A Dual-Recognition Fluorescence Enzyme-Linked Immunosorbent Assay for Specific Detection of Intact Lipid Nanoparticles via a Localized Scaffolding Autocatalytic DNA Circuit Amplifier.

Lipid nanoparticles (LNPs) are emerging as one of the most promising drug delivery systems. The long-circulating effect of intact LNPs (i-LNPs) is the key to efficacy and toxicity in vivo. However, the significant challenge is specific and sensitive detection of i-LNPs. Herein, a dual-recognition fluorescence enzyme-linked immunosorbent assay (DR-FELISA) was developed to directly isolate and detect i-LNPs by combining dual-recognition separation with a one-step signal amplification strategy. The microplates captured and enriched i-LNPs through antibody-antigen reaction. Dual-chol probes were spontaneously introduced into the lipid bilayer of captured i-LNPs, converting the detection of i-LNPs into the detection of double-cholesterol probes. Finally, the end of the dual-chol probes initiated the localized scaffolding autocatalytic DNA circuits (SADC) system for further signal amplification. The SADC system provides a sensitive and efficient amplifier through localized network structures and self-assembled triggers. Simultaneous recognition of i-LNPs surface PEG-lipid and lipid bilayer structures significantly eliminates interference from biological samples. i-LNPs were detected with high selectivity, ranging from 0.2 to 1.25 mg/mL with a limit of detection of 0.1 mg/mL. Moreover, this method allows the isolation and quantitative analysis of different formulations of i-LNPs in serum samples with a satisfactory recovery rate ranging from 94.8 to 116.3%. Thus, the DR-FELISA method provides an advanced platform for the exclusive and sensitive detection of i-LNPs, providing new insights for the study of the quality and intracorporal process of complex formulations.

Combining serum microRNAs and machine learning algorithms for diagnosing infectious fever after HSCT.

Infection post-hematopoietic stem cell transplantation (HSCT) is one of the main causes of patient mortality. Fever is the most crucial clinical symptom indicating infection. However, current microbial detection methods are limited. Therefore, timely diagnosis of infectious fever and administration of antimicrobial drugs can effectively reduce patient mortality. In this study, serum samples were collected from 181 patients with HSCT with or without infection, as well as the clinical information. And more than 80 infectious-related microRNAs in the serum were selected according to the bulk RNA-seq result and detected in the 345 time-pointed serum samples by Q-PCR. Unsupervised clustering result indicates a close association between these microRNAs expression and infection occurrence. Compared to the uninfected cohort, more than 10 serum microRNAs were identified as the combined diagnostic markers in one formula constructed by the Random Forest (RF) algorithms, with a diagnostic accuracy more than 0.90. Furthermore, correlations of serum microRNAs to immune cells, inflammatory factors, pathgens, infection tissue, and prognosis were analyzed in the infection cohort. Overall, this study demonstrates that the combination of serum microRNAs detection and machine learning algorithms holds promising potential in diagnosing infectious fever after HSCT.

Dual-band terahertz absorber based on square ring metamaterial structure.

In this paper, a dual-band terahertz absorber based on metamaterial structure is designed, fabricated, and measured. The metal periodic array is located on the upper surface of a silicon wafer with a metal ground plane, while the metamaterial structure is created utilizing a square metal ring with four T-shaped metal strips loaded inside of the ring. Two absorption peaks are realized at 0.715 and 1.013 THz with high Q-factors of 152.1 and 98.3, respectively, under normal TE and TM polarized incidence. A prototype of the proposed metamaterial absorber is fabricated by electron beam lithography (EBL) and electron beam evaporation (EBE) technology. Furthermore, a terahertz time-domain spectroscopy (TDS) measurement system is employed to test the absorber sample, with good measurement results obtained. This work provides a new option for the design of multi-band terahertz metamaterial absorbers.

Aflatoxin B1 triggers apoptosis in rabbit hepatocytes via mediating oxidative stress and switching on the mitochondrial apoptosis pathway.

