Improvement effect of compound Ento-PB on oxazolone-induced ulcerative colitis in rats.

PURPOSE: To investigate the impact of the Chinese medicine compound Ento-PB on oxazolone (OXZ)-induced ulcerative colitis (UC) in rats. METHODS: UC rats induced by OXZ were treated with Ento-PB. The damage to the colon was assessed using several measures, including the disease activity index (DAI), colon length, colon weight/length ratio, colonic mucosal damage index, and histological score. The levels of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), epidermal growth factor (EGF), inducible nitric oxide synthase, and total nitric oxide synthase (tNOS) in rat serum, as well as the levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in rat colon tissue, were determined using enzyme-linked immunosorbent assay and conventional kits. RESULTS: After being treated with Ento-PB, the DAI score and macroscopic lesion score of OXZ-induced UC rats were significantly reduced. Ento-PB prevented the shortening of rat colons, reduced the ratio of colon weight to length, and improved colon tissue lesions. Meanwhile, Ento-PB could significantly inhibit the activities of proinflammatory cytokines TNF-α, IL-13, and MPO, as well as tNOS and iNOS, while upregulating the expression of anti-inflammatory cytokines IL-4 and IL-10. Moreover, a significant increase in the expression level of EGF was observed in UC rats treated with Ento-PB, indicating that Ento-PB could enhance the repair of damaged intestinal epithelial tissue. CONCLUSIONS: Ento-PB demonstrates significant anti-UC activities in OXZ-induced UC rats by regulating the expression levels of inflammatory factors and promoting the repair of colon tissue. This study provides scientific evidence to support the further development of Ento-PB.

New insight into oxidative stress and inflammatory responses to kidney stones: Potential therapeutic strategies with natural active ingredients.

Kidney stones, a prevalent urological disorder, are closely associated with oxidative stress (OS) and the inflammatory response. Recent research in the field of kidney stone treatment has indicated the potential of natural active ingredients to modulate OS targets and the inflammatory response in kidney stones. Oxidative stress can occur through various pathways, increasing the risk of stone formation, while the inflammatory response generated during kidney stone formation further exacerbates OS, forming a detrimental cycle. Both antioxidant systems related to OS and inflammatory mediators associated with inflammation play roles in the pathogenesis of kidney stones. Natural active ingredients, abundant in resources and possessing antioxidative and anti-inflammatory properties, have the ability to decrease the risk of stone formation and improve prognosis by reducing OS and suppressing pro-inflammatory cytokine expression or pathways. Currently, numerous developed natural active ingredients have been clinically applied and demonstrated satisfactory therapeutic efficacy. This review aims to provide novel insights into OS and inflammation targets in kidney stones as well as summarize research progress on potential therapeutic strategies involving natural active ingredients. Future studies should delve deeper into exploring efficacy and mechanisms of action of diverse natural active ingredients, proposing innovative treatment strategies for kidney stones, and continuously uncovering their potential applications.

Enhanced generation of internal tides under global warming.

A primary driver of deep-ocean mixing is breaking of internal tides generated via interactions of barotropic tides with topography. It is important to understand how the energy conversion from barotropic to internal tides responds to global warming. Here we address this question by applying a linear model of internal tide generation to coupled global climate model simulations under a high carbon emission scenario. The energy conversion to high-mode internal tides is projected to rise by about 8% by the end of the 21st century, whereas the energy conversion to low-mode internal tides remains nearly unchanged. The intensified near-bottom stratification under global warming increases energy conversion into both low and high-mode internal tides. In contrast, the intensified depth-averaged stratification reduces the modal horizontal wavenumber of internal tides, leading to increased (decreased) energy conversion into high (low)- mode internal tides. Our findings imply stronger mixing over rough topography under global warming, which should be properly parameterized in climate models for more accurate projections of future climate changes.

[Characteristics of Soil Selenium-cadmium Migration and Accumulation and Its Bioeffectiveness in Typical Geological High Background Area].

