KRN5b regulates maize kernel row number through mediating phosphoinositol signalling.

Kernel row number (KRN) is a major yield related trait for maize (Zea mays L.) and is also a major goal of breeders, as it can increase the number of kernels per plant. Thus, identifying new genetic factors involving in KRN formation may accelerate improving yield-related traits genetically. We herein describe a new kernel number-related gene (KRN5b) identified from KRN QTL qKRN5b and encoding an inositol polyphosphate 5-phosphatase (5PTase). KRN5b has phosphatase activity towards PI(4,5)P2, PI(3,4,5)P3, and Ins(1,4,5)P3 in vitro. Knocking out KRN5b caused accumulation of PI(4,5)P2 and Ins(1,4,5)P3, resulting in disordered kernel rows and a decrease in the number of kernels and tassel branches. The introgression of the allele with higher expression abundance into different inbred lines could increase the ear weight of the inbred lines and the corresponding hybrids by 10.1%-12.2% via increasing KRN, with no adverse effects on other agronomic traits. Further analyses showed that KRN5b regulates inflorescence development through affecting the synthesis and distribution of hormones. Together, KRN5b contributes to spikelet pair meristem development through inositol phosphate and phosphatidylinositols, making it a selecting target for yield improvement.

Effect of chickpea protein modified with combined heating and high-pressure homogenization on enhancing the gelation of reduced phosphate myofibrillar protein.

The effects of chickpea protein (CP) modified by heating and/or high-pressure homogenization (HPH) on the gelling properties of myofibrillar protein under reduced phosphate conditions (5 mM sodium triphosphate, STPP) were investigated. The results showed that heating and HPH dual-modified CP could decrease the cooking loss by 29.57 %, elevate the water holding capacity by 17.08 %, and increase the gel strength by 126.88 %, which conferred myofibrillar protein with gelation performance comparable with, or even surpassing, that of the high-phosphate (10 mM STPP) control. This gelation behavior improvement could be attributed to enhanced myosin tail-tail interactions, decreased myosin thermal stability, elevated trans-gauche-trans disulfide conformation, strengthened hydrophobic interactions and hydrogen bonding, the uncoiling of α-helical structures, the formation of well-networked myofibrillar protein gel, and the disulfide linkages between the myosin heavy chain, actin, and CP subunits. Therefore, the dual-modified CP could be a promising phosphate alternative to develop healthier meat products.

Janus kinase inhibitors and adverse events of acne in dermatologic indications: a systematic review and network meta-analysis.

Background: The occurrence of acne in patients treated with Janus kinase (JAK) inhibitors for skin diseases is a potential issue, which may reduce treatment adherence.Purpose: To systematically analyzes randomized clinical trials (RCTs) of JAK inhibitors in dermatological indications for the risk of acne as an adverse event.Methods: A meta-analysis of odds ratios (ORs) for acne incidence was conducted. Data were quantitatively synthesized using random-effects meta-analysis. Surface under the cumulative ranking curve (SUCRA) values representing the relative ranking probabilities of treatments were obtained. Analyses were performed using R statistical software version 4.4.0.Results: A total of 11,396 patients were included from 24 studies. The incidence of acne for JAK inhibitors was ranked according to the SUCRA as follows: JAK1 inhibitors > TYK2 inhibitors > combined JAK1 and JAK2 inhibitors > combined JAK1 and TYK2 inhibitors > JAK3 + TEC inhibitors > pan-JAK inhibitors. ORs were higher for longer durations of drug use and larger dosages. Subgroup analyses by disease indication revealed increased ORs for psoriasis (5.52 [95% CI, 1.39-21.88]), vitiligo (4.15 [95% CI, 1.27-13.58]), alopecia areata (3.86 [95% CI, 1.58-9.42]), and atopic dermatitis (2.82 [95% CI, 1.75-4.54]). The use of JAK inhibitors in patients with systemic lupus erythematosus (SLE) may not significantly increase the incidence of acne.Conclusions: There are higher rates of acne following treatment with JAK inhibitors for dermatologic indications, particularly with longer durations and larger dosages. Pan-JAK inhibitors exhibit the lowest incidence of acne.

Intelligent MEMS Sensor Based on an Oxidized Medium-Entropy Alloy (FeCoNi) for H2 and CO Recognition.

