achieved in just 15 min. The method exhibited satisfactory limits of quantitation (ranging from 5 to 10 ng/L), commendable accuracy (ranging from 90.59 % to 106.80 %), good precision (with RSDs below 10 %), and less sample consumption (only 1 mL). The efficacy of this method was successfully validated through its application to actual wastewater samples collected from ten wastewater treatment plants. The results indicated that morphine, codeine, methamphetamine, and ketamine were the predominant illicit drugs present in the samples. The method developed is able to meet the needs of common illicit drug monitoring and high-throughput analysis requirements.

Effects of Short-Term Episodes of Atrial Fibrillation after Coronary Artery Bypass Grafting on the Long-term Incidence of Atrial Fibrillation and Ischemic Stroke.

BACKGROUND: To explore whether postoperative atrial fibrillation (POAF) has an impact on the incidence of late atrial fibrillation (AF) and late ischemic stroke after isolated coronary artery bypass grafting (CABG) compared to non-POAF patients. METHODS: A total of 243 eligible patients were followed for five years, and divided into a POAF group (n = 69) and a non-POAF group (n = 174). The primary end point was the incidence of late AF, and late ischemic stroke. Kaplan-Meier analyses and Cox proportional hazards models were used to examine whether POAF is an independent risk factor for the occurrence of late AF and late ischemic stroke. RESULTS: POAF patients were older than non-POAF patients. During the 5-year follow-up, the late occurrence of AF was significantly higher in POAF patients than in non-POAF (15.9% vs. 7.9% p = 0.006). There was no significant difference in the incidence of late ischemic stroke between POAF and non-POAF groups (p = 0.406). COX proportional regression analysis showed that POAF was independently associated with the late occurrence of AF (hazard ratio (HR) 3.27; 95% confidence interval (CI): 1.33-8.03, p = 0.01). CONCLUSION: POAF is an independent risk factor for the occurrence of late AF but not stroke after isolated CABG.

Protective effect of Tibetan medicine Qiwei Tiexie pills on liver injury induced by acetaminophen overdose: An integrated strategy of network pharmacology, metabolomics and transcriptomics.

BACKGROUND: Drug-induced liver injury, particularly from acetaminophen (APAP), has emerged as a significant public health concern. Unfortunately, there is currently no effective treatment strategy available. Qiwei Tiexie pills (QWTX), a traditional Tibetan medicine, have demonstrated considerable clinical efficacy in treating various liver diseases. Nevertheless, the protective effect of QWTX against drug-induced liver injury and its underlying mechanism remains poorly understood. PURPOSE: This study aimed to assess the therapeutic potential of QWTX, a Tibetan medicine, in an animal model of APAP-induced liver injury. Additionally, we sought to investigate the molecular mechanism through which QWTX exerts its effects. METHODS: We employed LC-MS and network pharmacology to predict the potential targets of QWTX in drug-induced liver injury. Subsequently, we employed HE staining, transcriptomics, metabolomics, and qRT-PCR to analyze the mechanism underlying QWTX treatment in drug-induced liver injury. RESULTS: Network pharmacology analysis revealed that the active components of QWTX are involved in inflammatory and drug metabolism-related pathways. In mouse models, pretreatment with QWTX effectively mitigated the elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory factors (IL-1ß, IL-6, and TNF-α) induced by APAP overdose. Moreover, APAP inhibited 1459 differentially expressed genes (DEGs) and 874 differential accumulation metabolites (DAMs), while QWTX promoted their expression. Conversely, APAP promoted 874 genes and 119 metabolites, which were inhibited by QWTX. Further analysis demonstrated that QWTX ameliorated the metabolic disorders induced by APAP overdose and potentially exerted a protective effect by inhibiting the expression of critical genes in crucial inflammatory pathways. QWTX also up-regulated antioxidant enzymes, thereby mitigating the oxidative stress resulting from APAP overdose. CONCLUSION: QWTX treatment effectively protects against APAP-induced liver damage in mice. Transcriptomic and metabolomic analyses further revealed that QWTX ameliorated hepatic metabolic disorders induced by APAP overdose while significantly suppressing the inflammatory response and oxidative stress associated with drug-induced liver injury. This study provides a new insight into the treatment of drug-induced liver injury by the TCM system and provides a basis for the development of new therapies for drug-induced liver injury by QWTX and its active ingredients.

