SEC61G assists EGFR-amplified glioblastoma to evade immune elimination.

Amplification of chromosome 7p11 (7p11) is the most common alteration in primary glioblastoma (GBM), resulting in gains of epidermal growth factor receptor (EGFR) copy number in 50 to 60% of GBM tumors. However, treatment strategies targeting EGFR have thus far failed in clinical trials, and the underlying mechanism remains largely unclear. We here demonstrate that EGFR amplification at the 7p11 locus frequently encompasses its neighboring genes and identifies SEC61G as a critical regulator facilitating GBM immune evasion and tumor growth. We found that SEC61G is always coamplified with EGFR and is highly expressed in GBM. As an essential subunit of the SEC61 translocon complex, SEC61G promotes translocation of newly translated immune checkpoint ligands (ICLs, including PD-L1, PVR, and PD-L2) into the endoplasmic reticulum and promotes their glycosylation, stabilization, and membrane presentation. Depletion of SEC61G promotes the infiltration and cytolytic activity of CD8+ T cells and thus inhibits GBM occurrence. Further, SEC61G inhibition augments the therapeutic efficiency of EGFR tyrosine kinase inhibitors in mice. Our study demonstrates a critical role of SEC61G in GBM immune evasion, which provides a compelling rationale for combination therapy of EGFR-amplified GBMs.

Autism patient-derived SHANK2BY29X mutation affects the development of ALDH1A1 negative dopamine neuron.

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions. Different mutations on a single ASD gene contribute to heterogeneity of disease phenotypes, possibly due to functional diversity of generated isoforms. SHANK2, a causative gene in ASD, demonstrates this phenomenon, but there is a scarcity of tools for studying endogenous SHANK2 proteins in an isoform-specific manner. Here, we report a point mutation on SHANK2, which is found in a patient with autism, located on exon of the SHANK2B transcript variant (NM_133266.5), hereby SHANK2BY29X. This mutation results in an early stop codon and an aberrant splicing event that impacts SHANK2 transcript variants distinctly. Induced pluripotent stem cells (iPSCs) carrying this mutation, from the patient or isogenic editing, fail to differentiate into functional dopamine (DA) neurons, which can be rescued by genetic correction. Available SMART-Seq single-cell data from human midbrain reveals the abundance of SHANK2B transcript in the ALDH1A1 negative DA neurons. We then show that SHANK2BY29X mutation primarily affects SHANK2B expression and ALDH1A1 negative DA neurons in vitro during early neuronal developmental stage. Mice knocked in with the identical mutation exhibit autistic-like behavior, decreased occupancy of ALDH1A1 negative DA neurons and decreased dopamine release in ventral tegmental area (VTA). Our study provides novel insights on a SHANK2 mutation derived from autism patient and highlights SHANK2B significance in ALDH1A1 negative DA neuron.

Organ-Specific Gene Expression Control Using DNA Origami-Based Nanodevices.

Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.

Size-Selective Capturing of Exosomes Using DNA Tripods.

Fractionating and characterizing target samples are fundamental to the analysis of biomolecules. Extracellular vesicles (EVs), containing information regarding the cellular birthplace, are promising targets for biology and medicine. However, the requirement for multiple-step purification in conventional methods hinders analysis of small samples. Here, we apply a DNA origami tripod with a defined aperture of binders (e.g., antibodies against EV biomarkers), which allows us to capture the target molecule. Using exosomes as a model, we show that our tripod nanodevice can capture a specific size range of EVs with cognate biomarkers from a broad distribution of crude EV mixtures. We further demonstrate that the size of captured EVs can be controlled by changing the aperture of the tripods. This simultaneous selection with the size and biomarker approach should simplify the EV purification process and contribute to the precise analysis of target biomolecules from small samples.

SIRPG expression positively associates with an inflamed tumor microenvironment and response to PD-1 blockade.

