Deep-potential enabled multiscale simulation of gallium nitride devices on boron arsenide cooling substrates.

High-efficient heat dissipation plays critical role for high-power-density electronics. Experimental synthesis of ultrahigh thermal conductivity boron arsenide (BAs, 1300 W m-1K-1) cooling substrates into the wide-bandgap semiconductor of gallium nitride (GaN) devices has been realized. However, the lack of systematic analysis on the heat transfer across the GaN-BAs interface hampers the practical applications. In this study, by constructing the accurate and high-efficient machine learning interatomic potentials, we perform multiscale simulations of the GaN-BAs heterostructures. Ultrahigh interfacial thermal conductance of 260 MW m-2K-1 is achieved, which lies in the well-matched lattice vibrations of BAs and GaN. The strong temperature dependence of interfacial thermal conductance is found between 300 to 450 K. Moreover, the competition between grain size and boundary resistance is revealed with size increasing from 1 nm to 1000 µm. Such deep-potential equipped multiscale simulations not only promote the practical applications of BAs cooling substrates in electronics, but also offer approach for designing advanced thermal management systems.

Integrating artificial intelligence into the modernization of traditional Chinese medicine industry: a review.

Traditional Chinese medicine (TCM) is the practical experience and summary of the Chinese nation for thousands of years. It shows great potential in treating various chronic diseases, complex diseases and major infectious diseases, and has gradually attracted the attention of people all over the world. However, due to the complexity of prescription and action mechanism of TCM, the development of TCM industry is still in a relatively conservative stage. With the rise of artificial intelligence technology in various fields, many scholars began to apply artificial intelligence technology to traditional Chinese medicine industry and made remarkable progress. This paper comprehensively summarizes the important role of artificial intelligence in the development of traditional Chinese medicine industry from various aspects, including new drug discovery, data mining, quality standardization and industry technology of traditional Chinese medicine. The limitations of artificial intelligence in these applications are also emphasized, including the lack of pharmacological research, database quality problems and the challenges brought by human-computer interaction. Nevertheless, the development of artificial intelligence has brought new opportunities and innovations to the modernization of traditional Chinese medicine. Integrating artificial intelligence technology into the comprehensive application of Chinese medicine industry is expected to overcome the major problems faced by traditional Chinese medicine industry and further promote the modernization of the whole traditional Chinese medicine industry.

Identification of a novel gene signature of lung adenocarcinoma based on epidermal growth factor receptor-tyrosine kinase inhibitor resistance.

Introduction: Tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) mutations are commonly administered to EGFR-positive lung cancer patients. However, resistance to EGFR-TKIs (mostly gefitinib and erlotinib) is presently a significant problem. Limited studies have focused on an EGFR-TKI resistance-related gene signature (ERS) in lung adenocarcinoma (LUAD). Methods: Gefitinib and erlotinib resistance-related genes were obtained through the differential analyses of three Gene Expression Omnibus datasets. These genes were investigated further in LUAD patients from The Cancer Genome Atlas (TCGA). Patients in the TCGA-LUAD cohort were split into two groups: one for training and one for testing. The training cohort was used to build the ERS, and the testing cohort was used to test it. GO and KEGG analyses were explored for the enriched pathways between the high-risk and low-risk groups. Various software, mainly CIBERSORT and ssGSEA, were used for immune infiltration profiles. Somatic mutation and drug sensitivity analyses were also explored. Results: An ERS based on five genes (FGD3, PCDH7, DEPDC1B, SATB2, and S100P) was constructed and validated using the TCGA-LUAD cohort, resulting in the significant stratification of LUAD patients into high-risk and low-risk groups. Multivariable Cox analyses confirmed that ERS had an independent prognostic value in LUAD. The pathway enrichment analyses showed that most of the genes that were different between the two risk groups were related to the immune system. Further immune infiltration results revealed that a lower immune infiltration score was observed in high-risk patients, and that various leukocytes were significantly related to the ERS. Importantly, samples from the high-risk group showed lower levels of PD-1, PD-L1, and CTLA-4, which are important biomarkers for immunotherapy responses. Patients in the high-risk group also had more gene mutation changes and were more sensitive to chemotherapy drugs like docetaxel and sorafenib. The ERS was also validated in the GSE30219, GSE11969 and GSE72094, and showed a favorable prognostic value for LUAD patients. Discussion: The ERS established during this study was able to predict a poor prognosis for LUAD patients and had great potential for predicting drug responses.

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications.

