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Chronic hepatitis B virus (HBV) infection is caused by inadequate anti-viral immunity. Activation of plasmacytoid dendritic cells (pDC) leading to IFNα production is important for effective anti-viral immunity. Hepatitis B virus (HBV) infection lacks IFNα induction in animal models and patients and chronic HBV patients display impaired IFNα production by pDC. Therefore, HBV and HBV-derived proteins were examined for their effect on human pDC in vitro. In addition, the in vitro findings were compared to the function of pDC derived from chronic HBV patients ex vivo. In contrast to other viruses, HBV did not activate pDC. Moreover, HBV and HBsAg abrogated CpG-A/TLR9-induced, but not Loxoribine/TLR7-induced, mTOR-mediated S6 phosphorylation, subsequent IRF7 phosphorylation and IFNα gene transcription. HBV/HBsAg also diminished upregulation of co-stimulatory molecules, production of TNFα, IP-10 and IL-6 and pDC-induced NK cell function, whereas TLR7-induced pDC function was hardly affected. In line, HBsAg preferentially bound to TLR9-triggered pDC demonstrating that once pDC are able to bind HBV/HBsAg, the virus exerts its immune regulatory effect. HBV not only directly interfered with pDC function, but also indirectly by interfering with monocyte-pDC interaction. Also HBeAg diminished pDC function to a certain extent, but via another unknown mechanism. Interestingly, patients with HBeAg-positive chronic hepatitis B displayed impaired CpG-induced IFNα production by pDC without significant alterations in Loxoribine-induced pDC function compared to HBeAg-negative patients and healthy controls. The lack of activation and the active inhibition of pDC by HBV may both contribute to HBV persistence. The finding that the interaction between pDC and HBV may change upon activation may aid in the identification of a scavenging receptor supporting immunosuppressive effects of HBV and also in the design of novel treatment strategies for chronic HBV.

Phototherapy has remarkable advantages in cancer treatment, owing to its high efficiency and minimal invasiveness. Indocyanine green (ICG) plays an important role in photo-mediated therapy. However, it has several disadvantages such as poor stability in aqueous solutions, easy aggregation of molecules, and short plasma half-life. This study aimed to develop an efficient nanoplatform to enhance the effects of photo-mediated therapy. We developed a novel bio-nanoplatform by integrating edible ginger-derived exosome-like nanoparticles (GDNPs) and the photosensitizer, ICG (GDNPs@ICG). GDNPs were isolated from ginger juice and loaded with ICG by co-incubation. The size distribution, zeta potential, morphology, total lipid content, and drug release behavior of the GDNPs@ICG were characterized. The photothermal performance, cellular uptake and distribution, cytotoxicity, anti-tumor effects, and mechanism of action of GDNPs@ICG were investigated both in vitro and in vivo. GDNPs@ICG were taken up by tumor cells via a lipid-dependent pathway. When irradiated by an 808 nm NIR laser, GDNPs@ICG generated high levels of ROS, MDA, and local hyperthermia within the tumor, which caused lipid peroxidation and ER stress, thus enhancing the photo-mediated breast tumor therapy effect. Furthermore, in vivo studies demonstrated that engineered GDNPs@ICG significantly inhibited breast tumor growth and presented limited toxicity. Moreover, by detecting the expression of CD31, N-cadherin, IL-6, IFN-γ, CD8, p16, p21, and p53 in tumor tissues, we found that GDNPs@ICG substantially reduced angiogenesis, inhibited metastasis, activated the anti-tumor immune response, and promoted cell senescence in breast tumor. Our study demonstrated that the novel bio-nanoplatform GDNPs@ICG enhanced the photo-mediated therapeutic effect in breast tumor. GDNPs@ICG could be an alternative for precise and efficient anti-tumor phototherapy.

