Intensive investigation of the synergistic effects between electrocatalysis and peroxymonosulfate activation for efficient organic elimination.

Hybrid systems combined eletrocatalysis and Fenton-like process attract a lot of attention due their outstanding performance and unique mechanism. Here, we proposed an efficient, cost-effective, and versatile electrochemical activation (ECA) system for efficient water purification, and intensively studied the synergistic effects between electrocatalysis and peroxymonosulfate (PMS)-based advanced oxidation. The ECA system achieved complete removal of 20 ppm tetracycline hydrochloride (TCH) in 15 min, with a rate constant of 0.338 min-1. Its performance was assessed across various operational parameters (PMS dosage, pH, applied voltage, electrode interval, temperature, co-existed ions, biomass, different oxidants), demonstrating its broad applicability and stability. Excellent degradation and mineralization for other 12 kinds of refractory organic pollutants were also achieved. The outstanding performance can be attributed to the synergistic effect in the system, in which electrocatalytic reduction of dissolved oxygen generated H2O2 and O2•-, boosting the number of reactive species, such as 1O2, by interacting with PMS. Furthermore, the presence of organic matter promotes electron transfer, amplifying the system's degradation capability. These findings not only highlight the ECA system's effectiveness in organic pollutant removal but also offer insights into the underlying degradation mechanisms, paving the way for future advancements in water purification technologies.

Water sorption studies with mesoporous multivariate monoliths based on UiO-66.

Hierarchical linker thermolysis has been used to enhance the porosity of monolithic UiO-66-based metal-organic frameworks (MOFs) containing 30 wt% 2-aminoterephthalic acid (BDC-NH2) linker. In this multivariate (i.e. mixed-linker) MOF, the thermolabile BDC-NH2 linker decomposed at ∼350 °C, inducing mesopore formation. The nitrogen sorption of these monolithic MOFs was probed, and an increase in gas uptake of more than 200 cm3 g-1 was observed after activation by heating, together with an increase in pore volume and mean pore width, indicating the creation of mesopores. Water sorption studies were conducted on these monoliths to explore their performance in that context. Before heating, monoUiO-66-NH2-30%-B showed maximum water vapour uptake of 61.0 wt%, which exceeded that reported for either parent monolith, while the highly mesoporous monolith (monoUiO-66-NH2-30%-A) had a lower maximum water vapour uptake of 36.2 wt%. This work extends the idea of hierarchical linker thermolysis, which has been applied to powder MOFs, to monolithic MOFs for the first time and supports the theory that it can enhance pore sizes in these materials. It also demonstrates the importance of hydrophilic functional groups (in this case, NH2) for improving water uptake in materials.

Exploring the Photophysical and Mechanical Behavior of Fluorescent Metal-Organic Framework Monoliths.

Luminescent metal-organic frameworks exhibit great potential as materials for nanophotonic applications because of their programmable properties and tunable structures. In particular, luminescent guests (LG) can be hosted by metal-organic frameworks due to their porosity and guest confinement capacity, forming LG@MOF composite systems. However, such guest-host systems are mainly produced as loose powders, preventing their widespread use in practical devices and technological applications that require implementation of a stable continuum solid. In this regard, using monolithic MOF hosts might be a workable option to solve this challenge. Herein, we reported the facile synthesis and fabrication of novel prototypical sol-gel monolithic systems, designated as LG@monoMOF. Red (rhodamine B), blue (7-methoxycoumarin), and yellow (fluorescein) emitting dyes were encapsulated in a robust UiO-66 monolithic host, resulting in the red, blue, and yellow light-emitting luminescent monoliths. The mechanical and photophysical characterization of the three LG@monoMOF systems was systematically carried out in order to unravel the role of guest-host interactions in the mechanical and optical response of the bespoke LG@monoMOF composites.

Modular synthesis of aryl amines from 3-alkynyl-2-pyrones.

