Broadband and fabrication-tolerant 3-dB couplers with topological valley edge modes.

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

Vitamin D3 attenuates autoimmune thyroiditis by regulating Th17/Treg cell differentiation via YAP/JAK1/STAT1 axis.

BACKGROUND: Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated. METHODS: An experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis. RESULTS: Administration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function. CONCLUSION: Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.

Pterostilbene alleviates MPTP-induced neurotoxicity by targeting neuroinflammation and oxidative stress.

Pterostilbene (PTE), a naturally occurring phenolic compound primarily found in blueberries, demonstrates neuroprotective properties. However, the role of PTE in Parkinson's disease (PD) remains unclear. This study aimed to investigate the neuroprotective role of PTE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Our findings demonstrate that administering PTE effectively reversed the diminished levels of dopamine in the striatum, thereby ameliorating motor impairments in the MPTP model. Moreover, PTE administration mitigated the loss of dopaminergic (DA) neurons and reduced the upregulation of α-synuclein (α-syn) induced by MPTP. Mechanistic analysis revealed that PTE administration inhibited the activation of microglia and astrocytes, as well as pro-inflammatory factors such as TNF-α and IL-1ß in the MPTP model. Additionally, PTE administration decreased MPTP-induced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing total antioxidant capacity (TAOC) and superoxide dismutase (SOD) activity, thereby attenuating oxidative stress. Collectively, these findings demonstrate that PTE exerts neuroprotective effects in the MPTP mouse model of PD by suppressing neuroinflammation and oxidative stress. Thus, PTE holds promise as a therapeutic agent for PD.

Self-Assembled Molecular Layers as Interfacial Engineering Nanomaterials in Rechargeable Battery Applications.

Rechargeable batteries have transformed human lives and modern industry, ushering in new technological advancements such as mobile consumer electronics and electric vehicles. However, to fulfill escalating demands, it is crucial to address several critical issues including energy density, production cost, cycle life and durability, temperature sensitivity, and safety concerns is imperative. Recent research has shed light on the intricate relationship between these challenges and the chemical processes occurring at the electrode-electrolyte interface. Consequently, a novel approach has emerged, utilizing self-assembled molecular layers (SAMLs) of meticulously designed molecules as nanomaterials for interface engineering. This research provides a comprehensive overview of recent studies underscoring the significant roles played by SAML in rechargeable battery applications. It discusses the mechanisms and advantageous features arising from the incorporation of SAML. Moreover, it delineates the remaining challenges in SAML-based rechargeable battery research and technology, while also outlining future perspectives.

Epitaxial Growth of the Large-Scale, Highly-Ordered 3D GaN-Truncated Pyramid Array Toward an Ultrahigh Rejection Ratio and Responsivity Visible-Blind Ultraviolet Photodetection.

The micro- and nanostructures of III-nitride semiconductors captivate strong interest owing to their distinctive properties and myriad potential applications. Nevertheless, challenges endure in managing the damage inflicted on crystals through top-down processes or achieving extensive control over the large-area growth of these microstructures via bottom-up methods, thereby impacting their optical and electronic properties. Here, we present novel epitaxially grown 3D GaN truncated pyramid arrays (TPAs) on patterned Si substrates, devoid of any catalyst. These GaN TPAs feature highly ordered, large-scale structures, attributed to the utilization of 3D Si substrates and thin AlN interlayers to alleviate epitaxial strains and limit dislocation formation. Comprehensive characterization via scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and cathodoluminescence attests to the superior structural and optical attributes of these crystals. Furthermore, photoluminescence and ultraviolet (UV)-visible diffuse reflectance spectroscopy reveal sharp band-edge emission and significant light trapping in the UV bands. Employing these GaN TPAs, we constructed metal-semiconductor-metal visible-blind UV photodetectors (PDs) incorporating Ti3C2 MXene as Schottky electrodes. These PDs display exceptional responsivity, achieving 5.32 × 103 mA/W at 255 nm and an ultrahigh UV/visible rejection ratio (R255nm/R450nm) approaching 106, which are 1-2 orders of magnitude higher than most recently reported works. This exploration showcases novel GaN-based microstructures characterized by uniformity, ordered geometry, and exemplary crystalline integrity, paving the way for developing optoelectronic applications.