This study aims to systematically search, screen, evaluate, and summarize the best evidence related to the dietary management of patients with high-output ileostomy, providing an evidence-based reference for the dietary management tailored to this specific demographic. A comprehensive search was conducted across multiple databases, including BMJ best practice, Up to Date, Guidelines International Network, Medlive, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, Registered Nurses Association of Ontario, JBI, Cochrane Library, PubMed, CNKI, Wanfang, and VIP databases. Additional searches included websites of professional organizations such as the European Society for Clinical Nutrition and Metabolism, Chinese Society for Parenteral and Enteral Nutrition, American Society for Parenteral and Enteral Nutrition, World Council of Enterostomal Therapists, United Ostomy Associations of America, and International Ostomy Association. Two researchers independently evaluated the quality of the included literature and extracted and summarized the evidence. Eighteen articles were included: 2 clinical decision documents, 5 guidelines, 3 expert consensus statements, 6 expert opinions, and 2 evidence summaries. Thirty pieces of evidence were synthesized, covering nutritional risk screening, dietary guidance, dietary behavior guidance, health education, and follow-up care. The summarized best evidence is scientific and comprehensive, offering an evidence-based guide for healthcare professionals managing the dietary needs of patients with high-output ileostomy.

It is a great challenge to improve the strength of disc superalloys without great loss of plasticity together since the microstructures benefiting the strength always do not avail the plasticity. Interestingly, this study shows that the trade-off relationship between strength and plasticity can be broken through decreasing stacking fault energy (SFE) in newly developed Ni-Co based disc superalloys. Axial tensile tests in the temperature range of 25 to 725 °C were carried out in these alloys with Co content ranging from 5% to 23% (wt.%). It is found that the ultimate tensile strength (UTS) and uniform elongation (UE) are improved synchronously when microtwinning is activated by decreasing the SFE at 650 and 725 °C. In contrast, only UTS is improved when stacking fault (SF) dominates the plastic deformation at 25 and 400 °C. These results may be helpful for designing advanced disc superalloys with relatively excellent strength and plasticity simultaneously.

Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Both behavioral and biological adaptations have contributed to their success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at >3,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan-specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations.

The machinability, including machined surface, edge quality, and the distribution of the subsurface residual stress, was studied during the orthogonal cutting of high-volume fraction SiCp/Al composites by both finite element analysis and experiments. The effect of cutting parameters on surface roughness, sizes of edge breakout, and residual stress were investigated. The elastic-plastic constitutive model and Johnson–Cook damage model for the Al alloy matrix, and the elastic-brittle failure for SiC particle were implemented in the mechanical properties of composites during the cutting simulation. The results indicate that the surface morphology is primarily dependent on the fracture models of SiC particles, and the formation of the negative shear plain is the main reason of edge breakout. Due to the inhomogeneity in the composites, the distribution of surface and subsurface residual stress is not uniform, and the high residual stress was distributed in the interface between irregular particles and matrix. The average value of residual stress of SiC particle is similar to that of the matrix. The predicted machined surface morphology and edge breakout sizes correlated well with the experimental observation. This study highlights the important role of the fracture model of SiC particles on surface finish and the edge quality. It provides useful information for better understanding of the mechanics in machining of the SiCp/Al composites.

Herein, the effect of Ta addition (0 and 2 wt pct) on the tensile properties of a Ni-Co base superalloy was investigated in the temperature range of 23–900 °C. The results revealed that the addition of Ta improved the strength of the superalloy at all experimental temperatures and increased the plasticity at 760 °C. In addition, the microstructural observations indicate that Ta addition promoted the precipitation of γ′ precipitates, as well as the precipitation of (Ta, Ti)-rich MC carbides. The addition of 2 wt pct Ta promoted twinning and, thus, transformed the fracture mechanism of the alloy from an intergranular brittle fracture to a mixed ductile and brittle fracture at 760 °C. Furthermore, the tensile properties and the related microstructures, deformation mechanisms, and fracture mechanisms of the experimental alloys are discussed. Finally, we demonstrated that the combined effect of the increase in the grain boundary strength, the reduction in the critical resolved shear stress, and the promotion of twinning induced the synchronous improvement of strength and plasticity of the alloy at 760 °C.