BACKGROUND: This study aimed to investigate the relationship between signal regulatory protein gamma (SIRPG) and tumor immune microenvironment phenotypes or T cell mediated-adaptive antitumor immunity, and its predictive value for response to PD-1 blockade in cancers. METHODS: Pan-cancer analysis of SIRPG expression and immune deconvolution was performed using transcriptomic data across 33 tumor types. Transcriptomic and clinical data from 157 patients with non-small-cell lung cancer (NSCLC) and melanoma received PD-1 blockade were analyzed. Expression characteristics of SIRPG were investigated using single-cell RNA sequencing (scRNA-seq) data of 103,599 cells. The effect of SIRPG expression was evaluated via SIRPG knockdown or overexpression in Jurkat T cells. RESULTS: The results showed that most cancers with high SIRPG expression had significantly higher abundance of T cells, B cells, NK cells, M1 macrophages and cytotoxic lymphocytes and increased expression level of immunomodulatory factors regulating immune cell recruitment, antigen presentation, T cell activation and cytotoxicity, but markedly lower abundance of neutrophils, M2 macrophages, and myeloid-derived suppressor cells. High SIRPG expression was associated with favorable response to PD-1 blockade in both NSCLC and melanoma. scRNA-seq data suggested SIRPG was mainly expressed in CD8+ exhausted T and CD4+ regulatory T cells, and positively associated with immune checkpoint expression including PDCD1 and CTLA4. In vitro test showed SIRPG expression in T cells could facilitate expression of PDCD1 and CTLA4. CONCLUSION: High SIRPG expression is associated with an inflamed immune phenotype in cancers and favorable response to PD-1 blockade, suggesting it would be a promising predictive biomarker for PD-1 blockade and novel immunotherapeutic target.

Photoaged Nanopolystyrene Affects Neurotransmission to Induce Transgenerational Neurotoxicity in Caenorhabditis elegans.

Nanopolystyrene (NPS), a frequently employed nanoplastic, is an emerging environmental contaminant known to cause neurotoxicity in various organisms. However, the potential for transgenerational neurotoxic effects, especially from photoaged NPS (P-NPS), remains underexplored. This study investigated the aging of virgin NPS (V-NPS) under a xenon lamp to simulate natural sunlight exposure, which altered the physicochemical characteristics of the NPS. The parental generation (P0) of Caenorhabditis elegans was exposed to environmental concentrations (0.1-100 µg/L) of V-NPS and P-NPS, with subsequent offspring (F1-F4 generations) cultured under NPS-free conditions. Exposure to 100 µg/L P-NPS resulted in more pronounced deterioration in locomotion behavior in the P0 generation compared to V-NPS; this deterioration persisted into the F1-F2 generations but returned to normal in the F3-F4 generations. Additionally, maternal exposure to P-NPS damaged dopaminergic, glutamatergic, and serotonergic neurons in subsequent generations. Correspondingly, there was a significant decrease in the levels of dopamine, glutamate, and serotonin, associated with reduced expression of neurotransmission-related genes dat-1, eat-4, and tph-1 in the P0 and F1-F2 generations. Further analysis showed that the effects of P-NPS on locomotion behavior were absent in subsequent generations of eat-4(ad572), tph-1(mg280), and dat-1(ok157) mutants, highlighting the pivotal roles of these genes in mediating P-NPS-induced transgenerational neurotoxicity. These findings emphasize the crucial role of neurotransmission in the transgenerational effects of P-NPS on locomotion behavior, providing new insights into the environmental risks associated with exposure to photoaged nanoplastics.

First report of sweet cherry root rot caused by Fusarium solani in China.

