253 research outputs found
Prediction of higher thermoelectric performance in BiCuSeO by weakening electron-polar optical phonon scattering
BiCuSeO is a promising thermoelectric material, but its applications are hindered by low carrier mobility. We use first-principles calculations to analyse electron–phonon scattering mechanisms and evaluate their contributions to the thermoelectric figure of merit ZT. The combined scattering of carriers by polar optical (PO) and longitudinal acoustic (LA) phonons yields an intrinsic hole mobility of 32 cm^{2} V^{−1} s^{−1} at room temperature and a temperature power law of T^{−1.5} between 100–875 K, which agree well with experiments. We demonstrate that electron–phonon scattering in the Cu–Se layer dominates at low T (< 500 K), while contributions from the Bi–O layer become increasingly significant at higher T. At room temperature, ZT is calculated to be 0.48 and can be improved by 30% through weakening PO phonon scattering in the Cu–Se layer. This finding agrees with the experimental observation that weakening the electron–phonon interaction by Te substitution in the Cu–Se layer improves mobility and ZT. At high T, the figure of merit is improved by weakening the electron–PO phonon scattering in the Bi–O layer instead. The theoretical ZT limit of BiCuSeO is calculated to be 2.5 at 875 K
Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?
The laboratory mouse has been widely used to test the efficacy of schistosome vaccines and a long list of candidates has emerged from this work, many of them abundant internal proteins. These antigens do not have an additive effect when co-administered, or delivered as SWAP homogenate, a quarter of which comprises multiple candidates; the observed protection has an apparent ceiling of 40–50 %. We contend that the low level of maturation of penetrating cercariae (~32 % for Schistosoma mansoni) is a major limitation of the model since 68/100 parasites fail to mature in naïve mice due to natural causes. The pulmonary capillary bed is the obstacle encountered by schistosomula en route to the portal system. The fragility of pulmonary capillaries and their susceptibility to a cytokine-induced vascular leak syndrome have been documented. During lung transit schistosomula burst into the alveolar spaces, and possess only a limited capacity to re-enter tissues. The acquired immunity elicited by the radiation attenuated (RA) cercarial vaccine relies on a pulmonary inflammatory response, involving cytokines such as IFNγ and TNFα, to deflect additional parasites into the alveoli. A principal difference between antigen vaccine protocols and the RA vaccine is the short interval between the last antigen boost and cercarial challenge of mice (often two weeks). Thus, after antigen vaccination, challenge parasites will reach the lungs when both activated T cells and cytokine levels are maximal in the circulation. We propose that “protection” in this situation is the result of physiological effects on the pulmonary blood vessels, increasing the proportion of parasites that enter the alveoli. This hypothesis will explain why internal antigens, which are unlikely to interact with the immune response in a living schistosomulum, plus a variety of heterologous proteins, can reduce the level of maturation in a non-antigen-specific way. These proteins are “successful” precisely because they have not been selected for immunological silence. The same arguments apply to vaccine experiments with S. japonicum in the mouse model; this schistosome species seems a more robust parasite, even harder to eliminate by acquired immune responses. We propose a number of ways in which our conclusions may be tested
Microstructure and dry sliding wear behavior of cast Al–Mg2Si in-situ metal matrix composite modified by Nd
AI-Driven Large Language Models in Health Consultations for HIV Patients
Chun-Yan Zhao,1,2,&ast; Chang Song,1,2,&ast; Tong Yang,3,&ast; Ai-Chun Huang,1 Hang-Biao Qiang,1 Chun-Ming Gong,1 Jing-Song Chen,4 Qing-Dong Zhu1 1Department of Tuberculosis, The Fourth People’s Hospital of Nanning, Nanning, Guangxi, People’s Republic of China; 2Clinical Medical School, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Rehabilitation, Hepu County People’s Hospital, Beihai, Guangxi, People’s Republic of China; 4Department of Gastroenterology, Hepu County People’s Hospital, Beihai, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-Dong Zhu, Department of Tuberculosis, The Fourth People’s Hospital of Nanning, No. 1 Changgang Two-Li, Xingning District, Nanning, Guangxi, 530023, People’s Republic of China, Tel +86 0771-5636973, Email [email protected] Jing-Song Chen, Department of Gastroenterology, Hepu County People’s Hospital, No. 95, Dinghai North Road, Hepu County, Beihai, Guangxi, 536100, People’s Republic of China, Tel +86 0779-7106010, Email [email protected]: This study endeavors to conduct a comprehensive assessment on the performance of large language models (LLMs) in health consultation for individuals living with HIV, delve into their applicability across a diverse array of dimensions, and provide evidence-based support for clinical deployment.Patients and Methods: A 23-question multi-dimensional HIV-specific question bank was developed, covering fundamental knowledge, diagnosis, treatment, prognosis, and case analysis. Four advanced LLMs—ChatGPT-4o, Copilot, Gemini, and Claude—were tested using a multi-dimensional evaluation system assessing medical accuracy, comprehensiveness, understandability, reliability, and humanistic care (which encompasses elements such as individual needs attention, emotional support, and ethical considerations). A five-point Likert scale was employed, with three experts independently scoring. Statistical metrics (mean, standard deviation, standard error) were calculated, followed by consistency analysis, difference analysis, and post-hoc testing.Results: Claude obtained the most outstanding performance with regard to information comprehensiveness (mean score 4.333), understandability (mean score 3.797), and humanistic care (mean score 2.855); Copilot demonstrated proficiency in diagnostic questions (mean score 3.880); Gemini illustrated exceptional performance in case analysis (mean score 4.111). Based on the post-hoc analysis, Claude outperformed other models in thoroughness and humanistic care (P < 0.05). Copilot showed better performance than ChatGPT in understandability (P = 0.045), while Gemini performed significantly better than ChatGPT in case analysis (P < 0.001). It is important to note that performance varied across tasks, and humanistic care remained a consistent weak point across all models.Conclusion: The superiority of diverse models in specific tasks suggest that LLMs hold extensive application potential in the management of HIV patients. Nevertheless, their efficacy in the realm of humanistic care still needs improvement.Keywords: artificial intelligence, large language model, HIV, health consultation, performance analysi
Modular Design via Multiple Anion Chemistry of the High Mobility van der Waals Semiconductor Bi₄O₄SeCl₂
Making new van der Waals materials with electronic or magnetic functionality is a chemical design challenge for the development of two-dimensional nanoelectronic and energy conversion devices. We present the synthesis and properties of the van der Waals material Bi4O4SeCl2, which is a 1:1 superlattice of the structural units present in the van der Waals insulator BiOCl and the three-dimensionally connected semiconductor Bi2O2Se. The presence of three anions gives the new structure both the bridging selenide anion sites that connect pairs of Bi2O2 layers in Bi2O2Se and the terminal chloride sites that produce the van der Waals gap in BiOCl. This retains the electronic properties of Bi2O2Se while reducing the dimensionality of the bonding network connecting the Bi2O2Se units to allow exfoliation of Bi4O4SeCl2 to 1.4 nm height. The superlattice structure is stabilized by the configurational entropy of anion disorder across the terminal and bridging sites. The reduction in connective dimensionality with retention of electronic functionality stems from the expanded anion compositional diversity
Clinical Characteristics Analysis of 30 Cases of Interferon-γ Autoantibody-Positive Patients with Concurrent Mycobacterial Infection: A 6-Year Retrospective Study
Chun-Yan Zhao,1,2,* Chang Song,1,2,* Hua-Wei He,1,* Xian-Zhen Huang,1 Xia-Yan Meng,1 Ai-Chun Huang,1 Chao-Yan Xu,1 Li-Li Luo,1 Shao-Yong Xi,3 Yan-Qun Lan,1 Wei-Wen Li,1 Yan-Rong Lin,1 Qing-Dong Zhu1 1Department of Tuberculosis, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China; 2Clinical Medical School, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Clinical Laboratory, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing-Dong Zhu; Yan-Rong Lin, Department of Tuberculosis, The Fourth People’s Hospital of Nanning, No. 1 Changgang Two-Li, Xingning District, Nanning, 530023, People’s Republic of China, Tel +8615207717261 ; +860771-5636973, Email [email protected]; [email protected]: This study aimed to investigate and elucidate the clinical characteristics, immune status, infection types and patterns, treatment responses, and disease progression in patients with positive anti-interferon-gamma (IFN-γ) autoantibodies in combination with Mycobacterium infections.Patients and Methods: We conducted a retrospective analysis of clinical data from patients with positive anti-IFN-γ autoantibodies and concurrent Mycobacterial infections, including Mycobacterial infections (MTB) and non-tuberculous mycobacteria (NTM). The study included cases treated at the Fourth People’s Hospital of Nanning, Guangxi, from 2018 to 2023. Data collected comprised symptoms, clinical signs, laboratory test results, imaging findings, and other relevant clinical information. Patients were also followed up to evaluate treatment responses and long-term therapeutic outcomes.Results: A total of 30 patients with MTB and NTM infections were analyzed. The majority presented with common symptoms, such as cough, sputum production, weight loss, extrapulmonary tuberculosis (TB), and a range of opportunistic infections. Laboratory and imaging studies revealed complex infection patterns and various pathological changes. Treatment primarily involved targeted anti-infective therapy combined with immunosupportive measures. However, frequent treatment relapses and side effects were observed, resulting in two deaths.Conclusion: Immune deficiency associated with positive anti-IFN-γ autoantibodies resembles the immunosuppression seen in advanced stages of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), rendering patients highly susceptible to opportunistic infections. These infections were predominantly caused by NTM, followed by MTB and Talaromyces marneffei (TM). This represents a novel immune deficiency syndrome that predisposes patients to a spectrum of opportunistic infections.Keywords: anti-interferon-gamma autoantibodies, Mycobacterium tuberculosis, nontuberculous mycobacteria, clinical characteristics, treatmen
