Generating High-Precision Force Fields for Molecular Dynamics Simulations to Study Chemical Reaction Mechanisms Using Molecular Configuration Transformer.

Theoretical studies on chemical reaction mechanisms have been crucial in organic chemistry. Traditionally, calculating the manually constructed molecular conformations of transition states for chemical reactions using quantum chemical calculations is the most commonly used method. However, this way is heavily dependent on individual experience and chemical intuition. In our previous study, we proposed a research paradigm that used enhanced sampling in molecular dynamics simulations to study chemical reactions. This approach can directly simulate the entire process of a chemical reaction. However, the computational speed limited the use of high-precision potential energy functions for simulations. To address this issue, we presented a scheme for training high-precision force fields for molecular modeling using a previously developed graph-neural-network-based molecular model, molecular configuration transformer. This potential energy function allowed for highly accurate simulations at a low computational cost, leading to more precise calculations of the mechanism of chemical reactions. We applied this approach to study a Claisen rearrangement reaction and a carbonyl insertion reaction catalyzed by manganese.

Voltage-gated potassium channel 1.3: A promising molecular target in multiple disease therapy.

Voltage-gated potassium channel 1.3 (Kv1.3) has emerged as a pivotal player in numerous biological processes and pathological conditions, sparking considerable interest as a potential therapeutic target across various diseases. In this review, we present a comprehensive examination of Kv1.3 channels, highlighting their fundamental characteristics and recent advancements in utilizing Kv1.3 inhibitors for treating autoimmune disorders, neuroinflammation, and cancers. Notably, Kv1.3 is prominently expressed in immune cells and implicated in immune responses and inflammation associated with autoimmune diseases and chronic inflammatory conditions. Moreover, its aberrant expression in certain tumors underscores its role in cancer progression. While preclinical studies have demonstrated the efficacy of Kv1.3 inhibitors, their clinical translation remains pending. Molecular imaging techniques offer promising avenues for tracking Kv1.3 inhibitors and assessing their therapeutic efficacy, thereby facilitating their development and clinical application. Challenges and future directions in Kv1.3 inhibitor research are also discussed, emphasizing the significant potential of targeting Kv1.3 as a promising therapeutic strategy across a spectrum of diseases.

Chief complaints and computed tomography results in the emergency department: a three-year retrospective cohort study.

BACKGROUND: Computed tomography (CT) is frequently performed in the patients who admitted to the emergency department (ED), discharged but returned to ED within 72 h. It is unknown whether the main complaints of patients assist physicians to use CT effectively. This study aimed to find the association between chief complaints and the CT results. METHODS: This three-year retrospective cohort study was conducted in the ED of a tertiary medical center. Adult patients who returned to the ED after the index visit were included from 2019 to 2021. Demographics, pre-existing diseases, chief complaints, and CT region were recorded by independent ED physicians. A logistic regression model with an odds ratio (OR) and 95% confidence interval (CI) was used to determine the relationship between chief complaints and positive CT results. RESULTS: In total, 7,699 patients revisited ED after the index visit; 1,202 (15.6%) received CT. The top chief complaints in patients who received CT were abdominal pain, dizziness, and muscle weakness. Patients with abdominal pain or gastrointestinal symptoms had a significantly higher rate of positive abdominopelvic CT than those without it (OR 2.83, 95% CI 1.98-4.05, p < 0.001), while the central nervous system and cardiopulmonary chief complaints were not associated (or negatively associated) with new positive CT findings. CONCLUSION: Chief complaints of patients on revisit to the ED are associated with different yields of new findings when CT scans of the chest, abdomen and head are performed. Physicians should consider these differential likelihoods of new positive findings based on these data.

Generative Adversarial Networks Accurately Reconstruct Pan-Cancer Histology from Pathologic, Genomic, and Radiographic Latent Features.

Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of novel molecular features. These approaches distill cancer histologic images into high-level features which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network - HistoXGAN - capable of reconstructing representative histology using feature vectors produced by common feature extractors. We evaluate HistoXGAN across 29 cancer subtypes and demonstrate that reconstructed images retain information regarding tumor grade, histologic subtype, and gene expression patterns. We leverage HistoXGAN to illustrate the underlying histologic features for deep learning models for actionable mutations, identify model reliance on histologic batch effect in predictions, and demonstrate accurate reconstruction of tumor histology from radiographic imaging for a 'virtual biopsy'.

