IFN-γ induces acute graft-versus-host disease by promoting HMGB1-mediated nuclear-to-cytoplasm translocation and autophagic degradation of p53.

Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our prior investigations disclosed a correlation between p53 downregulation in CD4+ T cells and the occurrence of aGVHD. Notably, the insufficiency of the CCCTC-binding factor (CTCF) emerged as a pivotal factor in repressing p53 expression. However, the existence of additional mechanisms contributing to the reduction in p53 expression remains unclear. Interferon (IFN)-γ, a pivotal proinflammatory cytokine, assumes a crucial role in regulating alloreactive T cell responses and plays a complex part in aGVHD development. IFN-γ has the capacity to induce autophagy, a vital catabolic process facilitating protein degradation, in various cell types. Presently, whether IFN-γ participates in the development of aGVHD by instigating the autophagic degradation of p53 in CD4+ T cells remains an unresolved question. In this study, we demonstrated that heightened levels of IFN-γ in the plasma during aGVHD promoted the activation, proliferation, and autophagic activity of CD4+ T cells. Furthermore, IFN-γ induced the nuclear-to-cytoplasm translocation and autophagy-dependent degradation of p53 in CD4+ T cells. The translocation and autophagic degradation of p53 were contingent upon HMGB1, which underwent upregulation and translocation from the nucleus to the cytoplasm following IFN-γ stimulation. In conclusion, our data unveil a novel mechanism underlying p53 deficiency in CD4+ T cells among aGVHD patients. This deficiency is induced by IFN-γ and relies on autophagy, establishing a link between IFN-γ, HMGB1-mediated translocation, and the autophagic degradation of p53.

Altered spontaneous brain activity patterns in hypertensive retinopathy using fractional amplitude of low-frequency fluctuations: a functional magnetic resonance imaging study.

AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P<0.001). The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores (r=0.9232; P<0.0001) and depression scores (r=0.9682; P<0.0001). CONCLUSION: fALFF values in multiple brain regions of HR patients are abnormal, suggesting that these brain regions in HR patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of HR.

Ferrostatin-1 alleviates skin inflammation and inhibits ferroptosis of neutrophils and CD8+ T cells in allergic contact dermatitis.

BACKGROUND: Ferroptosis is considered as an immunogenic type of regulated cell death and associated with the pathogenesis of inflammatory skin diseases. However, the involvement and function of ferroptosis in allergic contact dermatitis (ACD) remains unknown. OBJECTIVE: To explore the role of ferroptosis in ACD. To reveal which type of cells develops ferroptosis in ACD. METHODS: We detected the key markers of ferroptosis in 1-Chloro-2,4-dinitrochlorobenzene (DNCB)-induced ACD mice model. We applicated ferrostatin-1 (Fer-1) to restrain ferroptosis in ACD mice and then compared the severity of dermatitis and the level of inflammation and ferroptosis in dermis and epidermis, respectively. Keratinocyte-specific Gpx4 conditional knockout (cKO) mice were used to investigate the function of keratinocyte ferroptosis in the development of ACD. Single-cell RNA sequencing was conducted to analyze the affection of Fer-1 on different type of cells in ACD. RESULTS: Ferroptosis was involved in DNCB-induced ACD mice. Ferroptosis activation was more remarkable in dermis rather than in epidermis. Gpx4 cKO mice showed similar severity of skin dermatitis as control mice. Fer-1 alleviated skin inflammation in mice and reduced ferroptosis in neutrophils and CD8+ T cells both of which contribute to development of ACD. CONCLUSION: Ferroptosis was activated in immune cells, especially neutrophils and CD8+ T cells in DNCB-induced ACD mice. Fer-1 treatment inhibited ferroptosis of neutrophils and CD8+ T cells and relieved skin damage in ACD mice.

Three new flavonoid glycosides from the herbaceous stems of Ephedra intermedia.

