Hypoxia-inducible factor-1α promotes macrophage functional activities in protecting hypoxia-tolerant large yellow croaker (Larimichthys crocea) against Aeromonas hydrophila infection.

The immune system requires a high energy expenditure to resist pathogen invasion. Macrophages undergo metabolic reprogramming to meet these energy requirements and immunologic activity and polarize to M1-type macrophages. Understanding the metabolic pathway switching in large yellow croaker (Larimichthys crocea) macrophages in response to lipopolysaccharide (LPS) stimulation and whether this switching affects immunity is helpful in explaining the stronger immunity of hypoxia-tolerant L. crocea. In this study, transcript levels of glycolytic pathway genes (Glut1 and Pdk1), mRNA levels or enzyme activities of glycolytic enzymes [hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase A (LDHA)], aerobic respiratory enzymes [pyruvate dehydrogenase (PDH), isocitrate dehydrogenase (IDH), and succinate dehydrogenase (SDH)], metabolites [lactic acid (LA) and adenosine triphosphate (ATP)], levels of bactericidal products [reactive oxygen species (ROS) and nitric oxide (NO)], and transcripts and level changes of inflammatory factors [IL1ß, TNFα, and interferon (IFN) γ] were detected in LPS-stimulated L. crocea head kidney macrophages. We showed that glycolysis was significantly induced, the tricarboxylic acid (TCA) cycle was inhibited, and metabolic reprogramming occurred, showing the Warburg effect when immune cells were activated. To determine the potential regulatory mechanism behind these changes, LcHIF-1α was detected and found to be significantly induced and transferred to the nucleus after LPS stimulation. LcHif-1α interference led to a significant reduction in glycolytic pathway gene transcript expression, enzyme activity, metabolites, bactericidal substances, and inflammatory factor levels; a significant increase in the aerobic respiration enzymes; and decreased migration, invasion, and phagocytosis. Further ultrastructural observation by electron microscopy showed that fewer microspheres contained phagocytes and that more cells were damaged after LcHif-1α interference. LcHif-1α overexpression L. crocea head kidney macrophages showed the opposite trend, and promoter activities of Ldha and Il1ß were significantly enhanced after LcHif-1α overexpression in HEK293T cells. Our data showed that LcHIF-1α acted as a metabolic switch in L. crocea macrophages and was important in polarization. Hypoxia-tolerant L. crocea head kidney showed a stronger Warburg effect and inhibited the TCA cycle, higher metabolites, and bactericidal substance levels. These results collectively revealed that LcHif-1α may promote the functional activities of head kidney macrophages in protecting hypoxia-tolerant L. crocea from Aeromonas hydrophila infection.

[The surgical outcomes in management of jugular foramen paragangliomas with tension free anterior rerouting of the facial never and tunnel packing of the inferior petrous sinus].

Objective:The aim of this study is to evaluate the safety and efficacy of surgical interventions ofjugular foramen paragangliomas（JFP） utilizing modified surgical techniques, tensionfree anterior rerouting of the facial nerve and tunnel-packing or push-packing of the inferior petrous sinus. Methods:A retrospective analysis was conducted on a cohort of 88 patients diagnosed with JFP and treated at the Eye Ear Nose and Throat Hospital of Fudan University（in Shanghai, China） from October 2010 to June 2021. The surgical outcomes were analyzed for tumor classification, intraoperative conditions, and function of the postoperative facial nerve（FN） and lower cranial nerve（LCN）. Results:The study included a total of 88 patients, gross total resection was achieved in 70 patients（79.5%）, near total resection was obtained in 17 patients（19.3%）, and one patient undergoing subtotal resection. The average of intraoperative blood loss was 448.3 mL. Additionally, 24 patients underwent surgical total anterior rerouting（TAR）, 18 patients underwent surgical total FN tension free anterior rerouting（TF-TAR）, and 18 patients underwent surgical FN partial FN tension free anterior rerouting（TF-PAR）. Good postoperative FN function（House-Brackmann Ⅰ-Ⅱ） was achieved in 62.5% of TAR group. In the TF-TAR and PF_TAR groups, good postoperative FN function was demonstrated in 88.9% patients. It showed a significantly improvement of the FN function following application of tension-free FN anterior rerouting technique（P=0.007）. Twenty patients（22.7%） suffered from at least one LCN deficit in the preoperative evaluation. The postoperative LCN deficits was correlated with the Fisch classification of tumors, which showed a lower incidence of LCN dysfunction in classes C1-C2（4.9%, 2/41cases） and poorer outcomes of LCN dysfunction in classes C3-D（8.5%,4/47cases ）, it was likely less impacted the LCN function in the early stage tumor. Conclusion:The application of modified surgical techniques of FN tension-free anterior rerouting and tunnel-packing of the inferior petrous sinus has been shown to effectively preserve the function of the FN and LCN, decrease intraoperative blood loss, and ultimately improve patients' postoperative quality of life.

Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics.

PD-L1 is overexpressed on the surface of tumor cells and binds to PD-1, resulting in tumor immune escape. Therapeutic strategies to target the PD-1/PD-L1 pathway involve blocking the binding. Immune checkpoint inhibitors have limited efficacy against tumors because PD-L1 is also present in the cytoplasm. PD-L1 of post-translational modifications (PTMs) have uncovered numerous mechanisms contributing to carcinogenesis and have identified potential therapeutic targets. Therefore, small molecule inhibitors can block crucial carcinogenic signaling pathways, making them a potential therapeutic option. To better develop small molecule inhibitors, we have summarized the PTMs of PD-L1. This review discusses the regulatory mechanisms of small molecule inhibitors in carcinogenesis and explore their potential applications, proposing a novel approach for tumor immunotherapy based on PD-L1 PTM.

[Box: see text].

The intrabulbar or extrabulbar growth pattern and its surgical outcomes of jugular foramen paragangliomas.

OBJECTIVE: This study is to define a subclassification system of jugular foramen paragangliomas (JFPs) and to demonstrate corresponding microsurgical outcomes of JFPs. STUDY DESIGN: Retrospective study. SETTING: A single-center study. METHODS: We conducted a retrospective review of the clinical data of 44 patients with JFPs who underwent surgical management. Extrabulbar(Be) tumor and intrabulbar(Bi) tumor are defined based on the growth patterns, receiver operating characteristic (ROC) curves of the imaging profile were generated and was confirmed based on intraoperative findings. Area Under Curve (AUC), accuracy, sensitivity, and specificity for diagnostic imaging were revealed. We also compared the correlation between the two growth patterns with Fisch's classification, blood loss, lower cranial nerves (LCNs) deficit. RESULTS: There are 27 (69%) cases of Bi tumor and 17 (39%) cases of Be tumor. Significant radiomics features between the two growth patterns were demonstrated, ROC curves achieved excellent AUCs for MRI sequences (T1W1 MRI, MR contrast-enhanced sequence, MR complex sequences and MR complex + DSA by 0.833, 0.833, 0.875, 0.944) and had statistically significant in diagnosis of two growth patterns (P<0.05). There was no statistical correlation between growth patterns of JFPs and intra-operative blood loss. Preoperative LCNs deficits and Fisch's classification of tumors were correlated with the growth patterns of JFPs (P < 0.05). CONCLUSION: We proposetd two growth patterns of JFPs in term of the inferior petrous sinus involvement. Identification of Bi or Be growth patterns preoperatively is helpful to design optimal surgical strategies and minimize postoperative complications.

Brusatol alleviates pancreatic carcinogenesis via targeting NLRP3 in transgenic Krastm4Tyj Trp53tm1Brn Tg (Pdx1-cre/Esr1*) #Dam mice.