Sweet cherry (Prunus avium L.) has become an economically important fruit in China. And its cultivation area has significantly expanded over the last three decades (Wang et al. 2020; Zhao et al. 2023). In July 2023, wilting of cherry trees was observed in a cherry plantation in Wenchuan County (31°51'N, 103°56'E, altitude: 1,510 m) in Sichuan Province and approximately 27% of the trees showed symptoms of root rot including soft roots, dark brown to black lesions, yellowing and wilted leaves, and a distinct yellow-brown core discoloration of the inner root core when cut in cross-section. To isolate the causal pathogens, six infected sweet cherry plants with rootstock 'Daqingye' from Cerasus pseudocerasus were randomly selected from the orchard and then the intertwined diseased and healthy roots (5mm× 5mm × 2mm) were washed with sterile water to remove surface soil. The root samples were surface sterilized with 75% ethanol for 30 seconds and NaClO for 30 seconds and washed three times with distilled water. The disinfected tissues were placed on potato dextrose agar (PDA) and incubated at 27°C in darkness for 5 days (Zhao et al. 2024). A total of nine fungal isolates with similar morphological characteristics were obtained. The colony obtained through single-spore purification displays a red reverse side and a concentric ring pattern on the front, with a sparse surface. Macroconidia were relatively slender with a curve, like sickle shape, 0 to 3 septate measuring (25.8 to 46.1) µm× (4.2 to 7.5) µm, respectively (n=20). The morphological characteristics were consistent with the description of Fusarium spp. (Li et al. 2021). Among these isolates, only HB5 was selected for additional molecular identification. Three target genes, including the internal transcribed spacer (ITS), partial translation elongation factor 1-alpha (TEF), and RNA polymerase second largest subunit (RPB2) were amplified using the primers ITS1/ITS4, TEF1-728/FTEF1-re, and fRPB2-5F/fRPB2-7r, respectively (Groenewald et al. 2013; Carbone and Kohn 1999; Reeb et al. 2004). Sequences of HB5 was deposited in GenBank (ITS, PP388208; TEF, PP580036; RPB2, PP580035). A BLAST search revealed high similarity to those of F. solani sequences with 99%, 100% and 100% respectively (MN013858.1, JF740846.1, OR371902.1), and a multilocus phylogenetic tree was generated to represent the molecular identification results. Pathogenicity studies were conducted on the rootstocks from 'Daqingye' of Cerasus pseudocerasus in 1 liter plastic flowerpots. The seedlings were incubated in a constant temperature incubator at 25°C with a humidity level of 65% for two weeks. Following the growth of green leaves, 200ml (1x106 spores/ml) of spore suspensions were poured into pots. After 4 weeks of inoculation, the same symptoms of the inoculated plants were observed consistent with those shown in the field , while control plants were inoculated with distill water with asymptomatic. The inoculated pathogen was confirmed both morphologically and molecularly as described earlier, thereby fulfilling Koch's postulates. It has been reported that Fusarium solani has been reported to cause root rot in various plants in China, including Actinidia sppt, Zanthoxylum bungeanum, Fragaria×ananassa Duch (Song et al.2022; Li et al. 2023; Zhao et al. 2024). To our knowledge, this is the first report of Fusarium solani causing root rot in sweet cherry (Prunus avium). We here also report the severity and outbreak of this disease, which has been found in other regions in recent years and may become prevalent. Further research on disease management strategies is urgently needed to protect sweet cherry production.

A Multi-Modal Deep-Learning Air Quality Prediction Method Based on Multi-Station Time-Series Data and Remote-Sensing Images: Case Study of Beijing and Tianjin.

The profound impacts of severe air pollution on human health, ecological balance, and economic stability are undeniable. Precise air quality forecasting stands as a crucial necessity, enabling governmental bodies and vulnerable communities to proactively take essential measures to reduce exposure to detrimental pollutants. Previous research has primarily focused on predicting air quality using only time-series data. However, the importance of remote-sensing image data has received limited attention. This paper proposes a new multi-modal deep-learning model, Res-GCN, which integrates high spatial resolution remote-sensing images and time-series air quality data from multiple stations to forecast future air quality. Res-GCN employs two deep-learning networks, one utilizing the residual network to extract hidden visual information from remote-sensing images, and another using a dynamic spatio-temporal graph convolution network to capture spatio-temporal information from time-series data. By extracting features from two different modalities, improved predictive performance can be achieved. To demonstrate the effectiveness of the proposed model, experiments were conducted on two real-world datasets. The results show that the Res-GCN model effectively extracts multi-modal features, significantly enhancing the accuracy of multi-step predictions. Compared to the best-performing baseline model, the multi-step prediction's mean absolute error, root mean square error, and mean absolute percentage error increased by approximately 6%, 7%, and 7%, respectively.

Brominated flame retardants in surface sediment from Western Guangdong, South China: Occurrence, distribution and toxicity in Caenorhabditis elegans.