Aflatoxin B1 (AFB1) is considered the most toxic carcinogenic compound, and exposure to AFB1 is highly associated with hepatocellular carcinoma. The aim of this study was to investigate the effects of different doses of AFB1 on growth performance and the liver of rabbits, as well as explore its underlying mechanisms. A total of eighty 30-day-old meat rabbits were randomly divided into four treatments. The control group was fed a pollution-free diet, while the AFL, AFM, and AFH groups were fed contaminated diets containing 13 µg/kg, 19 µg/kg, and 25 µg/kg of AFB1, respectively. The results showed that AFB1 had detrimental effects on the production performance of rabbits, resulting in decreased weight gain. Additionally, AFB1 exposure was associated with increased activity of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), as well as decreased levels of total protein (TP) and albumin (ALB) in the serum. AFB1 induced the production of reactive oxygen species (ROS) and malondialdehyde (MDA) while inhibiting the activity of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity in liver tissues. AFB1 decreased the mRNA transcription and protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone-1 (NQO-1). AFB1 not only decreased the contents of cytochrome P4501A2 (CYP1A2), cytochrome P4502A6 (CYP2A6) and cytochrome P4503A4 (CYP3A4) but also increased the content of AFB1-DNA adducts in the liver. Furthermore, AFB1 enhanced the expression of cytochrome c (cyt-c), caspase-9, caspase-3, and Bcl-2-associated X protein (Bax), while inhibiting the expression of B-cell lymphoma 2 (Bcl-2). Therefore, we demonstrated that AFB1 triggered apoptosis in rabbit hepatocytes via mediating oxidative stress and switching on the mitochondrial apoptosis pathway, and decreased rabbit performance.

TPI1 activates the PI3K/AKT/mTOR signaling pathway to induce breast cancer progression by stabilizing CDCA5.

BACKGROUND: Triosephosphate isomerase 1 (TPI1), as a key glycolytic enzyme, is upregulated in multiple cancers. However, expression profile and regulatory mechanism of TPI1 in breast cancer (BRCA) remain mysterious. METHODS: Western blotting and immunohistochemistry (IHC) assays were used to investigate the expression of TPI1 in BRCA specimens and cell lines. TPI1 correlation with the clinicopathological characteristics and prognosis of 362 BRCA patients was analyzed using a tissue microarray. Overexpression and knockdown function experiments in cells and mice models were performed to elucidate the function and mechanisms of TPI1-induced BRCA progression. Related molecular mechanisms were clarified using co-IP, IF, mass spectrometric analysis, and ubiquitination assay. RESULTS: We have found TPI1 is highly expressed in BRCA tissue and cell lines, acting as an independent indicator for prognosis in BRCA patients. TPI1 promotes BRCA cell glycolysis, proliferation and metastasis in vitro and in vivo. Mechanistically, TPI1 activates phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway to regulate epithelial-mesenchymal transformation (EMT) and aerobic glycolysis, which is positively mediated by cell division cycle associated 5 (CDCA5). Moreover, TPI1 interacts with sequestosome-1 (SQSTM1)/P62, and P62 decreases the protein expression of TPI1 by promoting its ubiquitination in MDA-MB-231 cells. CONCLUSIONS: TPI1 promotes BRCA progression by stabilizing CDCA5, which then activates the PI3K/AKT/mTOR pathway. P62 promotes ubiquitin-dependent proteasome degradation of TPI1. Collectively, TPI1 promotes tumor development and progression, which may serve as a therapeutic target for BRCA.

THz absorbers with an ultrahigh Q-factor empowered by the quasi-bound states in the continuum for sensing application.

The exceptional resonances excited by symmetry-protected quasi-bound states in the continuum (QBICs) have provided significant potential in high-sensitive sensing applications. Herein, we have proposed a type of metal-insulator-metal (MIM) absorbers supported by QBIC-induced resonances, and the ideal Q-factors of QBIC-induced resonances can be enhanced up to 105 in the THz regime. The coupled mode theory and the multipole scattering theory are employed to thoroughly interpret the QBIC-induced absorption mechanism. Furthermore, the refractive index sensing capacities of the as-presented absorbers have been investigated, where the maximum values of the sensing sensitivity and figure of merit (FOM) can reach up to 187 GHz per refractive index unit and 286, respectively. Therefore, it is believed that the proposed absorbers enabled by QBIC-induced resonances hold promising potential in a broad range of highly demanding sensing applications.