A senescence-related lncRNA signature predicts prognosis and reflects immune landscape in HNSCC.

OBJECTIVE: Long noncoding RNAs (lncRNAs) regulate cancer cell senescence in many cancers. However, their specific involvement in head and neck squamous cell carcinoma (HNSCC) remains unclear. We are looking for an ingenious prognostic signature that utilizes senescence-related lncRNAs (SRlncRNAs) to predict prognosis and provide insights into the immune landscape in HNSCC. MATERIALS AND METHODS: HNSCC clinical and Cellular senescence genes information were collected from The Cancer Genome Atlas and Human Aging Genomic Resources. Then we performed Cox and Lasso regression to locate SRlncRNAs related to the prognosis of HNSCC and built a predictive signature. Further, prognosis assessment, potential mechanisms, and immune status were assessed by Kaplan-Meier analysis, Gene Set Enrichment Analysis (GSEA), and CIBERSORT, respectively. RESULTS: A prognosis prediction model based on sixteen SRlncRNAs was identified and internally validated. Then, patients with high-risk scores suffered an unfavorable overall survival (All p < 0.05). The risk score, age, and stage were independent prognostic parameters (all p < 0.001). Our model has good predictive ability (The AUC (area under the curves) 1-year = 0.707, AUC3-year = 0.748 and AUC5-year = 0.779). Subsequently, GESA revealed SRlncRNAs regulated immune responses. Patients in the high-risk group had higher tumor mutation burden and Tumor Immune Dysfunction and Exclusion but lower levels of 37 immune checkpoint genes, immune scores, and immune cells like CD8 + T cells, follicular helper T cells, and regulatory T cells. CONCLUSIONS: A prognostic model based on SRlncRNAs is the potential target for improving immunotherapy outcomes for HNSCC.

Development and validation of a model based on immunogenic cell death related genes to predict the prognosis and immune response to bladder urothelial carcinoma.

Background: Immunogenic cell death (ICD) has been categorized as a variant of regulated cell death that is capable of inducing an adaptive immune response. A growing body of evidence has indicated that ICD can modify the tumor immune microenvironment by releasing danger signals or damage-associated molecular patterns (DAMPs), potentially enhancing the efficacy of immunotherapy. Consequently, the identification of biomarkers associated with ICD that can classify patients based on their potential response to ICD immunotherapy would be highly advantageous. Therefore the goal of the study is to better understand and identify what patients with bladder urothelial carcinoma (BLCA) will respond to immunotherapy by analyzing ICD signatures and investigate ICD-related prognostic factors in the context of BLCA. Methods: The data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases regarding BLCA and normal samples was categorized based on ICD-related genes (IRGs). Specifically, we conducted an immunohistochemical (IHC) experiment to validate the expression levels of Calreticulin (CALR) in both tumor and adjacent tissues, and evaluated its prognostic significance using the Kaplan-Meier (KM) curve. Subsequently, the samples from TCGA were divided into two subtypes using consensus clustering. To obtain a more comprehensive comprehension of the biological functions, we utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The calculation of immune landscape between two subtypes was performed through ESTIMATE and CIBERSORT. Risk models were constructed using Cox and Lasso regression and their prognosis predictive ability was evaluated using nomogram, receiver operating characteristic (ROC), and calibration curves. Finally, Tumor Immune Dysfunction and Exclusion (TIDE) algorithms was utilized to predict the response to immunotherapy. Results: A total of 34 IRGs were identified, with most of them exhibiting upregulation in BLCA samples. The expression of CALR was notably higher in BLCA compared to the adjacent tissue, and this increase was associated with an unfavorable prognosis. The differentially expressed genes (DEGs) associated with ICD were linked to various immune-related pathways. The ICD-high subtypes exhibited an immune-activated tumor microenvironment (TME) compared to the ICD-low subtypes. Utilizing three IRGs including CALR, IFNB1, and IFNG, a risk model was developed to categorize BLCA patients into high- and low-risk groups. The overall survival (OS) was considerably greater in the low-risk group compared to the high-risk group, as evidenced by both the TCGA and GEO cohorts. The risk score was identified as an independent prognostic parameter (all p < 0.001). Our model demonstrated good predictive ability (The area under the ROC curve (AUC), AUC1-year= 0.632, AUC3-year= 0.637, and AUC5-year =0.653). Ultimately, the lower risk score was associated with a more responsive immunotherapy group. Conclusion: The potential of the ICD-based risk signature to function as a marker for evaluating the prognosis and immune landscape in BLCA suggests its usefulness in identifying the suitable population for effective immunotherapy against BLCA.