In this paper, we present the design and evaluation of an intelligent MEMS sensor employing the oxidized medium-entropy alloy (O-MEA) of FeCoNi as the gas-sensing material. Due to the specific catalytic exothermic reaction of the O-MEA on H2/CO, the sensor shows great selectivity for H2 and CO at 150 °C of the integrated microheater in the MEMS device, with the theoretical detection limit of 0.3 ppm for H2 and 0.29 ppm for CO. The MEMS heater, capable of instantaneous temperature changes in pulse operation mode, offers a novel approach for thermal modulation of the sensor, which is crucial for the adsorption and reaction of H2/CO molecules on the sensing layer surface. Consequently, we investigate the gas-sensing capabilities of the sensor under pulse heating modes (PHMs) of the MEMS heater and then propose the gas-sensing mechanism. The results indicate that PHMs significantly not only reduce the operating temperature and power consumption but also enhance the sensor's functionality by providing multivariable response signals, paving the way for intelligent gas detection. Based on the high selectivity to H2 and CO, transforming the transient sensing curves into two-dimensional images via Gramian Angular Field (GAF) model and subsequent modeling using a convolutional neural network (CNN) algorithm, we have realized efficient and intelligent recognition of H2 and CO. This work provides insight for the development of low-power, high-performance MEMS gas sensors and further intelligence of individual MEMS sensors.

GMP-compliant automated radiosynthesis of [18F] SynVesT-1 for PET imaging of synaptic vesicle glycoprotein 2 A (SV2A).

BACKGROUND: A novel positron emission tomography (PET) imaging tracer, [18F] SynVesT-1, targeting synaptic vesicle glycoprotein 2 (SV2A), has been developed to meet clinical demand. Utilizing the Trasis AllinOne-36 (AIO) module, we've automated synthesis to Good Manufacturing Practice (GMP) standards, ensuring sterile, pyrogen-free production. The fully GMP-compliant robust synthesis of [18F] SynVesT-1 boosting reliability and introducing a significant degree of simplicity and its comprehensive validation for routine human use. RESULTS: [18F] SynVesT-1 was synthesized by small modifications to the original [18F] SynVesT-1 synthesis protocol to better fit AIO module using an in-house designed cassette and sequence. With a relatively small precursor load of 5 mg, [18F] SynVesT-1 was obtained with consistently high radiochemical yields (RCY) of 20.6 ± 1.2% (the decay-corrected RCY, n = 3) at end of synthesis. Each of the final formulated batches demonstrated radiochemical purity (RCP) and enantiomeric purity surpassing 99%. The entire synthesis process was completed within a timeframe of 80 min (75 ± 3.1 min, n = 3), saves 11 min compared to reported GMP automated synthesis procedures. The in-human PET imaging of total body PET/CT and time-of-flight (TOF) PET/MR showed that [18F] SynVesT-1 is an excellent tracer for SV2A. It is advantageous for decentralized promotion and application in multi-center studies. CONCLUSION: The use of AIO synthesizer maintains high production yields and increases reliability, reduces production time and allows rapid training of production staff. Besides, the as-prepared [18F] SynVesT-1 displays excellent in vivo binding properties in humans and holds great potential for the imaging and quantification of synaptic density in vivo.

Remote sensing estimates of global sea surface nitrate: Methodology and validation.

Information about sea surface nitrate (SSN) concentrations is crucial for estimating oceanic new productivity and for carbon cycle studies. Due to the absence of optical properties in SSN and the intricate relationships with environmental factors affecting spatiotemporal dynamics, developing a more representative and widely applicable remote sensing inversion algorithm for SSN is challenging. Most methods for the remote estimation of SSN are based on data-driven neural networks or deep learning and lack mechanistic descriptions. Since fitting functions between the SSN and sea surface temperature (SST), mixed layer depth (MLD), and chlorophyll (Chl) content have been established for the open ocean, it is important to include the remote sensing indicator photosynthetically active radiation (PAR), which is critical in nitrate biogeochemical processes. In this study, we employed an algorithm for estimating the monthly average SSN on a global 1° by 1° resolution grid; this algorithm relies on the empirical relationship between the World Ocean Atlas 2018 (WOA18) monthly interpolated climatology of nitrate in each 1° × 1° grid and the estimated monthly SST and PAR datasets from Moderate Resolution Imaging Spectroradiometer (MODIS) and MLD from the Hybrid Coordinate Ocean Model (HYCOM). These results indicated that PAR potentially affects SSN. Furthermore, validation of the SSN model with measured nitrate data from different months and locations for the years 2018-2023 yielded a high prediction accuracy (N = 12,846, R2 = 0.93, root mean square difference (RMSE) = 3.12 µmol/L, and mean absolute error (MAE) = 2.22 µmol/L). Further independent validation and sensitivity tests demonstrated the validity of the algorithm for retrieving SSN.