Sediment is the ultimate sink of environmental pollutants. A total of 128 surface sediment samples were collected from 8 rivers and 3 reservoirs in Maoming City, Guangdong Province. This study assessed the content and distribution of brominated flame retardants in sediments. The acute toxicity effects of tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDs) in sediments were evaluated using Caenorhabditis elegans as model organisms. The concentration of TBBPA in sediments ranged from not detected (ND) to 12.59 µg/kg and was mainly distributed in the central area, which was affected by the emission of TBBPA from residential and factory. The concentration of HBCDs ranged from ND to 6.31 µg/kg, and the diastereoisomer distribution was consistent, showing a trend close to the South China Sea. The composition pattern of HBCDs in the surface sediments from rivers were 41.73%-62.33%, 7.89%-25.54%, and 18.76%-40.65% for α-, ß-, and γ-HBCD, respectively, and in the sediments from reservoirs were 26.15%-45.52%, 7.44%-19.23%, and 47.04%-61.89% for α-, ß-, and γ-HBCD, respectively. When the sum of concentrations of TBBPA and HBCD in sediments were above high levels, reactive oxygen species in nematodes significantly increased, resulting in an oxidative stress response. Intestinal permeability was also enhanced, causing intestinal damage. In addition, in terms of this study, TBBPA had a greater impact on biotoxicity compared to HBCDs, and more attention should be paid to the toxic effects of the river ecosystem organisms in Maoming City, Guangdong Province. This study can complement the pollution database in the study area and provide basic data for pollution control.

[Identification method of 2-methylisoborneol and geosmin in water by purge and trap-gas chromatography-mass spectrometry].

OBJECTIVE: To establishe an analysis and identification method for 2-methylisoborneol(2-MIB) and geosmin(GSM) in water using purge and trap-gas chromatography-mass spectrometry. METHODS: The samples were enriched and analyzed using a purge and trap system, followed by the separation on a DB-624(30 m×0.25 mm, 1.4 µm) chromatographic column. Quantification was performed using gas chromatography-mass spectrometry with the selected ion monitoring and internal standard calibration. RESULTS: The calibration curves for 2-MIB and GSM showed an excellent linearity in the range of 1 to 100 ng/L with R~2 values greater than 0.999. The detection limit and quantification limit for both 2-MIB and GSM were 0.33 ng/L and 1.0 ng/L, respectively. Spike recovery experiments were further carried on the source water and drinking water at three concentration levels. It showed that the average recoveries were from 82.0% to 111.0% for 2-MIB while 84.0% to 110% for GSM. Additionally, the test precision of 2-MIB and GSM ranged from 1.9% to 7.3% and 1.9% to 5.0%(n=6), respectively. The analysis of multiple samples including the local source water, treated water and distribution network water confirmed the existence of 2-MIB and GSM. CONCLUSION: Compared to the national standard(GB/T 5750.8-2023), the proposed method enables fully automated sample introduction and analysis without the extra pre-treatment. It provides the advantages of simplicity, good repeatability and high accuracy.

Neutralizing serum amyloid a protects against sinusoidal endothelial cell damage and platelet aggregation during acetaminophen-induced liver injury.

Serum amyloid A (SAA) is an acute response protein that mainly produced by hepatocytes, and it can promote endothelial dysfunction via a pro-inflammatory and pro-thrombotic effect in atherosclerosis and renal disease. Overdose of Acetaminophen (APAP) will cause hepatotoxicity accompany with hepatocyte necrosis, liver sinusoidal endothelial cells (LSECs) damage and thrombosis in liver. However, whether SAA plays a role in APAP-induced liver toxicity remains unclear. Here, we evaluated the Saa1/2 expression in APAP-induced liver injury, and found that Saa1/2 production was significantly increased in an autocrine manner in APAP injury model. Moreover, we used neutralizing antibody (anti-SAA) to block the function of serum Saa1/2. We found that neutralizing serum Saa1/2 protected against APAP-induced liver injuries and increased the survival rate of mice that were treated with lethal dose APAP. Further investigations showed that blocking Saa1/2 reduced APAP-induced sinusoidal endothelium damage, hemorrhage and thrombosis. In addition, in vitro experiments showed that Saa1/2 augmented the toxic effect of APAP on LSECs, and Saa1/2 promoted platelets aggregation on LSECs cell membrane. Taken together, this study suggests that Saa1/2 may play a critical role in APAP-induced liver damages through platelets aggregation and sinusoidal damage. Therefore, we conceptually demonstrate that inhibition of SAA may be a potential intervention for APAP-directed acute liver injuries.