Phytochemical investigation of the n-butanol extracts of the herbaceous stems of Epheda intermedia led to the isolation of eight flavonoids that included three new flavonoid glycosides (1-3) and five previously reported analogues (4-8). Their structures have been identified on the basis of various spectral data. Besides, all the flavonoids were tested in vitro for their ability to inhibit α-glucosidase under the positive control of acarbose, and the results indicated that none of them exhibited significant inhibitory effect on α-glucosidase at 100 µM.

Antiferromagnetic Frustration Behavior with Face-Sharing CuAs4 Tetrahedrons in Conducting ACu6As3 (A = Li and Na).

New mixed-valence copper pnictides ACu6As3 (A = Li and Na) adopt a quasi-2D structure type, featuring alkalis and [Cu6As3]- slabs along the c-axis alternatively. The face-sharing connection between CuAs4 polyhedra leads to a higher valence state for the inside Cu ions than that of Cu ions with the other connectivity way. This is confirmed by X-ray photoemission spectroscopy results. The Cu2+ with near spin 1/2 located on bilayer triangular lattice is found to exhibit a peculiar hump in magnetic susceptibility along the c-axis and, most strikingly, nearly a constant at low temperatures from 1.8 K down to 0.4 K. Besides, high hole mobilities, 68.58 and 645.16 cm2 V-1 S-1, are observed in LiCu6As3 and NaCu6As3, respectively. These compounds provide a novel material system for researching the relationship among structure, valence state, and spin correlation in frustrated lattice.

DeepPlaq: Dental plaque indexing based on deep neural networks.

OBJECTIVES: The selection of treatment for dental plaque is closely related to the condition of the plaque on different teeth. This study validated the ability of CNN models in assessing the dental plaque indices. MATERIALS AND METHODS: In 70 (20 male and 50 female) healthy adults (18 to 55 years old), frontal and lateral view intraoral images (210) of plaque disclosing agent stained permanent and deciduous dentitions were obtained. A three-stage method was employed, where the You Look Only Once version 8 (YOLOv8) model was first used to detect the target teeth, followed by the prompt-based Segment Anything Model (SAM) segmentation algorithm to segment teeth. A new single-tooth dataset consisting of 1400 photographs was obtained after applying a two-stage method. Finally, a multi-class classification model DeepPlaq was trained and evaluated on the accuracy of dental plaque indexing based on the Quigley-Hein Index (QHI) scoring system. Classification performance was measured using accuracy, recall, precision, and F1-score. RESULTS: The teeth detector exhibited an accuracy (mean average precision, mAP) of approximately 0.941 ± 0.005 in identifying teeth with plaque disclosing agents. The maximum accuracy attained in the plaque indexing through DeepPlaq was 0.84 (probability that DeepPlaq scored identical to experts), and the smallest average scoring error was less than 0.25 on a 0 to 5 scale for scoring. CONCLUSIONS: A three-stage approach demonstrated excellent performance in detecting and segmenting target teeth, and DeepPlaq model also showed strong performance in assessing dental plaque indices. CLINICAL RELEVANCE: Application of artificial intelligence to the evaluation of dental plaque distribution could enhance diagnostic accuracy and treatment efficiency and accuracy.

Robust, transparent, self-healable, recyclable all-starch-based gel with thermoelectric capability for wearable sensor.

Conventional all-starch-based (ASB) gels are weak and lack ductility. The preparation of a robust ASB gel with multi-functionalities e.g., self-healing, anti-freezing, conductivity, and so forth, is highly desirable but challenging. Herein, a new kind of ASB gel was prepared by gelatinizing starch in urea and choline chloride solution (UC) with the aid of water. Its tensile strength was up to 1.08 MPa with a tensile strain of 313 %, and this value hardly changed after 10 days ageing. A high healing efficiency of 98 % can be achieved after 1 h of healing at room temperature, and the healed tensile strength reaches up to ca. 1.06 MPa, which is almost the highest value for ASB gel. The resultant ASB gel can surfer from bending and twisting at -80 °C. Moreover, ASB gel also exhibits excellent biocompatibility and biodegradability. In addition, UC endowed the ASB gel with ion conductivity, allowing it to be used as a flexible strain sensor to monitor human movement. The ion-conductive ASB gel also exhibited thermoelectric ability with a Seebeck coefficient of 2.5 mV K-1, which can be further improved to 5 mV K-1 with a maximum output voltage of 252 mV by introducing a gradient of ionic concentration.