BACKGROUND: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored. METHODS: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Krastm4TyjTrp53tm1BrnTg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model. RESULTS: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression. CONCLUSIONS: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa.

Acesulfame potassium triggers inflammatory bowel disease via the inhibition of focal adhesion pathway.

Acesulfame potassium (ACK) was generally regarded as innocuous and extensively ingested. Nevertheless, ACK has recently gained attention as a burgeoning pollutant that has the potential to induce a range of health hazards, particularly to the digestive system. Herein, we uncover that ACK initiates inflammatory bowel disease (IBD) in mice and zebrafish, as indicated by the aggregation of macrophages in the intestine and the inhibition of intestinal mucus secretion. Transcriptome analysis of mice and zebrafish guts revealed that exposure to ACK typically impacts the cell cycle, focal adhesion, and PI3K-Akt signaling pathways. Using pharmacological approaches, we demonstrate that the PI3K-Akt signaling pathway and the generation of reactive oxygen species (ROS) triggered by cell division are not significant factors in the initiation of IBD caused by ACK. Remarkably, inhibition of the focal adhesion pathway is responsible for the IBD onset induced by ACK. Our results indicate the detrimental impacts and possible underlying mechanisms of ACK on the gastrointestinal system and provide insights for making informed choices about everyday dietary habits.

Spatial Transcriptome-Wide Profiling of Small Cell Lung Cancer Reveals Intra-Tumoral Molecular and Subtype Heterogeneity.

Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth and early metastasis and is susceptible to treatment resistance and recurrence. Understanding the intra-tumoral spatial heterogeneity in SCLC is crucial for improving patient outcomes and clinically relevant subtyping. In this study, a spatial whole transcriptome-wide analysis of 25 SCLC patients at sub-histological resolution using GeoMx Digital Spatial Profiling technology is performed. This analysis deciphered intra-tumoral multi-regional heterogeneity, characterized by distinct molecular profiles, biological functions, immune features, and molecular subtypes within spatially localized histological regions. Connections between different transcript-defined intra-tumoral phenotypes and their impact on patient survival and therapeutic response are also established. Finally, a gene signature, termed ITHtyper, based on the prevalence of intra-tumoral heterogeneity levels, which enables patient risk stratification from bulk RNA-seq profiles is identified. The prognostic value of ITHtyper is rigorously validated in independent multicenter patient cohorts. This study introduces a preliminary tumor-centric, regionally targeted spatial transcriptome resource that sheds light on previously unexplored intra-tumoral spatial heterogeneity in SCLC. These findings hold promise to improve tumor reclassification and facilitate the development of personalized treatments for SCLC patients.

[Anti-tumor mechanism of total saponins of Paridis Rhizoma on inducing ferroptosis of breast cancer MCF-7 cells].

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

An Improved Staging System of Adenoid Cystic Carcinoma in the External Auditory Canal.

OBJECTIVE: The purpose of this study was to define an improved staging system for adenoid cystic carcinoma (ACC) in the external auditory canal (EAC) based on biological behaviors, image findings, and the prognosis of patients with ACC in the EAC. STUDY DESIGN: A retrospective study. SETTING: A single center data. METHODS: We performed a single-institution retrospective review of 154 patients with ACC in the EAC between January 2004 and September 2021. Risk factors associated with disease-free survival (DFS) and cancer-specific survival (CSS) of ACC in the EAC were identified using univariate and multivariate cox regression analysis. Then an improved staging system was proposed and compared with the Pittsburgh-modified tumor, node, and metastasis (TNM) staging system for statistical differences in DFS and CSS. RESULTS: An improved staging system of ACC in the EAC was defined, in which stage T4 were subclassified into T4a and T4b and were statistically different from the Pittsburgh-modified TNM staging system in DFS and CSS. We also found that the dura mater, facial nerve, sigmoid sinus, deep lobe of parotid gland, and parapharyngeal space involvement were significantly associated with poor prognosis of ACC in the EAC. CONCLUSION: The improved staging system is more accurate in predicting survival prognosis than Pittsburgh-modified TNM staging system for patients with ACC in the EAC, and may provide more efficient guidance of treatment strategy. SUMMARY: The improved staging system of ACC in the EAC is more accurately to predict survival prognosis, and provide guidance of treatment plan than Pittsburgh-modified TNM staging system.