The performance of a visible light-responsive material Fe3O4/Bi2WO6 cooperating with peroxymonosulfate to degrade bisphenol A.

In this study, the visible light-responsive catalysts Fe3O4/Bi2WO6 were prepared and characterized by BET, SEM, EDS, XRD, XPS, and MPMS. The performances of five catalysts (0.05 Fe/Bi, 0.13 Fe/Bi, 0.17 Fe/Bi, 0.21 Fe/Bi, and 0.30 Fe/Bi) for photocatalytic degradation of bisphenol A under visible light (300-W Xe lamp) were compared. Among five catalysts, 0.17 Fe/Bi (the molar ratio of Fe3O4 to Bi2WO6 was 0.17) acquired the highest BPA photocatalytic removal of 90.2% at 120 min. With the synergistic effect between Vis/0.17 Fe/Bi and peroxymonosulfate (PMS), the BPA removal obtained was as high as 100% at 90 min ([BPA] = 100 mg/L, [0.17 Fe/Bi] = 1.25 g/L, [PMS] = 2.0 g/L, and T = 25 °C). After five times reused of 0.17 Fe/Bi, its removal of BPA dropped by 13.4% in presence of PMS, which demonstrated 0.17 Fe/Bi possessed relatively stable performance. High BPA degradation was attributed to the attacking effects of various oxide species (SO4•-, •OH, h+, O2•-) generated in the Fe3O4/Bi2WO6/PMS system under the cooperation of photocatalyst Fe3O4/Bi2WO6 and oxidizing agent PMS.

SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy.

BACKGROUND: SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer. METHODS: This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020. MSIsensor score, HRD score, RNAseq, mutational data, and corresponding clinical data were obtained from the TCGA and MSKCC cohort for seven solid tumor types. RESULTS: A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. SETD2 deleterious mutation dysfunction affected ICI treatment prognosis independently of TMB-H (p < 0.01) and had a lower death hazard than TMB-H in pancancer patients (0.511 vs 0.757). Significantly higher MSI and lower homologous recombination deficiency were observed in the SETD2 deleterious mutation group. Improved survival rate was found in the MSKCC-IO cohort (P < 0.0001) and was further confirmed in our Chinese cohort. CONCLUSION: We found that SETD2 dysfunction affects ICI treatment prognosis independently of TMB-H and has a lower death hazard than TMB-H in pancancer patients. Therefore, SETD2 has the potential to serve as a candidate biomarker for ICI treatment. Additionally, SETD2 should be considered when dMMR is detected by immunohistochemistry.

DWL-4-140: A allene small molecule targeting STING that alleviates lupus-like phenotype in Trex1-/- mice.

The innate immune system plays a critical role in the host response against pathogenic microbial infection. However, aberrant activation of the innate immune pathways is a characteristic feature of various diseases. Thus, targeted drugs must be developed based on the understanding of the innate immune signaling pathways. This study demonstrated that an allene small molecule (DWL-4-140) can efficiently and selectively exert regulatory effects on the stimulator of interferon genes (STING), resulting in the downregulation of DNA-induced interferon responses. Mechanistically, DWL-4-140 targeted the cyclized nucleotide-binding domain (CBD) of STING, inhibiting the assembly of the STING multimeric complex and the recruitment of downstream signaling mediators. In addition to downregulating the 10-carboxymethyl-9-acridanone-induced production of inflammatory factors, DWL-4-140 alleviated the pathological features of Trex1 deletion-induced lupus in mice. Thus, this study demonstrated that DWL-4-140 pharmacologically inhibits STING with potential therapeutic applications in auto-inflammatory diseases.

