Three-Dimensional Visualization of Breast Cancer Pathology Evolution in Clinical Patient Tissues with NIR-II Imaging.

Breast cancer (BC) is the most common tumor worldwide and requires crucial molecular typing for treatment and prognosis assessment. Currently, approaches like pathological staining, immunohistochemistry (IHC), and immunofluorescence (IF) face limitations due to the low signal-to-background ratio (SBR) and high tumor heterogeneity, resulting in a high misdiagnosis rate. Fluorescent assay in the second near-infrared region (NIR-II, 1000-1700 nm) exhibits ultrahigh SBR owing to diminished scattering and tissue autofluorescence. Here, we present a NIR-II strategy for accurate BC molecular typing and three-dimensional (3D) visualization based on the atomically precise fluorescent Au24Pr1 clusters. Single-atom Pr doping results in 3.9-fold fluorescence enhancement and long-term photostability. The Au24Pr1 clusters possess high fluorescence centered at ∼1100 nm and the SBR on pathological section diagnosis was 4 times higher than that of NIR-I imaging. This enables high spatial resolution 3D visualization of biopsy specimens, which can surmount tissue heterogeneity for clinical diagnosis of BC.

Ficus hirta Vahl. ameliorates liver fibrosis by triggering hepatic stellate cell ferroptosis through GSH/GPX4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus hirta Vahl., a traditional Chinese medicine commonly used in the Lingnan region, has been extensively used for liver disease treatment in China. Its notable antioxidant and anti-inflammatory properties have been reported in previous studies. However, its potential effect and underlying mechanism on liver fibrosis remains unclear. AIM OF STUDY: This study was aimed to investigate the effect and its underlying mechanism of Ficus hirta Vahl on liver fibrosis in vitro and in vivo. MATERIALS AND METHODS: The main components of Ficus hirta Vahl in blood were investigated by using UPLC-Q/TOF-MS/MS. Two animal models of liver fibrosis, the CCl4 and MCD induced mice, were used to assess the efficacy of Ficus hirta Vahl on liver fibrosis. Metabolomics was used to detect the level of metabolites in the serum of liver fibrosis mice after Ficus hirta Vahl treatment. Furthermore, the mechanism was validated in vitro using the human liver stellate cell line LX-2. The binding affinities of the active ingredients of Ficus hirta Vahl to the main targets of liver fibrosis were also determined. Finally, we identified the key active ingredients responsible for the treatment of liver fibrosis in vivo. RESULTS: Fibrosis and inflammatory markers were significant down-regulation in both CCl4 and MCD induced liver fibrosis mice after Ficus hirta Vahl administration in a dose-dependent manner. We found that Ficus hirta Vahl may primarily exert its effect on liver fibrosis through the glutathione metabolic pathway. Importantly, the glutathione metabolic pathway is closely associated with ferroptosis, and our subsequent in vitro experiments provided evidence supporting this association. Ficus hirta Vahl was found to modulate the GSH/GPX4 pathway, ultimately leading to the amelioration of liver fibrosis. Moreover, using serum pharmacochemistry and molecular docking, we successfully identified apigenin as a probable efficacious monomer for the management of liver fibrosis and subsequently validated its efficacy in mice with CCl4-induced hepatic fibrosis. CONCLUSION: Ficus hirta Vahl triggered the ferroptosis of hepatic stellate cell by regulating the GSH/GPX4 pathway, thereby alleviating liver fibrosis in mice. Moreover, apigenin is a key compound in Ficus hirta Vahl responsible for the effective treatment of liver fibrosis.

Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance.

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8+ T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4+ breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4+ cancer.

Bioactive components, pharmacological properties and underlying mechanism of Ganoderma lucidum spore oil: A review.