The synthesis of aryl amines from 3-alkynyl-2-pyrones and various amines is described. Mechanistically, the aryl amines are proposed to arise from the 3-alkynyl-2-pyrone substrates through their selective opening in a 1,6-fashion by secondary amines followed by decarboxylation and an unexpected rearrangement. The proposed mechanism is supported by quantum chemical transition-state calculations, which are consistent with the regiochemical outcome. The scope of this transformation spans a variety of 3-alkynyl-2-pyrones and a range of secondary amines. The influence of the secondary amine coupling partners on reaction efficiency was elucidated through data-driven modeling as well as scope exploration. These latter studies revealed that the steric bulk of the secondary amine coupling partner under the reaction conditions serves as a strong indicator of overall reaction efficiency.

Easily overlooked petiole traits are key factors that affect soil carbon sequestration in plantations in karst areas.

Vegetation restoration in karst areas has shifted from expanding planting areas to the collective enhancement of various ecological functions, especially carbon sequestration. Identifying and regulating key plant functional traits involved in the carbon cycle is an effective approach to increase carbon sequestration. However, reports on the significant contribution of petiole traits to the carbon cycle are scarce. Eucalyptus globulus and Bauhinia purpurea plantations in Liujiang river basin were investigated in this study. Petiole traits, understory characteristics, and soil organic carbon have been measured. The aim is to explore key effect of petiole traits for increasing soil carbon sequestration and to provide scientific evidence for the high-quality development of plantations in karst areas. The results indicate that in Eucalyptus globulus plantations, when the understory vegetation coverage is below 50 %, petioles tend to elongate rather than thicken, leading to an increase in specific petiole length. In Bauhinia purpurea plantations, petioles consistently tend to increase diameter. However, when specific leaf area decreases, specific petiole length increases. In both plantations, an increase in specific petiole length accelerates leaf shedding. It leads to increased litter accumulation so that soil carbon content increases. In Eucalyptus globulus plantations, to enhance soil carbon sequestration as an ecological goal, it is recommended to keep the soil total nitrogen below 1.20 mg/g, to control understory vegetation coverage below 50 %, and to limit the extension of Bidens pilosa. In Bauhinia purpurea plantations, within 100 m of altitude, the soil total nitrogen can be controlled below 1.00 mg/g to increase soil organic carbon from large leaf shedding due to the increase of specific petiole length. At lower altitudes, increasing soil total nitrogen can enhance understory vegetation coverage, allowing soil organic carbon to originate from both leaf shedding and understory vegetation residues.

Risk of bleeding after abdominal paracentesis in patients with chronic liver disease and coagulopathy: A systematic review and meta-analysis.

Abdominal paracentesis is a common procedure performed for both diagnostic and therapeutic purposes in patients with chronic liver disease and ascites. This review aims to provide an overview of the current evidence on the risk of bleeding associated with abdominal paracentesis. Electronic search was performed using PubMed, MEDLINE, and Ovid EMBASE from inception to 29 October 2023. Studies were included if they examined the risk of bleeding post-abdominal paracentesis or the efficacy of interventions to reduce bleeding in patients with chronic liver disease. Random-effects model was used to calculate the pooled proportions of bleeding events following abdominal paracentesis. Heterogeneity was determined by I 2, τ2 statistics, and P-value. Eight studies were included for review. Six studies reported incident events of post-abdominal paracentesis bleeding. Pooled proportion of bleeding events following abdominal paracentesis was 0.32% (95% CI: 0.15-0.69%). The mean values for pre-procedural INR and platelet count of patients in these studies ranged between 1.4 and 2.0, and 50 and 153 × 109/L, respectively. The highest recorded INR was 8.7, and the lowest platelet count was 19 × 109/L. Major bleeding after abdominal paracentesis occurred in 0-0.97% of the study cohorts. Two studies demonstrated that the use of thromboelastography (TEG) before paracentesis in patients with chronic liver disease identified those at risk of procedure-related bleeding and reduced transfusion requirements. The overall risk of major bleeding after abdominal paracentesis is low in patients with chronic liver disease and coagulopathy. TEG may be used to predict bleeding risk and guide transfusion requirements.

SnF2-Catalyzed Lithiophilic-Lithiophobic Gradient Interface for High-Rate PEO-based All-Solid-State Batteries.