Highly sensitive terahertz sensing with 3D-printed metasurfaces empowered by a toroidal dipole.

Highly sensitive terahertz (THz) sensing with metasurfaces has attracted considerable attention recently. However, ultrahigh sensing sensitivity remains a huge challenge for practical applications. To improve the sensitivity of these devices, herein we have proposed an out-of-plane metasurface-assisted THz sensor consisting of periodically arranged bar-like meta-atoms. Benefiting from elaborate out-of-plane structures, the proposed THz sensor with high sensing sensitivity of 325 GHz/RIU can be easily fabricated via a simple three-step fabrication process, and the maximum sensing sensitivity can be ascribed to toroidal dipole resonance-enhanced THz-matter interactions. The sensing ability of the fabricated sensor is experimentally characterized by the detection of three types of analytes. It is believed that the proposed THz sensor with ultrahigh sensing sensitivity and its fabrication method might provide great potential in emerging THz sensing applications.

Expression characteristic, immune signature, and prognosis value of EFNA family identified by multi-omics integrative analysis in pan-cancer.

BACKGROUND: EphrinA (EFNA) are Eph receptor ligands that regulate various disease processes. Nonetheless, the expression characteristics of EFNAs in pan-cancer, their relationship with tumor immune microenvironment, and prognostic value landscape remain unknown. METHODS: A comprehensive landscape of EFNAs was created using various statistical data extracted from 33 cancers. Subsequently, we identified differential expression, genetic variations, potential function enrichment, tumor immune-related analysis, and drug sensitivity. Further, we investigated the clinical features and diagnostic prognostic value of EFNAs. RT-qPCR, western blot and immunohistochemistry (IHC) were used to validate the expression level and significant clinical value of EFNA5 in lung adenocarcinoma cell lines and tissues. RESULTS: EFNAs were highly mutated in various cancers. Genomic and epigenetic alterations of EFNAs were observed in various tumors, where an oncogenic mutation in specific cancer types potentially affected EFNA expression. Moreover, tumor-derived EFNAs were significantly related to the tumor immune microenvironment, suggesting that they are promising therapeutic targets. The majority of EFNA family genes were significantly linked to patient prognosis. Eventually, EFNA5 was an independent prognostic factor in lung adenocarcinoma. CONCLUSION: In summary, EFNAs are crucial in tumor immune regulation, and EFNA5 is a prognostic marker in lung adenocarcinoma. Our findings provide new insights into EFNAs from a bioinformatics standpoint and highlight the significance of EFNAs in cancer diagnosis and treatment.

PGE2 promotes macrophage recruitment and neovascularization in murine wet-type AMD models.

Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is a leading cause of blindness worldwide. Activated macrophages recruited to the injured eyes greatly contribute to the pathogenesis of choroidal neovascularization (CNV) in exudative AMD (wet AMD). This study describes the effects of cyclooxygenase-2 (COX2)/prostaglandin E2 (PGE2) signalling on the macrophage activation and CNV formation of wet AMD. In a mouse model of laser-induced wet AMD, the mice received an intravitreal injection of celecoxib (a selective COX2 inhibitor). Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), choroidal histology of the CNV lesions, and biochemical markers were assessed. The level of PGE2 expression was high in the laser-induced CNV lesions. Macrophage recruitment and CNV development were significantly less after celecoxib treatment. E-prostanoid1 receptor (EP1R)/protein kinase C (PKC) signalling was involved in M2 macrophage activation and interleukin-10 (IL-10) production of bone marrow-derived macrophages (BMDMs) in vitro. In addition, IL-10 was found to induce the proliferation and migration of human choroidal microvascular endothelial cells (HCECs). Thus, the PGE2/EP1R signalling network serves as a potential therapeutic target for CNV of the wet-type AMD. Video abstract.