ITPRIPL1 binds CD3ε to impede T cell activation and enable tumor immune evasion.

Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical "signal one" phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.

A Novel Classification System and Surgical Strategies of First Branchial Cleft Anomalies.

OBJECTIVE: To define a novel classification of first branchial cleft anomalies (FBCAs) based on the relationship between lesions and the facial nerve in terms of radiographic imaging findings and to introduce the corresponding surgical managements. METHODS: The clinical data were retrospectively reviewed. Novel classification was proposed according to the head-neck MRI findings and surgical records. FBCAs limited in the cartilaginous segment of external auditory canal (EAC) or superficial parotid gland capsule were classified as type A. Lesions close to the FN and(or) involved into the parotid gland with no scar formation and no previous parotidectomy were classified as type B. FBCAs adhered to the FN and(or) invaded the parotid gland with scar formation due to previous surgery were classified as type C. Appropriate surgery approaches was also described, which was correlated with classification. RESULTS: Fifty-one patients were included, and one patient suffered from bilateral lesions. Thirty-one, twelve, and nine lesions were classified as type A, type B, and type C FBCAs, respectively. One type A patient (1.92%) suffered from recurrence during follow-up. Temporary facial palsy (House-Brackmann II) was identified in 2 type C patients (3.85%) after surgery and recovered to normal within 2 months. One type B patient (1.92%) suffered from facial paralysis due to the FN injury and underwent facial nerve graft simultaneously. No patients with type C complained of hearing loss postoperatively. CONCLUSION: This novel classification clearly illustrates definitely relationship between lesion and the facial nerve and appropriate surgical strategies were proposed based on the novel classification. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Effect of synthesis temperature on the structural morphology of a metal-organic framework and the capacitor performance of derived cobalt-nickel layered double hydroxides.

Three-dimensional interconnected nickel-cobalt layered double hydroxides (NiCo-LDHs) were prepared on nickel foam by ion exchange using a cobalt-based metal-organic framework (Co-MOF) as a template at different temperatures. The effects of the Co-MOF preparation temperature on the growth, mass, morphology, and electrochemical properties of the Co-MOF and derived NiCo-LDH samples were studied. The synthesis temperature from 30 to 50 °C gradually increased the mass of the active material and the thickness of the Co-MOF sheets grown on the nickel foam. The higher the temperature is, the larger the proportion of Co3+. ß-Cobalt hydroxide (ß-Co(OH)2) sheets were generated above 60 °C. The morphology and mass loading pattern of the derived flocculent layer clusters of NiCo-LDH were inherited from metal-organic frameworks (MOFs). The areal capacitance of NiCo-LDH shows an inverted U-shaped curve trend with increasing temperature. The electrode material synthesized at 50 °C had a tremendous specific capacitance of 7631 mF·cm-2 at a current density of 2 mA·cm-2. The asymmetric supercapacitor assembled with the sample and active carbon (AC) achieved an energy density of 55.0 Wh·kg-1 at a power density of 800.0 W·kg-1, demonstrating the great potential of the NiCo-LDH material for energy storage. This work presents a new strategy for designing and fabricating advanced green supercapacitor materials with large power and energy densities.

Prediction of prognosis and treatment response in ovarian cancer patients from histopathology images using graph deep learning: a multicenter retrospective study.

