Development and biomechanical analysis of an axially controlled compression spinal rod for lumbar spondylolysis.

BACKGROUND: To elucidate the differences in mechanical performance between a novel axially controlled compression spinal rod (ACCSR) for lumbar spondylolysis (LS) and the common spinal rod (CSR). METHODS: A total of 36 ACCSRs and 36 CSRs from the same batch were used in this study, each with a diameter of 6.0 mm. Biomechanical tests were carried out on spinal rods for the ACCSR group and on pedicle screw-rod internal fixation systems for the CSR group. The spinal rod tests were conducted following the guidelines outlined in the American Society for Testing and Materials (ASTM) F 2193, while the pedicle screw-rod internal fixation system tests adhered to ASTM F 1798-97 standards. RESULTS: The stiffness of ACCSR and CSR was 1559.15 ±â€…50.15 and 3788.86 ±â€…156.45 N/mm (P < .001). ACCSR's yield load was 1345.73 (1297.90-1359.97) N, whereas CSR's was 4046.83 (3805.8-4072.53) N (P = .002). ACCSR's load in the 2.5 millionth cycle of the fatigue four-point bending test was 320 N. The axial gripping capacity of ACCSR and CSR was 1632.53 ±â€…165.64 and 1273.62 ±â€…205.63 N (P = .004). ACCSR's torsional gripping capacity was 3.45 (3.23-3.47) Nm, while CSR's was 3.27 (3.07-3.59) Nm (P = .654). The stiffness of the pedicle screws of the ACCSR and CSR group was 783.83 (775.67-798.94) and 773.14 (758.70-783.62) N/mm (P = .085). The yield loads on the pedicle screws of the ACCSR and CSR group was 1345.73 (1297.90-1359.97) and 4046.83 (3805.8-4072.53) N (P = .099). CONCLUSION: Although ACCSR exhibited lower yield load, stiffness, and fatigue resistance compared to CSR, it demonstrated significantly higher axial gripping capacity and met the stress requirement of the human isthmus. Consequently, ACCSR presents a promising alternative to CSR for LS remediation.

Deep Learning Radiomics Model of Contrast-Enhanced CT for Differentiating the Primary Source of Liver Metastases.

RATIONALE AND OBJECTIVES: To develop and validate a deep learning radiomics (DLR) model based on contrast-enhanced computed tomography (CT) to identify the primary source of liver metastases. MATERIALS AND METHODS: In total, 657 liver metastatic lesions, including breast cancer (BC), lung cancer (LC), colorectal cancer (CRC), gastric cancer (GC), and pancreatic cancer (PC), from 428 patients were collected at three clinical centers from January 2018 to October 2023 series. The lesions were randomly assigned to the training and validation sets in a 7:3 ratio. An additional 112 lesions from 61 patients at another clinical center served as an external test set. A DLR model based on contrast-enhanced CT of the liver was developed to distinguish the five pathological types of liver metastases. Stepwise classification was performed to improve the classification efficiency of the model. Lesions were first classified as digestive tract cancer (DTC) and non-digestive tract cancer (non-DTC). DTCs were divided into CRC, GC, and PC and non-DTCs were divided into LC and BC. To verify the feasibility of the DLR model, we trained classical machine learning (ML) models as comparison models. Model performance was evaluated using accuracy (ACC) and area under the receiver operating characteristic curve (AUC). RESULTS: The classification model constructed by the DLR algorithm showed excellent performance in the classification task compared to ML models. Among the five categories task, highest ACC and average AUC were achieved at 0.563 and 0.796 in the validation set, respectively. In the DTC and non-DTC and the LC and BC classification tasks, AUC was achieved at 0.907 and 0.809 and ACC was achieved at 0.843 and 0.772, respectively. In the CRC, GC, and PC classification task, ACC and average AUC were the highest, at 0.714 and 0.811, respectively. CONCLUSION: The DLR model is an effective method for identifying the primary source of liver metastases.