Structure, ingredient, and function-based biomimetic scaffolds for accelerated healing of tendon-bone interface.

Background: Tendon-bone interface (TBI) repair is slow and challenging owing to its hierarchical structure, gradient composition, and complex function. In this work, enlightened by the natural characteristics of TBI microstructure and the demands of TBI regeneration, a structure, composition, and function-based scaffold was fabricated. Methods: The biomimetic scaffold was designed based on the "tissue-inducing biomaterials" theory: (1) a porous scaffold was created with poly-lactic-co-glycolic-acid, nano-hydroxyapatite and loaded with BMP2-gelatinmp to simulate the bone (BP); (2) a hydrogel was produced from sodium alginate, type I collagen, and loaded with TGF-ß3 to simulate the cartilage (CP); (3) the L-poly-lactic-acid fibers were oriented to simulate the tendon (TP). The morphology of tri-layered constructs, gelation kinetics, degradation rate, release kinetics and mechanical strength of the scaffold were characterized. Then, bone marrow mesenchymal stem cells (MSCs) and tenocytes (TT-D6) were cultured on the scaffold to evaluate its gradient differentiation inductivity. A rat Achilles tendon defect model was established, and BMSCs seeded on scaffolds were implanted into the lesionsite. The tendon-bone lesionsite of calcaneus at 4w and 8w post-operation were obtained for gross observation, radiological evaluation, biomechanical and histological assessment. Results: The hierarchical microstructures not only endowed the scaffold with gradual composition and mechanical properties for matching the regional biophysical characteristics of TBI but also exhibited gradient differentiation inductivity through providing regional microenvironment for cells. Moreover, the scaffold seeded with cells could effectively accelerate healing in rat Achilles tendon defects, attributable to its enhanced differentiation performance. Conclusion: The hierarchical scaffolds simulating the structural, compositional, and cellular heterogeneity of natural TBI tissue performed therapeutic effects on promoting regeneration of TBI and enhancing the healing quality of Achilles tendon. The translational potential of this article: The novel scaffold showed the great efficacy on tendon to bone healing by offering a structural and compositional microenvironment. The results meant that the hierarchical scaffold with BMSCs may have a great potential for clinical application.

Oxidative stress in alcoholic liver disease, focusing on proteins, nucleic acids, and lipids: A review.

Oxidative stress is one of the important factors in the development of alcoholic liver disease. The production of reactive oxygen species and other free radicals is an important feature of alcohol metabolism in the liver and an important substance in liver injury. When large amounts of ROS are produced, the homeostasis of the liver REDOX system will be disrupted and liver injury will be caused. Oxidative stress can damage proteins, nucleic acids and lipids, liver dysfunction. In addition, damaging factors produced by oxidative damage to liver tissue can induce the occurrence of inflammation, thereby aggravating the development of ALD. This article reviews the oxidative damage of alcohol on liver proteins, nucleic acids, and lipids, and provides new insights and summaries of the oxidative stress process. We also discussed the relationship between oxidative stress and inflammation in alcoholic liver disease from different perspectives. Finally, the research status of antioxidant therapy in alcoholic liver disease was summarized, hoping to provide better help for learning and developing the understanding of alcoholic liver disease.

Study on Synthesis and Regulation of PPVI and PPVII in Paris polyphylla with UV.