Early warning of atrial fibrillation using deep learning.

Atrial fibrillation (AF), the most prevalent cardiac rhythm disorder, significantly increases hospitalization and health risks. Reverting from AF to sinus rhythm (SR) often requires intensive interventions. This study presents a deep-learning model capable of predicting the transition from SR to AF on average 30.8 min before the onset appears, with an accuracy of 83% and an F1 score of 85% on the test data. This performance was obtained from R-to-R interval signals, which can be accessible from wearable technology. Our model, entitled Warning of Atrial Fibrillation (WARN), consists of a deep convolutional neural network trained and validated on 24-h Holter electrocardiogram data from 280 patients, with 70 additional patients used for testing and further evaluation on 33 patients from two external centers. The low computational cost of WARN makes it ideal for integration into wearable technology, allowing for continuous heart monitoring and early AF detection, which can potentially reduce emergency interventions and improve patient outcomes.

Triflate anion chemistry for enhanced four-electron zinc-iodine aqueous batteries.

I+ hydrolysis, sluggish iodine redox kinetics and the instability of Zn anodes are the primary challenges for aqueous four-electron zinc-iodine batteries (4eZIBs). Herein, the OTf- anion chemistry in aqueous electrolyte is essential for developing advanced 4eZIBs. It is elucidated that OTf- anions establish weak hydrogen bonds (H bonds) with water to stabilize I+ species while optimizing a water-lean Zn2+ coordination structure to mitigate Zn dendrites and corrosion. Moreover, the interaction of the OTf- anions with the iodine species results in an increased equilibrium average intermolecular bond length of the iodine species, facilitating the 4e redox kinetics of iodine with improved reversibility.

Real-world effectiveness of belimumab in patients with lupus in China: RELIABLE observational cohort study protocol.

INTRODUCTION: The efficacy of belimumab in SLE has been demonstrated in randomised clinical trials, and its real-world effectiveness has been shown in studies in several countries. While belimumab was approved for treating SLE in China in 2019, data on its benefit in clinical practice are limited. This study will evaluate belimumab's effectiveness in China, using practical clinical measures, such as Lupus Low Disease Activity State (LLDAS), to add to the body of real-world evidence. METHODS AND ANALYSIS: The Real-world Effectiveness of beLImumAB in patients with systemic Lupus Erythematosus in China (RELIABLE) is an ambidirectional, observational descriptive cohort study across approximately 15 centres in China. Adults with SLE newly initiating belimumab with ≥1 measure of all five LLDAS components (SLE Disease Activity Index-2000; no new lupus disease activity; Physician Global Assessment; prednisolone-equivalent dose; immunosuppressants/biologics use) in the 3 months preceding belimumab initiation (index date) will be eligible and retrospectively and/or prospectively enrolled, depending on data availability. The retrospective follow-up will be ≤6 months, and retrospective and prospective patients will have a maximum 24-month follow-up. The primary objectives will be to describe the proportion of patients achieving LLDAS at 12 and 24 months post-index. The key secondary objective will be to describe the proportion of patients achieving LLDAS and each component at 3, 6, 9 and 18 months post-index. All data will be analysed descriptively; a statistical estimand will be applied to account for intercurrent events expected in a real-world setting. ETHICS AND DISSEMINATION: This study will comply with all applicable laws regarding patient privacy; institutional review board approval will be obtained before the study commencement. CONCLUSIONS: This study will evaluate belimumab's effectiveness in patients with SLE initiating belimumab in clinical practice in China. Using LLDAS will provide clinicians with valuable insights into the impact of belimumab on the treat-to-target strategy with a relevant measure that can be repeated across the clinical practice.