Trilaciclib dosage in Chinese patients with extensive-stage small cell lung cancer: a pooled pharmacometrics analysis.

This study aimed to analyze potential ethnic disparities in the dose-exposure-response relationships of trilaciclib, a first-in-class intravenous cyclin-dependent kinase 4/6 inhibitor for treating chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer (ES-SCLC). This investigation focused on characterizing these relationships in both Chinese and non-Chinese patients to further refine the dosing regimen for trilaciclib in Chinese patients with ES-SCLC. Population pharmacokinetic (PopPK) and exposure-response (E-R) analyses were conducted using pooled data from four randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC. PopPK analysis revealed that trilaciclib clearance in Chinese patients was approximately 17% higher than that in non-Chinese patients with ES-SCLC. Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact. E-R analysis demonstrated that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m2, without notable changes in myeloprotective or antitumor efficacy. However, the incidence of infusion site reactions, headaches, and phlebitis/thrombophlebitis rose with increasing trilaciclib exposure in both Chinese and non-Chinese patients with ES-SCLC. These findings suggest no substantial ethnic disparities in the dose-exposure-response relationship between Chinese and non-Chinese patients. They support the adoption of a 240-mg/m2 intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.

Superionic fluoride gate dielectrics with low diffusion barrier for two-dimensional electronics.

Exploration of new dielectrics with a large capacitive coupling is an essential topic in modern electronics when conventional dielectrics suffer from the leakage issue near the breakdown limit. Here, to address this looming challenge, we demonstrate that rare-earth metal fluorides with extremely low ion migration barriers can generally exhibit an excellent capacitive coupling over 20 µF cm-2 (with an equivalent oxide thickness of ~0.15 nm and a large effective dielectric constant near 30) and great compatibility with scalable device manufacturing processes. Such a static dielectric capability of superionic fluorides is exemplified by MoS2 transistors exhibiting high on/off current ratios over 108, ultralow subthreshold swing of 65 mV dec-1 and ultralow leakage current density of ~10-6 A cm-2. Therefore, the fluoride-gated logic inverters can achieve notably higher static voltage gain values (surpassing ~167) compared with a conventional dielectric. Furthermore, the application of fluoride gating enables the demonstration of NAND, NOR, AND and OR logic circuits with low static energy consumption. In particular, the superconductor-insulator transition at the clean-limit Bi2Sr2CaCu2O8+δ can also be realized through fluoride gating. Our findings highlight fluoride dielectrics as a pioneering platform for advanced electronic applications and for tailoring emergent electronic states in condensed matter.

Magnetic field-assisted surface engineering technology for active regulation of Fe3O4 medium to enable the laccase electrochemical biosensing of catechol with visible stripe patterns.

BACKGROUND: Catechol (CC), a prevalent phenolic compound, is a byproduct in various agricultural, chemical, and industrial processes. CC detection is crucial for safeguarding water quality and plays a pivotal role in enhancing the overall quality of life of individuals. Electrochemical biosensors exhibit rapid responses, have small sizes, and can be used for real-time monitoring. Therefore, the development of a fast and sensitive electrochemical biosensor for CC detection is crucial. RESULT: In this study, a laccase-based electrochemical biosensor for detection of CC is successfully developed using Fe3O4 nanoparticles as medium and optimized by applying a magnetic field. This research proposes a unique strategy for biosensor enhancement by actively controlling the distribution of magnetic materials on the electrode surface through the application of a magnetic field, resulting in a visibly alternating stripe pattern. This approach effectively disperses magnetic particles, preventing their aggregation and reducing the boundary layer thickness, enhancing the electrochemical response of the biosensor. After fabrication condition optimization, CC is successfully detected using this biosensor. The fabricated sensor exhibits excellent performance with a wide linear detection range of 10-1000 µM, a low detection limit of 1.25 µM, and a sensitivity of 7.9 µA/mM. The fabricated sensor exhibits good selectivity and reliable detection in real water samples. In addition, the laccase-based sensor has the potential for the fast and accurate monitoring of CC in olive oil. SIGNIFICANCE: The magnetic field optimization in this study significantly improved the performance of the electrochemical biosensor for detecting CC in environmental samples. Overall, the sensor developed in this study has the potential for fast and accurate monitoring of CC in environmental samples, highlighting the potential importance of a magnetic field environment in improving the performance of catechol electrochemical biosensors.