The prevalence of selenium-cadmium （Se-Cd） symbiosis in soils of geologically high background areas directly affects the safe utilization of Se-rich land resources. To investigate the migration and accumulation characteristics and bio-effectiveness of Se-Cd in the soil-crop system in typical geological high background areas of Southwest China and to realize the safe use of natural Se-rich land resources in geological high background areas, we collected 84 samples of agricultural crops （maize） and their supporting root systems and analyzed the Se-Cd content and physicochemical properties. Se-Cd accumulation characteristics, influencing factors, and bio-effectiveness of the soil-crop system were evaluated using geostatistics, bioenrichment factors, and geographic detectors. The results showed that the Se-Cd content in the study area was significantly higher than the background value of the soil in the whole country and in Yunnan Province. Influenced by the geological background, secondary enrichment in the process of soil formation, and agricultural activities, the accumulation and enrichment characteristics of Se in the root soil varied from no enrichment to slightly enriched, and the occurrence form was dominated by the residue state. The accumulation index of soil Cd was mainly in the medium pollution level, and the occurrence form was mainly in the residual state and the combined state of iron and manganese. The Se-enrichment rate of crop seeds reached 98.8% （DB 50/T 524-2013 standard）, and the average value of bioconcentration factor was 5.8%. The exceeding rate of Cd content in crop seeds was only 1.19% （GB 2762-2022 standard）, and the average value of Cd bioconcentration factor was 2.11%, so the ecological risk of heavy metal Cd in crop seeds was relatively low. In the Se-Cd symbiosis area under geological background, the weak alkaline environment of the soil could effectively reduce the bioavailability of Cd in crop seeds, and the Se-rich soil could inhibit the uptake of Cd by the crops to a certain extent. Correlation analysis showed that the migration and accumulation of Se and Cd from soil to crop seeds in the soil-crop system were affected by the elemental accumulation pattern and the physical and chemical properties （pH） of the soil, and at the same time, there was a certain synergistic-antagonistic effect between Se and Cd in the soil-crop system. Correlation analysis showed that the migration and accumulation of Se and Cd from soil to crop seeds in the soil-crop system was influenced by the occurrence of elements, soil physicochemical properties （pH）, and other factors, and there was also a certain synergistic-antagonistic interaction between Se and Cd in the soil-crop system.

Concentrated Deoiled Fat: A Novel Method of Fat Processing to Improve Fat Graft Survival-A Basic Research.

BACKGROUND: Oil compromises graft outcomes via inflammation, which accounts for the unpredictability of volume retention rates as low as 20%. Existing techniques for oil removal are relatively inefficient. In this study, a novel approach was taken to prepare concentrated deoiled fat (CDF) by utilizing flocculation and centrifugation to remove the oil. The hypothesis put forward in this study was that CDF would exhibit improved volume retention and quality by enhancing purification efficiency and reducing inflammation. METHODS: This basic research involved both in vitro and in vivo experiments using samples obtained from women who underwent abdominal liposuction. The CDF was prepared by flocculation and centrifugation. In the vitro experiments, the microstructure of fat was assessed using Calcein acetoxymethyl ester (AM) staining for living cells and propidium iodide (PI) staining for dead nuclei in two groups: Coleman fat group and CDF group. Additionally, the glucose uptake capacity of these two groups was evaluated using the glucose transport test (GTT). In the vivo experiments, the study included three groups: two experimental groups (low-volume concentrated deoiled fat, LCDF; high-volume concentrated deoiled fat, HCDF) and one control group (Coleman fat), with 10 healthy female BALB/c nude mice in each group, 1ml of the graft was injected subcutaneously to each mouse. After 8 weeks, the fat grafts were harvested and subjected to volume evaluation, HE staining and immunostaining for perilipin to assess graft outcomes. RESULTS: In the vitro experiments, the concentration rate of the CDF was found to be 79.6% that of Coleman fat, with 15.1% more oil separated. Cell viability, as assessed by AM/PI staining, did not show a significant difference between the two grafts, but the results of the GTT showed that the tissue viability of the CDF was higher than that of Coleman fat. In the vivo experiments, the CDF had higher volume retention than Coleman fat, as measured by water displacement. Histopathologic scoring indicated that HCDF group and LCDF group had a more intact fat structure with fewer vacuoles, inflammation, and fibrosis compared to Coleman fat. Additionally, the percentages of perilipin-positive area in the LCDF group and HCDF group were higher than in the Coleman group, indicating improved graft quality and outcome with the use of concentrated deoiled fat. CONCLUSIONS: "Concentrated deoiled fat" refers to an autologous fat graft from which oil has been removed by flocculation and centrifugation. This process increases volume retention and viable cells and decreases infiltrated inflammatory cells. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Highly Responsive and Self-Powered Photodetector Based on PtSe2/MoS2 Heterostructure.