Prediction of high-risk emergency department revisits from a machine-learning algorithm: a proof-of-concept study.

BACKGROUND: High-risk emergency department (ED) revisit is considered an important quality indicator that may reflect an increase in complications and medical burden. However, because of its multidimensional and highly complex nature, this factor has not been comprehensively investigated. This study aimed to predict high-risk ED revisit with a machine-learning (ML) approach. METHODS: This 3-year retrospective cohort study assessed adult patients between January 2019 and December 2021 from National Taiwan University Hospital Hsin-Chu Branch with high-risk ED revisit, defined as hospital or intensive care unit admission after ED return within 72 hours. A total of 150 features were preliminarily screened, and 79 were used in the prediction model. Deep learning, random forest, extreme gradient boosting (XGBoost) and stacked ensemble algorithm were used. The stacked ensemble model combined multiple ML models and performed model stacking as a meta-level algorithm. Confusion matrix, accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) were used to evaluate performance. RESULTS: Analysis was performed for 6282 eligible adult patients: 5025 (80.0%) in the training set and 1257 (20.0%) in the testing set. High-risk ED revisit occurred for 971 (19.3%) of training set patients vs 252 (20.1%) in the testing set. Leading predictors of high-risk ED revisit were age, systolic blood pressure and heart rate. The stacked ensemble model showed more favourable prediction performance (AUROC 0.82) than the other models: deep learning (0.69), random forest (0.78) and XGBoost (0.79). Also, the stacked ensemble model achieved favourable accuracy and specificity. CONCLUSION: The stacked ensemble algorithm exhibited better prediction performance in which the predictions were generated from different ML algorithms to optimally maximise the final set of results. Patients with older age and abnormal systolic blood pressure and heart rate at the index ED visit were vulnerable to high-risk ED revisit. Further studies should be conducted to externally validate the model.

Spatial Contraction Based on Velocity Variation for Natural Walking in Virtual Reality.

Virtual Reality (VR) offers an immersive 3D digital environment, but enabling natural walking sensations without the constraints of physical space remains a technological challenge. Previous VR locomotion methods, including game controller, teleportation, treadmills, walking-in-place, and redirected walking (RDW), have made strides towards overcoming this challenge. However, these methods also face limitations such as possible unnaturalness, additional hardware requirements, or motion sickness risks. This paper introduces "Spatial Contraction (SC)", an innovative VR locomotion method inspired by the phenomenon of Lorentz contraction in Special Relativity. Similar to the Lorentz contraction, our SC contracts the virtual space along the user's velocity direction in response to velocity variation. The virtual space contracts more when the user's speed is high, whereas minimal or no contraction happens at low speeds. We provide a virtual space transformation method for spatial contraction and optimize the user experience in smoothness and stability. Through SC, VR users can effectively traverse a longer virtual distance with a shorter physical walking. Different from locomotion gains, the spatial contraction effect is observable by the user and aligns with their intentions, so there is no inconsistency between the user's proprioception and visual perception. SC is a general locomotion method that has no special requirements for VR scenes. The experimental results of our live user studies in various virtual scenarios demonstrate that SC has a significant effect in reducing both the number of resets and the physical walking distance users need to cover. Furthermore, experiments have also demonstrated that SC has the potential for integration with existing locomotion techniques such as RDW.

Biosynthetic pathway redesign in non-conventional yeast for enhanced production of cembratriene-ol.

Cembratriene-ol (CBT-ol), a plant-derived macrocyclic diterpene with notable insecticidal activity, has attracted considerable attention with respect to the development of sustainable and green biopesticides. Currently, CBT-ol production is limited by an inefficient and costly plant extraction strategy. Herein, CBT-ol production was enhanced by redesigning the CBT-ol biosynthetic pathway in Candida tropicalis, with subsequent truncation of CBT-ol synthase further increasing CBT-ol production. Moreover, bottlenecks in the CBT-ol biosynthetic pathway were eliminated by adjusting the gene dosage of the rate-limiting enzymes. Ultimately, the resulting strain C. tropicalis CPPt-03D produced 129.17 mg/L CBT-ol in shaking flasks (a 144-fold increase relative to that of the initial strain C01-CD) with CBT-ol production reaching 1,425.76 mg/L in a 5-L bioreactor, representing the highest CBT-ol titer reported to date. These findings provide a green process and promising platform for the industrial production of CBT-ol and lays the foundation for organic farming.