Energetic Information from Information-Theoretic Approach in Density Functional Theory as Quantitative Measures of Physicochemical Properties.

The Hohenberg-Kohn theorem of density functional theory (DFT) stipulates that energy is a universal functional of electron density in the ground state, so energy can be thought of having encoded essential information for the density. Based on this, we recently proposed to quantify energetic information within the framework of information-theoretic approach (ITA) of DFT (J. Chem. Phys. 2022, 157, 101103). In this study, we systematically apply energetic information to a variety of chemical phenomena to validate the use of energetic information as quantitative measures of physicochemical properties. To that end, we employed six ITA quantities such as Shannon entropy and Fisher information for five energetic densities, yielding twenty-six viable energetic information quantities. Then, they are applied to correlate with physicochemical properties of molecular systems, including chemical bonding, conformational stability, intermolecular interactions, acidity, aromaticity, cooperativity, electrophilicity, nucleophilicity, and reactivity. Our results show that different quantities of energetic information often behave differently for different properties but a few of them, such as Shannon entropy of the total kinetic energy density and information gain of the Pauli energy density, stand out and strongly correlate with several properties across different categories of molecular systems. These results suggest that they can be employed as quantitative measures of physicochemical properties. This work not only enriches the body of our knowledge about the relationship between energy and information, but also provides scores of newly introduced explicit density functionals to quantify physicochemical properties, which can serve as robust features for building machine learning models in future studies.

Gut fungi of black-necked cranes (Grus nigricollis) respond to dietary changes during wintering.

BACKGROUND: Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis). RESULTS: In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P < 0.05, LDA > 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal. CONCLUSIONS: This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host's food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.

A study on the configuration of factors influencing overweight and obesity in adolescents based on fuzzy set qualitative comparative analysis.

OBJECTIVE: Overweight and obesity among adolescents are grave public health issues around the world. Although the conditions that contribute to obesity have been extensively researched, little is known about how multiple conditions interact to cause overweight and obesity. The current study intends to investigate the histomorphic configuration pathways of several conditions of adolescent overweight and obesity by gender. METHOD: The data came from a social survey conducted in June 2021 in Changchun, Jilin Province, China. The sample collected was 14-year-old adolescents, including 167 boys and 137 girls. The school physicians examined the participants' weight and height, and questionnaires were used to collect risk indicators from adolescents, such as sleep duration, electronic screens times, consumption of sugary drinks and fried foods, and physical activity. Simultaneously, a Fuzzy Qualitative Comparative Analysis will be performed to investigate the combinations of diverse conditions. RESULT: We found that there is no determining necessary condition that, once present, directly determines that an individual is in a state of overweight and obesity. Simultaneously, this study revealed nine alternative configurational paths of overweight and obesity in teenagers of different genders, with a concordance of 0.805 for six male groupings and 0.916 for three female groupings. The outcomes of overweight obesity in adolescents under different genders are similar but not identical. CONCLUSION: This study examined the interactions of a number of conditions from the individual, behavioral, learning and living environment that led to the same overweight obese outcome among adolescents of different genders. Our research will be useful to policymakers in that interventions should take into account the combined effects of a number of different aspects rather than focusing on a single factor that causes overweight and obesity.

Butadiene Sulfone Based Binary Deep Eutectic Electrolyte for High Performance Lithium Metal Batteries.

Deep eutectic electrolytes (DEEs) have attracted significant interest due to the unique physiochemical properties, yet challenges persist in achieving satisfactory Li anode compatibility through a binary DEE formula. In this study, we introduce a nonflammable binary DEE electrolyte comprising of lithium bis(trifluoro-methane-sulfonyl)imide (LiTFSI) and solid butadiene sulfone (BdS), which demonstrates enhanced Li metal compatibility while exhibiting high Li+ ion migration number (0.52), ionic conductivity (1.48 mS·cm-1), wide electrochemical window (~4.5 V vs. Li/Li+) at room temperature. Experimental and theoretical results indicate that the Li compatibility derives from the formation of a LiF-rich SEI, attributed to the undesirable adsorption and deformation of BdS on Li surface that facilitates the preferential reactions between LiTFSI and Li metal. This stable SEI effectively suppresses dendrites growth and gas evolution reactions, ensuring a long lifespan and high coulombic efficiency in both the Li||Li symmetric cells, Li||LiCoO2 and Li||LiNi0.8Co0.1Mn0.1O2 full cells. Moreover, the BdS eutectic strategy exhibit universal applicability to other metal such as Na and Zn by pairing with the corresponding TFSI-based salts.