Paris polyphylla Smith var. Chinensis (Franch.) Hara is a medicinal plant that belongs to the Liliaceae family. Its main components are parissaponins, which have excellent medicinal effects such as anti-inflammatory, anti-tumor, etc. Improving the quality of parissaponins through artificial directional regulation has emerged as a practice to meet medical demand and is a new research hotspot. In this paper, P. polyphylla plants were treated with UVA, UVB, and UVC, and the contents of PolyPhyllin VI (PPVI) and PolyPhyllin VII (PPVII), saponin synthase (squalene synthase, SS; cycloartenol synthase, CAS; cytochrome P450, CYP450; and glycosyl transferases, GT) activity, MDA, and the photosynthetic pigment indexes were measured and analyzed. The results showed that PPVII content increased by 32.43% with UVC treatment after 4 h (3.43 mg/g), but the PPVI and PPVII contents in the other groups decreased compared with CK (control group) and they did not return to the original level after 4 h. SS, CAS, CYP450, and GT synthases were activated in varying degrees via UV treatment and increased, respectively, by 22.93%, 10.83%, 20.15%, and 25.98%. Among them, GT, as the last of the synthetases, had a shorter response time to UVB (30 min) and UVC (15 min); the difference was sensible compared with CK. Moreover, UV had a stressing effect and promoted the rapid accumulation of MDA content (increased 17.66%, 34.53%, and 9.65%) and carotenoid (increased 7.58, 5.60, and 7.76 times) within 4 h compared to CK. UVB and UVC radiation visibly improved chlorophyll a content (42.56% and 35.45%), but UVA did not, and the change in chlorophyll b content showed no overt statistical difference. In addition, PPVI and PPVII were negatively correlated with SS, CAS, carotenoids, and MDA (p < 0.05) and positively correlated with CYP450, GT, and chlorophyll a (p < 0.05). This study provides a theoretical basis for using UV light to regulate secondary metabolism in P. polyphylla, which is of great value for production management.

Neuroinflammation in Parkinson's disease: focus on the relationship between miRNAs and microglia.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that affects the central nervous system (CNS). Neuroinflammation is a crucial factor in the pathological advancement of PD. PD is characterized by the presence of activated microglia and increased levels of proinflammatory factors, which play a crucial role in its pathology. During the immune response of PD, microglia regulation is significantly influenced by microRNA (miRNA). The excessive activation of microglia, persistent neuroinflammation, and abnormal polarization of macrophages in the brain can be attributed to the dysregulation of certain miRNAs. Additionally, there are miRNAs that possess the ability to inhibit neuroinflammation. miRNAs, which are small non-coding epigenetic regulators, have the ability to modulate microglial activity in both normal and abnormal conditions. They also have a significant impact on promoting communication between neurons and microglia.

Restriction Spectrum Imaging and Diffusion Kurtosis Imaging for Assessing Proliferation Status in Rectal Carcinoma.

OBJECTIVES: To investigate the application of the three-compartment restriction spectrum imaging (RSI) model, diffusion kurtosis imaging (DKI), and diffusion-weighted imaging (DWI) in predicting Ki-67 status in rectal carcinoma. METHODS: A total of 80 rectal carcinoma patients, including 47 high-proliferation (Ki-67 > 50%) cases and 33 low-proliferation (Ki-67 ≤ 50%) cases, underwent pelvic MRI were enrolled. Parameters derived from RSI (f1, f2, and f3), DKI (MD and MK), and DWI (ADC) were calculated and compared between the two groups. Logistic regression (LR) analysis was conducted to identify independent predictors and assess combined diagnosis. Area under the receiver operating characteristic curve (AUC), DeLong analysis, and calibration curve analyses were performed to evaluate diagnostic performance. RESULTS: The patients with high-proliferation rectal carcinoma exhibited significantly higher f1 and MK values and significantly lower ADC, MD, f2, and f3 values than those with low-proliferation rectal carcinoma (P < 0.05). LR analysis showed that MD, MK, and f2 were independent predictors for Ki-67 status in rectal carcinoma. Moreover, the combination of these three parameters achieved an optimal diagnostic efficacy (AUC = 0.877, sensitivity = 80.85%, specificity = 84.85%) that was significantly better than that obtained using ADC (AUC = 0.783, Z = 2.347, P = 0.019), f2 (AUC = 0.732, Z = 2.762, P = 0.006), and f3 (AUC = 0.700, Z = 3.071, P = 0.002). The combined diagnosis also showed good performance (AUC = 0.859) in the internal validation analysis based on 1000 bootstrap samples, while the calibration curve demonstrated that the combined diagnosis provided good stability. CONCLUSION: RSI, DKI, and DWI can effectively differentiate between patients with high- and low-proliferation rectal carcinoma. Furthermore, the MD, MK, and f2 imaging parameters may be a novel and promising combination biomarker for examining Ki-67 status in rectal carcinoma.