Polyethylene oxide (PEO)-based all solid-state lithium metal batteries (ASSLMBs) are strongly hindered by the fast dendrite growth at the Li metal/electrolyte interface, especially under large rates. The above issue stems from the suboptimal interfacial chemistry and poor Li+ transport kinetics during cycling. Herein, a SnF2-catalyzed lithiophilic-lithiophobic gradient solid electrolyte interphase (SCG-SEI) of LixSny/LiF-Li2O is in-situ formed. The superior ionic LiF-Li2O rich upper layer (17.1 nm) possesses high interfacial energy and fast Li+ diffusion channels, wherein lithiophilic LixSny alloy layer (8.4 nm) could highly reduce the nucleation overpotential with lower diffusion barrier and promote rapid electron transportation for reversible Li+ plating/stripping. Simultaneously, the insoluble SnF2-coordinated PEO promotes the rapid Li+ ion transport in the bulk phase. As a result, an over 46.7 and 3.5 times improvements for lifespan and critical current density of symmetrical cells are achieved, respectively. Furthermore, LiFePO4-based ASSLMBs deliver a recorded cycling performance at 5 C (over 1000 cycles with a capacity retention of 80.0%). More importantly, impressive electrochemical performances and safety tests with LiNi0.8Mn0.1Co0.1O2 and pouch cell with LiFePO4, even under extreme conditions (i.e., 100 ℃), are also demonstrated, reconfirmed the importance of lithiophilic-lithiophobic gradient interfacial chemistry in the design of high-rate ASSLMBs for safety applications.

m6A-Mediated IRS1 Regulates the Development of Oral Squamous Cell Carcinoma through p53/Line-1 Signaling.

BACKGROUND: The importance of N6-methyladenosine (m6A) modification in tumorigenesis and progression have been highlighted. This study aimed to investigate the modification of insulin receptor substrate 1 (IRS1) by m6A and its role in oral squamous cell carcinoma (OSCC). METHODS: Bioinformatics was employed to predict differential genes related to epithelial-mesenchymal transition (EMT) in OSCC. Seventeen pairs of OSCC and paracancerous tissue samples were collected. The impact of IRS1 on OSCC cell growth and EMT was evaluated. The fluctuations in IRS1 enrichment and the involvement of p53/Line-1 were investigated. RESULTS: IRS1 was highly expressed in OSCC. IRS1 silencing decreased OSCC cell proliferation and increased apoptosis. IRS1 silencing hindered EMT by regulating related markers. IRS1 silencing upregulated p53 and downregulated Line-1 ORF1p. The p53 inhibition reversed the effects of IRS1 silencing and induced EMT in OSCC cells. Furthermore, the m6A modification of IRS1 was increased in OSCC cells. IRS1 were positively regulated by the m6A regulators methyltransferase-like 14 (METTL14) and YTH domain-containing protein 1 (YTHDC1). IRS1 bound to YTHDC1, and YTHDC1 knockdown inhibited the IRS1 nuclear export. The obesity-associated protein (FTO) negatively regulated IRS1, and FTO overexpression reversed the IRS1-induced OSCC tumor growth. CONCLUSIONS: m6A methylation-mediated IRS1 regulated EMT in OSCC through p53/Line-1. These findings provide potential therapeutic strategies for managing OSCC.

Novel OX40 and 4-1BB derived spacers enhance CD30 CAR activity and safety in CD30 positive lymphoma models.

The chimeric antigen receptor (CAR) derived from the CD30 specific murine antibody, HRS-3, has produced promising clinical efficacy with a favorable safety profile in the treatment of relapsed or refractory CD30-positive lymphomas. However, persistence of the autologous CAR-T cells was brief, and many patients relapsed a year after treatment. The lack of persistence may be attributed to the use of a wild-type immunoglobulin (Ig)G1 spacer that can associate with Fc receptors. We first identified the cysteine-rich domain (CRD) 5 of CD30 as the primary binding epitope of HRS-3 and armed with this insight, attempted to improve the HRS-3 CAR functionality with a panel of novel spacer designs. We demonstrate that HRS-3 CARs with OX40 and 4-1BB derived spacers exhibited similar anti-tumor efficacy, circumvented interactions with Fc receptors, and secreted lower levels of cytokines in vitro than a CAR employing the IgG1 spacer. Humanization of the HRS-3 scFv coupled with the 4-1BB spacer preserved potent on-target, on-tumor efficacy, and on-target, off-tumor safety. In a lymphoma mouse model of high tumor burden, T cells expressing humanized HRS-3 CD30.CARs with the 4-1BB spacer potently killed tumors with low levels of circulating inflammatory cytokines, providing a promising candidate for future clinical development in the treatment of CD30-positive malignancies.