BACKGROUND: Ovarian cancer (OV) is a prevalent and deadly disease with high mortality rates. The development of accurate prognostic tools and personalized therapeutic strategies is crucial for improving patient outcomes. METHODS: A graph-based deep learning model, the Ovarian Cancer Digital Pathology Index (OCDPI), was introduced to predict prognosis and response to adjuvant therapy using hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). The OCDPI was developed using formalin-fixed, paraffin-embedded (FFPE) WSIs from the TCGA-OV cohort, and was externally validated in two independent cohorts from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and Harbin Medical University Cancer Hospital (HMUCH). RESULTS: The OCDPI showed prognostic ability for overall survival prediction in the PLCO (HR, 1.916; 95% CI, 1.380-2.660; log-rank test, P < 0.001) and HMUCH (HR, 2.796; 95% CI, 1.404-5.568; log-rank test, P = 0.0022) cohorts. Patients with low OCDPI experienced better survival benefits and lower recurrence rates following adjuvant therapy compared to those with high OCDPI. Multivariable analyses, adjusting for clinicopathological factors, consistently identified OCDPI as an independent prognostic factor across all cohorts (all P < 0.05). Furthermore, OCDPI performed well in patients with low-grade tumors or fresh-frozen slides, and could differentiate between HRD-deficient or HRD-intact patients with and without sensitivity to adjuvant therapy. CONCLUSION: The results from this multicenter cohort study indicate that the OCDPI may serve as a valuable and labor-saving tool to improve prognostic and predictive clinical decision-making in patients with OV.

Histopathology images-based deep learning prediction of prognosis and therapeutic response in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer characterized by rapid tumor growth and early metastasis. Accurate prediction of prognosis and therapeutic response is crucial for optimizing treatment strategies and improving patient outcomes. In this study, we conducted a deep-learning analysis of Hematoxylin and Eosin (H&E) stained histopathological images using contrastive clustering and identified 50 intricate histomorphological phenotype clusters (HPCs) as pathomic features. We identified two of 50 HPCs with significant prognostic value and then integrated them into a pathomics signature (PathoSig) using the Cox regression model. PathoSig showed significant risk stratification for overall survival and disease-free survival and successfully identified patients who may benefit from postoperative or preoperative chemoradiotherapy. The predictive power of PathoSig was validated in independent multicenter cohorts. Furthermore, PathoSig can provide comprehensive prognostic information beyond the current TNM staging system and molecular subtyping. Overall, our study highlights the significant potential of utilizing histopathology images-based deep learning in improving prognostic predictions and evaluating therapeutic response in SCLC. PathoSig represents an effective tool that aids clinicians in making informed decisions and selecting personalized treatment strategies for SCLC patients.

The Role of Parotid Gland Invasion in Adenoid Cystic Carcinoma of the External Auditory Canal.

OBJECTIVE: This study aimed to investigate the significance of parotid gland invasion in predicting distant metastasis of adenoid cystic carcinoma in the external auditory canal. STUDY DESIGN: Single-institution retrospective cohort study. METHODS: A retrospective review of patients with adenoid cystic carcinoma of the external auditory canal who underwent surgery was performed. Information on patient demographics, parotid gland invasion, tumor stage, perineural invasion, lymphovascular invasion, and follow-up data were collected and analyzed. RESULTS: One hundred twenty-nine patients were identified for review. Parotid gland invasion was noted in 45 patients (34.9%). Parotid gland invasion was significantly associated with tumor stage, perineural invasion, distant metastasis, and postoperative adjuvant therapy. Distant metastasis was noted in 30 patients (23.3%). Multivariate Cox proportional hazards analysis identified parotid gland invasion as an independent risk factor for predicting distant metastasis. The 5-year distant metastasis-free survival rate was 83.6% for patients without parotid gland invasion and 61.8% for patients with parotid gland invasion (p = 0.010). CONCLUSIONS: The parotid gland invasion rate is relatively high in adenoid cystic carcinoma of the external auditory canal and is significantly related to tumor stage. Parotid gland invasion is associated with worse distant metastasis-free survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:419-425, 2024.