Quercetin 7-rhamnoside from Sorbaria sorbifolia exerts anti-hepatocellular carcinoma effect via DHRS13/apoptotic pathway.

BACKGROUND: Previous research demonstrated the effects of Sorbaria sorbifolia (SS) in combating hepatocellular carcinoma (HCC). Despite SS's proven efficacy in treating HCC, the precise bioactive constituents contributing to its therapeutic benefits, along with the mechanisms behind them, warrant further exploration. PURPOSE: The objective of our study was to illuminate the possible elements, targets, and modulatory pathways employed by specific bioactive components in SS for HCC treatment. STUDY DESIGN: Using UPLC-Q-TOF-MS to analyze and quantify the bioactive constituents in the SS sample. By literature review, we gathered potential chemical constituents of SS. We used network pharmacology approaches to identify HCC-related targets of SS components, with an emphasis on core targets. To examine the core targets' importance in HCC biological processes, bioinformatics methods were utilized. Finally, molecular docking, MD simulations, and CESTA were employed to screen SS active ingredients capable of stably binding with core targets. To verify the anti-HCC effectiveness of these active components, we conducted several cellular experiments, including CCK8, wound healing, transwell, cell cycle, and apoptosis assays, as well as animal experiments like zebrafish HepG2 cell xenotransplantation, apoptosis assays, and HE staining. We also used lentivirus transfection to modulate core protein expression in HepG2 cells, creating cell models. Further cellular tests were performed to evaluate the ability of SS active ingredients to exert anti-HCC effects by interacting with the core protein to induce apoptosis. Finally, Western Blot and ELISA experiments were carried out to track changes in core protein and apoptosis-related pathway proteins after SS active ingredient treatment RESULTS: Our study identified 50 components in SS and 119 HCC-related target genes, with DHRS13 emerging as a core target. Further bioinformatics analysis indicated that DHRS13 expression in HCC patients correlated with prognosis and apoptotic pathways. Molecular docking revealed 20 active SS constituents effectively binding to DHRS13, MD simulations and CESTA pinpointed Quercetin 7-rhamnoside (Q7R) as the most stable binder. In-vitro and in-vivo tests verified Q7R's anti-HCC properties. Lentivirus transfection results showed that knockdown DHRS13 led to reduced cell growth and increased apoptosis, while overexpression DHRS13 led to increase cell growth and decrease apoptosis. Remarkably, our experiments found that Q7R acts as an inhibitor of DHRS13 and can reverse the suppressed apoptosis and excessive HCC proliferation caused by DHRS13 overexpression. CONCLUSION: Elevated DHRS13 expression contributes to HCC progression. Q7R effectively downregulates DHRS13, encouraging apoptosis and impeding HCC growth. As a result, Q7R shows potential as a therapeutic agent for HCC treatment, targeting the apoptotic pathway through DHRS13 regulation.

Tumor Microenvironment-Derived Exosomes: A Double-Edged Sword for Advanced T Cell-Based Immunotherapy.

The tumor microenvironment (TME) plays a crucial role in cancer progression and immune evasion, partially mediated by the activity of the TME-derived exosomes. These extracellular vesicles are pivotal in shaping immune responses through the transfer of proteins, lipids, and nucleic acids between cells, facilitating a complex interplay that promotes tumor growth and metastasis. This review delves into the dual roles of exosomes in the TME, highlighting both their immunosuppressive functions and their emerging therapeutic potential. Exosomes can inhibit T cell function and promote tumor immune escape by carrying immune-modulatory molecules, such as PD-L1, yet they also hold promise for cancer therapy as vehicles for delivering tumor antigens and costimulatory signals. Additionally, the review discusses the intricate crosstalk mediated by exosomes among various cell types within the TME, influencing both cancer progression and responses to immunotherapies. Moreover, this highlights current challenges and future directions. Collectively, elucidating the detailed mechanisms by which TME-derived exosomes mediate T cell function offers a promising avenue for revolutionizing cancer treatment. Understanding these interactions allows for the development of targeted therapies that manipulate exosomal pathways to enhance the immune system's response to tumors.