Ultrasonic-assisted green extraction and incorporation of Spirulina platensis bioactive components into turmeric essential oil-in-water nanoemulsion for enhanced antioxidant and antimicrobial activities.

The utilization of essential oils as natural antioxidants and preservatives is limited by high volatility, poor water solubility, and long-term instability. To address this, a novel ultrasonic-assisted method was used to prepare and stabilize a nanoemulsion of turmeric essential oil-in-water, incorporating bioactive components extracted from Spirulina platensis. Ultrasonic treatment enhanced the extraction efficacy and nanoemulsion stability. Algal biomass subjected to ultrasonic treatment (30 min at 80% amplitude) yielded a dry extract of 73.66 ± 3.05%, with the highest protein, phenolic, phycocyanin, and allophycocyanin content, as well as maximum emulsifying activity. The resulting nanoemulsion (5% oil, 0.3% extract, 10 min ultrasonic treatment) showed reduced particle size (173.31 ± 2.24 nm), zeta potential (-36.33 ± 1.10 mV), low polydispersity index, and enhanced antioxidant and antibacterial properties. Rheology analysis indicated shear-thinning behavior, while microscopy and spectroscopy confirmed structural changes induced by ultrasonic treatment and extract concentration. This initiative developed a novel ultrasonic-assisted algal-based nanoemulsion with antioxidant and antibacterial properties.

The association of impulsivity with depression and anxiety symptoms: A transdiagnostic network analysis and replication.

BACKGROUND: Impulsivity increases the risk for depression and anxiety. However, the granular pathways among them remain unknown. A network approach that moves from disorder-level analysis to symptom-level analysis can provide further understanding of psychopathological mechanisms. In this study, we examined the network structure of impulsivity and separate and comorbid symptoms of depression and anxiety. METHODS: Regularized partial-correlation networks were estimated using cross-sectional data from 1047 Chinese participants aged 18-26 years (main dataset, mean age = 21.45 ± 2.01 years) and 325 Chinese participants aged 18-36 years (an independent replication dataset, mean age = 21.49 ± 3.73 years), including impulsivity-depression, impulsivity-anxiety, and impulsivity-depression-anxiety networks. The datasets were collected from 1 June 2023 to 4 August 2023 and from 27 April 2022 to 16 May 2022, respectively. Impulsivity, depression, and anxiety were assessed using Barratt Impulsiveness Scale Version 11, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, respectively. Bridge centrality was analyzed, and a network comparison test (NCT) was conducted to investigate the differences between the main dataset and replication dataset. RESULTS: The motor impulsivity dimension was revealed to be closely connected with individual symptoms of depression and anxiety regardless of whether they were in separate disorder forms or comorbid forms. In all the networks, motor impulsivity was the most important bridge node. The NCT showed comparable network connectivity and network structure between the main and replication datasets. LIMITATIONS: The use of cross-sectional data limited the inferences about the direction of causality between variables. CONCLUSIONS: These findings elucidate the psychopathological mechanisms underlying how impulsivity functions within depression, anxiety, and comorbidity and support that motor impulsivity is an important risk factor across different mental disorders and is responsible for comorbidity. The implications of these findings are discussed.

Establishment of a two-hit mouse model of environmental factor induced autism spectrum disorder.