In recent years, 2D materials and their heterostructures have started to offer an ideal platform for high-performance photodetection devices. In this work, a highly responsive, self-powered photodetector based on PtSe2/MoS2 van der Waals heterostructure is demonstrated. The device achieves a noteworthy wide band spectral response from visible (405 nm) range to the near infrared region (980 nm). The remarkable photoresponsivity and external quantum efficiency up to 4.52 A/W, and 1880% are achieved, respectively, at 405 nm illumination with fast response time of 20 ms. In addition, the photodetector exhibits a decent photoresponsivity of 33.4 mA/W at zero bias, revealing the photodetector works well in the self-driven mode. Our work suggests that a PtSe2/MoS2 heterostructure could be a potential candidate for the high-performance photodetection applications.

Shotgun metagenomics reveals the gut microbial diversity and functions in Vespa mandarinia (Hymenoptera: Vespidae) at multiple life stages.

Wasps play important roles as predators and pollinators in the ecosystem. The Jingpo minority residing in Yunnan Province, China, has a traditional practice of using wine infused with mature wasps as a customary remedy for managing rheumatoid arthritis. The larva of the wasp is also a tasteful folk dish that has created a tremendous market. There is a paucity of survival knowledge, which has greatly restricted their potential applications in food and healthcare. Recent research has highlighted the importance of gut microbiota in insect growth. Nevertheless, there is still a lack of understanding regarding the composition, changes, and functions of the gut microbiota in Vespa mandarinia during development. In this research, the gut microbiota were investigated across three growth stages of Vespa mandarinia using a metagenomic technology. The result revealed that there are significant variations in the proportion of main gut microbes during the metamorphosis of Vespa mandarinia. Tenericutes were found to dominate during the larval stage, while Proteobacteria emerged as the dominant group post-pupation. Through a comprehensive analysis of the gut microbiota metagenome, this study revealed functional differences in the wasp gut microbiota at various growth stages. During the larval stage, the gut microbiota plays a central role in promoting metabolism. Following pupation, the gut microbiota exhibited diversified functions, likely due to the complex environments and diverse food sources encountered after metamorphosis. These functions included amino acid metabolism, compound degradation, and defense mechanisms. This research provides an extensive dataset on the gut microbiota during the metamorphosis of Vespa mandarinia, contributing to a deeper understanding of the influence of gut microbiota on wasp growth. Furthermore, this study uncovers a unique microbial treasure within insect guts, which is important for advancing the application of wasps in the fields of food and medicine.

Machine learning application for predicting key properties of activated carbon produced from lignocellulosic biomass waste with chemical activation.

The successful application of gradient boosting regression (GBR) in machine learning to forecast surface area, pore volume, and yield in biomass-derived activated carbon (AC) production underscores its potential for enhancing manufacturing processes. The GBR model, collecting 17 independent variables for two-step activation (2-SA) and 14 for one-step activation (1-SA), demonstrates effectiveness across three datasets-1-SA, 2-SA, and a combined dataset. Notably, in 1-SA, the GBR model yields R2 values of 0.76, 0.90, and 0.83 for TPV, yield, and SSA respectively, and records R2 of 0.90 and 0.91 for yield in 2-SA and combined datasets. The model highlights the significance of the soaking procedure alongside activation temperature in shaping AC properties with 1-SA or 2-SA, illustrating machine learning's potential in optimizing AC production processes.

Simultaneous Activation of Immunogenic Cell Death and cGAS-STING Pathway by Liver- and Mitochondria-Targeted Gold(I) Complexes for Chemoimmunotherapy of Hepatocellular Carcinoma.

Induction of immunogenic cell death (ICD) and activation of the cyclic GMP-AMP synthase stimulator of interferon gene (cGAS-STING) pathway are two potent anticancer immunotherapeutic strategies in hepatocellular carcinoma (HCC). Herein, 12 liver- and mitochondria-targeting gold(I) complexes (9a-9l) were designed and synthesized. The superior complex 9b produced a considerable amount of reactive oxygen species (ROS) and facilitated DNA excretion, the ROS-induced ICD and DNA activated the cGAS-STING pathway, both of which evoked an intense anticancer immune response in vitro and in vivo. Importantly, 9b strongly inhibited tumor growth in a patient-derived xenograft model of HCC. Overall, we present the first case of simultaneous ICD induction and cGAS-STING pathway activation within the same gold-based small molecule, which may provide an innovative strategy for designing chemoimmunotherapies for HCC.

Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis.

Genomics and bioinformatics methods were used to screen genes and molecular markers correlated with colorectal cancer incidence and progression, and their biological functions were analyzed. Differentially expressed genes were obtained using the GEO2R program following colorectal cancer chip data GSE44076 retrieval from the Gene Expression Omnibus gene expression comprehensive database. An online database (David) that combines annotation, visualization, and gene discovery was utilized for investigating genes. Pathway and protein analyses were performed via resources from the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Visual analysis of the KEGG pathway was carried out according to ClueGO and CluePedia to establish the PPI network of gene interaction between pathways; the genes with the highest connectivity were screened by the molecular complex detection analysis method as Hub genes in this study; gene expression was verified by GEPIA online analysis tool, and Kaplan-Meier survival curve was drawn for prognosis analysis. By analyzing GSE44076 microarray data, 86 genes were selected, and colorectal cancer tissues' upregulation was observed in 27 genes and downregulation in 59 ones. GO assessment revealed that the differentially expressed genes were basically correlated with retinol dehydrogenase activity, carbon dehydrogenase activity, collagen-containing extracellular matrix, anchored component of memory, and cellular hormone metabolic process. Moreover, the KEGG assessment revealed that the differential genes contained various signal pathways such as retinol metabolism, chemical carotenogenesis, and nitrogen metabolism. Through further analysis of the PPI protein network, 4 clusters were obtained, and 16 Hub genes were screened out by combining the degree of each gene. Through the analysis of each gene on the prognosis of colon cancer through the GEPIA online analysis website, it was found that the expression levels of AQP8, CXCL8, and ZG16 genes were remarkably associated with colon cancer prognosis (P < 0.05). Genomics and bioinformatics methods can effectively analyze the genes and molecular markers correlated with colorectal cancer incidence and progression, help to systematically clarify the molecular mechanism of 16 key genes in colorectal cancer development and progression, and provide a theoretically valid insight for the screening of diagnostic markers of colorectal cancer and the selection of accurate targets for drug therapy.

Nanoengineering of electrodes via infiltration: an opportunity for developing large-area solid oxide fuel cells with high power density.

Although nanoengineering of electrodes opens up the way to the development of solid oxide fuel cells (SOFCs) with improved performance, the practical implementation of such advances in cells suitable for widespread use remains a challenge. Here, the demonstration of large-area, commercially relevant SOFCs with two nanoengineered electrodes that display excellent performance is reported. The self-assembled nanocomposite La0.6Sr0.4CoO3-δ and Co3O4 is strategically designed and deposited into the well-interconnected Ce0.9Gd0.1O2-δ backbone as a cathode to enable an ultra-large electrochemically active region. The nanometer-scale Ce0.8Gd0.2O2-δ is deposited into a conventional Ni/yttria-stabilized zirconia (YSZ) anode to provide more active oxygen exchange kinetics and electronic conductivity compared to YSZ. The resulting nanoengineered cell with an effective size of 4 cm × 4 cm delivers a remarkable power output of 19.2 W per single cell at 0.6 V and 750 °C. These advancements have potential to facilitate the future development of high-performance SOFCs at a large scale by nanoengineering of electrodes and are expected to pave the way for the commercialization of this technology.

Transcriptome sequencing of wolf spider Lycosa sp. (Araneae: Lycosidae) venom glands provides insights into the evolution and diversity of disulfide-rich toxins.

Wolf spiders in the genus Lycosa are important pest predators in agroforestry ecosystems, capable of feeding on a wide range of pests through the use of complex venom which can to quickly immobilize and kill prey. Because of these characteristics the toxins in wolf spiders venom may prove to be natural sources for novel drug development and biopesticides. To better understand the toxins in Lycosa venom we sequenced the transcriptome from venom glands from an undescribed species of Lycosa and comparatively analyzed the data using known protein motifs. A series of 19 disulfide-rich peptide (DRP) toxin sequences were identified and categorized into seven groups based on the number and arrangement of cysteine residues. Notably, we identified three peptide sequences with low identity to any known toxin, which may be toxin peptides specific to this species of Lycosa. In addition, to further understand the evolutionary relationships of disulfide-rich peptide toxins in spider venom, we constructed phylogenetic trees of DRP toxins from three spiders species and found that the Lycosa sp. DRPs are comparatively diverse with previous research results. This study reveals the toxin diversity of wolf spiders (Lycosa sp.) at the transcriptomic level and provides initial insights into the evolution of DRP toxins in spiders, enriching our knowledge of toxin diversity and providing new compounds for functional studies.