Extracellular vesicles (EVs) can contain DNA, RNA, proteins and metabolic molecules from primary origins; they are coated with a phospholipid bilayer membrane and released by cells into the extracellular matrix. EVs can be obtained from various body liquids, including the blood, saliva, cerebrospinal fluid, and urine. As has been proved, EVs-mediated transfer of biologically active molecules is crucial for various physiological and pathological processes. Extensive investigations have already begun to explore the diagnosis and prognosis potentials for EVs. Furthermore, research has continued to recognize the critical role of nucleic acids and proteins in EVs. However, our understanding of the comprehensive effects of metabolites in these nanoparticles is currently limited and in its infancy. Therefore, we have attempted to summarize the recent research into the metabolomics of EVs in relation to potential clinical applications and discuss the problems and challenges that have occurred, to provide more guidance for the future development in this field.

Exploration of a Novel Circadian miRNA Pair Signature for Predicting Prognosis of Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the primary histological subtype of lung cancer with a markedly heterogeneous prognosis. Therefore, there is an urgent need to identify optimal prognostic biomarkers. We aimed to explore the value of the circadian miRNA (cmiRNA) pair in predicting prognosis and guiding the treatment of LUAD. We first retrieved circadian genes (Cgenes) from the CGDB database, based on which cmiRNAs were predicted using the miRDB and mirDIP databases. The sequencing data of Cgenes and cmiRNAs were retrieved from TCGA and GEO databases. Two random cmiRNAs were matched to a single cmiRNA pair. Finally, univariate Cox proportional hazard analysis, LASSO regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature consisting of seven cmiRNA pairs. The signature exhibited good performance in predicting the overall and progression-free survival. Patients in the high-risk group also showed lower IC50 values for several common chemotherapy and targeted medicines. In addition, we constructed a cmiRNA-Cgenes network and performed a corresponding Gene Ontology and Gene Set enrichment analysis. In conclusion, the novel circadian-related miRNA pair signature could provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for LUAD.

Ischemia and reperfusion injury combined with cisplatin induces immunogenic cell death in lung cancer cells.

A first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), cisplatin (CDDP), fails to induce immunogenic cell death (ICD) because it fails to induce calreticulin (CRT) exposure on the cell surface. We investigated the potential of ischemia and reperfusion injury (I/R) combined with CDDP to induce ICD in lung cancer cells. The in vitro model of I/R, oxygen-glucose deprivation and reperfusion (OGD/R), effectively induced CRT exposure, ATP secretion, high mobility group box 1 (HMGB1) release and eIF2α phosphorylation in both Lewis lung carcinoma (LLC) and A549 cells when combined with CDDP. By using a vaccine assay and coculture with bone marrow-derived dendritic cells (BMDCs), we showed that OGD/R restored the immunogenicity of CDDP by phosphorylating eIF2α and demonstrated that OGD/R + CDDP (O + C) is an ICD inducer. Using the inguinal tumor model, we found that I/R significantly enhanced the tumor-killing effect of CDDP and Mitomycin C, and this effect relied on adaptive antitumor immunity. Consistently, I + C altered the ratio of interferon-gamma-secreting T lymphocytes, thus overcoming the immunosuppressive effect induced by CDDP. In conclusion, our research presents a new combination strategy and indicates that I/R is a potential anticancer immunogenic modality when combined with nonimmunogenic chemotherapy.

Study on Instant Delivery Service Riders' Safety and Health by the Effects of Labour Intensity in China: A Mediation Analysis.

The Instant Delivery Service (IDS) riders' overwork by "self-pressurisation" will not only reduce the level of their physical and mental health but also lose their lives in safety accidents caused by their fatigue riding. The purpose of this article is to examine whether there is overwork among IDS riders in big and medium cities in China? What's going on with them? Based on the Cobb-Douglas production function in the input-output theory, this study characterised the factors on IDS riders' safety and health associated with labour intensity. A mediating model with moderating effect was adopted to describe the mediation path for the 2,742 IDS riders who were surveyed. The results of moderating regression demonstrated that (1) 0.4655 is the total effect of labour intensity on the safety and health of IDS riders. (2) 0.3124 is the moderating effect that working hours make a greater impact on labour intensity. (3) The mediating effect of work pressure is the principal means of mediation both upstream and downstream.