Triboelectric behaviour of selected zeolitic-imidazolate frameworks: exploring chemical, morphological and topological influences.

Tribo- and contact electrification remain poorly understood, baffling and discombobulating scientists for millennia. Despite the technology needed to harvest mechanical energy with triboelectric generators being incredibly rudimentary and the fact that a triboelectric output can be obtained from almost any two material combinations, research into triboelectric generator materials typically focuses on achieving the highest possible output; meanwhile, understanding trends and triboelectric behaviours of related but lower performing materials is often overlooked or not studied. Metal-organic frameworks, a class of typically highly porous and crystalline coordination polymers are excellent media to study to fill this knowledge gap. Their chemistry, topology and morphology can be individually varied while keeping other material properties constant. Here we study 5 closely related zeolitic-imidazolate type metal-organic frameworks for their triboelectric performance and behaviour by contact-separating each one with five counter materials. We elucidate the triboelectric electron transfer behaviour of each material, develop a triboelectric series and characterise the surface potential by Kelvin-probe force microscopy. From our results we draw conclusions on how the chemistry, morphology and topology affect the triboelectric output by testing and characterising our series of frameworks to help better understand triboelectric phenomena.

Psychometric testing of the training needs for advance care planning scale for clinicians and nurses.

BACKGROUND: Studies have shown that Chinese Clinicians and nurses have positive attitudes toward ACP, but no local tools exist to assess their need for ACP knowledge and skills training. resulting in their inability to initiate ACP conversations as well as poor end-of-life care for patients. Therefore, this study aims to assess the needs of Chinese Clinicians and nurses for ACP knowledge and skills training and assess the validity and reliability of a questionnaire on the Training Needs for Advance Care Planning (TNACP) scale. METHODS: From October to November 2021, 170 clinicians and nurses were pre-surveyed using a preliminary draft of the questionnaire. The responses were screened using item analysis, Cronbach's alpha coefficient, and the intraclass correlation coefficient (ICC) to describe the internal consistency and stability of the questionnaire. The Content validity index (CVI), Exploratory factor analysis (EFA) and Confirmatory factor analysis (CFA) were used to test the validity of the questionnaire. RESULTS: After independent samples t-test analysis, Except for the entry "A2", the critical ratio between the two groups of the remaining 23 items was statistically significant (p < 0.05). Based on the above screening methods, the "A2" item was deleted, and the final number of questionnaire items was 23. The I-CVI was 0.79-1.00, and the S-CVI/Ave was 0.90. Three common factors were extracted-the cumulative contribution rate was 69.969%, and the factor loading of all items was 0.506-0.843 (all > 0.40). The results of confirmatory factor analysis showed that the Training Needs for Advance Care Planning (TNACP) scale model fit well(X2/df = 2.504, RMSEA = 0.092, GFI = 0.809, AGFI = 0.745, CFI = 0.931, IFI = 0.932, TLI = 0.916); the Cronbach's α = 0.888 for the total questionnaire, and the three dimensions of Cronbach's α were 0.729 to 0.959; and the ICC for the overall scores between the test-retest evaluations was 0.884 (p < 0.001). CONCLUSIONS: The TNACP scale has good reliability and validity and can be used to assess Chinese Clinicians and nurses' training needs for implementing ACP.

High Sensitive and Stable UV-Vis Photodetector Based on MoS2/MoO3 vdW Heterojunction.