Conductive and Eco-friendly Biomaterials-based Hydrogels for Noninvasive Epidermal Sensors: A Review.

As noninvasive wearable electronic devices, epidermal sensors enable continuous, real-time, and remote monitoring of various human physiological parameters. Conductive biomaterials-based hydrogels as sensor matrix materials have good biocompatibility, biodegradability, and efficient stimulus response capabilities and are widely applied in motion monitoring, healthcare, and human-machine interaction. However, biomass hydrogel-based epidermal sensing devices still need excellent mechanical properties, prolonged stability, multifunctionality, and extensive practicality. Therefore, this paper reviews the common biomass hydrogel materials for epidermal sensing (proteins, polysaccharides, polyphenols, etc.) and the various types of noninvasive sensing devices (strain/pressure sensors, temperature sensors, glucose sensors, electrocardiograms, etc.). Moreover, this review focuses on the strategies of scholars to enhance sensor properties, such as strength, conductivity, stability, adhesion, and self-healing ability. This work will guide the preparation and optimization of high-performance biomaterials-based hydrogel epidermal sensors.

Wearable Gas Sensor Based on Reticular Antimony-Doped SnO2/PANI Nanocomposite Realizing Intelligent Detection of Ammonia within a Wide Range of Humidity.

Wearable gas sensors demonstrate broad potential for environmental monitoring and breath analysis applications. Typically, they require a highly stable and high-performance flexible gas sensing unit that can work with a small, flexible circuit to enable real-time accurate concentration analysis and prediction. This work proposes a flexible gas sensor using antimony-doped tin dioxide composite polyaniline as the sensing material for room-temperature ammonia detection over a wide humidity range. The sensor exhibits high sensitivity (response value at 33.1 toward 100 ppm ammonia at 70% relative humidity), excellent selectivity, and good long-term and mechanical stability. The increased sensitivity is due to a reduction in the hole concentration of polyaniline in air, achieved through compositing and doping. Subsequently, regression analysis equations are developed to establish the relationship between the gas concentration and sensor response under varying environmental humidity conditions. The sensor was integrated with a small, low-power circuit module to form a wearable smart bracelet with signal acquisition, processing, and wireless transmission functions, which could achieve early and remote warning of gas leakage in different humidity environments. This research demonstrates a promising approach to designing high-performance, high-stability, and flexible gas sensors and their corresponding wireless sensing systems.

Correlation between preoperative Doppler ultrasonography-assessed specific accessory cephalic vein diameter-cephalic vein diameter ratio (r) and early dysfunction of Radial artery-Cephalic vein arteriovenous fistula: a single-center cross-sectional study.

Background: Accessory cephalic vein (ACV) ligation can circumvent immature arteriovenous fistula (AVF). However, no consensus has been reached on the definite timing of ACV ligation. This study aimed to retrospectively analyze the correlation between preoperative Doppler ultrasonography (DUS)-assessed specific ACV diameter-cephalic vein diameter ratio (r) and early dysfunction of Radial artery-Cephalic vein (RC)-AVF in order to improve the early maturity rate of RC-AVF. Methods: A total of 258 patients who underwent RC-AVF at The Third Affiliated Hospital, Sun Yat-sen University from 1 June 2018 to 31 March 2022 were included in this study. The inclusion criteria were as follows: (I) cephalic vein ≥2.0 mm and radial artery ≥1.5 mm, suitable for RC-AVF establishment; (II) presence of an ACV. As per the specific r determined using preoperative DUS assessment, all patients were classified into two groups: Group A (r<0.8) and Group B (r≥0.8). Furthermore, patients in each group were divided into intervention and non-intervention subgroups based on the presence or absence of intraoperative ACV ligation, respectively. Patient data including age, sex, underlying disease, AVF side, and radial diameter were compared. The difference of maturity rate between participants in the intervention group and non-intervention group with different r values was analyzed, so as to obtain the relationship between different r values and maturity rate. Results: No statistical differences were observed between the intervention and non-intervention subgroups in the two groups in terms of sex, age, comorbidities, complications, AVF side, radial artery, cephalic vein, and ACV diameters (P>0.05). When r<0.8, the maturity rates of the intervention group and the non-intervention group were 80% and 92.98%, respectively, χ2=4.561. The difference in maturation rate between the intervention and non-intervention subgroups was insignificant (P=0.075) when r<0.8. When r≥0.8, the maturity rates of the intervention group and the non-intervention group were 89.83% and 45.45%, respectively, χ2=25.943. The difference in maturation rates between the intervention and non-intervention subgroups was significant when r≥0.8 (P<0.001). Conclusions: Preoperative DUS suggested a correlation between r≥0.8 and early immaturity of RC-AVF. Therefore, concurrent intraoperative ACV ligation should be carried out when preoperative r is ≥0.8, as it may reduce the early power dysfunction of RC-AVF.