Optimizing the robustness of higher-low order coupled networks.

Enhancing the robustness of complex networks is of great practical significance as it ensures the stable operation of infrastructure systems. We measure its robustness by examining the size of the largest connected component of the network after initial attacks. However, traditional research on network robustness enhancement has mainly focused on low-order networks, with little attention given to higher-order networks, particularly higher-low order coupling networks(the largest connected component of the network must exist in both higher-order and low-order networks). To address this issue, this paper proposes robust optimization methods for higher-low order coupled networks based on the greedy algorithm and the simulated annealing algorithm. By comparison, we found that the simulated annealing algorithm performs better. The proposed method optimizes the topology of the low-order network and the higher-order network by randomly reconnecting the edges, thereby enhancing the robustness of the higher-order and low-order coupled network. The experiments were conducted on multiple real networks to evaluate the change in the robustness coefficient before and after network optimization. The results demonstrate that the proposed method can effectively improve the robustness of both low-order and higher-order networks, ultimately enhancing the robustness of higher-low order coupled networks.

Dracotangusions A and B, two new sesquiterpenes from Dracocephalum tanguticum Maxim. with anti-inflammatory activity.

Two new guaiane sesquiterpenoids were isolated from the dried aerial parts of Dracocephalum tanguticum Maxim., named as dracotangusions A (1) and B (2), together with four known sesquiterpenoids, which were identified as Curcumenone (3), (4Z,7Z,9Z)-11-Hydroxy-4,7,9-germacratriene-1,6-dione (4), Kobusone (5), and (1S,10S), (4S, 5S)-(+)-germacrone-1(10)-4-diepoxide (6). The structures of isolates were determined by UV, IR, HR-ESI-MS, and NMR analysis. What is noteworthy is that four known sesquiterpenoids were isolated for the first time from the genus of Dracocephalum L. All compounds inhibited the extremely significant difference (p < 0.01) in anti-inflammatory activity, suggesting that these compounds may be promising candidates as an anti-inflammatory agent.

The interaction of sex and age on outcomes in emergency medical services-treated out-of-hospital cardiac arrest: A 5-year multicenter retrospective analysis.

Background: Studies have established that sex and age influence outcomes following out-of-hospital cardiac arrest (OHCA). However, a knowledge gap exists regarding their interaction. This study aimed to investigate the interaction of age and sex and how they cooperatively influence OHCA outcomes. Methods: This retrospective cohort study included adult, nontraumatic OHCA patients admitted to a university hospital and its affiliated hospitals in Taiwan from January 2017 to December 2021. Data including sex, age, body mass index, cardiac rhythm, and resuscitation information in the emergency department (ED) were collected from medical records. The study outcomes encompassed survival to intensive care unit (ICU) admission, survival to hospital discharge, and a favorable neurological outcome. Multivariable logistic regression was performed to estimate the influence of sex on study outcomes. Results: We analyzed a total of 2,826 eligible subjects categorized into three groups: young (18-44 years, 149 males and 57 females), middle-aged (45-64 years, 524 males and 188 females), and old (≥65 years, 1,049 males and 859 females). Analysis of the effects of sex according to age stratification showed that old males had higher odds for survival to ICU admission (OR: 1.49, 95% CI: 1.21-1.83) and favorable neurological outcomes (OR: 2.74, 95% CI: 1.58-4.76) than did old females. Analysis of the effects of age according to sex stratification revealed that old males had lower odds for survival to hospital discharge (OR: 0.33, 95% CI: 0.21-0.51) and favorable neurological outcomes (OR: 0.26, 95% CI: 0.16-0.43) than did young males. Old females also showed the same trend as males, with lower odds for survival to hospital discharge (OR: 0.37, 95% CI: 0.17-0.78) and favorable neurological outcomes (OR: 0.11, 95% CI: 0.05-0.25) than did young females. Conclusions: The interaction between sex and age in patients with OHCA results in diverse outcomes. Within the same sex, age demonstrated varying effects on distinct outcomes.

MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis.