Prognostic values of regulatory T cells (Tregs) and Treg-related genes in gastric cancer.

Introduction: This study attempted to investigate the potential of a risk model constructed for regulatory T cells (Tregs) and their related genes in predicting gastric cancer (GC) prognosis. Material and methods: We used flow cytometry to detect the content of CD4+CD25+ Tregs. After detecting expression of five Treg-related genes by quantitative real-time polymerase chain reaction (qRT-PCR), Pearson analysis was employed to analyze the correlation between Tregs and related gene expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation and transwell assays were used to detect the effects of a disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAMTS12) on cell functions. A prognostic risk model was built after Cox regression analysis. The Kaplan-Meier method was employed to assess how Tregs, 5-gene risk scores and expression of 5 genes were correlated with the survival time. Results: A significantly increased content of Tregs was found in GC tissues (p < 0.05). 5 Treg- related genes were significantly up-regulated in GC with a positive correlation with the content of Tregs (p < 0.05). Overexpression of ADAMTS12 significantly enhanced the viability, proliferation, migration and invasion of tumor cells. Kaplan-Meier analysis demonstrated poor overall survival and disease-free survival in the high-risk group. The results of survival analysis of Treg content and related gene expression were consistent with those of Cox analysis. Conclusions: The risk model constructed based on five Treg-related genes can enable effective prediction in the prognosis of GC patients.

In vitro study of deltamethrin-induced extracellular traps in hemocytes of Ruditapes philippinarum.

Deltamethrin (DLM), a broad-spectrum pesticide, has been proven to have toxic effects on aquatic organisms. Here, we detected the formation of extracellular traps (ETosis) formation in Manila clam (Ruditapes philippinarum) hemocytes stimulated by three concentrations of DLM (0.01, 0.1 and 1 µg/mL) in vitro, and explored the underlying mechanisms induced by this pesticide. Extracellular DNA structure observation and quantitative results indicated that DLM exposure could obviously induce hemocytes ETosis, especially under high concentration of DLM induction. Moreover, DLM increased the levels of myeloperoxidase (MPO) and reactive oxygen species (ROS) in a dose-dependent manner, and enhanced the mRNA expression of several ROS-related genes. DPI (NADPH oxidase inhibitor) and ABAH (MPO inhibitor) could substantially inhibit DLM-induced extracellular traps (ETs), suggesting that the induced ETs release was caused by the induction of the ROS burst and MPO production. In addition, three concentrations of DLM-induced ETs were also accompanied by mitochondrial dysfunction, such as increasing the production of mitochondrial ROS, leading to a decrease in mitochondrial membrane potential (MMP) and activation of mitochondrial permeability transition pore (MPTP). Taken together, these results will shed new light on the immunotoxicity of DLM in clams and perhaps lays the foundation for health assessment in bivalves.

Prenatal ultrasound diagnosis of congenital vertical talus.

OBJECTIVE: This study aimed to analyze the ultrasound characteristics of fetal congenital vertical talus (CVT) to provide a detailed basis for the prenatal diagnosis of CVT. METHODS: We retrospectively analyzed the ultrasonographic findings of fetuses with CVT confirmed by X-ray, surgery, or autopsy from 2010 to 2020. Clinical characteristics and ultrasonographic findings of CVT, including foot morphology, ossification center of the calcaneus and talus, associated deformities, and chromosomal test results, were recorded. RESULTS: Thirteen patients diagnosed with CVT by prenatal ultrasound were confirmed postpartum. Nine cases were bilateral, and four were unilateral. Under two-dimensional ultrasound, 13/13 cases had abnormal foot morphology, and 10 of 13 cases (76.9%) showed that the ossification center of the talus moved downward, and the calcaneus moved laterally. Under three-dimensional ultrasound, 11 cases (84.6%) presented a "rocking chair" appearance, and two cases did not obtain satisfactory three-dimensional image due to oligohydramnios and fetal position. In this group of cases, two cases (15.4%) were isolated CVT, and the other 11 cases (84.6%) were complicated with other abnormalities. Eleven cases of non-isolated CVT and 1 case of isolated CVT were induced, and another patient with isolated CVT had undergone postnatal surgery, which had been followed up for 8 years and recovered well. CONCLUSIONS: The combination of fetal foot morphology, ossification center position of the calcaneus and talus, and three-dimensional ultrasound can provide a reliable diagnosis of CVT. Furthermore, we should pay more attention to the evaluation of other systemic and chromosomal abnormalities in CVT cases.