The development of new high-performance photodetectors (PDs) is currently focused on achieving small size, low power consumption, low cost, and large bandwidth. Two-dimensional (2D) materials and heterostructures offer promising approaches for the future development of optoelectronic devices. However, there has been limited research on 2D wide-bandgap semiconductor heterostructures. In this study, we successfully constructed a MoS2/MoO3 vdW heterojunction PD. This PD exhibited excellent response and significant photovoltaic behavior in the ultraviolet (UV) to visible (Vis) range. Under 365 nm UV light and 1 V bias voltage, the PD demonstrated a high responsivity of 645 mA/W, a high specific detectivity of 8.98 × 1010 Jones, and fast response speeds of 55.9/59.6 ms. At 0 V bias voltage, the responsivity reached as high as 157 mA/W. Furthermore, the PD exhibited remarkable stability in its performance. These outstanding characteristics can be attributed to the strong internal electric field created by the type II heterojunction structure and the chemical stability of the materials. This work opens a route for the application of 2D wide-bandgap semiconductor materials in optoelectronic devices.

Cytosolic Escape of Mitochondrial DNA Triggers cGAS-STING Pathway-Dependent Neuronal PANoptosis in Response to Intermittent Hypoxia.

Intermittent hypoxia (IH) is the predominant pathophysiological disturbance in obstructive sleep apnea (OSA), characterized by neuronal cell death and neurocognitive impairment. We focus on the accumulated mitochondrial DNA (mtDNA) in the cytosol, which acts as a damage-associated molecular pattern (DAMP) and activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a known trigger for immune responses and neuronal death in degenerative diseases. However, the specific role and mechanism of the mtDNA-cGAS-STING axis in IH-induced neural damage remain largely unexplored. Here, we investigated the involvement of PANoptosis, a novel type of programmed cell death linked to cytosolic mtDNA accumulation and the cGAS-STING pathway activation, in neuronal cell death induced by IH. Our study found that PANoptosis occurred in primary cultures of hippocampal neurons and HT22 cell lines exposed to IH. In addition, we discovered that during IH, mtDNA released into the cytoplasm via the mitochondrial permeability transition pore (mPTP) activates the cGAS-STING pathway, exacerbating PANoptosis-associated neuronal death. Pharmacologically inhibiting mPTP opening or depleting mtDNA significantly reduced cGAS-STING pathway activation and PANoptosis in HT22 cells under IH. Moreover, our findings indicated that the cGAS-STING pathway primarily promotes PANoptosis by modulating endoplasmic reticulum (ER) stress. Inhibiting or silencing the cGAS-STING pathway substantially reduced ER stress-mediated neuronal death and PANoptosis, while lentivirus-mediated STING overexpression exacerbated these effects. In summary, our study elucidates that cytosolic escape of mtDNA triggers cGAS-STING pathway-dependent neuronal PANoptosis in response to IH, mainly through regulating ER stress. The discovery of the novel mechanism provides theoretical support for the prevention and treatment of neuronal damage and cognitive impairment in patients with OSA.

Efficacy and safety of topical clobetasol propionate in comparison with alternative treatments in oral lichen planus: an updated systematic review and meta-analysis.

Background: Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease characterized by pain and inflammation. Clobetasol propionate (CLO) is the first-line drug in the treatment of OLP. The meta-analysis aimed to evaluate the efficacy and safety of CLO for treating patients with OLP. Methods: PubMed, Embase and Web of Science were systematically searched from the database inception date up to August 2023. There were no restrictions on language or date of publication. The outcomes of our interest were as follows: improvement of clinical signs and/or symptoms, total lesion size, relapse and adverse events. Results: A total of 17 RCTs evaluating the effects of CLO were included in this study. The results revealed no significant difference in the clinical score (WMD = 0.14, 95% CI: -0.39, 0.66; p = 0.609) and pain score (WMD = 0.17, 95% CI: -0.44, 0.79; p = 0.582) between CLO and other treatments. However, clinical resolution (RR = 1.61, 95% CI: 1.17, 2.22; p = 0.003) and symptoms improvement (RR = 1.80, 95% CI: 1.17, 2.77; p = 0.008) were significantly different between CLO and other treatments. Moreover, there was a significant reduction in the total lesion size with CLO treatment (WMD = -0.58, 95% CI: -1.03, -0.13; p = 0.011). In addition, CLO showed no statistical incidence of adverse events (RR = 1.46, 95% CI: 0.86, 2.50; p = 0.161) and relapse (RR = 1.56, 95% CI: 0.66, 3.71; p = 0.314) than other therapies. Conclusion: This systematic review and meta-analysis of 17 randomized clinical trials supported the long-term application of CLO as an effective regimen in OLP patients.