Ganoderma lucidum is a Chinese medicinal fungus with a long history of use in healthcare and disease treatment. G. lucidum spores (GLS) are tiny germ cells released from the mushroom cap during the mature stage of growth. They contain all the genetic active substances of G. lucidum. G. lucidum spore oil (GLSO) is a lipid component extracted from broken-walled Ganoderma spores using supercritical CO2 extraction technology. GLSO contains fatty acids, Ganoderma triterpenes, sterols and other bioactive compounds. Previous studies have demonstrated that GLSO has a wide range of pharmacological properties, including anti-tumor, anti-aging, neuroprotection, immunomodulation, hepatoprotection and modulation of metabolic diseases. This review summarizes the research progress of GLSO over the past two decades in terms of its bioactive components, extraction and processing techniques, pharmacological effects and safety evaluation. This provides a solid foundation for further research and application of GLSO.

Expression of a single inhibitory Ly49 receptor is sufficient to license NK cells for effector functions.

Natural killer (NK) cells recognize target cells through germline-encoded activation and inhibitory receptors enabling effective immunity against viruses and cancer. The Ly49 receptor family in the mouse and killer immunoglobin-like receptor family in humans play a central role in NK cell immunity through recognition of MHC class I and related molecules. Functionally, these receptor families are involved in licensing and rejection of MHC-I-deficient cells through missing-self. The Ly49 family is highly polymorphic, making it challenging to detail the contributions of individual Ly49 receptors to NK cell function. Herein, we showed mice lacking expression of all Ly49s were unable to reject missing-self target cells in vivo, were defective in NK cell licensing, and displayed lower KLRG1 on the surface of NK cells. Expression of Ly49A alone on a H-2Dd background restored missing-self target cell rejection, NK cell licensing, and NK cell KLRG1 expression. Thus, a single inhibitory Ly49 receptor is sufficient to license NK cells and mediate missing-self in vivo.

Lu's approach for video-assisted thoracoscopic surgery.

OBJECTIVES: Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from UVATS, is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach. METHODS: The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected, and analyzed. According to whether applied Lu's approach during the VATS operation, patients were divided into the LVATS group and the UVATS group. The propensity score (PS) matching method was used to reduce selection bias by creating two groups. After generating the PSs, 1:1 ratio and nearest-neighbor score matching was completed. Perioperative variables, including the operation time, intraoperative blood loss, lymph node stations dissected, total drainage volume, drainage duration, postoperative hospital stay, pain score (VAS, Visual Analogue Scale) on the postoperative first day (POD1) and third day (POD3), and incidence of postoperative complications, were compared between the two groups. The data were analyzed statistically with P<0.05 defined as statistically significant. RESULTS: A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144)min, P <0.001), less intraoperative blood loss(20 (20, 30) VS 25 (20, 50)ml, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50)cm, P <0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600)ml, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected(5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4)days, P = 0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6)days, P = 0.608), VAS on the POD1(4 (4, 4) VS 4 (4, 4), P = 0.058)and POD3 (3 (3, 4) VS 4 (3, 4), P = 0.219), and incidence of postoperative complications (P = 0.521) between the two groups. CONCLUSIONS: Lu's approach is a safe and feasible approach for video-assisted thoracoscopic surgery for the lobectomy of NSCLC. This approach can shorten surgical time, reduce incision length and intraoperative blood loss.

Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke: Insights from Network Pharmacology and in vivo Experiments.

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

[Research progress in preparations of Panax ginseng].

Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits, among which the roots are the most commonly used. The main active components of this medicinal plant include triterpenoid saponins, polysaccharides, peptides, and volatile oils. The chemical components and active metabolites endow this herb with a variety of pharmacological effects, and thus this herb is used to treat various diseases and play healthcare roles. Currently, a wide range of preparations of P. ginseng have been officially registered and marketed, including tablets, oral liquids, and injections, which demonstrate good clinical efficacy in regulating immunity, adjuvant treatment of tumors, alleviating fatigue, delaying the aging process, improving glucose and lipid metabolism, treating cardiovascular diseases, and relieving inflammation and pain. The production process and quality standards of these drugs are of great significance to ensure their efficacy. According to the theory that Ginseng Radix et Rhizoma can greatly replenish original Qi, tonify the spleen and lung, promote fluid production to quench thirst, tranquilize mind and enrich the intelligence, this paper systematically summarized the clinical application progress of P. ginseng and rela-ted preparations on the market and prospected the further development of preparations from P. ginseng, providing a reference for further exploring the medicinal value and healthcare function of this herb. The above contents, as an important basis for the in-depth development of P. ginseng and related drugs, increase the possibilities for the application of P. ginseng.