Prostaglandin E2 promotes pathological retinal neovascularisation via EP4R-EGFR-Gab1-AKT signaling pathway.

Proliferative retinopathies, such as proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP) are major causes of visual impairment and blindness in industrialized countries. Prostaglandin E2 (PGE2) is implicated in cellular proliferation and migration via E-prostanoid receptor (EP4R). The aim of this study was to investigate the role of PGE2/EP4R signaling in the promotion of retinal neovascularisation. In a streptozotocin (STZ)-induced diabetic model and an oxygen-induced retinopathy (OIR) model, rats received an intravitreal injection of PGE2, cay10598 (an EP4R agonist) or AH23848 (an EP4R antagonist). Optical coherence tomography, retinal histology and biochemical markers were assessed. Treatment with PGE2 or cay10598 accelerated pathological retinal angiogenesis in STZ and OIR-induced rat retina, which was ameliorated in rats pretreated with AH23848. Serum VEGF-A was upregulated in the PGE2-treated diabetic rats vs non-treated diabetic rats and significantly downregulated in AH23848-treated diabetic rats. PGE2 or cay10598 treatment also significantly accelerated endothelial tip-cell formation in new-born rat retina. In addition, AH23848 treatment attenuated PGE2-or cay10598-induced proliferation and migration by repressing the EGF receptor (EGFR)/Growth factor receptor bound protein 2-associated binder protein 1 (Gab1)/Akt/NF-κB/VEGF-A signaling network in human retinal microvascular endothelial cells (hRMECs). PGE2/EP4R signaling network is thus a potential therapeutic target for pathological intraocular angiogenesis.

Synergistic use of florfenicol and Salvia miltiorrhiza polysaccharide can enhance immune responses in broilers.

To explore the effect of florfenicol (FFC) combined with Salvia miltiorrhiza polysaccharide (SMPs) on immune function of Broilers. One hundred and twenty-one-day-old chicks were chosen and divided into 6 groups. The group A received standard basal diet only, the group B received a basal diet with FFC (0.15 g/L diet), and the group C, D, E received a basal diet with FFC (0.15 g/L diet) and SMPs (1.25 g/L, 2.5 g/L, 5 g/L diet)，the group F received a basal diet with SMPs (5 g/L diet). FFC can significantly inhibit the growth performance of broilers, but has no significant damage to the immune function of broilers. The combination of FFC and SMPs can improve the growth performance of broilers, increase the number of leukocyte subtypes in blood (P < 0.05), increase the number of Newcastle disease (ND) and avian influenza (AI) antibodies in blood, the number of immunoglobulins, and the content of cytokines (P < 0.05). In addition, it significantly improve the lymphocyte conversion rate of broiler peripheral blood (P < 0.05). So that, synergistic use of FFC and SMPs can enhance immune responses in Broilers.

Florfenicol causes excessive lipid peroxidation and apoptosis induced renal injury in broilers.

In order to study the effects and mechanism of florfenicol (FFC) on the kidney function of broilers, 180 1-day-old broilers were randomly divided into 6 groups, 30 in each group. Except for the control group, different doses of FFC were added to drinking water in the other 5 groups (0.15 g/L, 0.3 g/L, 0.6 g/L, 1.2 g/L and 1.8 g/L). After continuous administration for 5 days, renal histopathological changes, serum renal function indicators, renal peroxidation products and antioxidant factors, and apoptotic factors were detected in broilers aged 21 and 42 days. The results showed that compared with the control group, the kidney tissue structure was disordered, the glomerulus was atrophic, the cystic cavity was enlarged, and the epithelial cells of renal tubules were seriously vacuolated in broilers of treatment groups. And with the growth of broilers, the kidney injury of broilers in the low-dose FFC group was relieved. FFC significantly increased the contents of uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE) in serum and malondialdehyde (MDA) in kidney of broilers, but significantly reduced the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in kidney. FFC significantly inhibited the mRNA relative transcriptional levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1), and increased the mRNA and protein expression levels of p53, Caspase-3 and Caspase-6 in kidney tissue of broilers. It is concluded that FFC has certain nephrotoxicity to broilers, and its effect on kidney is dose-dependent and reversible. FFC causes intense lipid peroxidation in broiler kidney by inhibiting the expression of related factors in the downstream signal pathway of Nrf2. FFC can also up-regulate the expression of pro-apoptotic factors and accelerate the abnormal apoptosis of renal cells, thus seriously affecting the renal function of broilers.