Autism spectrum disorder (ASD) is a group of developmental diseases characterized by social dysfunction and repetitive stereotype behaviors. Besides genetic mutations, environmental factors play important roles in the development of ASD. Valproic acid (VPA) is widely used for modeling environmental factor induced ASD in rodents. However, traditional VPA modeling is low-in-efficiency and the phenotypes often vary among different batches of experiments. To optimize this ASD-modeling method, we tested "two-hit" hypothesis by single or double exposure of VPA and poly:IC at the critical time points of embryonic and postnatal stage. The autistic-like behaviors of mice treated with two-hit schemes (embryonic VPA plus postnatal poly:IC, embryonic poly:IC plus postnatal VPA, embryonic VPA plus poly: IC, or postnatal VPA plus poly:IC) were compared with mice treated with traditional VPA protocol. The results showed that all single-hit and two-hit schemes produced core ASD phenotypes as VPA single treatment did. Only one group, namely, mice double-hit by VPA and poly:IC simultaneously at E12.5 showed severe impairment of social preference, social interaction and ultrasonic communication, as well as significant increase of grooming activity and anxiety-like behaviors, in comparation with mice treated with the traditional VPA protocol. These data demonstrated that embryonic two-hit of VPA and poly:IC is more efficient in producing ASD phenotypes in mice than the single-hit of VPA, indicating this two-hit scheme could be utilized for modeling environmental factors induced ASD.

Region of Interest Detection in Melanocytic Skin Tumor Whole Slide Images - Nevus & Melanoma.

Automated region of interest detection in histopathological image analysis is a challenging and important topic with tremendous potential impact on clinical practice. The deep-learning methods used in computational pathology may help us to reduce costs and increase the speed and accuracy of cancer diagnosis. We started with the UNC Melanocytic Tumor Dataset cohort that contains 160 hematoxylin and eosin whole-slide images of primary melanomas (86) and nevi (74). We randomly assigned 80% (134) as a training set and built an in-house deep-learning method to allow for classification, at the slide level, of nevi and melanomas. The proposed method performed well on the other 20% (26) test dataset; the accuracy of the slide classification task was 92.3% and our model also performed well in terms of predicting the region of interest annotated by the pathologists, showing excellent performance of our model on melanocytic skin tumors. Even though we tested the experiments on the skin tumor dataset, our work could also be extended to other medical image detection problems to benefit the clinical evaluation and diagnosis of different tumors.

Prenatal ultrasound findings and clinical outcomes of uniparental disomy: a retrospective study.

BACKGROUND: Uniparental disomy is the inheritance of a homologous chromosome pair or part of homologous chromosomes from only one parent. However, the clinical significance of uniparental disomy and the difference among the prognosis of involvement of different chromosomes remain unclear. OBJECTIVE: To assess the associated prenatal ultrasound presentations and clinical outcomes of uniparental disomy on different chromosomes and to analyze the relationship between prenatal ultrasound markers and clinical outcomes. STUDY DESIGN: We retrospectively analyzed data from fetuses with uniparental disomy diagnosed using chromosome microarray analysis with the Affymetrix CytoScan HD array at our institution between January 2013 and September 2022. The relationship between prenatal ultrasound findings, the involved chromosome(s), and clinical outcomes was evaluated. RESULTS: During the study period, 36 fetuses with uniparental disomy were diagnosed, and two cases were excluded for non-available postnatal data. Finally, 34 fetuses were included in our study, of which 30 (88.2%) had uniparental disomy occurring on a single chromosome, while four (11.8%) were identified with uniparental disomy on different chromosomes. The most frequently involved chromosomes were chromosomes 16, X and 2, which presented in 8 (23.5%), 5 (14.7%) and 4 (11.8%), respectively. Prenatal ultrasound abnormalities were detected in 21 fetuses, with the most common category being multiple abnormalities (12 (57.1%)). Fetal growth restriction was identified in 14 (41.2%) fetuses, all of which coexisted with other abnormal findings. The rate of adverse perinatal outcomes in patients with uniparental disomy and fetal abnormalities was significantly higher than those without abnormalities (76.2% versus 15.4%, P = 0.002). The incidence of fetal or neonatal death was significantly higher in fetuses with fetal growth restriction than those without (85.7% versus 30.0%, P = 0.004). CONCLUSIONS: The prognosis of fetuses with uniparental disomy combined with fetal abnormalities, especially fetal growth restriction, was much poorer than those without.