Successful Treatment of pMMR MSS IVB Colorectal Cancer Using Anti-VEGF and Anti-PD-1 Therapy in Combination of Gut Microbiota Transplantation: A Case Report.

Immune checkpoint inhibitors (ICI) have shown great promise in treating advanced or metastatic colorectal cancer (mCRC), especially for CRC patients with deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H). For the remainder of CRC patients presenting with proficient mismatch repair (pMMR) and microsatellite stable (MSS) or low microsatellite instability (MSI-L), ICI showed a low-level response. This study describes a 57-year-old Chinese man diagnosed with pMMR MSS IVb CRC with liver metastasis. Primarily, the patient was administered two consecutive treatments, one composed of an anti-EGFR and modified FOLFOX6 and the other composed of an anti-VEGF and FOLFOXIRI. Due to severe chemotherapy side effects, the patient discontinued treatment and decided to take a third investigational treatment, where an anti-PD-1 and an anti-VEGF were given in combination with fecal microbiota transplantation (FMT) capsules. The patient achieved a partial response (PR), and the tumor size decreased to the extent amenable to surgical resection. After surgery, the patient achieved a pathological complete response (pCR). Patients with pMMR MSS or MSI-L hardly benefit from anti-PD-1 immunotherapy. This study indicated that, to a limited extent, FMT might improve the response to ICI for pMMR MSS CRC patients.

The therapeutic effect of wasp venom (Vespa magnifica, Smith) and its effective part on rheumatoid arthritis fibroblast-like synoviocytes through modulating inflammation, redox homeostasis and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica, Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. AIM OF THE STUDY: The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3-10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. MATERIALS AND METHODS: The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1ß and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RESULTS: RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1ß and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. CONCLUSIONS: Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future.

NSAID-Au(I) Complexes Induce ROS-Driven DAMPs and Interpose Inflammation to Stimulate the Immune Response against Ovarian Cancer.

Inflammation contributes to the development of ovarian cancer, and chemoresistance is a principal obstacle in ovarian cancer treatment. Herein, we designed and synthesized a series of gold(I) complexes derived from NSAIDs or their analogues. Among them, complex B3 (Npx-Au) displayed higher antitumor activity than cisplatin and other gold(I) complexes. Npx-Au could induce oxidative stress and the damage-associated molecular patterns (DAMPs) process by the inhibition of TrxR activity. Mechanistic studies revealed that simultaneous downregulation of COX-2 and PD-L1 was observed after Npx-Au treatment. Interestingly, in vivo experiments demonstrated that Npx-Au treatment could stimulate the immune response via reducing the expression of PD-L1, inducing DC maturation and increasing the infiltration of T (CD4+ and CD8+) cells. Collectively, our studies found that the gold(I) complex Npx-Au could elicit immunogenic cell death (ICD) and provide a promising strategy for chemotherapy combined with immunotherapy in the treatment of ovarian cancer.

Targeted passivation and optimized interfacial carrier dynamics improving the efficiency and stability of hole transport layer-free narrow-bandgap perovskite solar cells.

Narrow-bandgap mixed Sn-Pb perovskite solar cells (PSCs) have showcased great potential to approach the Shockley-Queisser limit. Nevertheless, the practical application and long-term deployment of mixed Sn-Pb PSCs are still largely impeded by the rapid oxidation of Sn2+ ions and under-optimized carrier transport layer (CTL)/perovskite interfaces that would inevitably incur serious interfacial charge recombination and device performance degradation. Herein, we successfully removed the hole transport layer (HTL) by incorporating a small amount of organic phosphonic acid molecules into perovskites, which could preferably interact with Sn2+ ions (relative to Pb2+ analogues) at the grain boundaries (GBs) throughout the perovskite film thickness via coordination bonding, thus effectively retarding the oxidation of Sn2+, passivating the defects and suppressing the non-radiative recombination. Targeted modification effectively reinforced built-in potential by ∼100 mV, and favorably induced energy level cascade, thus accelerating spatial charge separation and facilitating the hole extraction from perovskite layer to underlying conductive electrodes even in the absence of HTL. Consequently, enhanced power conversion efficiencies up to 20.21% have been achieved, which is the record efficiency for the HTL-free mixed Sn-Pb PSCs, accompanied by a decent photovoltage of 0.87 V and improved long-term stability over 2400 h.