Pharmacological Gq inhibition induces strong pulmonary vasorelaxation and reverses pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease with limited survival. Herein, we propose the pharmacological inhibition of Gq proteins as a novel concept to counteract pulmonary vasoconstriction and proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in PAH. We demonstrate that the specific pan-Gq inhibitor FR900359 (FR) induced a strong vasorelaxation in large and small pulmonary arteries in mouse, pig, and human subjects ex vivo. Vasorelaxation by FR proved at least as potent as the currently used triple therapy. We also provide in vivo evidence that local pulmonary application of FR prevented right ventricular systolic pressure increase in healthy mice as well as in mice suffering from hypoxia (Hx)-induced pulmonary hypertension (PH). In addition, we demonstrate that chronic application of FR prevented and also reversed Sugen (Su)Hx-induced PH in mice. We also demonstrate that Gq inhibition reduces proliferation and migration of PASMCs in vitro. Thus, our work illustrates a dominant role of Gq proteins for pulmonary vasoconstriction as well as remodeling and proposes direct Gq inhibition as a powerful pharmacological strategy in PH.

Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23.

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

Burden re-analysis of neurodevelopmental disorder cohorts for prioritization of candidate genes.

This study aimed to uncover novel genes associated with neurodevelopmental disorders (NDD) by leveraging recent large-scale de novo burden analysis studies to enhance a virtual gene panel used in a diagnostic setting. We re-analyzed historical trio-exome sequencing data from 745 individuals with NDD according to the most recent diagnostic standards, resulting in a cohort of 567 unsolved individuals. Next, we designed a virtual gene panel containing candidate genes from three large de novo burden analysis studies in NDD and prioritized candidate genes by stringent filtering for ultra-rare de novo variants with high pathogenicity scores. Our analysis revealed an increased burden of de novo variants in our selected candidate genes within the unsolved NDD cohort and identified qualifying de novo variants in seven candidate genes: RIF1, CAMK2D, RAB11FIP4, AGO3, PCBP2, LEO1, and VCP. Clinical data were collected from six new individuals with de novo or inherited LEO1 variants and three new individuals with de novo PCBP2 variants. Our findings add additional evidence for LEO1 as a risk gene for autism and intellectual disability. Furthermore, we prioritize PCBP2 as a candidate gene for NDD associated with motor and language delay. In summary, by leveraging de novo burden analysis studies, employing a stringent variant filtering pipeline, and engaging in targeted patient recruitment, our study contributes to the identification of novel genes implicated in NDDs.

Multi-scale brain attributes contribute to the distribution of diffuse glioma subtypes.

Gliomas are primary brain tumors and are among the most malignant types. Adult-type diffuse gliomas can be classified based on their histological and molecular signatures as IDH-wildtype glioblastoma, IDH-mutant astrocytoma, and IDH-mutant and 1p/19q-codeleted oligodendroglioma. Recent studies have shown that each subtype of glioma has its own specific distribution pattern. However, the mechanisms underlying the specific distributions of glioma subtypes are not entirely clear despite partial explanations such as cell origin. To investigate the impact of multi-scale brain attributes on glioma distribution, we constructed cumulative frequency maps for diffuse glioma subtypes based on T1w structural images and evaluated the spatial correlation between tumor frequency and diverse brain attributes, including postmortem gene expression, functional connectivity metrics, cerebral perfusion, glucose metabolism, and neurotransmitter signaling. Regression models were constructed to evaluate the contribution of these factors to the anatomic distribution of different glioma subtypes. Our findings revealed that the three different subtypes of gliomas had distinct distribution patterns, showing spatial preferences toward different brain environmental attributes. Glioblastomas were especially likely to occur in regions enriched with synapse-related pathways and diverse neurotransmitter receptors. Astrocytomas and oligodendrogliomas preferentially occurred in areas enriched with genes associated with neutrophil-mediated immune responses. The functional network characteristics and neurotransmitter distribution also contributed to oligodendroglioma distribution. Our results suggest that different brain transcriptomic, neurotransmitter, and connectomic attributes are the factors that determine the specific distributions of glioma subtypes. These findings highlight the importance of bridging diverse scales of biological organization when studying neurological dysfunction.

Measuring food access using least-cost diets: Results for global monitoring and targeting of interventions to improve food security, nutrition and health.