Treatment advances in high-grade gliomas.

High-grade gliomas (HGG) pose significant challenges in modern tumour therapy due to the distinct biological properties and limitations of the blood-brain barrier. This review discusses recent advancements in HGG treatment, particularly in the context of immunotherapy and cellular therapy. Initially, treatment strategies focus on targeting tumour cells guided by the molecular characteristics of various gliomas, encompassing chemotherapy, radiotherapy and targeted therapy for enhanced precision. Additionally, technological enhancements are augmenting traditional treatment modalities. Furthermore, immunotherapy, emphasising comprehensive tumour management, has gained widespread attention. Immune checkpoint inhibitors, vaccines and CAR-T cells exhibit promising efficacy against recurrent HGG. Moreover, emerging therapies such as tumour treating fields (TTFields) offer additional treatment avenues for patients with HGG. The combination of diverse treatments holds promise for improving the prognosis of HGG, particularly in cases of recurrence.

Evolution and Interplay of Lithium Metal Interphase Components Revealed by Experimental and Theoretical Studies.

Lithium metal batteries (LMB) have high energy densities and are crucial for clean energy solutions. The characterization of the lithium metal interphase is fundamentally and practically important but technically challenging. Taking advantage of synchrotron X-ray, which has the unique capability of analyzing crystalline/amorphous phases quantitatively with statistical significance, we study the composition and dynamics of the LMB interphase for a newly developed important LMB electrolyte that is based on fluorinated ether. Pair distribution function analysis revealed the sequential roles of the anion and solvent in interphase formation during cycling. The relative ratio between Li2O and LiF first increases and then decreases during cycling, suggesting suppressed Li2O formation in both initial and long extended cycles. Theoretical studies revealed that in initial cycles, this is due to the energy barriers in many-electron transfer. In long extended cycles, the anion decomposition product Li2O encourages solvent decomposition by facilitating solvent adsorption on Li2O which is followed by concurrent depletion of both. This work highlights the important role of Li2O in transitioning from an anion-derived interphase to a solvent-derived one.

Molecular tuning boosts asymmetric C-C coupling for CO conversion to acetate.

Electrochemical carbon dioxide/carbon monoxide reduction reaction offers a promising route to synthesize fuels and value-added chemicals, unfortunately their activities and selectivities remain unsatisfactory. Here, we present a general surface molecular tuning strategy by modifying Cu2O with a molecular pyridine-derivative. The surface modified Cu2O nanocubes by 4-mercaptopyridine display a high Faradaic efficiency of greater than 60% in electrochemical carbon monoxide reduction reaction to acetate with a current density as large as 380 mA/cm2 in a liquid electrolyte flow cell. In-situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy reveals stronger *CO signal with bridge configuration and stronger *OCCHO signal over modified Cu2O nanocubes by 4-mercaptopyridine than unmodified Cu2O nanocubes during electrochemical CO reduction. Density function theory calculations disclose that local molecular tuning can effectively regulate the electronic structure of copper catalyst, enhancing *CO and *CHO intermediates adsorption by the stabilization effect through hydrogen bonding, which can greatly promote asymmetric *CO-*CHO coupling in electrochemical carbon monoxide reduction reaction.

Advances in Adjoint Functions of Connection Number in Water Resources Complex Systems: A Systematic Review.