Florfenicol induces oxidative stress and hepatocyte apoptosis in broilers via Nrf2 pathway.

In order to explore the mechanism of liver injury induced by florfenicol (FFC) in broilers, one hundred and twenty broilers were randomly divided into six groups, twenty broilers in each group. Except for control group, the other five groups were given different doses of FFC (0.15 g/L, 0.3 g/L, 0.6 g/L, 1.2 g/L and 1.8 g/L) in drinking water. After five days of continuous use, blood was collected from the subpterional vein and the chickens' liver were obtained. Chicken weight gain and liver indices were calculated; blood routine analysis was performed; the oxidative stress and apoptosis of hepatocytes was detected. The results showed that compared with the control group, except for 0.15 g/L FFC, the other doses of FFC significantly decreased the weight gain, white blood cell (WBC) and platelet (PLT) contents in blood, 0.3 g/mL FFC and 1.8 g/L FFC significantly reduced the content of hemoglobin (RGB) (P < 0.05); all doses of FFC significant decreased red blood cell (RBC) increased Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) contents in serum of chickens (P < 0.05), and significantly decreased the contents of albumin (ALB) and total protein (TP) in serum (P < 0.05), but had no significant effect on alkaline phosphatase (ALP) contents(P > 0.05). FFC significantly increased malondialdehyde (MDA) content in serum and liver tissues, but decreased glutathione (GSH), Superoxide dismutase (SOD) and catalase (CAT) content (P < 0.05), and significantly inhibited the mRNA transcription and protein expression of antioxidant proteins nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1)(P < 0.05). FFC also inhibited the content and the transcription level of cytochrome P4501A1(CYP1A1) and CYP2H1 in liver (P < 0.05). At the same time, FFC significantly promoted the apoptotic rate of hepatocytes and the mRNA transcription and protein expression of caspase-3 and caspase-6 (P < 0.05). With the increase of FFC concentration, liver injury became more and more serious, which affected liver function in chickens by inhibiting enzyme activity in Nrf2-ARE pathway to increase oxidative stress and promoting apoptotic protein expression to accelerate hepatocyte apoptosis.

Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing.

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.

A phospholipid complex to improve the oral bioavailability of flavonoids.

AIM: A phospholipid complex (TFH-PC) was prepared to increase the oral bioavailability of isorhamnetin, kaempferol, and quercetin from TFH (total flavones of Hippophae rhamnoides L.). METHODS: Solvent evaporation was used to prepare TFH-PC. Relevant parameters were investigated based on the complexation rate of isorhamnetin, kaempferol, and quercetin. Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray power diffraction (X-RPD), and scanning electron microscopy (SEM) were used for characterization. Solubility, octanol-water partition coefficient (log P), dissolution rate, and in vivo pharmacokinetics were also investigated. RESULTS: TFH-PC was successfully prepared in tetrahydrofuran with a drug to phospholipid ratio of 1:1, reaction temperature of 20 °C, and a reaction time of 1 h. The complexation rates of isorhamnetin, kaempferol, and quercetin were 97.7%, 95.97%, and 92.23%, respectively. FT-IR, DSC, X-RPD, and SEM confirmed the formation of TFH-PC. The aqueous solubilities of the three flavonoids in TFH-PC increased 22.0-26.8-fold compared with TFH. The dissolution of isorhamnetin, kaempferol, and quercetin in TFH-PC was 84.32%, 90.77%, and 100% within 10 min, respectively, greatly improved over TFH. After oral administration of TFH-PC in rats, the bioavailability of isorhamnetin, kaempferol, and quercetin in TFH-PC relative to TFH was 223%, 172%, and 242%, respectively. CONCLUSION: The oral absorption of isorhamnetin, kaempferol, and quercetin was significantly improved in TFH-PC, mainly due to increased solubility and dissolution rate. This phospholipid complex shows potential for oral delivery of the flavonoids in TFH.