Improving Aerobic Digestion of Food Waste by Adding a Personalized Microbial Inoculum.

In the context of China's garbage classification policy, on-site aerobic food waste (FW) digestion is crucial for reducing transportation and disposal costs. The efficiency of this process is largely determined by the microbial community structure and its functions. Therefore, this study aimed to analyze the impact of a personalized microbial consortium (MCM) on the efficiency of aerobic FW digestion and to reveal the underlying mechanisms. An MCM, sourced from naturally degrading FW, was selected to enrich degrading bacteria with relatively high hydrolyzing ability. The functionality of the MCM was evaluated by tracing the successions of microbial communities, and comparing the differences in the forms of organic compounds, metabolic functions, and hydrolase activities. X-ray photoelectron spectroscopy demonstrated that the MCM metabolized faster, and produced more acidic metabolites. Metagenomic analysis indicated that FW inoculated with the personalized MCM increased abundance of Bacillaceae producing hydrolysis enzymes and promoted glycolysis metabolic pathways, enhancing energy generation for metabolism, compared to the commercial effective bacterial agent. This paper provides both theoretical and practical evidence for the improvement of biochemical processor of FW with the personalized MCM, which has promising application prospects and economic value.

Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus.

BACKGROUND & AIMS: Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for hepatitis B virus (HBV). However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection. METHODS: Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection. RESULTS: Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of the HBV envelope protein LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both in vitro and in vivo. CONCLUSIONS: Our findings indicate that NRP1 is a novel host factor for HBV infection, which interacts with preS1 and NTCP to modulate HBV entry into hepatocytes. IMPACT AND IMPLICATIONS: HBV infection is a global public health problem, but the understanding of the early infection process of HBV remains limited. Through single-cell sequencing, we identified a novel host factor, NRP1, which modulates HBV entry by interacting with HBV preS1 and NTCP. Moreover, antagonists targeting NRP1 can inhibit HBV infection both in vitro and in vivo. This study could further advance our comprehension of the early infection process of HBV.

Superconductivity with T c of 116 K discovered in antimony polyhydrides.

Superconductivity (SC) was experimentally observed for the first time in antimony polyhydride. The diamond anvil cell combined with a laser heating system was used to synthesize the antimony polyhydride sample at high pressure and high temperature. In-situ high pressure transport measurements as a function of temperature with an applied magnetic field were performed to study the SC properties. It was found that the antimony polyhydride samples show superconducting transition with critical temperature T c 116 K at 184 GPa. The investigation of SC at magnetic field revealed the superconducting coherent length of ∼40 Å based on the Ginzburg Landau (GL) equation. Antimony polyhydride superconductor has the second highest T c in addition to sulfur hydride among the polyhydrides of elements from main groups IIIA to VIIA in the periodic table.

The safety and feasibility of mini-invasive Bentall surgery via right anterior mini-thoracotomy.