The adjoint function of connection number has unique advantages in solving uncertainty problems of water resource complex systems, and has become an important frontier and research hotspot in the uncertainty research of water resource complex problems. However, in the rapid evolution of the adjoint function, some problems greatly limit the application of the adjoint function in the research of water resources. Therefore, based on bibliometric analysis, development, practical application issues, and prospects of the hot directions are analyzed. It is found that the development of the connection number of water resource set pair analysis can be divided into three stages: (1) relatively sluggish development before 2005, (2) a period of rapid advancement in adjoint function research spanning from 2005 to 2017, and (3) a subsequent surge post-2018. The introduction of the adjoint function of connection number promotes the continuous development of set pair analysis of water resources. Set pair potential and partial connection number are the crucial research directions of the adjoint function. Subtractive set pair potential has rapidly developed into a relatively independent and important trajectory. The research on connection entropy is comparatively less, which needs to be further strengthened, while that on adjacent connection number is even less. The adjoint function of set pair potential can be divided into three major categories: division set pair potential, exponential set pair potential, and subtraction set pair potential. The subtraction set pair potential, which retains the original dimension and quantity variation range of the connection number, is widely used in water resources and other fields. Coupled with the partial connection number, a series of new connection number adjoint functions have been developed. The partial connection number can be mainly divided into two categories: total partial connection number, and semi-partial connection number. Among these, the calculation expression and connotation of total partial connection numbers have not yet reached a consensus, accompanied by the slow development of high-order partial connection numbers. Semi-partial connection number can describe the mutual migration movement between different components of the connection number, which develops rapidly. With the limitations and current situation described above, promoting the exploration and application of the adjoint function of connection number in the field of water resources and other fields of complex systems has become the focus of future research.

Transversus Thoracic Muscle Plane Block For Postoperative Pain in Pediatric Cardiac Surgery: A Systematic Review And Meta-Analysis of Randomized And Observational Studies.

OBJECTIVES: Pediatric patients undergoing cardiac surgery usually experience significant surgical pain. Additionally, the effect of poor surgical analgesia creates a pain continuum that extends to the postoperative period. Transversus thoracic muscle plane block (TTMPB) is a novel plane block technique that can provide analgesia to the anterior chest wall. The analgesic role of TTMPB in pediatric cardiac surgery is still uncertain. A meta-analysis was conducted to determine the analgesic efficacy of this procedure. DESIGN AND SETTING: Systematic review and meta-analysis. PubMed, Embase, Web of Science, CENTRAL, WanFang Data, and the China National Knowledge Infrastructure were searched to November 2023, and the Grading of Recommendations Assessment, Development, and Evaluation approach was followed to evaluate the certainty of evidence. PARTICIPANTS: Eligible studies enrolled pediatric patients from 2 months to 12 years old scheduled to undergo cardiac surgery, and randomized them to receive a TTMPB or no block/sham block. MEASUREMENTS AND MAIN RESULTS: Six studies that enrolled 601 pediatric patients were included. Low-certainty evidence from randomized trials showed that, compared with no block or sham block, TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative modified objective pain score at 12 hours (weighted mean difference [WMD] -2.20, 95% CI -2.73 to -1.68) and 24 hours (WMD -1.76, 95% CI -2.09 to -1.42), intraoperative opioid consumption (WMD -3.83, 95% CI -5.90 to -1.76 µg/kg), postoperative opioid consumption (WMD -2.51, 95% CI -2.84 to -2.18 µg/kg), length of intensive care unit (ICU) stay (WMD -5.56, 95% CI -8.30 to -2.83 hours), and extubation time (WMD -2.13, 95% CI -4.21 to -0.05 hours). Retrospective studies provided very low certainty that the results were consistent with the randomized trials. CONCLUSION: Very low- to low-certainty evidence showed that TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative pain, opioid consumption, ICU length of stay, and extubation time.

A method to synthesize specific active Cu sites of single-atom catalysts with high stability for acetylene hydration.