Towards Stem/Progenitor Cell-Based Therapies for Retinal Degeneration.

Retinal degeneration (RD) is a leading cause of blindness worldwide and includes conditions such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt's disease (STGD). These diseases result in the permanent loss of vision due to the progressive and irreversible degeneration of retinal cells, including photoreceptors (PR) and the retinal pigment epithelium (RPE). The adult human retina has limited abilities to regenerate and repair itself, making it challenging to achieve complete self-replenishment and functional repair of retinal cells. Currently, there is no effective clinical treatment for RD. Stem cell therapy, which involves transplanting exogenous stem cells such as retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), or activating endogenous stem cells like Müller Glia (MG) cells, holds great promise for regenerating and repairing retinal cells in the treatment of RD. Several preclinical and clinical studies have shown the potential of stem cell-based therapies for RD. However, the clinical translation of these therapies for the reconstruction of substantial vision still faces significant challenges. This review provides a comprehensive overview of stem/progenitor cell-based therapy strategies for RD, summarizes recent advances in preclinical studies and clinical trials, and highlights the major challenges in using stem/progenitor cell-based therapies for RD.

Cellular communication network factor 1 promotes retinal leakage in diabetic retinopathy via inducing neutrophil stasis and neutrophil extracellular traps extrusion.

BACKGROUND: Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated. METHODS: We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells. RESULTS: We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils. CONCLUSION: In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.

Mammalian orthoreovirus capsid protein σ3 antagonizes RLR-mediated antiviral responses by degrading MAVS.

Mammalian orthoreovirus (MRV) outer capsid protein σ3 is a multifunctional protein containing a double-stranded RNA-binding domain, which facilitates viral entry and assembly. We reasoned that σ3 has an innate immune evasion function. Here, we show that σ3 protein localizes in the mitochondria and interacts with mitochondrial antiviral signaling protein (MAVS) to activate the intrinsic mitochondria-mediated apoptotic pathway. Consequently, σ3 protein promotes the degradation of MAVS through the intrinsic caspase-9/caspase-3 apoptotic pathway. Moreover, σ3 protein can also inhibit the expression of the components of the RNA-sensing retinoic acid-inducible gene (RIG)-like receptor (RLR) signaling pathway to block antiviral type I interferon responses. Mechanistically, σ3 inhibits RIG-I and melanoma differentiation-associated gene 5 expression is independent of its inhibitory effect on MAVS. Overall, we demonstrate that the MRV σ3 protein plays a vital role in negatively regulating the RLR signaling pathway to inhibit antiviral responses. This enables MRV to evade host defenses to facilitate its own replication providing a target for the development of effective antiviral drugs against MRV. IMPORTANCE: Mammalian orthoreovirus (MRV) is an important zoonotic pathogen, but the regulatory role of its viral proteins in retinoic acid-inducible gene-like receptor (RLR)-mediated antiviral responses is still poorly understood. Herein, we show that MRV σ3 protein co-localizes with mitochondrial antiviral signaling protein (MAVS) in the mitochondria and promotes the mitochondria-mediated intrinsic apoptotic pathway to cleave and consequently degrade MAVS. Furthermore, tryptophan at position 133 of σ3 protein plays a key role in the degradation of MAVS. Importantly, we show that MRV outer capsid protein σ3 is a key factor in antagonizing RLR-mediated antiviral responses, providing evidence to better unravel the infection and transmission mechanisms of MRV.

Quinomycins with an unusual N-methyl-3-methylsulfinyl-alanine residue from a Streptomyces sp.

Four new echinomycin congeners, quinomycins M-P (1-4) were isolated from the cultures of the soil-derived Streptomyces sp. CPCC205575. The planar structures were determined by comprehensive analyses of NMR and HRESIMS/MS data. The absolute configurations were elucidated by the advanced Marfey's method combined with biosynthetic gene analysis. Compounds 1-4 represent the first examples of quinomycin-type natural products with the sulfur atom at the N,S-dimethylcysteine residue oxidized as a sulfoxide group forming the unusual N-methyl-3-methylsulfinyl-alanine residue. Bioassay results revealed that the oxidation of the sulfur atom at the Cys or Cys' residues led to dramatic decrease of cytotoxicity and antimicrobial activity.

Ultrasound-targeted microbubble destruction rapidly improves left ventricular function in rats with ischemic cardiac dysfunction.

BACKGROUND: Previous studies have demonstrated the efficacy of ultrasound-targeted microbubble destruction (UTMD) in the treatment of ischemic heart failure (HF). The purpose of this study was to explore the mechanism by which UTMD improves ischemic HF. METHODS: An ischemic heart failure model was established using Sprague-Dawley rats. Rats were randomly divided into 7 groups: sham group, HF group, HF + MB group, HF + ultrasound (US) group, HF + UTMD group, HF + UTMD+LY294002 group, and HF + LY294002 group. Serum BNP level and echocardiographic parameters were measured to evaluate cardiac function. PI3K/Akt/eNOS signaling pathway protein levels were detected by immunohistochemistry (IHC) and western blotting. The concentrations of nitrous oxide (NO) and ATP were detected by ELISA, and hematoxylin and eosin (HE) staining was used to evaluate myocardial tissue. RESULTS: UTMD rapidly improved ejection fraction (EF) (HF: 37.16 ± 1.21% vs. HF + UTMD: 46.31 ± 3.00%, P < 0.01) and fractional shortening (FS) (HF: 18.53 ± 0.58% vs. HF + UTMD: 24.05 ± 1.84%, P < 0.01) in rats with ischemic HF. UTMD activated the PI3K/AKT/eNOS signaling pathway (HF vs. HF + UTMD, P < 0.01) and promoted the release of NO and ATP (HF vs. HF + UTMD, both, P < 0.05). Inhibition of the PI3K/AKT/eNOS signaling pathway by LY294002 worsened EF (HF: 37.16 ± 1.21% vs. HF + LY294002: 32.73 ± 3.05%, P < 0.05), and the release of NO and ATP by UTMD (HF + UTMD vs. HF + UTMD+LY294002, P < 0.05). CONCLUSIONS: UTMD can rapidly improve cardiac function in ischemic HF by activating the PI3K/Akt/eNOS signaling pathway and promoting the release of NO and ATP.

Histone H1.2 Inhibited EMCV Replication through Enhancing MDA5-Mediated IFN-ß Signaling Pathway.

Histone H1.2 is a member of the linker histone family, which plays extensive and crucial roles not only in the regulation of chromatin dynamics, cell cycle, and cell apoptosis, but also in viral diseases and innate immunity response. Recently, it was discovered that H1.2 regulates interferon-ß and inhibits influenza virus replication, whereas its role in other viral infections is poorly reported. Here, we first found the up-regulation of H1.2 during Encephalomyocarditis virus (EMCV) infection, implying that H1.2 was involved in EMCV infection. Overexpression of H1.2 inhibited EMCV proliferation, whereas knockdown of H1.2 showed a significant promotion of virus infection in HEK293T cells. Moreover, we demonstrated that overexpression of H1.2 remarkably enhanced the production of EMCV-induced type I interferon, which may be the crucial factor for H1.2 proliferation-inhibitory effects. We further found that H1.2 up-regulated the expression of the proteins of the MDA5 signaling pathway and interacted with MDA5 and IRF3 in EMCV infection. Further, we demonstrated that H1.2 facilitated EMCV-induced phosphorylation and nuclear translocation of IRF3. Briefly, our research uncovers the mechanism of H1.2 negatively regulating EMCV replication and provides new insight into antiviral targets for EMCV.

Innovative Techniques in Video-Assisted Thoracoscopic Surgery: Lu's Approach.

Purpose: Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from Uniportal Video-Assisted Thoracoscopic Surgery(UVATS), is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach. Patients and Methods: The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected and analyzed. Patients were divided into the LVATS group and the UVATS group. Propensity score matching (PSM) was used to reduce selection bias and create two comparable groups. Perioperative variables were compared, and a p-value < 0.05 was deemed statistically significant. Results: A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144) min, P <0.001), less intraoperative blood loss (20 (20, 30) VS 25 (20, 50) mL, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50) cm, P <0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600) mL, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected (5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4) days, P =0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6) days, P = 0.608), VAS on the POD1 (4 (4, 4) VS 4 (4, 4), P=0.058) and POD3 (3 (3, 4) VS 4 (3, 4), P=0.219), and incidence of postoperative complications (P=0.521) between the two groups. Conclusion: Lu's approach for video-assisted thoracoscopic lobectomy is safe and feasible, potentially reducing surgery time, incision length, and intraoperative blood loss.

Proton-Gradient-Driven Porphyrin-Based Liposome Remote-Loaded with Imiquimod as In Situ Nanoadjuvants for Synergistically Augmented Tumor Photoimmunotherapy.

Cancer immunotherapy is expected to achieve tumor treatment mainly by stimulating the patient's own immune system to kill tumor cells. However, the low immunogenicity of the tumor and the poor efficiency of tumor antigen presentation result in a variety of solid tumors that do not respond to immunotherapy. Herein, we designed a proton-gradient-driven porphyrin-based liposome (PBL) with highly efficient Toll-like receptor 7 (TLR7) agonist (imiquimod, R837) encapsulation (R837@PBL). R837@PBL rapidly released R837 in the acid microenvironment to activate the TLR in the endosome inner membrane to promote bone-marrow-derived dendritic cell maturation and enhance antigen presentation. R837@PBL upon laser irradiation triggered immunogenic cell death of tumor cells and tumor-associated antigen release after subcutaneous injection, activated TLR7, formed in situ tumor nanoadjuvants, and enhanced the antigen presentation efficiency. Photoimmunotherapy promoted the infiltration of cytotoxic T lymphocytes into tumor tissues, inhibited the growth of the treated and abscopal tumors, and exerted highly effective photoimmunotherapeutic effects. Hence, our designed in situ tumor nanoadjuvants are expected to be an effective treatment for treated and abscopal tumors, providing a novel approach for synergistic photoimmunotherapy of tumors.

SRCAP complex promotes lung cancer progression by reprograming the oncogenic transcription of Hippo-YAP/TAZ signaling pathway.

The activation of YAP/TAZ, a pair of paralogs of transcriptional coactivators, initiates a dysregulated transcription program, which is a key feature of human cancer cells. However, it is not fully understood how YAP/TAZ promote dysregulated transcription for tumor progression. In this study, we employed the BioID method to identify the interactome of YAP/TAZ and discovered that YAP/TAZ interact with multiple components of SRCAP complex, a finding that was further validated through endogenous and exogenous co-immunoprecipitation, as well as immunofluorescence experiments. CUT&Tag analysis revealed that SRCAP complex facilitates the deposition of histone variant H2A.Z at target promoters. The depletion of SRCAP complex resulted in a decrease in H2A.Z occupancy and the oncogenic transcription of YAP/TAZ target genes. Additionally, the blockade of SRCAP complex suppressed YAP-driven tumor growth. In a genetically engineered lung adenocarcinoma mouse model and non-small cell lung cancer patients, SRCAP complex and H2A.Z deposition were found to be upregulated. This upregulation was statistically correlated with YAP expression, pathological stages, and poor survival in lung cancer patients. Together, our study uncovers that SRCAP complex plays a critical role in YAP/TAZ oncogenic transcription by coordinating H2A.Z deposition during cancer progression, providing potential targets for cancer diagnosis and prevention.

Incorporation of cellulose nanocrystals to improve the physicochemical and bioactive properties of pectin-konjac glucomannan composite films containing clove essential oil.

This study aimed to investigate the effectiveness of cellulose nanocrystals (CNC) isolated from cotton in augmenting pectin (PEC)/konjac glucomannan (KGM) composite films containing clove essential oil (CEO) for food packaging application. The effects of CNC dosage on film properties were examined by analyzing the rheology of film-forming solutions and the mechanical, barrier, antimicrobial, and CEO-release properties of the films. Rheological and FTIR analysis revealed the enhanced interactions among the film components after CNC incorporation due to its high aspect ratio and abundant hydroxyl groups, which can also prevent CEO droplet aggregation, contributing to form a compact microstructure as confirmed by SEM and 3D surface topography observations. Consequently, the addition of CNC reinforced the polysaccharide matrix, increasing the tensile strength of the films and improving their barrier properties to water vapor. More importantly, antibacterial, controlled release and kinetic simulation experiments proved that the addition of CNC could further slow down the release rate of CEO, prolonging the antimicrobial properties of the films. PEC/KGM/CEO composite films with 15 wt% CNC was found to have relatively best comprehensive properties, which was also most effective in delaying deterioration of grape quality during the storage of 9 days at 25 °C.

Chromatin accessibility complex subunit 1 enhances tumor growth by regulating the oncogenic transcription of YAP in breast and cervical cancer.

Background: As a component of chromatin remodeling complex, chromatin accessibility complex subunit 1 (CHRAC1) is critical in transcription and DNA replication. However, the significance of CHRAC1 in cancer progression has not been investigated extensively. This research aimed to determine the function of CHRAC1 in breast and cervical cancer and elucidate the molecular mechanism. Methods: The Bio-ID method was used to identify the interactome of transcriptional activator Yes-associated protein (YAP) and the binding between YAP and CHRAC1 was verified by immunofluorescence. CCK8, colony formation and subcutaneous xenograft assays were conducted to explore the function of CHRAC1 in cancer cell proliferation. RNA-seq analysis and RT-PCR were used to analyze the transcription program change after CHRAC1 ablation. The diagnostic value of CHRAC1 was analyzed by TCGA database and further validated by immunohistochemistry staining. Results: In the current study, we found that the chromatin remodeler CHRAC1 was a potential YAP interactor. CHRAC1 depletion suppressed breast and cervical cancer cell proliferation and tumor growth. The potential mechanism may be that CHRAC1 interacts with YAP to facilitate oncogenic transcription of YAP target genes in Hippo pathway, thereby promoting tumorigenesis. CHRAC1 was elevated in cervical and breast cancer biopsies and the upregulation correlated with shorter survival, poor pathological stages and metastasis of cancer patients. Moreover, CHRAC1 expression was statistically associated with YAP in breast and cervical cancer biopsies. Conclusions: These findings highlight that CHRAC1 contributes to cancer progression through regulating the oncogenic transcription of YAP, which makes it a potential therapeutic target for cancer treatment.

Accelerating Pharmaceutical Process Development with an Acoustic Droplet Ejection-Multiple Reaction Monitoring-Mass Spectrometry Workflow.

Fast-paced pharmaceutical process developments (e.g., high-throughput experimentation, directed evolution, and machine learning) involve the introduction of fast, sensitive, and accurate analytical assays using limited sample volumes. In recent years, acoustic droplet ejection (ADE) coupled with an open port interface has been invented as a sampling technology for mass spectrometry, providing high-throughput nanoliter analytical measurements directly from the standard microplates. Herein, we introduce an ADE-multiple reaction monitoring-mass spectrometry (ADE-MRM-MS) workflow to accelerate pharmaceutical process research and development (PR&D). This systematic workflow outlines the selection of MRM transitions and optimization of assay parameters in a data-driven manner using rapid measurements (1 sample/s). The synergy between ADE sampling and MRM analysis enables analytical assays with excellent sensitivity, selectivity, and speed for PR&D reaction screenings. This workflow was utilized to develop new ADE-MRM-MS assays guiding a variety of industrial processes, including (1) screening of Ni-based catalysts for C-N cross-coupling reaction at 1 Hz and (2) high-throughput regioisomer analysis-enabled enzyme library screening for peptide ligation reaction. ADE-MRM-MS assays were demonstrated to deliver accurate results that are comparable to conventional liquid chromatography (LC) experiments while providing >100-fold throughput enhancement.