Crosstalk between Chemokine Receptor CXCR4 and Cannabinoid Receptor CB2 in Modulating Breast Cancer Growth and Invasion
Cannabinoids bind to cannabinoid receptors CB(1) and CB(2) and have been reported to possess anti-tumorigenic activity in various cancers. However, the mechanisms through which cannabinoids modulate tumor growth are not well known. In this study, we report that a synthetic non-psychoactive cannabinoid that specifically binds to cannabinoid receptor CB(2) may modulate breast tumor growth and metastasis by inhibiting signaling of the chemokine receptor CXCR4 and its ligand CXCL12. This signaling pathway has been shown to play an important role in regulating breast cancer progression and metastasis.We observed high expression of both CB(2) and CXCR4 receptors in breast cancer patient tissues by immunohistochemical analysis. We further found that CB(2)-specific agonist JWH-015 inhibits the CXCL12-induced chemotaxis and wound healing of MCF7 overexpressing CXCR4 (MCF7/CXCR4), highly metastatic clone of MDA-MB-231 (SCP2) and NT 2.5 cells (derived from MMTV-neu) by using chemotactic and wound healing assays. Elucidation of the molecular mechanisms using various biochemical techniques and confocal microscopy revealed that JWH-015 treatment inhibited CXCL12-induced P44/P42 ERK activation, cytoskeletal focal adhesion and stress fiber formation, which play a critical role in breast cancer invasion and metastasis. In addition, we have shown that JWH-015 significantly inhibits orthotopic tumor growth in syngenic mice in vivo using NT 2.5 cells. Furthermore, our studies have revealed that JWH-015 significantly inhibits phosphorylation of CXCR4 and its downstream signaling in vivo in orthotopic and spontaneous breast cancer MMTV-PyMT mouse model systems.This study provides novel insights into the crosstalk between CB(2) and CXCR4/CXCL12-signaling pathways in the modulation of breast tumor growth and metastasis. Furthermore, these studies indicate that CB(2) receptors could be used for developing innovative therapeutic strategies against breast cancer
Mild hypothermia reduces cardiac post-ischemic reactive hyperemia
BACKGROUND: In experimentally induced myocardial infarction, mild hypothermia (33–35°C) is beneficial if applied prior to ischemia or reperfusion. Hypothermia, when applied after reperfusion seems to confer little or no benefit. The mechanism by which hypothermia exerts its cell-protective effect during cardiac ischemia remains unclear. It has been hypothesized that hypothermia reduces the reperfusion damage; the additional damage incurred upon the myocardium during reperfusion. Reperfusion results in a massive increase in blood flow, reactive hyperemia, which may contribute to reperfusion damage. We postulated that hypothermia could attenuate the post-ischemic reactive hyperemia. METHODS: Sixteen 25–30 kg pigs, in a closed chest model, were anesthetized and temperature was established in all pigs at 37°C using an intravascular cooling catheter. The 16 pigs were then randomized to hypothermia (34°C) or control (37°C). The left main coronary artery was then catheterized with a PCI guiding catheter. A Doppler flow wire was placed in the mid part of the LAD and a PCI balloon was then positioned proximal to the Doppler wire but distal to the first diagonal branch. The LAD was then occluded for ten minutes in all pigs. Coronary blood flow was measured before, during and after ischemia/reperfusion. RESULTS: The peak flow seen during post-ischemic reactive hyperemia (during the first minutes of reperfusion) was significantly reduced by 43 % (p < 0.01) in hypothermic pigs compared to controls. CONCLUSION: Mild hypothermia significantly reduces post-ischemic hyperemia in a closed chest pig model. The reduction of reactive hyperemia during reperfusion may have an impact on cardiac reperfusion injury
Precise Regulation of Gene Expression Dynamics Favors Complex Promoter Architectures
Promoters process signals through recruitment of transcription factors and RNA polymerase, and dynamic changes in promoter activity constitute a major noise source in gene expression. However, it is barely understood how complex promoter architectures determine key features of promoter dynamics. Here, we employ prototypical promoters of yeast ribosomal protein genes as well as simplified versions thereof to analyze the relations among promoter design, complexity, and function. These promoters combine the action of a general regulatory factor with that of specific transcription factors, a common motif of many eukaryotic promoters. By comprehensively analyzing stationary and dynamic promoter properties, this model-based approach enables us to pinpoint the structural characteristics underlying the observed behavior. Functional tradeoffs impose constraints on the promoter architecture of ribosomal protein genes. We find that a stable scaffold in the natural design results in low transcriptional noise and strong co-regulation of target genes in the presence of gene silencing. This configuration also exhibits superior shut-off properties, and it can serve as a tunable switch in living cells. Model validation with independent experimental data suggests that the models are sufficiently realistic. When combined, our results offer a mechanistic explanation for why specific factors are associated with low protein noise in vivo. Many of these findings hold for a broad range of model parameters and likely apply to other eukaryotic promoters of similar structure
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