Distribution characteristics and clinical phenotype analyses of hemoglobin variants in the Z region of Central Guangxi, Southern China.

OBJECTIVE: To investigate the molecular diagnosis of hemoglobin variants in Z region by Capillary electrophoresis in Central Guangxi, Southern China, and analyze their distribution and phenotypic characteristics, to provide a reference for clinical consultation and prenatal diagnosis for couples. METHODS: A total of 23,709 subjects were collected for blood routine analysis, hemoglobin analysis, and common α- and ß-globin gene loci in Chinese population. The hemoglobin electrophoresis components were divided into Zone 1-Zone 15 (Z1-Z15) by Capillary zone electrophoresis (CE). For samples not clearly detected by the conventional technology, Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) were used. Single-molecule real-time (SMRT) sequencing technology was used to analyze rare-type genes in a sample with a structural variation. RESULTS: Ten rare hemoglobin variants distributed in Z region were detected in 23,709 samples, including Hb Cibeles, which was reported for the first time in Asia; Hb J-Broussais, Hb G-Honolulu and J-Wenchang-Wuming, they were first reported in Guangxi; 1 case of Hb Anti-Lepore Liuzhou, which was a newly discovered hemoglobin variant; hemoglobin variants Hb G-Siriraj, Hb Handsworth, Hb Q-Thailand, Hb Ube-2, Hb NewYork were also detected. CONCLUSION: There are a few studies on rare hemoglobin variants in Z region in Southern China. Ten rare hemoglobin variants were found in this study. The hematological phenotype and component content of hemoglobin variants are related to the occurrence of thalassemia. This study enriched the data of rare hemoglobin variants in Southern China and provided a comprehensive data basis for prenatal diagnosis of hemoglobin variants in this area.

Mean Platelet Volume to Platelet Count Ratio Predicts Left Atrial Stasis in Patients with Non-Valvular Atrial Fibrillation.

Background: The mean platelet volume to platelet count ratio (MPV/PC) has been investigated in the diagnosis, prognosis and risk stratification in several diseases. However, the predictive role of MPV/PC in left atrial stasis (LAS) of non-valvular atrial fibrillation (NVAF) patients remains unknown. Methods: A total of 217 consecutive NVAF patients undergoing transesophageal echocardiogram (TEE) evaluation were retrospectively enrolled. The demographic, clinical, admission laboratory and TEE data were extracted and analyzed. Patients were categorized into those with or without LAS. The associations between the MPV/PC ratio and LAS were assessed by multivariate logistic regression analysis. Results: There were 24.9% (n = 54) patients with LAS according to TEE. Compared with patients without LAS, the MPV/PC ratio was significantly higher in those with LAS (5.6±1.6 vs 4.8±1.0, P < 0.001). After multivariable adjustment, higher MPV/PC ratio levels (OR 1.747, 95% CI 1.193-2.559, P = 0.004) were positively associated with LAS, with the optimal cut-point for LAS prediction of 5.36 (area under the curve, AUC = 0.683, sensitivity 48%, specificity 73%, 95% CI 0.589-0.777, P < 0.001). The stratification analysis showed that a significant positive correlation between MPV/PC ratio ≥5.36 and LAS in patients of male, younger (<65 years), paroxysmal AF, without history of stroke/TIA, CHA2DS2-VASc score ≥2, left atrial diameter (LAD) ≥40mm and left atrial volume index (LAVI) >34mL/m2 (all P < 0.05). Conclusion: Increasing MPV/PC ratio was associated with an increased risk of LAS, which was mainly reflected in the subgroups of male, younger (<65 years), paroxysmal AF, without history of stroke/TIA, CHA2DS2-VASc score ≥2, LAD ≥40mm and LAVI >34mL/m2 patients.