Parasitic behaviour and developmental morphology of Anastatus japonicus reared on the factitious host Antheraea pernyi.

The egg parasitoid Anastatus japonicus is a key natural enemy in the biological control of various agricultural and forestry pests. It is particularly used against the brown marmorated stink bug Halyomorpha halys and the emerging defoliator pest Caligula japonica in East Asia. It has been proved that the eggs of Antheraea pernyi can be used as a factitious host for the mass production of A. japonicus. This study systematically documented the parasitic behaviour and developmental morphology exhibited by A. japonicus on the eggs of A. pernyi. The parasitic behaviour of A. japonicus encompassed ten steps including searching, antennation, locating, digging, probing, detecting, oviposition, host-feeding, grooming, and resting. Oviposition, in particular, was observed to occur in three stages, with the parasitoids releasing eggs during the second stage when the body remained relatively static. Among all the steps of parasitic behaviour, probing accounted for the longest time, constituting 33.1% of the whole time. It was followed by digging (19.3%), oviposition (18.5%), antennation (9.6%), detecting (7.4%), and the remaining steps, each occupying less than 5.0% of the total event time. The pre-emergence of adult A. japonicus involves four stages: egg (0 to 2nd day), larva (3rd to 9th day), pre-pupa (10th to 13th day), pupa (14th to 22nd day), and subsequent development into an adult. Typically, it takes 25.60 ± 0.30 days to develop from an egg to an adult at 25℃. This information increases the understanding of the biology of A. japonicus and may provide a reference for optimising reproductive devices.

Innovative 3D Navigation Module for Precise Unilateral Pedicle Screw Combined with Contralateral Translaminar Facet Screw Placement in Lumbar Spine Surgery.

OBJECTIVE: The incidence of degenerative diseases of the lumbar spine has increased in recent years. Unilateral pedicle screw combined with contralateral translaminar facet screw fixation offers the advantages of less trauma, better stability, and fewer complications. However, the surgical difficulty and suboptimal pinning accuracy of translaminar facet screw placement in clinical practice limit its use. Therefore, in this study, we designed a novel suspended 3D-printed navigation module to facilitate fast and accurate intraoperative screw placement. The aim of this study is to investigate the digital design, precise implementation, and evaluation methods for placing unilateral pedicle screws in the lumbar spine combined with translaminar facet screw placement using a new suspended 3D navigation module. METHODS: This retrospective study included 46 patients with single-level lumbar lesions who underwent spine surgery at the Affiliated Hospital of Putian University between June 2022 and December 2023. The suspended navigation module was designed digitally. Preoperative screw placement was simulated using 3D printed models, followed by an intraoperative accurate screw placement facilitated by the navigation module and a postoperative evaluation of the accuracy of screw placement. The absolute difference in three-dimensional coordinates of the inlet and outlet points of the preoperative design and the postoperative screw-nail channel served as the precision index. RESULTS: In a study involving 46 patients, surgery was successful with 92 pedicle screws and 46 translaminar facet screws placed without any penetration of the cortex. The difference in coordinates before and after screw insertion was minimal, with entry points varying between 1.21 to 1.36 mm and exit points between 1.97 to 2.46 mm. When screw accuracy met certain thresholds, there was no significant difference between preoperative design and postoperative coordinates, indicating precise replication of the surgical plan. CONCLUSION: The new suspended 3D navigation module enables the precise placement of unilateral pedicle screws in the lumbar spine combined with translaminar pedicle screws for precise surgery.