Development of europium(III) complex fluorescent probe for hydrogen sulfide detection and its application in water samples.

Hydrogen sulfide (H2 S) is a crucial endogenous signaling component in organisms that is involved in redox homeostasis and numerous biological processes. Modern medical research has confirmed that hydrogen sulfide plays an important role in the pathogenesis of many diseases. Herein, a fluorescent probe Eu(ttbd)3 abt based on europium(III) complex was designed and synthesized for the detection of H2 S. Eu(ttbd)3 abt exhibited significant quenching for H2 S at long emission wavelength (625 nm), with rapid detection ability (less than 2 min), high sensitivity [limit of detection (LOD) = 0.41 µM], and massive Stokes shift (300 nm). Additionally, this probe showed superior selectivity for H2 S despite the presence of other possible interference species such as biothiols. Furthermore, the probe Eu(ttbd)3 abt was successfully applied to detect H2 S in water samples.

Emerging role of toll-like receptors signaling and its regulators in preterm birth: a narrative review.

INTRODUCTION: Despite intensive research, preterm birth (PTB) rates have not decreased significantly in recent years due to a lack of understanding of the underlying causes and insufficient treatment options for PTB. We are committed to finding promising biomarkers for the treatment of PTB. METHODS: An extensive search of the literature was conducted with MEDLINE/PubMed, and in total, 151 studies were included and summarized in the present review. RESULTS: Substantial evidence supports that the infection and/or inflammatory cascade associated with infection is an early event in PTB. Toll-like receptor (TLR) is a prominent pattern recognition receptor (PRR) found on both immune and non-immune cells, including fetal membrane cells. The activation of TLR downstream molecules, followed by TLR binding to its ligand, is critical for infection and inflammation, leading to the involvement of the TLR signaling pathway in PTB. TLR ligands are derived from microbial components and molecules released by damaged and dead cells. Particularly, TLR4 is an essential TLR because of its ability to recognize lipopolysaccharide (LPS). In this comprehensive overview, we discuss the role of TLR signaling in PTB, focus on numerous host-derived genetic and epigenetic regulators of the TLR signaling pathway, and cover ongoing research and prospective therapeutic options for treating PTB by inhibiting TLR signaling. CONCLUSION: This is a critical topic because TLR-related molecules and mechanisms may enable obstetricians to better understand the physiological changes in PTB and develop new treatment and prevention strategies.

Development and validation of a multivariate model for predicting heart failure hospitalization and mortality in patients receiving maintenance hemodialysis.

BACKGROUND: Heart failure (HF) in patients undergoing maintenance hemodialysis (MHD) increases their hospitalization rates, mortality, and economic burden significantly. We aimed to develop and validate a predictive model utilizing contemporary deep phenotyping for individual risk assessment of all-cause mortality or HF hospitalization in patients on MHD. MATERIALS AND METHODS: A retrospective review was conducted from January 2017 to October 2022, including 348 patients receiving MHD from four centers. The variables were adjusted by Cox regression analysis, and the clinical prediction model was constructed and verified. RESULTS: The median follow-up durations were 14 months (interquartile range [IQR] 9-21) for the modeling set and 14 months (9-20) for the validation set. The composite outcome occurred in 72 (29.63%) of 243 patients in the modeling set and 39 (37.14%) of 105 patients in the validation set. The model predictors included age, albumin, history of cerebral hemorrhage, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/"sacubitril/valsartan", left ventricular ejection fraction, urea reduction ratio, N-terminal prohormone of brain natriuretic peptide, and right atrial size. The C-index was 0.834 (95% CI 0.784-0.883) for the modeling set and 0.853 (0.798, 0.908) for the validation set. The model exhibited excellent calibration across the complete risk profile, and the decision curve analysis (DCA) suggested its ability to maximize patient benefits. CONCLUSION: The developed prediction model offered an accurate and personalized assessment of HF hospitalization risk and all-cause mortality in patients with MHD. It can be employed to identify high-risk patients and guide treatment and follow-up.

A phase 2 study of sorafenib combined with conventional therapies in refractory central nervous system leukemia.