An Immunogenic Cell Death-Related Gene Signature Reflects Immune Landscape and Predicts Prognosis in Melanoma Independently of BRAF V600E Status.

Immunogenic cell death (ICD) is a type of regulated cell death that can activate adaptive immune response, and its ability to reshape the tumor microenvironment via multiple mechanisms may contribute to immunotherapy. The treatment options for patients with skin cutaneous melanoma (SKCM) vary based on BRAF V600E statuses. However, all standard treatments include immunotherapy. Therefore, it is critical to identify ICD-associated signatures that can help classify patients according to benefits from ICD immunotherapy. In this study, data on melanoma samples with BRAF V600E mutation (BRAF V600E-mutant melanoma) and melanoma samples with wild-type BRAF V600E alleles (BRAF V600E WT melanoma) were collected from The Cancer Genome Atlas (TCGA) database. The ICD-related (ICD-high and ICD-low) subgroups of patients with BRAF V600E WT melanoma were established via consensus clustering. The analyses of survival, differentially expressed genes (DEGs), functional annotation, and immune landscape were performed in these two subgroups. Results showed that ICD-high subgroup was correlated with a positive overall survival (OS) and active tumor immune landscape. A model comprising seven prognosis ICD-related gene biomarkers was developed. Survival analysis and receiver operating characteristic (ROC) curve evaluation in both cohorts with BRAF V600E WT and BRAF V600E-mutant melanoma showed an accurate prognostic estimation of ICD-related risk signature. There was a correlation between immune cell infiltration and immunotherapy response and risk score. Thus, the ICD risk signature was closely associated with the tumor's immune microenvironment. Our results may provide insights to further individualize and improve precision therapeutic decision-making in BRAF V600E-mutant and WT melanoma.

C-type lectin (CTL) and sialic acid-binding lectin (SABL) from Venerupis philippinarum: Function on PAMP binding and opsonic activities in immune responses.

Lectins are a superfamily of carbohydrate-recognition proteins that bind to specific carbohydrate structures and play significant roles in immune recognition and clearance of invaders. In the study, we investigated the potential mechanisms of PAMP binding and opsonic activities of a c-type lectin and a sialic acid-binding lectin from manila clam Venerupis philippinarum (designed as VpCTL and VpSABL). Both recombinant proteins (rVpCTL and rVpSABL) could bind LPS, PGN, glucan and zymosan in vitro. Coinciding with the PAMPs binding assay, a broad agglutination spectrum was displayed by rVpSABL including gram-positive bacteria Staphyloccocus aureus, gram-negative bacteria Escherichia coli, Vibrio parahaemolyticus, Vibrio harveyi, Pseudomonas putida, Proteus mirabilis and fungi Pichia pastoris, while no agglutinative activities on P. mirabilis and P. putida was observed in rVpCTL. Moreover, the phagocytosis and encapsulation ability of hemocytes could be significantly enhanced by rVpCTL and rVpSABL. More remarkable, VpCTL and VpSABL were highly detected in all the examined tissues, especially in gills and hepatopancreas. All the results showed that VpCTL and VpSABL could function as pattern recognition receptors (PRRs) with distinct recognition spectrum, perhaps involved in the innate immune responses of V. philippinarum.

Prediction of Fetal Biliary Atresia Based on Second and Third-Trimester Ultrasound Characteristics.

OBJECTIVE: To explore the diagnostic performance of prenatal ultrasound in the prediction of biliary atresia (BA). METHODS: We prospectively collected cases of suspected biliary abnormalities in the 2nd trimester of pregnancy and performed a series (at least 3) of prenatal ultrasound examinations in the 2nd and 3rd trimester. The presence of the gallbladder was examined each time, and its size and shape were assessed if the gallbladder was visible. The existence of other abnormalities was carefully evaluated. Neonatal ultrasound examination was conducted within 1 month after birth, and clinical data were followed-up for 6 months after birth. RESULTS: Among the 41 895 patients, 298 were suspected to have biliary abnormalities, while 82 patients were excluded due to loss to follow-up or induced labor caused by other abnormalities. A total of 216 patients were included in this study, and 15 were diagnosed with BA. We summarized the ultrasound findings of the gallbladders and defined a high-risk gallbladder for the prenatal diagnosis of BA. This was demonstrated to have the best diagnostic performance as a single parameter, with an area under the curve of 0.914 (95 %CI: 0.869-0.948). In addition, higher incidences of biliary cysts, right hepatic artery dilation, echogenic bowel, and ascites were observed in BA fetuses. Logistic regression analysis showed that the combination of 5 parameters had better diagnostic performance, with an area under the curve of 0.995 (95 %CI: 0.973-0.999). CONCLUSION: The fetal gallbladder was found to be a critical feature for the identification of BA. Concomitant abnormalities could be helpful to improve the accuracy of the diagnosis.