Oroxylin A attenuates psoriasiform skin inflammation by direct targeting p62 (sequestosome 1) via suppressing M1 macrophage polarization.

BACKGROUND AND PURPOSE: Psoriasis results from the interplay of innate and adaptive immunity in the skin. Oroxylin A (OA) has shown anti-inflammatory effects in various disorders. This study explores oroxylin A potential in treating psoriasis, particularly its impact on type I macrophage (Mφ1) polarization. EXPERIMENTAL APPROACH: Oroxylin A-mediated therapeutic effects were evaluated using imiquimod-induced or IL-23-injected psoriatic mice models, followed by proteomics assays to predict potential signalling and targeting proteins. Immunofluorescence and immunoblot assays verified that oroxylin A suppresses NF-kB signalling in M1 macrophages. Co-immunoprecipitation and microscale thermophoresis (MST) assays further demonstrated that p62 (sequestosome 1) is the target protein for oroxylin A in macrophages. Oroxylin A-p62-mediated suppression of psoriasis was validated in an imiquimod-induced p62 conditional knockout (cKO) mice model. KEY RESULTS: Oroxylin A demonstrated therapeutic efficacy in murine models induced by imiquimod or IL-23 by attenuating cutaneous inflammation and mitigating Mφ1 polarization via NF-κB signalling. Proteomics analysis suggested SQSTM1/p62 as a key target, confirmed to interact directly with oroxylin A. Oroxylin A disrupted the p62-PKCζ interaction by binding to PB1 domain of p62. Its anti-inflammatory effects were significantly reduced in macrophages from p62 cKO mice compared to the wild-type (WT) mice in psoriasis model, supporting oroxylin A role in suppressing Mφ1 polarization through its interaction with p62. CONCLUSION AND IMPLICATIONS: Our findings demonstrated oroxylin A suppressed psoriasiform skin inflammation in mouse models by blocking the PKCζ-p62 interaction, subsequently inhibiting the activation of NF-κB p65 phosphorylation in macrophages.

Multi-interpenetration driven ultra-robust ionic HOF with high proton conductivity for DMFCs.

Herein, a novel ionic hydrogen-bonded organic framework (iHOF-12) was synthesized. The 5-fold interpenetrating network structure and charge-assisted synergistic effects enable iHOF-12 to maintain robustness under demanding conditions and attain excellent proton conductivity of 1.23 × 10-2 S cm-1, which contributes to the enhancement of the DMFC performance.

miR-137: a potential therapeutic target for lung cancer.

Lung cancer is a prevalent malignancy and the leading cause of cancer-related deaths, posing a significant threat to human health. Despite advancements in treatment, the prognosis for lung cancer patients remains poor due to late diagnosis, cancer recurrence, and drug resistance. Epigenetic research, particularly in microRNAs, has introduced a new avenue for cancer prevention and treatment. MicroRNAs, including miR-137, play a vital role in tumor development by regulating various cellular processes. MiR-137 has garnered attention for its tumor-suppressive properties, with studies showing its potential in inhibiting cancer progression. In lung cancer, miR-137 is of particular interest, with numerous reports exploring its role and mechanisms. A comprehensive review is necessary to consolidate current evidence. This review highlights recent studies on miR-137 in lung cancer, covering cell proliferation, migration, apoptosis, drug resistance, and therapy, emphasizing its potential as a biomarker and therapeutic target for lung cancer treatment and prognosis.

Efficient Deep-Blue Organic Light-Emitting Diodes Employing Doublet Sensitization.