Background: The right anterior mini-thoracotomy (RAMT) approach has become a popular technique in cardiac surgery and applied in valve surgery. However, there is very limited evidence on the application of RAMT in the Bentall surgery. In the present study, we aimed to evaluate the safety and feasibility of the RAMT approach in Bentall surgery. Methods: A retrospective analysis was performed on 27 patients who underwent Bentall surgery between September 2020 and April 2022 in the First Affiliated Hospital of Xi'an Jiaotong University. Follow-ups were undertaken 1 and 6 months after their operations. The baseline, perioperative, and follow-up results were retrospectively analyzed. Results: A total of 27 male patients aged 48-61 years were included in the study. The operation time ranged from 4.0 to 5.0 hours, with a median of 4.5 hours. The median aortic cross-clamping time was 122 minutes [interquartile range (IQR): 109-145 minutes], and the median cardiopulmonary bypass (CPB) time was 156 minutes (IQR: 143-183 minutes). The median intensive care unit stay was 3 days (IQR: 1.75-4.25 days). The ventilation time ranged from 6.5 to 22.0 hours, with a median of 13.0 hours. The median drainage volume in the first 24 hours was 210 mL. In the following-up data, no deaths or severe complications were observed. Conclusions: The mini-Bentall procedure through an RAMT approach is a feasible and safe approach with few wounds and good clinical results in patients undergoing aortic root replacement.

Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare in the United States. AIM: To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease (IBD) decedents. METHODS: We performed a register-based study using data from the National Vital Statistics System, which reports death data from over 99% of the United States population, from January 1, 2006 through December 31, 2021. IBD-related deaths among adults 25 years and older were stratified by age, sex, race/ethnicity, place of death, and primary cause of death. Predicted and actual age-standardized mortality rates (ASMRs) per 100000 persons were compared. RESULTS: 49782 IBD-related deaths occurred during the study period. Non-COVID-19-related deaths increased by 13.14% in 2020 and 18.12% in 2021 [2020 ASMR: 1.55 actual vs 1.37 predicted, 95% confidence interval (CI): 1.26-1.49; 2021 ASMR: 1.63 actual vs 1.38 predicted, 95%CI: 1.26-1.49]. In 2020, non-COVID-19-related mortality increased by 17.65% in ulcerative colitis (UC) patients between the ages of 25 and 65 and 36.36% in non-Hispanic black (NHB) Crohn's disease (CD) patients. During the pandemic, deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased. CONCLUSION: IBD patients suffered excess non-COVID-19-related death during the pandemic. Excess death was associated with younger age among UC patients, and with NHB race among CD patients. Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

An Effective Ultrasound Features-Based Diagnostic Model via Principal Component Analysis Facilitated Differentiating Subtypes of Mucinous Breast Cancer From Fibroadenomas.

BACKGROUND: Mucinous breast carcinoma (MBC) is often misdiagnosed as fibroadenoma (FA),which can lead to inappropriate or delayed treatments. This study aimed to establish an efficient ultrasound (US)-based diagnostic model to distinguish MBC subtypes from FAs. METHODS: Between January 2017 and February 2024, 240 lesions were enrolled, comprising 65 cases of pure mucinous breast carcinoma (PMBC), 47 cases of mixed mucinous breast carcinoma (MMBC), and 128 cases of FAs. Ten US feature variables underwent principal component analysis (PCA). Models were constructed based on components explaining over 75% of the total variation, with varimax rotation applied for interpretability. Comprehensive models were developed to distinguish PMBCs and MMBCs from FAs. RESULTS: Six principal components were selected, achieving a cumulative contribution rate of 77.46% for PMBCs vs. FAs and 78.62% for MMBCs vs. FAs. The principal component of cystic-solid composition and posterior acoustic enhancement demonstrated the highest diagnostic value for distinguishing PMBCs from FAs (AUC: 0.86, ACC: 80.31%). Features including vascularization, irregular shape, ill-defined border, and larger size exhibited the highest diagnostic value for distinguishing MMBCs from FAs (AUC: 0.90, ACC: 87.43%). The comprehensive models showed excellent clinical value in distinguishing PMBCs (AUC = 0.86, SEN = 86.15%, SPE = 73.44%, ACC = 77.72%) and MMBCs (AUC = 0.92, SEN = 80.85%, SPE = 95.31%, ACC = 91.43%) from FAs. CONCLUSION: This diagnostic model holds promise for effectively distinguishing PMBCs and MMBCs from FAs, assisting radiologists in mitigating diagnostic biases and enhancing diagnostic efficiency.

Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.