Oncogene-induced replication stress generates endogenous DNA damage that activates cGAS-STING-mediated signalling and tumour suppression1-3. However, the precise mechanism of cGAS activation by endogenous DNA damage remains enigmatic, particularly given that high-affinity histone acidic patch (AP) binding constitutively inhibits cGAS by sterically hindering its activation by double-stranded DNA (dsDNA)4-10. Here we report that the DNA double-strand break sensor MRE11 suppresses mammary tumorigenesis through a pivotal role in regulating cGAS activation. We demonstrate that binding of the MRE11-RAD50-NBN complex to nucleosome fragments is necessary to displace cGAS from acidic-patch-mediated sequestration, which enables its mobilization and activation by dsDNA. MRE11 is therefore essential for cGAS activation in response to oncogenic stress, cytosolic dsDNA and ionizing radiation. Furthermore, MRE11-dependent cGAS activation promotes ZBP1-RIPK3-MLKL-mediated necroptosis, which is essential to suppress oncogenic proliferation and breast tumorigenesis. Notably, downregulation of ZBP1 in human triple-negative breast cancer is associated with increased genome instability, immune suppression and poor patient prognosis. These findings establish MRE11 as a crucial mediator that links DNA damage and cGAS activation, resulting in tumour suppression through ZBP1-dependent necroptosis.

Endocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor-Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination: A Phase 3 Randomized Clinical Trial.

Importance: Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast cancer. However, the combination has not been tested in early-stage disease. Objective: To determine whether neoadjuvant fulvestrant or A+F increases the rate of pathologic complete response or ypT1-2N0/N1mic/Ki67 2.7% or less residual disease (referred to as endocrine-sensitive disease) over anastrozole alone. Design, Setting, and Participants: A phase 3 randomized clinical trial assessing differences in clinical and correlative outcomes between each of the fulvestrant-containing arms and the anastrozole arm. Postmenopausal women with clinical stage II to III, ER-rich (Allred score 6-8 or >66%)/ERBB2-negative breast cancer were included. All analyses were based on data frozen on March 2, 2023. Interventions: Patients received anastrozole, fulvestrant, or a combination for 6 months preoperatively. Tumor Ki67 was assessed at week 4 and optionally at week 12, and if greater than 10% at either time point, the patient switched to neoadjuvant chemotherapy or immediate surgery. Main Outcomes and Measures: The primary outcome was the endocrine-sensitive disease rate (ESDR). A secondary outcome was the percentage change in Ki67 after 4 weeks of neoadjuvant endocrine therapy (NET) (week 4 Ki67 suppression). Results: Between February 2014 and November 2018, 1362 female patients (mean [SD] age, 65.0 [8.2] years) were enrolled. Among the 1298 evaluable patients, ESDRs were 18.7% (95% CI, 15.1%-22.7%), 22.8% (95% CI, 18.9%-27.1%), and 20.5% (95% CI, 16.8%-24.6%) with anastrozole, fulvestrant, and A+F, respectively. Compared to anastrozole, neither fulvestrant-containing regimen significantly improved ESDR or week 4 Ki67 suppression. The rate of week 4 or week 12 Ki67 greater than 10% was 25.1%, 24.2%, and 15.7% with anastrozole, fulvestrant, and A+F, respectively. Pathologic complete response/residual cancer burden class I occurred in 8 of 167 patients and 17 of 167 patients, respectively (15.0%; 95% CI, 9.9%-21.3%), after switching to neoadjuvant chemotherapy due to week 4 or week 12 Ki67 greater than 10%. PAM50 subtyping derived from RNA sequencing of baseline biopsies available for 753 patients (58%) identified 394 luminal A, 304 luminal B, and 55 nonluminal tumors. A+F led to a greater week 4 Ki67 suppression than anastrozole alone in luminal B tumors (median [IQR], -90.4% [-95.2 to -81.9%] vs -76.7% [-89.0 to -55.6%]; P < .001), but not luminal A tumors. Thirty-six nonluminal tumors (65.5%) had a week 4 or week 12 Ki67 greater than 10%. Conclusions and Relevance: In this randomized clinical trial, neither fulvestrant nor A+F significantly improved the 6-month ESDR over anastrozole in ER-rich/ERBB2-negative breast cancer. Aromatase inhibition remains the standard-of-care NET. Differential NET response by PAM50 subtype in exploratory analyses warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT01953588.