Dysmorphic Gallbladder Found on Prenatal Ultrasound as a Hint for Biliary Atresia.

Biliary atresia (BA) is a rare but devastating cholangiopathy. We report a case series of dysmorphic gallbladders detected during prenatal ultrasound, which were confirmed as BA after birth. We present the prenatal ultrasound findings as well as integral follow-up, with an aim to raise awareness regarding the association between BA and dysmorphic gallbladder. Although this dysmorphic gallbladder is a strong hint for BA, it is also important to search for other related sonographic features, such as the presence of microcysts at the hepatic hilum, dilated right hepatic artery, and seroperitoneum, which may provide more evidence for the diagnosis of BA.

FAM3D as a Prognostic Indicator of Head and Neck Squamous Cell Carcinoma Is Associated with Immune Infiltration.

Background: Globally, head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor with high morbidity and mortality. Hence, it is important to find effective biomarkers for the diagnosis and prediction of the prognosis of patients with HNSCC. FAM3D had been proven to be vital in other cancers. However, its predictive and therapeutic value in HNSCC is unclear. Therefore, it is valuable to explore the association between the expression level of FAM3D and its impacts on the prognosis and tumor microenvironment in HNSCC. Methods: The Cancer Genome Atlas (TCGA) dataset, Genotype-Tissue Expression (GTEx) dataset, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset, and The Human Protein Atlas (THPA) website were used to assess HNSCC expressions in tumor and nontumor tissues. Then, we further conducted immunohistochemistry experiment as internal cohort to validate the same results. The Cox regression analysis, Kaplan-Meier analysis, and nomograms were performed to find the predictive prognostic value of FAM3D in HNSCC patients and its relationship with the clinicopathological features in HNSCC. The Gene Expression Omnibus (GEO) dataset was utilized to externally verify the prognosis value of FAM3D in HNSCC. Gene Set Enrichment Analysis (GESA) was applied to search the molecular and biological functions of FAM3D. The association between FAM3D and immune cell infiltration was investigated with the Tumor Immune Estimating Resource, version 2 (TIMER2). The relationships between FAM3D expression and tumor microenvironment (TME) scores, immune checkpoints, and antitumor compound half-maximal inhibitory concentration predictions were also explored. Results: In different datasets, FAM3D mRNA and protein levels were all significantly lower in HNSCC tissues than in normal tissues, and they were strongly inversely associated with tumor grade, stage, lymph node metastasis, and T stage. Patients with high-FAM3D-expression displayed better prognosis than those with low-FAM3D-expression. FAM3D was also determined to be a suitable biomarker for predicting the prognosis of patients with HNSCC. This was externally validated in the GEO dataset. As for gene and protein level, the functional and pathway research results of FAM3D indicated that it was enriched in alteration of immune-related pathways in HNSCC. The low-expression group had higher stromal and ESTIMATE scores by convention than the high-expression group. FAM3D expression were found to be positively correlated with immune infiltrating cells, such as cancer-associated fibroblasts, myeloid-derived suppressor cells, macrophage cells, T cell CD8+ cells, regulatory T cells, and T cell follicular helper cells. FAM3D's relationships with immune checkpoints and sensitivity to antitumor drugs were also investigated. Conclusion: Our study explored the impact of FAM3D as a favorable prognostic marker for HNSCC on the tumor immune microenvironment from multiple perspectives. The results may provide new insights into HNSCC-targeted immunotherapy.