Clinical characteristics of delirium in older patients with first-ever acute myocardial infarction who underwent percutaneous coronary intervention : A retrospective study.

OBJECTIVES: Delirium is a serious complication of cardiac surgery and a common clinical problem. The study aimed to identify the incidence, risk factors, and outcomes of delirium in older patients (≥ 65 years) with first-ever acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI). METHODS: A retrospective cohort study was performed in a hospital in northern China. A total of 1033 older patients with first-ever AMI who underwent PCI between January 2018 and April 2021 were screened for delirium using the CAM-ICU method. Clinical and laboratory data were collected. RESULTS: A total of 134 (12.97%) patients were diagnosed with delirium. Patients with delirium were older. The most common concomitant diseases were cardiac arrest, chronic renal failure, and a history of coronary artery bypass graft (CABG). Delirious patients experienced more times of mechanical ventilation, more intra-aortic balloon pump (IABP) support, high postoperative immediate pain score (VAS), more non-bedside cardiac rehabilitation, and longer total length of stay and cardiac care unit (CCU) time. Multivariable logistic regression showed that age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently associated with delirium. Delirium was an independent predictor of prolonged CCU stay, total length of stay, and 1­year mortality. CONCLUSION: Age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently closely related to delirium in older patients with first-ever AMI who underwent PCI. Delirium was associated with a higher 1­year all-cause mortality.

One-Step Preparation of Magnetic Lipid Bubbles: Magnetothermal Effect Induces the Simultaneous Formation of Gas Nuclei and Self-Assembly of Phospholipids.

In recent years, enveloped micro-nanobubbles have garnered significant attention in research due to their commendable stability, biocompatibility, and other notable properties. Currently, the preparation methods of enveloped micro-nanobubbles have limitations such as complicated preparation process, large bubble size, wide distribution range, low yield, etc. There exists an urgent demand to devise a simple and efficient method for the preparation of enveloped micro-nanobubbles, ensuring both high concentration and a uniform particle size distribution. Magnetic lipid bubbles (MLBs) are a multifunctional type of enveloped micro-nanobubble combining magnetic nanoparticles with lipid-coated bubbles. In this study, MLBs are prepared simply and efficiently by a magneto internal heat bubble generation process based on the interfacial self-assembly of iron oxide nanoparticles induced by the thermogenic effect in an alternating magnetic field. The mean hydrodynamic diameter of the MLBs obtained was 384.9 ± 8.5 nm, with a polydispersity index (PDI) of 0.248 ± 0.021, a zeta potential of -30.5 ± 1.0 mV, and a concentration of (7.92 ± 0.46) × 109 bubbles/mL. Electron microscopy results show that the MLBs have a regular spherical stable core-shell structure. The superparamagnetic iron oxide nanoparticles (SPIONs) and phospholipid layers adsorbed around the spherical gas nuclei of the MLBs, leading the particles to demonstrate commendable superparamagnetic and magnetic properties. In addition, the effects of process parameters on the morphology of MLBs, including phospholipid concentration, phospholipid proportiona, current intensity, magnetothermal time, and SPION concentration, were investigated and discussed to achieve controlled preparation of MLBs. In vitro imaging results reveal that the higher the concentration of MLBs loaded with iron oxide nanoparticles, the better the in vitro ultrasound (US) imaging and magnetic resonance imaging (MRI) results. This study proves that the magneto internal heat bubble generation process is a simple and efficient technique for preparing MLBs with high concentration, regular structure, and commendable properties. These findings lay a robust foundation for the mass production and application of enveloped micro-nanobubbles, particularly in biomedical fields and other related domains.

Application of deep learning algorithms in classification and localization of implant cutout for the postoperative hip.