18F-FP-DTBZ PET/CT detectable associations between monoaminergic depletion in the putamen with rigidity and the pallidus with tremor in Parkinson's disease.

INTRODUCTION: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. METHODS: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. RESULTS: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. CONCLUSION: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.

Application of remote electrocardiogram monitoring systems in chest pain centers for patients with high-risk chest pain.

BACKGROUND: Chinese chest pain centers (CPCs) have been expanding and maturing for the past decade, but patient wait times for pre-hospital care remain long. OBJECTIVE: To demonstrate that the remote electrocardiogram (ECG) monitoring system can ensure more efficient treatment for patients with ST-elevation myocardial infarction (STEMI) in CPCs, we compared patients with high-risk chest pain who used remote ECG monitoring systems to those who used conventional ECGs in retrospective cohort study. METHODS: Based on the inclusion and exclusion criteria, 290 patients who visited our CPC between June 2019 and March 2022 with acute chest pain and a diagnosis of STEMI as well as patients who had undergone an emergency primary percutaneous coronary intervention were selected. Among them, 73 patients with STEMI had employed remote real-time dynamic 12-lead ECG monitoring devices, while 217 patients with STEMI (i.e., the controls) had used conventional ECG monitoring. The effectiveness of treatment procedures for the two groups was investigated. As statistical measures, the symptom onset-to-wire times, first medical contact (FMC)-to-wire times, door-to-wire times, major adverse cardiac events in hospital, and the troponin T levels were analyzed. RESULTS: Compared with the control group, the patients with remote real-time dynamic 12-lead ECG monitoring devices showed shorter times for both symptom onset-to-wire (234.8 ± 95.8 min vs. 317.6 ± 129.6 min, P= 0.0321) and from symptom onset-to-FMC (170.5 ± 86.3 min vs. 245.3 ± 115.6 min, P= 0.0287); this group also had a lower 30-day mortality rate (2.73% vs. 4.14%, P= 0.003). The differences between the two groups were statistically significant (P< 0.05). CONCLUSION: With remote real-time dynamic 12-lead ECG monitoring equipment, myocardial ischemia can be treated more quickly, leading to fewer possible cardiac events and a better prognosis.

Updated trends in the outcomes of out-of-hospital cardiac arrest from 2017-2021: Prior to and during the coronavirus disease (COVID-19) pandemic.

Objective: This study aims to describe out-of-hospital cardiac arrest (OHCA) characteristics and trends before and during the coronavirus disease-2019 (COVID-19) pandemic in Taiwan. Methods: We conducted a retrospective cohort study using a 5-year interrupted time series analysis. Eligible adults with non-traumatic OHCAs from January 2017 to December 2021 in 3 hospitals (university medical center, urban second-tier hospital, and rural second-tier hospital) were retrospectively enrolled. Variables were extracted from the emergency medical service reports and medical records. The years 2020 and 2021 were defined as the COVID-19 pandemic period. Outcomes included survival to admission after a sustained return of spontaneous circulation, survival to hospital discharge, and good neurological outcomes (cerebral performance category score 1 or 2). Results: We analyzed 2819 OHCA, including 1227 from a university medical center, 617 from an urban second-tier hospital, and 975 from a rural second-tier hospital. The mean age was 71 years old, and 60% of patients were males. During the COVID-19 pandemic period, video-assisted endotracheal tube intubation replaced the traditional direct laryngoscopy intubation. The trends of outcomes in the pre-pandemic and pandemic periods varied among different hospitals. Compared with the pre-pandemic period, the outcomes at the university medical center during the COVID-19 pandemic were significantly poorer in several respects. The survival rate on admission dropped from 44.6% to 39.4% (P = 0.037), and the survival rate to hospital discharge fell from 17.5% to 14.9% (P = 0.042). Additionally, there was a notable decrease in patients' good neurological outcomes, declining from 13.2% to 9.7% (P = 0.048). In contrast, the outcomes in urban and rural second-tier hospitals during the COVID-19 pandemic did not significantly differ from those in the pre-pandemic period. Conclusions: COVID-19 may alter some resuscitation management in OHCAs. There were no overall significant differences in outcomes before and during COVID-19 pandemic, but there were significant differences in outcomes when stratified by hospital types.