Single-atom catalysts (SACs) have received much attention in the realm of energy and catalytic conversion due to their maximum atomic efficiency. Herein, we report a cascade anchoring strategy for the preparation of a Cu-S1O2 species of single-atom catalyst attached to a carbon carrier containing P and S (Cu-S1O2 SA/CPS) with a content of 12.4 wt%. Over the Cu-S1O2 SA/CPS catalyst, the conversion of 95.8% and selectivity of 87.2% for acetylene hydration could still be achieved at 70 h (T = 200°C, GHSV(C2H2) = 90 h-1 and VH2O/VC2H2 = 4). X-ray absorption spectroscopy (XAS) and X-ray photoelectron spectroscopy (XPS) tests reveal that the Cu atoms of Cu-S1O2 SA/CPS are predominantly coordinated in a trinary manner (Cu-S1O2). Based on high-resolution aberration-corrected high-angle annular dark-field scanning transmission electron microscope (HAADF-STEM), it is demonstrated that the Cu single-atom sites are highly dispersed in Cu-S1O2 SA/CPS. It is evident from the scanning electron microscopy (SEM) that Cu-S1O2 SA/CPS has a two-dimensional layered structure. The specific structure of the active site Cu is primarily attributed to the coordination of S and O atoms, resulting in its superior stability for acetylene hydration towards the synthesis of acetaldehyde. Density functional theory (DFT) calculations confirm that the formation of the Cu-S1O2 site facilitates the activation of acetylene, which is a pivotal step in the acetylene hydration process and considered as the rate-determining step. This article not only introduces an innovative strategy in the synthesis of Cu SACs but also represents a significant breakthrough in the stability of Cu SACs in acetylene hydration.

Identification and Validation of the Pyroptosis-Related Hub Gene Signature and the Associated Regulation Axis in Diabetic Keratopathy.

Background: Diabetic keratopathy (DK) poses a significant challenge in diabetes mellitus, yet its molecular pathways and effective treatments remain elusive. The aim of our research was to explore the pyroptosis-related genes in the corneal epithelium of the streptozocin-induced diabetic rats. Methods: After sixteen weeks of streptozocin intraperitoneal injection, corneal epithelium from three diabetic rats and three normal groups underwent whole-transcriptome sequencing. An integrated bioinformatics pipeline, including differentially expressed gene (DEG) identification, enrichment analysis, protein-protein interaction (PPI) network, coexpression, drug prediction, and immune deconvolution analyses, identified hub genes and key drivers in DK pathogenesis. These hub genes were subsequently validated in vivo through RT-qPCR. Results: A total of 459 DEGs were screened out from the diabetic group and nondiabetic controls. Gene Set Enrichment Analysis highlighted significant enrichment of the NOD-like receptor, Toll-like receptor, and NF-kappa B signaling pathways. Intersection of DEGs and pyroptosis-related datasets showed 33 differentially expressed pyroptosis-related genes (DEPRGs) associated with pathways such as IL-17, NOD-like receptor, TNF, and Toll-like receptor signaling. A competing endogenous RNA network comprising 16 DEPRGs, 22 lncRNAs, 13 miRNAs, and 3 circRNAs was constructed. After PPI network, five hub genes (Nfkb1, Casp8, Traf6, Ptgs2, and Il18) were identified as upregulated in the diabetic group, and their expression was validated by RT-qPCR in streptozocin-induced rats. Immune infiltration characterization showed that diabetic corneas owned a higher proportion of resting mast cells, activated NK cells, and memory-resting CD4 T cells. Finally, several small compounds including all-trans-retinoic acid, Chaihu Shugan San, dexamethasone, and resveratrol were suggested as potential therapies targeting these hub genes for DK. Conclusions: The identified and validated hub genes, Nfkb1, Casp8, Traf6, Ptgs2, and Il18, may play crucial roles in DK pathogenesis and serve as therapeutic targets.

The efficacy-associated biomarkers for immune checkpoint inhibitors in gastrointestinal cancer: a literature review.