OBJECTIVE: This study aims to explore the feasibility of employing convolutional neural networks for detecting and localizing implant cutouts on anteroposterior pelvic radiographs. MATERIALS AND METHODS: The research involves the development of two Deep Learning models. Initially, a model was created for image-level classification of implant cutouts using 40191 pelvic radiographs obtained from a single institution. The radiographs were partitioned into training, validation, and hold-out test datasets in a 6/2/2 ratio. Performance metrics including the area under the receiver operator characteristics curve (AUROC), sensitivity, and specificity were calculated using the test dataset. Additionally, a second object detection model was trained to localize implant cutouts within the same dataset. Bounding box visualizations were generated on images predicted as cutout-positive by the classification model in the test dataset, serving as an adjunct for assessing algorithm validity. RESULTS: The classification model had an accuracy of 99.7%, sensitivity of 84.6%, specificity of 99.8%, AUROC of 0.998 (95% CI: 0.996, 0.999) and AUPRC of 0.774 (95% CI: 0.646, 0.880). From the pelvic radiographs predicted as cutout-positive, the object detection model could achieve 95.5% localization accuracy on true positive images, but falsely generated 14 results from the 15 false-positive predictions. CONCLUSION: The classification model showed fair accuracy for detection of implant cutouts, while the object detection model effectively localized cutout. This serves as proof of concept of using a deep learning-based approach for classification and localization of implant cutouts from pelvic radiographs.

B7-H3-Targeting Chimeric Antigen Receptors Epstein-Barr Virus-specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3-positive Solid Tumors.

Encouraged by the observations of significant B7-H3 protein overexpression in many human solid tumors compared to healthy tissues, we directed our focus towards targeting B7-H3 using chimeric antigen receptor (CAR) T cells. We utilized a nanobody as the B7-H3-targeting domain in our CAR construct to circumvent the stability issues associated with single-chain variable fragment-based domains. In efforts to expand patient access to CAR T-cell therapy, we engineered our nanobody-based CAR into human Epstein-Barr virus-specific T cells (EBVST), offering a readily available off-the-shelf treatment. B7H3.CAR-armored EBVSTs demonstrated potent in vitro and in vivo activities against multiple B7-H3-positive human tumor cell lines and patient-derived xenograft models. Murine T cells expressing a murine equivalent of our B7H3.CAR exhibited no life-threatening toxicities in immunocompetent mice bearing syngeneic tumors. Further in vitro evaluation revealed that while human T, B, and natural killer cells were unaffected by B7H3.CAR EBVSTs, monocytes were targeted because of upregulation of B7-H3. Such targeting of myeloid cells, which are key mediators of cytokine release syndrome (CRS), contributed to a low incidence of CRS in humanized mice after B7H3.CAR EBVST treatment. Notably, we showed that B7H3.CAR EBVSTs can target B7-H3-expressing myeloid-derived suppressor cells (MDSC), thereby mitigating MDSC-driven immune suppression. In summary, our data demonstrate that our nanobody-based B7H3.CAR EBVSTs are effective as an off-the-shelf therapy for B7-H3-positive solid tumors. These cells also offer an avenue to modulate the immunosuppressive tumor microenvironment, highlighting their promising clinical potential in targeting solid tumors. SIGNIFICANCE: Clinical application of EBVSTs armored with B7-H3-targeting CARs offer an attractive solution to translate off-the-shelf CAR T cells as therapy for solid tumors.

Nitrogen-mediated volatilisation of defensive metabolites in tomato confers resistance to herbivores.

Plants synthesise a vast array of volatile organic compounds (VOCs), which serve as chemical defence and communication agents in their interactions with insect herbivores. Although nitrogen (N) is a critical resource in the production of plant metabolites, its regulatory effects on defensive VOCs remain largely unknown. Here, we investigated the effect of N content in tomato (Solanum lycopersicum) on the tobacco cutworm (Spodoptera litura), a notorious agricultural pest, using biochemical and molecular experiments in combination with insect behavioural and performance analyses. We observed that on tomato leaves with different N contents, S. litura showed distinct feeding preference and growth and developmental performance. Particularly, metabolomics profiling revealed that limited N availability conferred resistance upon tomato plants to S. litura is likely associated with the biosynthesis and emission of the volatile metabolite α-humulene as a repellent. Moreover, exogenous application of α-humulene on tomato leaves elicited a significant repellent response against herbivores. Thus, our findings unravel the key factors involved in N-mediated plant defence against insect herbivores and pave the way for innovation of N management to improve the plant defence responses to facilitate pest control strategies within agroecosystems.