Male breast cancer differs from female breast cancer in molecular features that affect prognoses and drug responses.

BACKGROUND: Male breast cancer (MBC) is a rare malignancy with a worse prognosis than female breast cancer (FBC). Current MBC treatment strategies are based on those for FBC. However, molecular differences between MBC and FBC with respect to prognosis and drug responses remain unclear. METHODS: After controlling for confounding factors with propensity score matching (PSM), differences between MBC and FBC were comprehensively analyzed using many types of data: survival, immune microenvironments, sex hormone responses, drug sensitivity, transcriptomes, genomes, epigenomes, and proteomes. RESULTS: Overall survival (OS) and cancer-specific survival (CSS) were both worse for MBC than for FBC. Differentially expressed mRNAs were enriched in numerous cancer-related functions and pathways, with SPAG16 and STOX1 being as the most important prognosis-related mRNAs for MBC. Competing endogenous RNA (ceRNA) and transcription factor (TF)-mRNA regulatory networks contain potential prognostic genes. Nine genes had higher mutation frequencies in MBC than in FBC. MBC shows a comparatively poor response to immunotherapy, with five proteins that promote breast cancer progression being highly expressed in MBC. MBC may be more responsive than FBC to estrogen. We detected six United States Food and Drug Administration (FDA)-approved therapeutic target genes as being differentially expressed between MBC and FBC. CONCLUSION: The poor prognosis of MBC compared to FBC is due to numerous molecular differences and resulting drug responses.

A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma.

Osteosarcoma (OS) is one of the most prevalent bone tumors in adolescents, and the correlation between aging and OS remains unclear. Currently, few accurate and reliable biomarkers have been determined for OS prognosis. To address this issue, we carried out a detailed bioinformatics analysis based on OS with data from the Cancer Genome Atlas data portal and Human Aging Genomic Resources database, as well as in vitro experiments. A total of 88 OS samples with gene expression profiles and corresponding clinical characteristics were obtained. Through univariate Cox regression analysis and survival analysis, 10 aging-associated survival lncRNAs (AASRs) were identified to be associated with the overall survival of OS patients. Based on the expression levels of the 10 AASRs, the OS patients were classified into two clusters (Cluster A and Cluster B). Cluster A had a worse prognosis, while Cluster B had a better prognosis. Then, 5 AASRs were ultimately included in the signature through least absolute shrinkage and selection operator-Cox regression analysis. Kaplan‒Meier survival analysis verified that the high-risk group exhibited a worse prognosis than the low-risk group. Furthermore, univariate and multivariate Cox regression analyses confirmed that the riskScore was an independent prognostic factor for OS patients. Subsequently, we discovered that the risk signature was correlated with the properties of the tumor microenvironment and immune cell infiltration. Specifically, there was a positive association between the risk model and naïve B cells, resting dendritic cells and gamma delta T cells, while it was negatively related to CD8+ T cells. Finally, in vitro experiments, we found that UNC5B-AS1 inhibited OS cells from undergoing cellular senescence and apoptosis, thereby promoting OS cells proliferation. In conclusion, we constructed and verified a 5 AASR-based signature, that exhibited excellent performance in evaluating the overall survival of OS patients. In addition, we found that UNC5B-AS1 might inhibit the senescence process, thus leading to the development and progression of OS. Our findings may provide novel insights into the treatment of OS patients.

An antihypertensive drug-AT1 inhibitor attenuated BRCA development promoted by chronic psychological stress via Ang II/PARP1/FN1 pathway.