BACKGROUND: Patients with refractory central nervous system leukemia (CNSL) have a dismal prognosis and lack effective therapy. Case reports have shown that sorafenib is effective against brain metastases, including leukemia. METHODS: To explore the efficacy of sorafenib combined with conventional therapies for refractory CNSL, a phase 2 study was conducted. The primary end point was the complete remission rate (CRR) within 8 weeks of treatment. Secondary end points included the overall response rate (ORR), event-free survival (EFS), overall survival (OS), and adverse events (AEs). RESULTS: Twenty-six patients with refractory CNSL were enrolled; they included 17 with isolated CNSL, 7 with hematological relapse, and 2 with another extramedullary relapse. After 8 weeks of treatment, 21 patients achieved complete remission, 2 achieved partial remission, and 3 achieved no remission for a CRR of 80.8% (95% CI, 62.1%-91.5%) and an ORR of 88.5% (95% CI, 71.0%-96.0%). Twenty patients survived, and 6 died. The 2-year EFS and OS rates were 75.0% (95% CI, 54.5%-88.3%) and 76.9% (95% CI, 54.2%-90.4%), respectively. Six patients experienced grade 3 or 4 treatment-related AEs, including moderate chronic graft-vs-host disease (n = 3), grade 3 or 4 acute graft-vs-host disease (n = 2), and grade 3 skin rash (n = 1). No treatment-related deaths occurred during the therapy of refractory CNSL. CONCLUSIONS: Sorafenib combined with conventional therapies is effective and safe for refractory CNSL. LAY SUMMARY: Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia.

Rational Design of Tungsten Selenide @ N-Doped Carbon Nanotube for High-Stable Potassium-Ion Batteries.

Potassium-ion batteries (PIBs) are deemed as one of the most promising energy storage systems due to their high energy density and low cost. However, their commercial application is far away from satisfactory because of limited suitable electrode materials. Herein, core-shell structured WSe2 @N-doped C nanotubes are rationally designed and synthesized via selenizing WO3 @ polypyrrole for the first time. The large interlayer spacing of WSe2 can facilitate the intercalation/deintercalation of K+ . Meanwhile, the core-shell structured nanotube provides favorable interior void space to accommodate the volume expansion of WSe2 during cycling. Thus, the obtained electrode exhibits superb electrochemical performance with a high capacity of 301.7 mAh g-1 at 100 mA g-1 over 120 cycles, and 122.1 mAh g-1 can remain at 500 mA g-1 even after 1300 cycles. Ex-situ X-ray diffraction analysis reveals the K-ion storage mechanism of WSe2 @N-doped C includes intercalation and conversion reaction. Density function theory (DFT) calculation demonstrates the reasonable diffusion pathway of K+ . In addition, the obtained WSe2 @N-doped C nanotubes have been used as anode material for lithium-ion batteries, which also show good rate performance and high cycle stability. Therefore, this work offers a new methodology for the ration design of new structure electrode materials with long cycle stability.

Robotic laser position versus freehand in CT-guided percutaneous microwave ablation for single hepatocellular carcinoma (diameter < 3 cm): a preliminary study.

PURPOSE: To compare the accuracy and safety of robotic laser position (RLP) versus freehand for antenna CT-guided microwave ablation (MWA) of single hepatocellular carcinoma (HCC) (diameter < 3 cm). MATERIALS AND METHODS: This retrospective study was conducted between May 2020 and June 2021. A total of 40 patients with early HCC who underwent CT-guided MWA were divided into two groups: a freehand group (n = 20) and a RLP group (n = 20). Based on in-plane and out-of-plane data, the actual puncture point error (APPE), number of repositioning procedures, and operative duration were compared using the Mann-Whitney U test. Ablation-related complications were compared using the Chi-squared test. RESULTS: The mean diameter of HCC patients who received MWA was 2.4 ± 0.5 cm. For in-plane APPE, APPE was comparable between the two groups (p = 0.299). However, for the out-of-plane position, the APPE in the freehand group was higher than that in the RLP group (p = 0.027). The number of repositioning procedures was 0 (range, 0-0) for RLP-guided procedures and 3 (range, 2-5) for freehand procedures, showing a statistically significant difference between the two groups (p < 0.001). The mean operative duration for freehand procedures was 39 min, compared with 26 min for RLP-guided procedures, showing a significant difference (p = 0.013). No deaths or major complications were directly related to MWA. Minor complications in the freehand group were comparable with those in the RLP group (p = 0.313). CONCLUSION: RLP guidance significantly reduces the number of antenna repositioning procedures in MWA and improves puncture accuracy for target HCC out-of-plane. In addition, the operative duration of robotic guidance was shorter than that of freehand guidance.