Identification of Ubiquitin-Related Gene-Pair Signatures for Predicting Tumor Microenvironment Infiltration and Drug Sensitivity of Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer worldwide, and new biomarkers are urgently required to guide more effective individualized therapy for patients. Ubiquitin-related genes (UbRGs) partially participate in the initiation and progression of lung cancer. In this study, we used ubiquitin-related gene pairs (UbRGPs) in tumor tissues to access the function of UbRGs in overall survival, immunocyte infiltration, and tumor mutation burden (TMB) of patients with LUAD from The Cancer Genome Atlas (TCGA) database. In addition, we constructed a prognostic signature based on six UbRGPs and evaluated its performance in an internal (TCGA testing set) and an external validation set (GSE13213). The prognostic signature revealed that risk scores were negatively correlated with the overall survival, immunocyte infiltration, and expression of immune checkpoint inhibitor-related genes and positively correlated with the TMB. Patients in the high-risk group showed higher sensitivity to partially targeted and chemotherapeutic drugs than those in the low-risk group. This study contributes to the understanding of the characteristics of UbRGPs in LUAD and provides guidance for effective immuno-, chemo-, and targeted therapy.

Electrically-driven robust tuning of lattice thermal conductivity.

The two-dimensional (2D) materials, represented by graphene, stand out in the electrical industry applications of the future and have been widely studied. As commonly existing in electronic devices, the electric field has been extensively utilized to modulate the performance. However, how the electric field regulates thermal transport is rarely studied. Herein, we investigate the modulation of thermal transport properties by applying an external electric field ranging from 0 to 0.4 V Å-1, with bilayer graphene, monolayer silicene, and germanene as study cases. The monotonically decreasing trend of thermal conductivity in all three materials is revealed. A significant effect on the scattering rate is found to be responsible for the decreased thermal conductivity driven by the electric field. Further evidence shows that the reconstruction of internal electric field and generation of induced charges lead to increased scattering rate from strong phonon anharmonicity. Thus, the ultralow thermal conductivity emerges with the application of external electric fields. Applying an external electric field to regulate thermal conductivity illustrates a constructive idea for highly efficient thermal management.

Targeting Cancer Cell Ferroptosis to Reverse Immune Checkpoint Inhibitor Therapy Resistance.

In recent years, cancer therapies using immune checkpoint inhibitors (ICIs) have achieved meaningful success, with patients with advanced tumors presenting longer survival times and better quality of life. However, several patients still do not exhibit good clinical outcomes for ICI therapy due to low sensitivity. To solve this, researchers have focused on identifying the cellular and molecular mechanisms underlying resistance to ICI therapy. ICI therapy induces apoptosis, which is the most frequent regulated cell death (RCD) but lacks immunogenicity and is regarded as an "immune silent" cell death. Ferroptosis, a unique type of non-apoptotic-RCD, has been preliminarily identified as an immunogenic cell death (ICD), stimulating tumor-antigen-specific immune responses and augmenting anti-tumor immune effects. However, ferroptosis has rarely been used in clinical practice. Present evidence strongly supports that the interferon-γ signaling pathway is at the crossroads of ICI therapy and ferroptosis. TYRO3, a receptor tyrosine kinase, is highly expressed in tumors and can induce anti-programmed cell death (PD)-ligand 1/PD-1 therapy resistance by limiting tumoral ferroptosis. Therefore, in this review, we summarize the clinical practice and effects of ICI therapy in various cancers. We also provide an overview of ferroptosis and report the molecular connections between cancer cell ferroptosis and ICI therapy, and discuss the possibility to reverse ICI therapy resistance by inducing cancer cell ferroptosis.

Accessing negative Poisson's ratio of graphene by machine learning interatomic potentials.

The negative Poisson's ratio (NPR) is a novel property of materials, which enhances the mechanical feature and creates a wide range of application prospects in lots of fields, such as aerospace, electronics, medicine, etc. Fundamental understanding on the mechanism underlying NPR plays an important role in designing advanced mechanical functional materials. However, with different methods used, the origin of NPR is found different and conflicting with each other, for instance, in the representative graphene. In this study, based on machine learning technique, we constructed a moment tensor potential for molecular dynamics (MD) simulations of graphene. By analyzing the evolution of key geometries, the increase of bond angle is found to be responsible for the NPR of graphene instead of bond length. The results on the origin of NPR are well consistent with the start-of-art first-principles, which amend the results from MD simulations using classic empirical potentials. Our study facilitates the understanding on the origin of NPR of graphene and paves the way to improve the accuracy of MD simulations being comparable to first-principle calculations. Our study would also promote the applications of machine learning interatomic potentials in multiscale simulations of functional materials.

Analysis of the Failure of Removal of the Urinary Catheter for Patients With Intracerebral Hemorrhage Postoperatively.