Fast and efficient exciton utilization is a crucial solution and highly desirable for achieving high-performance blue organic light-emitting diodes (OLEDs). However, the rate and efficiency of exciton utilization in traditional OLEDs, which employ fully closed-shell materials as emitters, are inevitably limited by spin statistical limitations and transition prohibition. Herein, a new sensitization strategy, namely doublet-sensitized fluorescence (DSF), is proposed to realize high-performance deep-blue electroluminescence. In the DSF-OLED, a doublet-emitting cerium(III) complex, Ce-2, is utilized as sensitizer for multi-resonance thermally activated delayed fluorescence emitter ν-DABNA. Experimental results reveal that holes and electrons predominantly recombine on Ce-2 to form doublet excitons, which subsequently transfer energy to the singlet state of ν-DABNA via exceptionally fast (over 108 s-1) and efficient (≈100%) Förster resonance energy transfer for deep-blue emission. Due to the circumvention of spin-flip in the DSF mechanism, near-unit exciton utilization efficiency and remarkably short exciton residence time of 1.36 µs are achieved in the proof-of-concept deep-blue DSF-OLED, which achieves a Commission Internationale de l'Eclairage coordinate of (0.13, 0.14), a high external quantum efficiency of 30.0%, and small efficiency roll-off of 14.7% at a luminance of 1000 cd m-2. The DSF device exhibits significantly improved operational stability compared with unsensitized reference device.

Comparative single-cell transcriptomic analysis across tissues of aging primates reveals specific autologous activation of ZNF281 to mitigate oxidative stress in cornea.

Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age-related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single-cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue-specific aging and developing new therapies targeting ROS damage.

The influence of occupant control behaviour on thermal comfort under different heating charging modes in residential buildings in cold regions.

In China's central heating, there are two modes for calculating heating costs, which are divided into Charging by flow mode which charges according to the amount of use and Charging by area mode which charges according to the floor area. The Charging by flow mode has been increasingly adopted by numerous urban central heating buildings. Thus it is worth investigating whether occupants experience varying levels of thermal comfort under these two modes. To address this, a field test and subjective questionnaire survey were conducted on residential buildings in cold regions of China during the heating season. The study assessed 134 residential occupants utilizing radiator heating, comprising 66 in Charging by area and 68 in Charging by flow modes. A collection of 1206 valid data points was obtained, with 609 in Charging by area mode and 597 in Charging by flow mode. The findings reveal noteworthy disparities in the duration, area, and strength of heating equipment usage between the two modes. While there are no marked variances in the interior and exterior environmental conditions under both modes, residents in the Charging by flow mode experience enhanced thermal comfort, acceptability and expectation, as well as better air quality satisfaction. Perceived control can greatly enhance individuals' thermal sensation in temperatures below 18 °C and above 24 °C. The impact of perceived control on thermal expectation is linear with temperature adjustments. The heightened degree of sensing control in Charging by flow mode lowers residents' expectations of high temperatures, broadens the range of acceptable low temperatures and accomplishes energy conservation and carbon reduction while ensuring optimal comfort.

The influence of partner trustworthiness and relationship closeness on interpersonal trust in individuals with attachment anxiety: An ERP study.

Interpersonal trust (IT) is a combination of individuals' cognitive evaluations of others' trustworthiness and affective considerations related to the relationships. Individuals' trust decisions overly relying on the intimacy of the relationship can be detrimental to their socialization. Attachment styles provide a theoretical framework for explaining individual differences in IT and the balance between cognition control and affective evaluation in social-information processing. However, it remains unclear whether high attachment anxiety (AX) individuals with high interpersonal needs exhibit non-socially adaptive trust decisions, characterized by an over-reliance on relationship closeness (RC), independent of partner trustworthiness (PT). A coin-toss task, combined with event-related potential (ERP), was utilized to explore the performance and temporal characteristics of trust decision-making among individuals with high and low AX under the influence of the two factors. The behavioral results showed that high-AX individuals tended to trust close others regardless of their trustworthiness, while low-AX individuals only trusted close others under low-PT conditions, with no differences in RC for high-PT. The ERP results revealed that high-AX individuals exhibited an enhanced positive P1 by low-trust partners, only discerning differences in RC for high-trust partners (more negative N2 by strangers than friends), reflecting poor conflict-detection abilities confronted with low-trust partners. Low-AX individuals' neural activity showed higher consistency with their behavioral performance, indicating that trust in close others under low-trust conditions was due to the fewer conflicts elicited and higher expectations of them, reflecting smaller N2 and larger P3. Overall, these findings indicated that high-AX individuals' IT decision-making was primarily influenced by their reliance on affective evaluation in information processing and weaker cognitive-control abilities, highlighting the contribution of attachment to social-information processing.