Chronic psychological stress contributes to the occurrence of cancer and activates the renin-angiotensin system (RAS). However, the mechanisms by which RAS promotes the progression of breast cancer (BRCA) under chronic psychological stress are remain unknown. In this study, we observed elevated levels of Angiotensin II (Ang II) in both serum and BRCA tissue under chronic stress, leading to accelerated BRCA growth in a mouse model. An antihypertensive drug, candesartan (an AT1 inhibitor), effectively attenuated Ang II-induced cell proliferation and metastasis. Utilizing mass spectrometry and weighted gene co-expression network analysis (WGCNA), we identified fibronectin 1 (FN1) as the hub protein involved in chronic stress-Ang II/AT1 axis. Focal adhesion pathway was identified as a downstream signaling pathway activated during the progression of chronic stress. Depletion of FN1 significantly attenuated Ang II-induced proliferation and metastasis of BRCA cells. Poly (ADP-ribose) polymerase 1 (PARP1) was found to bind to the DNA promoter of FN1, leading to the transcription of FN1. Ang II upregulated PARP1 expression, resulting in increased FN1 levels. Recombinant FN1 partially restored the progress of BRCA malignancy induced by the Ang II/PARP1 pathway. In vivo, candesartan reversed the progressive effect of chronic psychological stress on BRCA. In clinical samples, Ang II levels in both serum and tumor tissues are higher in stressed patients compared to control patients. Serum Ang II levels were positively correlated with chronic stress indicators. In conclusion, our study demonstrated that chronic psychological stress accelerates the malignancy of BRCA, and the AT1 inhibitor candesartan counteracts these effects by suppressing the Ang II-AT1 axis and the downstream PARP1/FN1/focal adhesion pathway.

The inhibition effects of chlorogenic acid on the formation of colored oxidation products of (-)-epigallocatechin gallate under enzymatic oxidation.

Untargeted Liquid chromatography tandem mass spectrometry (LC-MS) based metabolomics in combination with UV-visible and colorimeter was applied in identifying critical colored enzymatically oxidized products of (-)-epigallocatechin gallate (EGCG). Pearson correlation coefficient analysis between marker compounds and a* value was conducted, and then a series of colored oxidation products were targeted and subsequently identified by diode array detection and mass fragmentation ions. The quinone of oolongtheanin 3-O'-gallate degraded product with quasi-molecular mass ion at m/z 711 was identified as a critical colored oxidation product of single EGCG. To explore the effect of chlorogenic acid on the formation of colored EGCG enzymatic oxidation products, the variation of oxidation products on the oolongtheanin pathway was semi-quantitatively determined. The result showed chlorogenic acid significantly inhibited the formation of colored oxidation products, thus lightened the color of EGCG oxidation mixture. The addition of chlorogenic acid influences the process of tea polyphenols' enzymatic oxidation.

Compound small peptide of Chinese medicine alleviates cyclophosphamide induced immunosuppression in mice by Th17/Treg and jejunum intestinal flora.

The aim of this study was to explore the efficacy of Compound small peptide of Chinese medicine (CSPCM) on cyclophosphamide (CTX) induced immunosuppression in mice. The 100 male Kunming mice were divided into 5 groups: group A (control group), group B (model group), group C (100 mg/kg.bw CSPCM), group D (200 mg/kg.bw CSPCM) and group E (400 mg/kg.bw CSPCM). At 1-3 days, mice of group B, C, D and E were intraperitoneally injected with 80 mg/kg.bw CTX. The results showed that compared with group A, the immune organ index, body weight change, RORγ T gene expression, RORγ T protein expression, CD3+ cell number, Th17 number and Alpha index, white blood cell count, lymphocyte count and monocyte count were significantly decreased in group B (p < 0.05), while Foxp3 gene expression, Foxp3 protein expression and Treg cell number were significantly increased (p < 0.05), CSPCM has a good therapeutic effect on the above abnormalities caused by CTX. CTX caused the decrease of intestinal flora richness and the abnormal structure of intestinal flora, and CSPCM could change the intestinal flora destroyed by CTX to the direction of intestinal flora of healthy mice. On the whole, CSPCM has a good therapeutic effect on CTX-induced immunosuppression in mice, which is reflected in the index of immune organs, the number of T lymphocytes and Th17 cells increased, the number of Treg cells decreased and the structure of intestinal flora was reconstructed.