Resistance to traditional treatments has spurred research into innovative therapeutic approaches for tumors. Among these innovative treatments, photothermal therapy (PTT) has gained increasing attention for its use of photothermal agents (PTAs) to convert light into heat for localized tumor ablation. However, PTT faces limitations due to heat shock protein 70 (HSP70)-mediated resistance in tumor cells. Combining PTT via indocyanine green (ICG) with siRNA HSP70 could reduce the thermal resistance of the tumor, thereby enhancing treatment efficacy. Albumin-based nanoparticles (NPs) can effectively deliver ICG and siRNA into tumor cells. When exposed to near-infrared (NIR) light, these nanoparticles trigger lysosomal escape and release, further enhancing gene silencing activity. This study aimed to develop a biocompatible delivery system, HSA@ICG/siRNA NPs, for photothermal-enhanced tumor therapy. The nanoparticles were characterized for size, charge, surface functionalization, and photoconversion properties. In vitro antitumor efficacy was evaluated using MTT assay, calcein AM/PI staining, RT-PCR, and Western blot in 4T1 tumor cells. In vivo, we assessed photothermal effects, biodistribution, tumor inhibition, and biosafety following irradiation. Characterization confirmed the successful synthesis of uniform, stable HSA@ICG/siRNA NPs with effective photothermal conversion properties. Cellular uptake studies revealed high siRNA internalization, with laser-induced lysosomal escape enhancing cytoplasmic delivery. In vitro, gene silencing reduced mRNA and protein levels by 82.8% and 65%, respectively. In vivo, local tumor temperature increased to 42°C within 3 minutes, indicating a mild but effective photothermal effect. Tumor inhibition rates were 50.00% ± 9.16% for HSA@ICG and 71.26% ± 7.92% for HSA@ICG/siRNA, demonstrating enhanced tumor suppression. The treatment achieved sustained tumor targeting with minimal off-target toxicity. As a dual-function photothermal therapy agent, HSA@ICG/siRNA NPs combine targeted gene silencing with photothermal effects, demonstrating significant therapeutic promise. This integrated approach addresses tumor resistance, offering a potential advancement in cancer treatment strategies.

Silk protein, as a natural polymer material with unique structures and properties, exhibits tremendous potential in the biomedical field. Given the limited production and restricted properties of natural silk proteins, molecular biotechnology has been extensively applied in silk protein genetic engineering to produce novel silk proteins with specific properties. This review outlines the roles of major model organisms, such as silkworms and spiders, in silk protein production, and provides a detailed introduction to the applications of gene editing technologies (eg, CRISPR-Cas9), transgenic expression technologies, and synthetic biology techniques in silk protein genetic engineering. By analyzing the genetic factors influencing silk protein expression, this review further elaborates on the innovative applications of silk proteins in drug delivery systems, tissue engineering and regenerative medicine (eg, skin, bone, cartilage, and vascular repair), as well as antibacterial immune strategies. Notably, modified silk proteins expressed by transgenic silkworms demonstrate significant advantages in enhancing drug bioavailability and promoting cell proliferation and differentiation. In conclusion, silk protein gene engineering, through continuous innovations in molecular biotechnology, has provided an effective pathway for the production of high-performance silk protein materials. The extensive applications of these modified silk proteins in the biomedical field have not only expanded the functionality of silk proteins but also offered new approaches to address medical challenges. In the future, the development of silk protein gene engineering will further rely on interdisciplinary integration to promote in-depth research and the expansion of industrial applications of silk proteins.

Chronic inflammation plays a pivotal role in the development of frailty in patients with cardiovascular diseases (CVD). Systemic inflammatory response index (SIRI) has been shown to reflect the overall inflammatory status. This study aimed to investigate the relationship between SIRI and frailty in older patients with CVD, and to develop a nomogram for predicting the risk of frailty in this population. A total of 234 older patients with CVD were included. Inflammation markers were derived from routine blood tests, and frailty status was assessed using the FRAIL scale. Clinical and laboratory characteristics were compared between patients with or without frailty. Multivariate logistic regression was employed to identify significant variables for inclusion in the nomogram. The performance of the nomogram, including its discrimination and calibration, was rigorously evaluated. A total of 98 cases were assigned to the frailty group and 136 to the non-frailty group. Patients in the non-frailty group were generally younger, more likely to have normal kidney function, and better blood pressure control. Frail patients exhibited a higher degree of systemic inflammation compared to non-frail patients (P < 0.05). Age, LDL-C and SIRI were identified as three independent risk factors with significant potential for predicting frailty in CVD patients. Therefore, we constructed a clinical nomogram model for frailty based on age, LDL-C and SIRI. The nomogram for frailty had considerable discriminative and calibrating abilities. In summary, our study demonstrated a significant association between elevated levels of inflammation markers, particularly SIRI, and an increased risk of frailty. Furthermore, by integrating age, LDL-C and SIRI, we established a nomogram to predict the risk of frailty in older patients with CVD.