PTBP1 Regulates DNMT3B Alternative Splicing by Interacting With RALY to Enhance the Radioresistance of Prostate Cancer.

Radiotherapy is a curative arsenal for prostate cancer (PCa), but radioresistance seriously compromises its effectiveness. Dysregulated RNA splicing factors are extensively involved in tumor progression. Nonetheless, the role of splicing factors in radioresistance remains largely unexplored in PCa. Here, 23 splicing factors that are differentially expressed between PCa and adjacent normal tissues across multiple public PCa databases are identified. Among those genes, polypyrimidine tract binding protein 1 (PTBP1) is significantly upregulated in PCa and is positively associated with advanced clinicopathological features and poor prognosis. Gain- and loss-of-function experiments demonstrate that PTBP1 markedly reinforces genomic DNA stability to desensitize PCa cells to irradiation in vitro and in vivo. Mechanistically, PTBP1 interacts with the heterogeneous nuclear ribonucleoproteins (hnRNP) associated with lethal yellow protein homolog (RALY) and regulates exon 5 splicing of DNA methyltransferase 3b (DNMT3B) from DNMT3B-S to DNMT3B-L. Furthermore, upregulation of DNMT3B-L induces promoter methylation of dual-specificity phosphatase-2 (DUSP2) and subsequently inhibits DUSP2 expression, thereby increasing radioresistance in PCa. The findings highlight the role of splicing factors in inducing aberrant splicing events in response to radiotherapy and the potential role of PTBP1 and DNMT3B-L in reversing radioresistance in PCa.

Constructing a Large Language Model to Generate Impressions from Findings in Radiology Reports.

Background The specialization and complexity of radiology makes the automatic generation of radiologic impressions (ie, a diagnosis with differential diagnosis and management recommendations) challenging. Purpose To develop a large language model (LLM) that generates impressions based on imaging findings and to evaluate its performance in professional and linguistic dimensions. Materials and Methods Six radiologists recorded imaging examination findings from August 2 to 31, 2023, at Shanghai General Hospital and used the developed LLM before routinely writing report impressions for multiple radiologic modalities (CT, MRI, radiography, mammography) and anatomic sites (cranium and face, neck, chest, upper abdomen, lower abdomen, vessels, bone and joint, spine, breast), making necessary corrections and completing the radiologic impression. A subset was defined to investigate cases where the LLM-generated impressions differed from the final radiologist impressions by excluding identical and highly similar cases. An expert panel scored the LLM-generated impressions on a five-point Likert scale (5 = strongly agree) based on scientific terminology, coherence, specific diagnosis, differential diagnosis, management recommendations, correctness, comprehensiveness, harmlessness, and lack of bias. Results In this retrospective study, an LLM was pretrained using 20 GB of medical and general-purpose text data. The fine-tuning data set comprised 1.5 GB of data, including 800 radiology reports with paired instructions (describing the output task in natural language) and outputs. Test set 2 included data from 3988 patients (median age, 56 years [IQR, 40-68 years]; 2159 male). The median recall, precision, and F1 score of LLM-generated impressions were 0.775 (IQR, 0.56-1), 0.84 (IQR, 0.611-1), and 0.772 (IQR, 0.578-0.957), respectively, using the final impressions as the reference standard. In a subset of 1014 patients (median age, 57 years [IQR, 42-69 years]; 528 male), the overall median expert panel score for LLM-generated impressions was 5 (IQR, 5-5), ranging from 4 (IQR, 3-5) to 5 (IQR, 5-5). Conclusion The developed LLM generated radiologic impressions that were professionally and linguistically appropriate for a full spectrum of radiology examinations. © RSNA, 2024 Supplemental material is available for this article.