Benchmark diets using the most affordable locally available items to meet health and nutrition needs have long been used to guide food choice and nutrition assistance. This paper describes the result of recent innovations scaling up the use of such least-cost diets by UN agencies, the World Bank, and national governments for a different purpose, which is monitoring food environments and targeting systemic interventions to improve a population's access to sufficient food for an active and healthy life. Measuring food access using least-cost diets allows a clearer understanding of where poor diets are caused by unavailability or high prices for even the lowest-cost healthy foods, insufficient income or other resources to acquire those foods, or the use of other foods instead due to reasons such as time use and meal preparation costs, or cultural factors such as taste and aspirations. This paper reviews the data, methods and results that have led to official FAO and the World Bank adoption of cost and affordability metrics for global monitoring, and the parallel use of similar methods to guide interventions in country studies led by the World Food Programme with partner agencies across Africa, Asia and Latin America. We conclude by summarizing how increasing availability of food price data, matched to food composition and dietary requirements, allows analysts to use recently developed software tools for least-cost diet assessment to improve food access in a wide range of settings.

Instant and Multifunctional Nanofibers Loaded with Proanthocyanidins and Hyaluronic Acid for Skincare Applications.

Hyaluronic-acid- and silk-fibroin-based nanofibrous mats loaded with proanthocyanidins and collagen peptides were fabricated as multifunctional facial masks using electrospinning. Their morphology, hygroscopicity and moisture retention, DPPH, ABTS free radical scavenging abilities, and cytocompatibility were investigated. The results showed that the nanofibrous mats were dense and uniform, with an average diameter ranging from 300 to 370 nm. The nanofibrous mats exhibited satisfactory moisture retention, oxidation resistance, biocompatibility, especially excellent DPPH, and ABTS free radical scavenging capacities. DPPH free radical scavenging activity was 90% with 15 mg/L nanofibers, and ABTS free radical scavenging activity was 90% with 0.005 mg/L nanofibers. The nanofibrous mats protected fibroblasts from oxidative stress damage induced by tert-butyl hydroperoxide (t-BHP) and significantly promoted their proliferation. Compared with traditional liquid masks and semi-solid facial masks, the multifunctional nanofibrous mats prepared in this study contained fewer additives, which has significant advantages in terms of safety. The nanofibrous mats were rapidly dissolved within 5 s after being sprayed with water, which facilitated the release and penetration of active ingredients for skincare. Therefore, the multifunctional nanofibrous mats displayed excellent moisture retention, oxidation resistance, and biocompatibility, indicating promising translational potential as facial masks and providing a valuable reference for skincare.

Evaluating Large Language Models for Automated Reporting and Data Systems Categorization: Cross-Sectional Study.

BACKGROUND: Large language models show promise for improving radiology workflows, but their performance on structured radiological tasks such as Reporting and Data Systems (RADS) categorization remains unexplored. OBJECTIVE: This study aims to evaluate 3 large language model chatbots-Claude-2, GPT-3.5, and GPT-4-on assigning RADS categories to radiology reports and assess the impact of different prompting strategies. METHODS: This cross-sectional study compared 3 chatbots using 30 radiology reports (10 per RADS criteria), using a 3-level prompting strategy: zero-shot, few-shot, and guideline PDF-informed prompts. The cases were grounded in Liver Imaging Reporting & Data System (LI-RADS) version 2018, Lung CT (computed tomography) Screening Reporting & Data System (Lung-RADS) version 2022, and Ovarian-Adnexal Reporting & Data System (O-RADS) magnetic resonance imaging, meticulously prepared by board-certified radiologists. Each report underwent 6 assessments. Two blinded reviewers assessed the chatbots' response at patient-level RADS categorization and overall ratings. The agreement across repetitions was assessed using Fleiss κ. RESULTS: Claude-2 achieved the highest accuracy in overall ratings with few-shot prompts and guideline PDFs (prompt-2), attaining 57% (17/30) average accuracy over 6 runs and 50% (15/30) accuracy with k-pass voting. Without prompt engineering, all chatbots performed poorly. The introduction of a structured exemplar prompt (prompt-1) increased the accuracy of overall ratings for all chatbots. Providing prompt-2 further improved Claude-2's performance, an enhancement not replicated by GPT-4. The interrun agreement was substantial for Claude-2 (k=0.66 for overall rating and k=0.69 for RADS categorization), fair for GPT-4 (k=0.39 for both), and fair for GPT-3.5 (k=0.21 for overall rating and k=0.39 for RADS categorization). All chatbots showed significantly higher accuracy with LI-RADS version 2018 than with Lung-RADS version 2022 and O-RADS (P<.05); with prompt-2, Claude-2 achieved the highest overall rating accuracy of 75% (45/60) in LI-RADS version 2018. CONCLUSIONS: When equipped with structured prompts and guideline PDFs, Claude-2 demonstrated potential in assigning RADS categories to radiology cases according to established criteria such as LI-RADS version 2018. However, the current generation of chatbots lags in accurately categorizing cases based on more recent RADS criteria.