Prediction of early recurrence of hepatocellular carcinoma after liver transplantation based on computed tomography radiomics nomogram.

BACKGROUND: Early recurrence results in poor prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). This study aimed to explore the value of computed tomography (CT)-based radiomics nomogram in predicting early recurrence of patients with HCC after LT. METHODS: A cohort of 151 patients with HCC who underwent LT between December 2013 and July 2019 were retrospectively enrolled. A total of 1218 features were extracted from enhanced CT images. The least absolute shrinkage and selection operator algorithm (LASSO) logistic regression was used for dimension reduction and radiomics signature building. The clinical model was constructed after the analysis of clinical factors, and the nomogram was constructed by introducing the radiomics signature into the clinical model. The predictive performance and clinical usefulness of the three models were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Calibration curves were plotted to assess the calibration of the nomogram. RESULTS: There were significant differences in radiomics signature among early recurrence patients and non-early recurrence patients in the training cohort (P < 0.001) and validation cohort (P < 0.001). The nomogram showed the best predictive performance, with the largest area under the ROC curve in the training (0.882) and validation (0.917) cohorts. Hosmer-Lemeshow testing confirmed that the nomogram showed good calibration in the training (P = 0.138) and validation (P = 0.396) cohorts. DCA showed if the threshold probability is within 0.06-1, the nomogram had better clinical usefulness than the clinical model. CONCLUSIONS: Our CT-based radiomics nomogram can preoperatively predict the risk of early recurrence in patients with HCC after LT.

Transcriptome comparative analysis of ovarian follicles reveals the key genes and signaling pathways implicated in hen egg production.

BACKGROUND: Ovarian follicle development plays an important role in determination of poultry egg production. The follicles at the various developmental stages possess their own distinct molecular genetic characteristics and have different biological roles in chicken ovary development and function. In the each stage, several genes of follicle-specific expression and biological pathways are involved in the vary-sized follicular development and physiological events. Identification of the pivotal genes and signaling pathways that control the follicular development is helpful for understanding their exact regulatory functions and molecular mechanisms underlying egg-laying traits of laying hens. RESULTS: The comparative mRNA transcriptomic analysis of ovarian follicles at three key developmental stages including slow growing white follicles (GWF), small yellow follicles (SYF) of recruitment into the hierarchy, and differentiated large yellow follicles (LYF), was accomplished in the layers with lower and higher egg production. Totally, 137, 447, and 229 of up-regulated differentially expressed genes (DEGs), and 99, 97, and 157 of down-regulated DEGs in the GWF, SYF and LYF follicles, including VIPR1, VIPR2, ADRB2, and HSD17B1 were identified, respectively. Moreover, NDUFAB1 and GABRA1 genes, two most promising candidates potentially associated with egg-laying performance were screened out from the 13 co-expressed DEGs in the GWF, SYF and LYF samples. We further investigated the biological effects of NDUFAB1 and GABRA1 on ovarian follicular development and found that NDUFAB1 promotes follicle development by stimulating granulosa cell (GC) proliferation and decreasing cell apoptosis, increases the expression of CCND1 and BCL-2 but attenuates the expression of caspase-3, and facilitates steroidogenesis by enhancing the expression of STAR and CYP11A1. In contrast, GABRA1 inhibits GC proliferation and stimulates cell apoptosis, decreases the expression of CCND1, BCL-2, STAR, and CYP11A1 but elevates the expression of caspase-3. Furthermore, the three crucial signaling pathways such as PPAR signaling pathway, cAMP signaling pathway and neuroactive ligand-receptor interaction were significantly enriched, which may play essential roles in ovarian follicle growth, differentiation, follicle selection, and maturation. CONCLUSIONS: The current study provided new molecular data for insight into the regulatory mechanism underlying ovarian follicle development associated with egg production in chicken.

Prospective assessment of a nasopharyngeal carcinoma risk score in a population undergoing screening.

Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction.