Rhodium(III)-Catalyzed Switchable ß-C(sp2)-H Alkenylation and Alkylation of Acyclic Enamides with Allyl Alcohols.

Herein, rhodium(III)-catalyzed ß-C(sp2)-H alkenylation and alkylation of enamides are presented using readily accessible allylic alcohols by switching the reaction conditions. This tunable transformation has been applied to a wide range of substrates and typically proceeded with excellent regioselectivity and stereoselectivity as well as with good functional group tolerance. The catalytic system offers an efficient approach for synthesizing various functionalized enamides bearing N-(2Z,4E)-butadiene and (Z)-ß-C(sp2)-H alkylated enamides. In addition, mechanistic experiments suggest that Rh(III)-catalyzed C-H activation is not related to the critical step.

HO-1 upregulation promotes mitophagy-dependent ferroptosis in PM2.5-exposed hippocampal neurons.

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.

Application of Natural Medicinal Plants Active Ingredients in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant cancer of the head and neck, with high morbidity and mortality, ranking as the sixth most common cancer in the world. The treatment of OSCC is mainly radiotherapy, chemotherapy and surgery, however, the prognosis of patients is still poor and the recurrence rate is high. This paper reviews the range of effects of natural medicinal plant active ingredients (NMPAIs) on OSCC cancer, including the types of NMPAIs, anti-cancer mechanisms, involved signaling pathways, and clinical trials. The NMPAIs include terpenoids, phenols, flavonoids, glycosides, alkaloids, coumarins, and volatile oils. These active ingredients inhibit proliferation, induce apoptosis and autophagy, inhibit migration and invasion of OSCC cells, and regulate cancer immunity to exert anti-cancer effects. The mechanism involves signaling pathways such as mitogen-activated protein kinase, phosphatidylinositol 3 kinase/protein kinase B, nuclear factor kappa B, miR-22/WNT1/ß-catenin and Nrf2/Keap1. Clinically, NMPAIs can inhibit the growth of OSCC, and the combined drug is more effective. Natural medicinal plants are promising candidates for the treatment of OSCC.

PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment.

This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence of apoptosis, pyroptosis, and necroptosis, plays a crucial role in cell death and immune response regulation. The study delves into the molecular pathways of each cell death mechanism and their crosstalk within PANoptosis, emphasizing the shared components like caspases and the PANoptosome complex. It highlights the significant role of PANoptosis in various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers, showing its impact on tumorigenesis and patient survival rates. We further discuss the interwoven relationship between PANoptosis and the tumor microenvironment (TME), illustrating how PANoptosis influences immune cell behavior and tumor progression. It underscores the dynamic interplay between tumors and their microenvironments, focusing on the roles of different immune cells and their interactions with cancer cells. Moreover, the review presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. It outlines various strategies to manipulate PANoptosis pathways for therapeutic purposes, such as targeting key signaling molecules like caspases, NLRP3, RIPK1, and RIPK3. The potential of novel treatments like immunogenic PANoptosis-initiated therapies and nanoparticle-based strategies is also explored.

A newly-discovered tea population variety processed Bai Mu Dan white tea: Flavor characteristics and chemical basis.

The quality of white tea (WT) is impacted by selected tea cultivars. To explore the organoleptic quality of a recently-discovered WT ("Caicha", CC), HS-SPME/GC-MS and UPLC were employed to identify volatile and non-volatile compounds in tea samples. Multiple statistical methods demonstrated the distinctions between CC and four mainstream WT varieties from main producing areas. CC exhibited abundant volatile alcohol, terpenoids, ketone, aldehyde and ester, as well as non-volatile lignans and coumarins, phenolic acids and low-molecular carbohydrates. These substances combinedly contributed to the flavor attributes of CC, characterized by an intense herbal/citrus-like cleanness and flower/fruit-like sweetness, scarce in existing commercial WT varieties. Sensory evaluation corroborated these findings. In conclusion, we have processed a new tea variety (CC) with WT manufacturing technology, and discovered the unique cleanness and sweetness of it. This study enriches the raw material database for WT production and blending, and boosts the development of more premium WT varieties.

Intelligent chemical profiling of 73 edible flowers by liquid chromatography-high resolution mass spectrometry combined with HRMS database and their authentication based on large-scale fingerprints.

A commercial high-resolution MS database "TCM-PCDL" was innovatively introduced to automatically identify multi-components in 73 edible flowers rapidly and accurately by liquid chromatography-high resolution mass spectrometry, which can be time-consuming and labor-intensive in traditional manual method. The database encompasses over 2565 natural products with various energy levels. Unknown compounds can be identified through direct matching and scoring MS2 spectra with database. A total of 870 compounds were identified from 73 flowers, with polyphenols constituting up to 75%. Focusing on polyphenols, a high performance liquid chromatography (HPLC) method was developed to generate fingerprints from 510 batches, establishing an "HPLC database" that enabled accurate authentication using similarity scores and rankings. This method demonstrated an accuracy rate of 100% when applied to 30 unknown samples. For flowers prone to confusion, additional statistical analysis methods could be employed as aids in authentication. This study provides valuable insights for large-scale sample chemical profiling and authentication.

Potential targets of diosgenin for the treatment of oral squamous cell carcinoma and their bioinformatics and transcriptional profiling analyses.

Diosgenin can inhibit the proliferation and cause apoptosis of various tumor cells, and its inhibitory effect on oral squamous cell carcinoma (OSCC) and its mechanism are still unclear. In this study, we predicted the targets of diosgenin for the treatment of OSCC through the database, then performed bioinformatics analysis of the targets, and further verified the effect of diosgenin on the activity of OSCC cell line HSC-3, the transcriptional profile of the targets and the molecular docking of the targets with diosgenin. The results revealed that there were 146 potential targets of diosgenin for OSCC treatment, which involved signaling pathways such as Ras, TNF, PI3K-AKT, HIF, NF-κB, and could regulate cellular activity through apoptosis, autophagy, proliferation and differentiation, inflammatory response, DNA repair, etc. Diosgenin significantly inhibited HSC-3 cell activity. The genes such as AKT1, MET1, SRC1, APP1, CCND1, MYC, PTGS2, AR, NFKB1, BIRC2, MDM2, BCL2L1, MMP2, may be important targets of its action, not only their expression was regulated by diosgenin but also their proteins had a high binding energy with diosgenin. These results suggest that diosgenin may have a therapeutic effect on OSCC through AKT1, MMP2 and other targets and multiple signaling pathways, which is of potential clinical value.

[Application of optical genome mapping technology for the detection of chromosomal structural variations].

OBJECTIVE: To assess the value of optical genome mapping (OGM) for the detection of chromosomal structural abnormalities including ring chromosomes, balanced translocations, and insertional translocations. METHODS: Clinical data of four patients who underwent pre-implantation genetic testing concurrently with OGM and chromosomal microarray analysis at the Center of Reproductive Medicine of the Sixth Affiliated Hospital of Sun Yat-sen University from January to October 2022 due to chromosomal structural abnormalities were selected as the study subjects. Some of the results were verified by multi-color fluorescence in situ hybridization. RESULTS: The OGM has successfully detected a balanced translocation and fine mapped the breakpoints in a patient. Among two patients with insertional translocations, OGM has provided more refined breakpoint locations than karyotyping analysis in a patient who had chromosome 3 inserted into chromosome 6 and determined the direction of the inserted fragment. However, OGM has failed to detect the chromosomal abnormality in a patient with chromosome 8 inserted into the Y chromosome. It has also failed to detect circular signals in a patient with ring chromosome mosaicism. CONCLUSION: OGM has successfully detected chromosomal structural variations in the four patients and provided assistance for their diagnosis.

Decitabine-containing conditioning improved outcomes for children with higher-risk myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation.

Myelodysplastic syndrome (MDS) is a rare clonal hematopoietic disorder in children. The risk stratification system and treatment strategy for adults are unfit for children. The role of hypomethylating agents (HMAs) in higher-risk childhood MDS has not been identified. This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS. The clinical characteristics and transplantation information were reviewed and analyzed. A total of 27 patients were analyzed, including 11 with MDS with excess blasts (MDS-EB), 14 with MDS-EB in transformation (MDS-EBt) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 2 with therapy-related MDS/AML (t-MDS/AML). Eight patients harbored monosomy 7. Before transplantation, induction therapy was administered to 25 patients, and 19 of them achieved bone marrow blasts <5% before HSCT. The stem cell source was unmanipulated-related bone marrow or peripheral blood stem cells for nineteen patients and unrelated cord blood for eight. All patients received decitabine-containing and Bu/Cy-based myeloablative conditioning; 26 patients achieved initial engraftment. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GvHD) at 100 days were 65.4% and 42.3%, respectively. The incidence of cGvHD was 38.5%. The median follow-up was 26 (range 4-49) months after transplantation. By the end of follow-up, two patients died of complications and two died of disease progression. The probability of 3-year overall survival (OS) was 84.8% (95%CI, 71.1 to 98.5%). In summary, decitabine-containing myeloablative conditioning resulted in excellent outcomes for children with higher-risk MDS undergoing allogeneic HSCT.

MMP14high macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis.

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.

[Corrigendum] PRIMA­1met induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK­ULK1­Vps34 signaling cascade.

Following the publication of the above article, the authors contacted the Editorial Office to explain that the strips of ß­actin, LC3 and p62 proteins of the RKO cell line shown in Fig. 2A and B, and those of the SW620 cell line shown in Fig. 3A and B, were assembled in these figures incorrectly. To rectify the presentation of these two figures, the authors proposed that they replace the strips of ß­actin and p62 proteins in the original Figs. 2B and 3B with the ß­actin bands from one of the repeated western blotting experiments.  The revised and corrected versions of Figs. 2 and 3 are shown on the next page. The authors wish to emphasize that these corrections do not grossly affect either the results or the conclusions reported in this work. The authors all agree to the publication of this Corrigendum, and are grateful to the Editor of Oncology Reports for granting them the opportunity to correct the errors that were made during the assembly of these figures. Lastly, the authors apologize to the readership for any inconvenience these errors may have caused. [Oncology Reports 45: 86, 2021; DOI: 10.3892/or.2021.8037].

Assessment of Angiography-Based Renal Quantitative Flow Ratio Measurement in Patients with Atherosclerotic Renal Artery Stenosis.

Background: Quantitative flow ratio (QFR) is an angiography-based fractional flow reserve measurement without pressure wire or induction of hyperemia. A recent innovation that uses combined geometrical data and hemodynamic boundary conditions to measure QFR from a single angiographic view has shown the potential to measure QFR of the renal artery-renal QFR (rQFR). Objective: The aim of this pilot study was to assess the feasibility of rQFR measurement and the contribution of rQFR in selecting patients with atherosclerotic renal artery stenosis (ARAS) undergoing revascularization. Methods: This retrospective trial enrolled patients who had ARAS (50-90%) and hypertension. The enrolled patients were treated by optimal antihypertensive medication or revascularization, respectively, and the therapeutic strategies were based on rFFR measurement and/or clinical feature. Results: A total of 55 patients underwent rQFR measurement. Among the enrolled patients, 18 underwent optimal antihypertensive medication and 37 underwent revascularization, 19 patients in whom rQFR and rFFR were both assessed. During the 180-day follow-up, 25 patients saw an improvement in their blood pressure among the 37 patients that underwent revascularization. ROC analysis revealed that rQFR had a high diagnostic accuracy for predicting blood pressure improvement (AUCrQFR = 0.932, 95% CI 0.798-0.998). The ideal cut-off value of rQFR for predicting blood pressure improvement after revascularization is ≤0.72 (sensitivity: 72.00%, specificity: 100%). The paired t test and Bland-Altman analyses demonstrated good agreement between rQFR and rFFR (t = 1.887, 95% CI -0.021 to 0.001, 95% limits of agreement: -0.035 to 0.055, p = 0.075). The Spearman correlation test reveals that there was a significant positive correlation between rQFR and rFFR (r = 0.952, 95% CI 0.874 to 0.982, p < 0.001). Conclusion: The rQFR has the potential to enhance the ability of angiography to detect functionally significant renal artery stenosis during angiography and to produce results that are comparable to invasive hemodynamic assessment.

Systematical targeted multicomponent characterization and comparison of Arnebiae Radix and its three confusing species by offline two-dimensional liquid chromatography/LTQ-Orbitrap mass spectrometry.

Arnebiae Radix, commonly known as "Zicao," can be easily confused with other compounding species, posing challenges for its clinical use. Here, we developed a comprehensive strategy to systematically characterize the diverse components across Arnebiae Radix and its three confusing species. First, an offline two-dimensional liquid chromatography (2D-LC) system integrating hydrophilic interaction chromatography (HILIC) and reverse phase (RP) separations was established, enabling effective separation and detection of more trace constituents. Second, a polygonal mass defect filtering (MDF) workflow was implemented to screen target ions and generate a precursor ion list (PIL) to guide multistage mass (MSn) data acquisition. Third, a three-step characterization strategy utilizing diagnostic ions and neutral losses was developed for rapid determination of molecular formulas, structure classes, and compound identification. This approach enabled systematic characterization of Arnebiae Radix and its three confusing species, with 437 components characterized including 112 shikonins, 22 shikonfurans, 144 phenolic acids, 131 glycosides, 18 flavonoids, and 10 other compounds. Additionally, 361, 230, 340, and 328 components were identified from RZC, YZC, DZC, and ZZC, respectively, with 142 common components and 30 characteristic components that may serve as potential markers for distinguishing the four species. In summary, this is the first comprehensive characterization and comparison of the phytochemical profiles of Arnebiae Radix and its three confusing species, advancing our understanding of this herbal medicine for quality control.

Single-Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging.

Female fecundity declines in a nonlinear manner with age during the reproductive years, even as ovulatory cycles continue, which reduces female fertility, disrupts metabolic homeostasis, and eventually induces various chronic diseases. Despite this, the aging-related cellular and molecular changes in human ovaries that occur during these reproductive years have not been elucidated. Here, single-cell RNA sequencing (scRNA-seq) of human ovaries is performed from different childbearing ages and reveals that the activation of the pyroptosis pathway increased with age, mainly in macrophages. The enrichment of pyroptotic macrophages leads to a switch from a tissue-resident macrophage (TRM)-involve immunoregulatory microenvironment in young ovaries to a pyroptotic monocyte-derived macrophage (MDM)-involved proinflammatory microenvironment in middle-aged ovaries. This remolded ovarian immuno-microenvironment further promotes stromal cell senescence and accelerated reproductive decline. This hypothesis is validated in a series of cell and animal experiments using GSDMD-KO mice. In conclusion, the work expands the current understanding of the ovarian aging process by illustrating a pyroptotic macrophage-involved immune mechanism, which has important implications for the development of novel strategies to delay senescence and promote reproductive health.

Whole-brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice.

Corticotropin-releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus-based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.

Sustainable bio-manufacturing of D-arabitol through combinatorial engineering of Zygosaccharomyces rouxii, bioprocess optimization and downstream separation.

Biosynthesis of D-arabitol, a high value-added platform chemical, from renewable carbon sources provides a sustainable and eco-friendly alternative to the chemical industry. Here, a robust brewing yeast, Zygosaccharomyces rouxii, capable of naturally producing D-arabitol was rewired through genome sequencing-based metabolic engineering. The recombinant Z. rouxii obtained by reinforcing the native D-xylulose pathway, improving reductive power of the rate-limiting step, and inhibiting the shunt pathway, produced 73.61% higher D-arabitol than the parent strain. Subsequently, optimization of the fermentation medium composition for the engineered strain provided 137.36 g/L D-arabitol, with a productivity of 0.64 g/L/h in a fed-batch experiment. Finally, the downstream separation of D-arabitol from the complex fermentation broth using an ethanol precipitation method provided a purity of 96.53%. This study highlights the importance of D-xylulose pathway modification in D-arabitol biosynthesis, and pave a complete and efficient way for the sustainable manufacturing of this value-added compound from biosynthesis to preparation.

MATLAB language assisted data acquisition and processing in liquid chromatography Orbitrap mass spectrometry: Application to the identification and differentiation of Radix Bupleuri from its adulterants.

Comprehensive and rapid analysis of secondary metabolites like saponins remains challenging. This study aimed to establish a semi-automated workflow for filtration, identification, and characterization of saikosaponins in six Bupleurum species. Radix Bupleuri, a high-sales herbal medicine, is often adulterated, restricting its quality control and applications. Two authentic Radix Bupleuri species and four major adulterants were analyzed through UHPLC-LTQ-Orbitrap-MS for targeted saikosaponin analysis. To reveal trace saikosaponins and obtain quality fragment data, a MATLAB-based process automatically enumerating "sugar chain + aglycone + side chain" combinations and deduplicating generated a predicted saikosaponin database covering all possible saikosaponins as a precursor ion list for comprehensive targeted acquisition. To focus on informative ions and reduce MS analysis workload, we utilized MATLAB to automatically filtrate the false positive ions by MS1 and MS2 spectrometry. The newly established MATLAB-assisted data acquisition approach exhibited 50 % improvement in characterization of targeted saikosaponins. Furthermore, positive and negative ionization workflows were designed for accurate saikosaponins characterization based on fragmentation rules. In total, 707 saikosaponins were characterized, including over 500 potential new compounds and previously unreported C29 aglycones. We identified 25 saikosaponins present in both authentic species but absent in adulterants as potential markers. This unprecedented comprehensive multi-origin species differentiation demonstrates the promise of MATLAB-assisted acquisition and processing to advance saponin identification and standardize the Radix Bupleuri market.

Total flavonoids of Litchi chinensis Sonn. seed inhibit prostate cancer growth in bone by regulating the bone microenvironment via inactivation of the HGFR/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Litchi chinensis Sonn. (Litchi) seed, a traditional Chinese medicine, is habitually used in the clinical treatment of prostate cancer (PCa)-induced bone pain. In our previous study, flavonoids have been identified as the active ingredient of litchi seed against PCa. However, its anti-tumor activities in bone and associated molecular mechanisms are still unclear. AIM OF THE STUDY: To investigate the effects and underlying mechanisms of total flavonoids of litchi seed (TFLS) on the growth of PCa in bone. MATERIALS AND METHODS: The effect of TFLS on the growth of PCa in bone was observed using a mouse model constructed with tibial injection of luciferase-expressing RM1-luc cells. Conditioned medium (CM) from bone marrow stromal cells OP9 and CM treated with TFLS (T-CM) was used to investigate the effect on the proliferation, colony formation, and apoptosis of PCa cells (LNCaP, PC3, RM1). An antibody microarray was performed to detect cytokine expression in the supernatant fraction of OP9 cell cultures treated with TFLS or left untreated. Western blot assay was employed to determine the expression and activity of HGFR and its key downstream proteins, Akt, mTOR, NF-κB, and Erk, in PCa cells. The potential target was further verified using immunofluorescence and immunohistochemistry assays. RESULTS: Treatment with TFLS (80 mg/kg, 24 days) significantly suppressed the growth of RM1 cells in bone. CM from bone marrow stromal cells OP9 stimulated the proliferation and colony formation of the PCa cells as well as inhibited the apoptosis of PC3 cells, while T-CM reversed the effects mediated by OP9 cells in vitro. In an antibody array assay, TFLS regulated the majority of cytokines in OP9 cell culture supernatant, among which HGF, HGFR, IGF-1R, and PDGF-AA showed the greatest fold changes. Mechanistically, CM upregulated HGFR and promoted phosphorylation of NF-κB while T-CM induced reduction of HGFR and dephosphorylation of NF-κB in PC3 cells. Moreover, T-CM inhibited NF-κB entry into PC3 cell nuclei. Data from in vivo experiments further confirmed the inhibitory effects of TFLS on NF-κB. CONCLUSION: TFLS suppresses the growth of PCa in bone through regulating bone microenvironment and the underlying mechanism potentially involves attenuation of the HGFR/NF-κB signaling axis.

Light and Humidity Dual-Responsive Anti-Counterfeiting Films Based on Hydrogen-Bonded Cholesteric Liquid Crystal Polymers with Spiropyran.

There is still significant room for improvement when combining structural color with fluorescence patterns in dual anti-counterfeiting and dynamic anti-counterfeiting labels. In this study, we achieved significant breakthroughs under dual anti-counterfeiting conditions by using the structural color properties of the hydrogen-bonded cholesteric liquid crystal (HBCLC) and combining them with the fluorescence dye spiropyran (SP) to create anti-counterfeiting patterns. The anti-counterfeiting label can only display storage information after meeting the conditions of humidity and ultraviolet light (UV) and has the functions of dynamic encryption and repeated reading. We adjusted the center of the reflection band of the HBCLC film to transition from red to infrared under 40-90% relative humidity (RH) conditions and used it as a background film to draw anti-counterfeiting patterns with SP. Since these fluorescence dyes can switch between merocyanine (MC) (red) and SP (colorless) under UV and visible light conditions, when combined with the HBCLC, orthogonal dynamic encryption was achieved. Additionally, with the adsorption of SP, the reflection band of HBCLC films under the same humidity range increased from around 160 nm to around 260 nm, greatly improving the sensitivity to humidity changes. Furthermore, under UV conditions, it can still emit red fluorescence, demonstrating a polymorphic encryption feature, which greatly increased the complexity of the anti-counterfeiting pattern with significant significance to dynamic anti-counterfeiting and information storage.