SAIF plays anti-angiogenesis via blocking VEGF-VEGFR2-ERK signal in tumor treatment.

Shark cartilage was created as a cancer-fighting diet because it was believed to have an element that may suppress tumor growth. Due to overfishing, sharks have become endangered recently, making it impossible to harvest natural components from shark cartilage for therapeutic development research. Previously, we identified a peptide SAIF from shark cartilage with an-tiangiogenic and anti-tumor effects, successfully expressed it in Escherichia coli by using genetic engineering techniques. However, we did not elucidate the specific target of SAIF and its antiangiogenic molecular mechanism, which hindered its further drug development. Therefore, in this work, the exact mechanism of action was studied using various techniques, including cellular and in vivo animal models, computer-aided simulation, molecular target capture, and transcriptome sequencing analysis. With VEGF-VEGFR2 interaction and preventing the activation of VEGFR2/ERK signaling pathways, SAIF was discovered to decrease angiogenesis and hence significantly limit tumor development. The findings further demonstrated SAIF's strong safety and pharmaceutically potential. The evidence showed that SAIF, which is expressed by, is a potent and safe angiogenesis inhibitor and might be developed as a candidate peptide drug for the treatment of solid tumors such as hepatocellular carcinoma and other conditions linked with angiogenic overgrowth.

Multi-omics Deep-learning Prediction of Homologous Recombination Deficiency-like Phenotype Improved Risk Stratification and Guided Therapeutic Decisions in Gynecological Cancers.

Homologous recombination deficiency (HRD) is a well-recognized important biomarker in determining the clinical benefits of platinum-based chemotherapy and PARP inhibitor therapy for patients diagnosed with gynecologic cancers. Accurate prediction of HRD phenotype remains challenging. Here, we proposed a novel Multi-Omics integrative Deep-learning framework named MODeepHRD for detecting HRD-positive phenotype. MODeepHRD utilizes a convolutional attention autoencoder that effectively leverages omics-specific and cross-omics complementary knowledge learning. We trained MODeepHRD on 351 ovarian cancer (OV) patients using transcriptomic, DNA methylation and mutation data, and validated it in 2133 OV samples of 22 datasets. The predicted HRD-positive tumors were significantly associated with improved survival (HR = 0.68; 95% CI, 0.60-0.77; log-rank p < 0.001 for meta-cohort; HR = 0.5; 95% CI, 0.29-0.86; log-rank p = 0.01 for ICGC-OV cohort) and higher response to platinum-based chemotherapy compared to predicted HRD-negative tumors. The translational potential of MODeepHRDs was further validated in multicenter breast and endometrial cancer cohorts. Furthermore, MODeepHRD outperforms conventional machine-learning methods and other similar task approaches. In conclusion, our study demonstrates the promising value of deep learning as a solution for HRD testing in the clinical setting. MODeepHRD holds potential clinical applicability in guiding patient risk stratification and therapeutic decisions, providing valuable insights for precision oncology and personalized treatment strategies.