Comparison of Microfat, Nanofat, and Extracellular Matrix/Stromal Vascular Fraction Gel for Skin Rejuvenation: Basic Animal Research.

BACKGROUND: Although stromal vascular fraction (SVF) cells and adipose-derived stem cells have well-defined antiaging effects on skin, certain disadvantages have limited their clinical application. OBJECTIVES: The aim of this study was to evaluate the effects of microfat, nanofat, and SVF-gel in improving ultraviolet (UV)-induced photoaged skin injury in nude mice. METHODS: After successfully establishing a photoaging model by UVA and UVB irradiation in nude mice, the back of each mouse was divided into 2 regions and randomly injected under the dermis with 0.5 mL of microfat, nanofat, SVF-gel, and phosphate-buffered saline. Inflammatory infiltration, dermis thickness, hydroxyproline content, Type I/Type III collagen ratio, elastic fiber morphology, skin cell proliferation, and adipocyte viability were measured. The overall structure of the skin was also observed by scanning electron microscopy. RESULTS: In the microfat group, the grafts survived well, with intact structure and viable adipocytes and little infiltration of inflammatory cells. Microfat promoted skin cell proliferation, collagen content increased, the ratio of Type I and III collagen reversed, and new oxytalan fibers formed, which to some extent improved the photoaging skin. In the nanofat and SVF-gel groups, a large amount of inflammatory cell infiltration and foam cell deposition in the grafts and dermis led to fibrosis and proliferation of skin tissue. Although the skin thickness and collagen content were also increased, these factors did not improve the photoaging skin. CONCLUSIONS: Microfat survives well, and improves photoaged skin injury in nude mice by promoting skin tissue regeneration and supplementing the capacity of subcutaneous adipose tissue.

SERD-NHC-Au(I) complexes for dual targeting ER and TrxR to induce ICD in breast cancer.

The development of selective estrogen receptor degraders (SERDs) has brought new ideas for the clinical treatment of ER-positive advanced breast cancer. The successful application of combinational therapy inspired the exploration of other targets to prevent breast cancer progression. Thioredoxin reductase (TrxR) is an important enzyme that can regulate redox balance in cells and it was considered as a potential target for anticancer treatment. In this study, we firstly combine a clinical SERD candidate--G1T48 (NCT03455270), with a TrxR inhibitor--N-heterocyclic carbene gold(I) [NHC-Au(I)] to form dual targeting complexes that can regulate both signaling pathways. The most efficacious complex 23 exhibited significant antiproliferative profile through degrading ER and inhibiting TrxR activity. Interestingly, it can induce immunogenic cell death (ICD) caused by ROS. This is the first evidence to elucidate the role of ER/TrxR-ROS-ICD axis in ER positive breast cancer and this research may inspire new drug development with novel mechanisms. The in vivo xenograft study demonstrated that complex 23 had excellent antiproliferative activity toward MCF-7 cells in mice model.

Tumor-Targeting NHC-Au(I) Complex Induces Immunogenic Cell Death in Hepatocellular Carcinoma.

Immunogenic cell death (ICD) is a promising direction of cancer immunotherapy in hepatocellular carcinoma (HCC). A series of novel NHC-Au(I) complexes derived from 4,5-diarylimidazole, containing glycyrrhetinic acid (GA) as an efficient targeting ligand for HCC, were herein designed and synthesized. Among these, complex 4C exhibited excellent effectiveness for tumor targeting and antitumor activity, which induced the occurrence of ICD in HCC cells. Additionally, 4C can effectively inhibit TrxR enzyme activity, increase reactive oxygen species (ROS) expression, lead to redox homeostasis disorder, mediate mitochondrial dysfunction and endoplasmic reticulum stress (ERS), and cause the characteristic discharge of damage-associated molecular patterns (DAMPs) in HCC cells. More importantly, 4C showed a great ICD-inducing effect in a vaccination mouse model and activated antitumor immunity in a tumor-bearing C57BL/6 mouse model, which is consistent with the in vitro results. In conclusion, we found the potential of Au(I) complex with HCC-targeted capability for effective tumor immunotherapy.