Ultralow Glassy Thermal Conductivity and Controllable, Promising Thermoelectric Properties in Crystalline o-CsCu5S3.

We thoroughly investigated the anharmonic lattice dynamics and microscopic mechanisms of the thermal and electronic transport characteristics in orthorhombic o-CsCu5S3 at the atomic level. Taking into account the phonon energy shifts and the wave-like tunneling phonon channel, we predict an ultralow κL of 0.42 w/mK at 300 K with an extremely weak temperature dependence following ∼T-0.33. These findings agree well with experimental values along with the parallel to the Bridgman growth direction. The κL in o-CsCu5S3 is suppressed down to the amorphous limit, primarily due to the unconventional Cu-S bonding induced by the p-d hybridization antibonding state coupled with the stochastic oscillation of Cs atoms. The nonstandard temperature dependence of κL can be traced back to the critical or dominant role of wave-like tunneling of phonon contributions in thermal transport. Moreover, the p-d hybridization of Cu(3)-S bonding results in the formation of a valence band with "pudding-mold" and high-degeneracy valleys, ensuring highly efficient electron transport characteristics. By properly adjusting the carrier concentration, excellent thermoelectric performance is achieved with a maximum thermoelectric conversion efficiency of 18.4% observed at 800 K in p-type o-CsCu5S3. Our work not only elucidates the anomalous electronic and thermal transport behavior in the copper-based chalcogenide o-CsCu5S3 but also provides insights for manipulating its thermal and electronic properties for potential thermoelectric applications.

An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer's Disease with Berberine and Palmatine.

Introduction: Neuroinflammation is one of the major pathogeneses in Alzheimer's disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inefficient ability of therapeutic drugs to permeate through the blood‒brain barrier (BBB). Accordingly, drug combination treatment and drug carrier delivery have become important therapeutic tools for the treatment of multifactorial diseases, especially AD. Methods: Inflammatory cytokine levels in microglia, including NO, TNF-α, IL-1ß, IL-4, and IL-10, were detected. The Morris water maze and object location task were used to investigate the learning and memory functions of APP/PS1 mice in different treatment groups. The number of neurons and plasticity of synapses were evaluated by immunofluorescence double labelling. Additionally, the ratio of ß-amyloid plaques and the number of activated microglia were evaluated by immunofluorescence staining. The concentrations of ß-amyloid plaques and inflammatory factors in the hippocampus were determined by ELISA. Microglia-derived exosomes (Exos) were extracted and purified by size exclusion chromatography. The distribution of exosomes and drugs was investigated in vitro and in vivo. Results: Compared to single drug interventions, the combination of Ber and Pal (Ber/Pal) modulated microglial inflammatory cytokine levels. Ber/Pal promoted the recovery of learning and memory impairment in APP/PS1 mice. Immunofluorescence staining indicated that Ber/Pal restored neurons, inhibited Aß plaque formation and microglial activation, and regulated the secretion of inflammatory factors. Exos promoted the accumulation of drugs in cells and tissues and improved the targeting of drugs across the BBB. Conclusion: Ber/Pal could offer a synergistic and more comprehensive therapeutic effect in AD. Additionally, the microglia-derived Exos-Ber/Pal delivery system promoted the targeting and permeation of drugs into the brain, suggesting a creative strategy for targeting AD therapy by regulating neuroinflammation in microglial cells.

Vitamin D signaling maintains intestinal innate immunity and gut microbiota: potential intervention for metabolic syndrome and NAFLD.

A lack of sunlight exposure, residence in the northern latitudes, and dietary vitamin D insufficiency are coprevalent with metabolic syndrome (MetS), Type 2 diabetes (T2D), and nonalcoholic fatty liver diseases (NAFLD), implying a potential causality and underlying mechanism. Whether vitamin D supplementation or treatment can improve these disorders is controversial, in part, because of the absence of large-scale trials. Experimental investigations, on the other hand, have uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin that maintained calcium homeostasis. While the large intestine harbors massive numbers of microbes, the small intestine has a minimal quantity of bacteria, indicating the existence of a gating system located in the distal region of the small intestine that may restrain bacterial translocation to the small intestine. Vitamin D receptor (VDR) was found to be highly expressed at the distal region of small intestine, where the vitamin D signaling promotes innate immunity, including the expression of α-defensins by Paneth cells, and maintains the intestinal tight junctions. Thus, a new hypothesis is emerging, indicating that vitamin D deficiency may impair the intestinal innate immunity, including downregulation of Paneth cell defensins, leading to bacterial translocation, endotoxemia, systemic inflammation, insulin resistance, and hepatic steatosis. Here, we review the studies for vitamin D for innate immunity and metabolic homeostasis, and we outline the clinical trials of vitamin D for mitigating MetS, T2D, and NAFLD.