Discovery and Development of 4-Hydroxyphenylpyruvate Dioxygenase as a Novel Crop Fungicide Target.

Plant pathogenic fungi pose a significant threat to crop yields and quality, and the emergence of fungicide resistance has further exacerbated the problem in agriculture. Therefore, there is an urgent need for efficient and environmentally friendly fungicides. In this study, we investigated the antifungal activity of (+)-Usnic acid and its inhibitory effect on crop pathogenic fungal 4-hydroxyphenylpyruvate dioxygenases (HPPDs) and determined the structure of Zymoseptoria tritici HPPD (ZtHPPD)-(+)-Usnic acid complex. Thus, the antifungal target of (+)-Usnic acid and its inhibitory basis toward HPPD were uncovered. Additionally, we discovered a potential lead fungicide possessing a novel scaffold that displayed remarkable antifungal activities. Furthermore, our molecular docking analysis revealed the unique binding mode of this compound with ZtHPPD, explaining its high inhibitory effect. We concluded that HPPD represents a promising target for the control of phytopathogenic fungi, and the new compound serves as a novel starting point for the development of fungicides and dual-purpose pesticides.

Thickness-variation-insensitive near-infrared quantum dot LEDs.

In terms of tunable luminescence and high quantum efficiency, colloidal quantum dots (CQDs) are promising semiconductors for constructing near-infrared light-emitting diodes (NIR-LEDs). However, currently available NIR-LEDs are susceptible to variations in the emission layer thickness (EMLT), the highest external quantum efficiency (EQE) decreases to below 50% (relative to peak EQE) when the EMLT varies out of a narrow range of (±30 nm). This is due to the thickness-dependent carrier recombination rate and current density variation, resulting in batch-to-batch EQE fluctuations that limit LED reproducibility. Here we report efficient NIR-LEDs that exhibit EQE variations of less than 15% (relative to the champion EQE) over an EMLT range of 40-220 nm; the highest achievable EQE of ∼11.5% was obtained by encapsulating a 212 nm-thick CQD within a type-I inorganic shell to enhance the radiative recombination in the dots, resulting in a high photoluminescence quantum yield of 80%, and by post-treating the films with a bifunctional linking agent to improve and balance the hole and electron mobilities in the entire film (electron mobility: 8.23 × 10-3 cm2 V-1 s-1; hole mobility: 7.0 × 10-3 cm2 V-1 s-1). This work presents the first NIR-LEDs that exhibit EMLT-invariant EQE over an EMLT range of 40-220 nm, which represents the highest EQE among reported CQD NIR-LEDs with a QD thickness exceeding 100 nm.

Process Optimization of Polishing Titanium Alloy Material with a Pulsating Air Jet.

Titanium alloy is a widely used metal material, which can be applied in fields such as healthcare, petroleum exploration, aerospace, etc. In this paper, a new method for polishing the titanium alloy by a pulsating air jet is proposed. Compared with traditional abrasive jet polishing, this method has the advantages of simple structure, low nozzle wear, and high polishing flexibility. The working principle and material removal mechanism of the pulsating air jet polishing (PAJP) are introduced. Combined with orthogonal experiments, range analysis and variance analysis were used to find out the influence degree of each process parameter on the PAJP of titanium alloy, and the optimal level of each parameter was found. Through the experiments, a prediction model of surface roughness was established by regression analysis, and the predicted value was compared with the measured value. The maximum relative error of the prediction model was 10.3%, and the minimum relative error was 1.1%. The average relative error was 6.2%.

Targeting EIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer.

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A by Zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages towards an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade. Mechanistic studies revealed that Zotatifin reprograms the tumor translational landscape, inhibits the translation of Sox4 and Fgfr1, and induces an interferon response uniformly across models. The induction of an interferon response is partially due to the inhibition of Sox4 translation by Zotatifin. A similar induction of interferon-stimulated genes was observed in breast cancer patient biopsies following Zotatifin treatment. Surprisingly, Zotatifin significantly synergizes with carboplatin to trigger DNA damage and an even heightened interferon response resulting in T cell-dependent tumor suppression. These studies identified a vulnerability of eIF4A in TNBC, potential pharmacodynamic biomarkers for Zotatifin, and provide a rationale for new combination regimens comprising Zotatifin and chemotherapy or immunotherapy as treatments for TNBC.