Background and Objective: Immune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer. Methods: The literature on ICI treatment in GI cancers was searched in the PubMed, Embase, and Cochrane Library databases for publications up to April 2023. Key Content and Findings: Clinical practice and research has gradually revealed some biomarkers related to the treatment of GI cancers with ICIs, which can be roughly divided into three types: biomarkers that predict the effectiveness of ICIs treatment, biomarkers associated with resistance to ICIs, and biomarkers associated with immune related adverse events (irAEs). This review article provides a literature review on biomarkers related to the efficacy of ICIs in the treatment of GI cancers. Conclusions: According to existing clinical research results, there are multiple biomarkers that can be used for predicting and monitoring the efficacy and risk of adverse events of ICIs in the treatment of digestive system malignant tumors.

Silencing NlFAR7 destroyed the pore canals and related structures of the brown planthopper.

Fatty acyl-CoA reductase (FAR) is one of the key enzymes, which catalyses the conversion of fatty acyl-CoA to the corresponding alcohols. Among the FAR family members in the brown planthopper (Nilaparvata lugens), NlFAR7 plays a pivotal role in both the synthesis of cuticular hydrocarbons and the waterproofing of the cuticle. However, the precise mechanism by which NlFAR7 influences the formation of the cuticle structure in N. lugens remains unclear. Therefore, this paper aims to investigate the impact of NlFAR7 through RNA interference, transmission electron microscope, focused ion beam scanning electron microscopy (FIB-SEM) and lipidomics analysis. FIB-SEM is employed to reconstruct the three-dimensional (3D) architecture of the pore canals and related cuticle structures in N. lugens subjected to dsNlFAR7 and dsGFP treatments, enabling a comprehensive assessment of changes in the cuticle structures. The results reveal a reduction in the thickness of the cuticle and disruptions in the spiral structure of pore canals, accompanied by widened base and middle diameters. Furthermore, the lipidomics comparison analysis between dsNlFAR7- and dsGFP-treated N. lugens demonstrated that there were 25 metabolites involved in cuticular lipid layer synthesis, including 7 triacylglycerols (TGs), 5 phosphatidylcholines (PCs), 3 phosphatidylethanolamines (PEs) and 2 diacylglycerols (DGs) decreased, and 4 triacylglycerols (TGs) and 4 PEs increased. In conclusion, silencing NlFAR7 disrupts the synthesis of overall lipids and destroys the cuticular pore canals and related structures, thereby disrupting the secretion of cuticular lipids, thus affecting the cuticular waterproofing of N. lugens. These findings give significant attention with reference to further biochemical researches on the substrate specificity of FAR protein, and the molecular regulation mechanisms during N. lugens life cycle.

Stable Interfacial Ruthenium Species for Highly Efficient Polyolefin Upcycling.

The present polyolefin hydrogenolysis recycling cases acknowledge that zerovalent Ru exhibits high catalytic activity. A pivotal rationale behind this assertion lies in the propensity of the majority of Ru species to undergo reduction to zerovalent Ru within the hydrogenolysis milieu. Nonetheless, the suitability of zerovalent Ru as an optimal structural configuration for accommodating multiple elementary reactions remains ambiguous. Here, we have constructed stable Ru0-Ruδ+ complex species, even under reaction conditions, through surface ligand engineering of commercially available Ru/C catalysts. Our findings unequivocally demonstrate that surface-ligated Ru species can be stabilized in the form of a Ruδ+ state, which, in turn, engenders a perturbation of the σ bond electron distribution within the polyolefin carbon chain, ultimately boosting the rate-determining step of C-C scission. The optimized catalysts reach a solid conversion rate of 609 g·gRu-1·h-1 for polyethylene. This achievement represents a 4.18-fold enhancement relative to the pristine Ru/C catalyst while concurrently preserving a remarkable 94% selectivity toward valued liquid alkanes. Of utmost significance, this surface ligand engineering can be extended to the gentle mixing of catalysts in ligand solution at room temperature, thus rendering it amenable for swift integration into industrial processes involving polyolefin degradation.