Impact of Vitamin D and Vitamin D Receptor on Risk of Cardiovascular Diseases in Children and Adolescents with Obesity in Sichuan, China: A Cross-Sectional Study.

BACKGROUND: Previous studies have demonstrated the close relationship between vitamin D, vitamin D receptor (VDR), and obesity. Nevertheless, few studies have reported wherther the relationship among these is associated with the risk of cardiovascular diseases (CVDs) in Chinese children and adolescents. OBJECTIVE: The present study aimed to reveal the effects of obesity, serum vitamin D levels, and VDR FokI genotype on the risk of CVDs in children and adolescents in Sichuan, China. METHODS: Children and adolescents were recruited into a cross-sectional study. Serum vitamin D levels, serum lipid levels, and VDR FokI gene polymorphisms were measured in the laboratory. The selected lipid factors were used as biomarkers of CVD risk. The impact of obesity, vitamin D levels and VDR FokI genotype on CVD risk factors were investigated. RESULTS: Higher lipid levels were observed in children and adolescents in the obese group, when compared to the nonobese group. In the obese group, the C allele carriers had significantly lower concentrations of lipids, when compared to the TT genotype. C allele carriers who were vitamin D deficient had lower levels of total cholesterol (TC), triglycerides (TG), apolipoprotein B (Apo-B), total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C), when compared to those with the TT genotype in obese children and adolescents. For vitamin D-insufficient obese children and adolescents, the TC, Apo-B, and TC/HDL-C in the C allele carriers were significantly lower, when compared to those in the TT genotype in obese children and adolescents. CONCLUSION: Obese children with low vitamin D levels, who are carriers of the C allele of the FokI gene, have lower levels of several biochemical markers of CVD risk, when compared to those who were TT homozygous. Obese children and adolescents may benefit from vitamin D supplementation, terms of lowering their CVD risk, particularly when they are carriers of the C allele of the FokI gene.

Nano-pulse stimulation induces potent immune responses, eradicating local breast cancer while reducing distant metastases.

Nano-pulse stimulation (NPS) as a developing technology has been studied for minimally invasive, nonthermal local cancer elimination for more than a decade. Here we show that a single NPS treatment results in complete regression of the poorly immunogenic, metastatic 4T1-Luc mouse mammary carcinoma. Impressively, spontaneous distant organ metastases were largely prevented, even in those animals with incomplete tumor regression. All tumor-free mice were protected from secondary tumor cell challenge, demonstrating a vaccine-like effect. NPS treatment induced antitumor immunity, long-term memory T cells, destruction of tumor microenvironment and reversal of the massive increase of immune suppressor cells in the tumor microenvironment and blood. NPS-treated 4T1 cells exhibited release of damage-associated molecular patterns (DAMPs), including calreticulin, HMGB1 and ATP, and activated dendritic cells. Those findings suggest that NPS is a potent immunogenic cell death inducer that elicits antitumor immunity to prevent distant metastases in addition to local tumor eradication.

Controllable Moderate Heating Enhances the Therapeutic Efficacy of Irreversible Electroporation for Pancreatic Cancer.

Irreversible electroporation (IRE) as a non-thermal tumor ablation technology has been studied for the treatment of pancreatic carcinoma and has shown a significant survival benefit. We discovered that moderate heating (MH) at 43 °C for 1-2 minutes significantly enhanced ex vivo IRE tumor ablation of Pan02 cells by 5.67-fold at 750 V/cm and by 1.67-fold at 1500 V/cm. This amount of heating alone did not cause cell death. An integrated IRE system with controllable laser heating and tumor impedance monitoring was developed to treat mouse ectopic pancreatic cancer. With this novel IRE system, we were able to heat and maintain the temperature of a targeted tumor area at 42 °C during IRE treatment. Pre-heating the tumor greatly reduced the impedance of tumor and its fluctuation. Most importantly, MHIRE has been demonstrated to significantly extend median survival and achieve a high rate of complete tumor regression. Median survival was 43, 46 and 84 days, for control, IRE with 100 µs, 1 Hz, 90 pulses and electric fields 2000-2500 V/cm and MHIRE treatment respectively. 55.6% of tumor-bearing mice treated with MHIRE were tumor-free, whereas complete tumor regression was not observed in the control and IRE treatment groups.