Abnormal static and dynamic brain network connectivity associated with chronic tinnitus.

In order to comprehensively understand the changes of brain networks in patients with chronic tinnitus, this study combined static and dynamic analysis methods to explore the abnormalities of brain networks. Thirty-two patients with chronic tinnitus and 30 age-, sex- and education-matched healthy controls (HC) were recruited. Independent component analysis was used to identify resting-state networks (RSNs). Static and dynamic functional network connectivity (FNC) were performed. The temporal properties of brain network including mean dwell time (MDT), fraction time (FT) and numbers of transitions (NT) were calculated. Two-sample t test and Spearman's correlation were used for group compares and correlation analysis. Four RSNs showed abnormal FNC including auditory network (AUN), default mode network (DMN), attention network (AN) and sensorimotor network (SMN). For static analysis, tinnitus patients showed significantly decreased FNC in AUN-DMN, AUN-AN, DMN-AN, and DMN-SMN than HC [p < 0.05, false discovery rate (FDR) corrected]. For dynamic analysis, tinnitus patients showed significantly decreased FNC in DMN-AN in state 3 (p < 0.05, FDR corrected). MDT in state 3 was significantly decreased in tinnitus patients (t = 2.039, P = 0.046). In the tinnitus group, the score of tinnitus functional index (TFI) was negatively correlated with MDT and FT in state 4, and the duration of tinnitus was positively correlated with FT in state 1 and NT. Chronic tinnitus causes abnormal brain network connectivity. These abnormal brain networks help to clarify the mechanism of tinnitus generation and chronicity, and provide a potential basis for the treatment of tinnitus.

Linking soil nutrients, microbial community composition, and enzyme activities to saponin content of Paris polyphylla after addition of biochar and organic fertiliser.

The application of organic fertilisers and biochar has become widespread in agroforestry ecosystems to enhance the yield and quality of crops and medicinal plants. However, their specific impact on both the yield and quality of Paris polyphylla (P. polyphylla), along with the underlying mechanisms, remains unclear. In this study, we investigated the distinct effects of organic fertiliser (at concentrations of 5% and 10%) and biochar application (at levels of 2% and 4%) on P. polyphylla saponin content. This content is intricately regulated by available soil nutrients, enzyme activities, and microbial community compositions and activities. Our results clearly demonstrated a significant increase in the saponin content, including total saponin, polyphyllin I (PPI), polyphyllin II (PPII), polyphyllin VI (PPVI), and polyphyllin VII (PPVII), in P. polyphylla following the application of both biochar and organic fertiliser. Moreover, in comparison to the control group, the addition of biochar and organic fertiliser led to a considerable rise in the activity of glycosyltransferase enzyme (GTS) and cycloartenol synthase (CAS) in P. polyphylla. Additionally, it increased soil available potassium (AK) and soil organic matter (SOM) concentration, along with the activity of urease, acid phosphatase, and catalase, although biochar amendment resulted in a decrease in nitrate nitrogen (NO3--N) concentration. Crucially, our findings revealed a positive correlation between total saponin content and the activity of CAS in P. polyphylla, soil AK, SOM concentration, and the activities of urease, acid phosphatase, and catalase. Conversely, there was a negative correlation with NO3--N content. Furthermore, the application of organic fertiliser and biochar significantly influenced microbial community structures and specific microbial taxa. Notably, total saponin content exhibited a positive relationship with the relative abundances of Dehalococcoidia, Saccharomycetes, and Agaricomycetes taxa while showing a negative correlation with the abundance of Verrucomicrobiae. In conclusion, the observed increase in saponin content can be attributed to the modulation of specific microbial taxa in soils, as well as alterations in soil nutrients and enzyme activities resulting from the application of biochar and organic fertiliser. This study identifies a potential mechanism for enhancing saponin content in the artificial cultivation of P. polyphylla.