BACKGROUND: We conducted this study to assess the value of clinically relevant data for predicting the failure of removing urinary catheters among patients with intracerebral hemorrhage postoperatively. MATERIALS AND METHODS: We retrospectively analyzed the medical records of all patients with intracerebral hemorrhage who underwent surgery for removal of intracerebral hematoma between January 2014 and December 2019, all of whom retained their urinary catheter. The patients were classified into 2 groups. Group A included patients who underwent successful removal of the catheter while group B included patients who underwent a failed removal. Univariate analysis was performed to determine the relationship between the failure of catheter removal and the patients' preoperative clinical characteristics. Independent prognostic predictors were identified using multivariate analyses. RESULTS: The site of intracerebral hematoma ( P =0.004), volume of hematoma ( P <0.001), intraventricular hemorrhage ( P <0.001), admitted Glasgow Coma Scale (GCS) ( P <0.001), GCS before urinary catheter removal ( P <0.001), smoking ( P =0.011), herniation ( P <0.001), urine protein ( P =0.013), creatinine ( P =0.037), and timing of urinary catheter removal ( P <0.001) were significantly different among the 2 groups. Multiple logistical regression analysis indicated that GCS before urinary catheter removal (odds ratio=1.171; 95% confidence interval=1.050-1.306; P =0.005) and timing for urinary catheter removal (odds ratio=0.962; 95% confidence interval=0.944-0.981; P <0.001) were associated with failure of urinary catheter removal. CONCLUSIONS: This study demonstrated that GCS before urinary catheter removal and the timing of urinary catheter removal are independent factors associated with failure of urinary catheter removal among patients with intracerebral hemorrhage.

Shared Cultural Values Influence Mental Health Help-Seeking Behaviors in Asian and Latinx College Students.

The current study sought to understand the influence of cultural values on mental health attitudes and help-seeking behaviors in college students of diverse ethnic backgrounds. Asian and Latinx college students (N = 159) completed an online survey in which they reported on their adherence to cultural values as measured by ethnicity-specific cultural values and general attitudes towards mental health. Factor analysis revealed two common factors of cultural values irrespective of ethnicity: Interdependent Orientation (IO) and Cultural Obligation (CO). Regardless of ethnicity, the more students endorsed IO values, the less likely they were to perceive a need for mental health treatment. IO value adherence was also predictive of more negative attitudes towards mental health. CO values were not predictive of perceived need or help-seeking behaviors. Findings highlight the importance of understanding shared cultural values across ethnic-racial groups and considering how the multidimensionality of culture may help explain shared mental health behaviors crossing lines of ethnic group membership.

Unique Arrangement of Atoms Leads to Low Thermal Conductivity: A Comparative Study of Monolayer Mg2C.

Two-dimensional Mg2C, one of the typical representative MXene materials, is attracting lots of attention due to its outstanding properties. In this study, we find the thermal conductivity of monolayer Mg2C is more than 2 orders of magnitude lower than graphene and is even lower than MoS2 despite the relatively lighter atoms of Mg and C. Based on the comparative analysis with graphene, silicene, and MoS2, the underlying mechanism is found lying in the unique arrangement of atoms (lighter atoms in the middle plane) and large electronegativity difference in Mg2C. The phonon anharmonicity is strong due to the resonant bonding. In addition, dual band gaps emerge in the phonon dispersion of Mg2C, which limit the phonon-phonon scattering and reduce the phonon relaxation time. This study reveals a new mechanism responsible for low thermal conductivity, which would be helpful for designing thermal functional materials and pave the way for applications in thermoelectrics.

The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study.

Background: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited. Methods: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups. Results: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, p = 0.05; OS: 20.73 vs 14.35 months, p = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, p = 0.07; OS: 19.07 vs 18.00 months, p = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, p = 0.05; OS: 19.53 vs 15.10 months, p = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS. Conclusion: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.

Ear fullness characteristics and prognosis in patients with all-frequency sudden sensorineural hearing loss.

OBJECTIVE: This study investigated the characteristics and prognosis of the feeling of ear fullness in patients with unilateral all-frequency sudden sensorineural hearing loss. METHODS: Our study included 56 patients with a diagnosis of unilateral all-frequency sudden sensorineural hearing loss accompanied by a feeling of ear fullness and 48 patients without a feeling of ear fullness. The condition of these patients was prospectively observed. RESULTS: Positive correlations were observed between grading of feeling of ear fullness and hearing loss in patients with a feeling of ear fullness (r = 0.599, p < 0.001). No significant differences were observed in the total effective rate of hearing recovery between patients with and without a feeling of ear fullness after one month of treatment (Z = -0.641, p = 0.521). Eighty-six per cent of patients (48 out of 56) showed complete recovery from the feeling of ear fullness. There was no correlation between feeling of ear fullness recovery and hearing recovery (r = 0.040, p = 0.769). CONCLUSION: The prognosis of feeling of ear fullness is good. There was no correlation between feeling of ear fullness recovery and hearing recovery for all-frequency sudden sensorineural hearing loss patients.