The high expression of TOP2A and MELK induces the occurrence of psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease. However, the influence of the TOP2A and MELK genes on psoriasis remains unclear. METHODS: Psoriasis datasets GSE166388 and GSE181318 were downloaded from the Gene Expression Omnibus (GEO) database generated from GPL570 and GPL22120. Differential gene expression (DEGs) was identified. Functional enrichment analysis, gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and immune infiltration analysis were conducted. The protein-protein interaction (PPI) network was constructed and analyzed. Gene expression heat map was generated. The most relevant diseases associated with core genes were determined through comparison with the Comparative Toxicogenomics Database (CTD) website. TargetScan was used to select miRNAs regulating central DEGs. RESULTS: A total of 773 DEGs were identified. According to Gene Ontology (GO) analysis, they were mainly enriched in mitochondrial gene expression, oxidative phosphorylation, mitochondrial envelope, mitochondria and ribosome. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that target cells were mainly enriched in metabolic pathways, proteasome, and oxidative phosphorylation. Seven core genes (TOP2A, NUF2, MELK, ASPM, DLGAP5, CCNA2, DEPDC1B) were obtained. The gene expression heatmap showed high expression of core genes (TOP2A, MELK) in psoriasis samples, while DEPDC1B, CCNA2, DLGAP5, NUF2, ASPM were lowly expressed in psoriasis samples. CTD analysis found that TOP2A and MELK were related to skin neoplasms, skin diseases, psoriasis, erythema, dermatitis, and infections. CONCLUSION: TOP2A and MELK genes are highly expressed in psoriasis, and higher expression of TOP2A and MELK genes is associated with poorer prognosis.

Oligo/polysaccharides from Cyathula officinalis and Achyranthes bidentata: a review of structures and bioactivities.

OBJECTIVES: Oligo-/polysaccharides from Cyathula officinalis Kuan (COPs) and Achyranthes bidentata Blume (ABPs) have attracted researchers' attention in the fields of healthy food supplements and traditional Chinese medicine (Niúxi) due to their multiple bioactivities combined with their nontoxic and highly biocompatible nature. The purpose of this paper was to provide a systematic and comprehensive overview of the extraction, purification, and structural analysis methods, chemical characteristics, biological activities, and structure bioactivity relationship. Furthermore, the possible development trends and perspectives for future research, and traditional uses of Niúxi are also summarized. METHODS: All the information was gathered from a library search and scientific databases. KEY FINDINGS: Although COPs and ABPs are derived from different plants, they have similar structural features in type, structure, and glycosidic linkage patterns and biological activities in vivo and in vitro. However, there are differences in monosaccharide compositions, which can be used as an identification mark. CONCLUSIONS: As traditional Chinese herbal medicine, C. officinalis and A. bidentata have similar pharmacological activities. The COPs and ABP possess wide pharmacological effects such as antitumor, antioxidant, anti-osteoporosis, and anti-inflammatory. Meanwhile, the biological activity and structure-activity relationship of purified COPs and ABPs are less studied, future research should focus on them.

The study of the role of purified anti-mouse CD193 (CCR3) antibody in allergic rhinitis mouse animal models.

The pathogenesis of allergic asthma is similar to that of allergic rhinitis, with inflammation cells producing and releasing inflammatory mediators and cytokines closely related to CCR3.Based on the theory of "one airway, one disease", the use of CCR3 monoclonal antibody may have a similar effect on allergic rhinitis. However, there are few studies on CCR3 monoclonal antibody in allergic rhinitis. Therefore, the aim of this study was to investigate the effective concentration of CCR3 monoclonal antibody, to compare the effects of different methods of administration, and to examine the lung condition of allergic mice to investigate whether antibody treatment protects the lungs. In this study, we constructed a mouse model of allergic rhinitis and intraperitoneally injected different doses of CCR3 monoclonal antibody (5, 10, and 20 uL/mg) to observe its therapeutic effect: observing changes in tissue morphology of nasal mucosa, infiltration of inflammation, and using ELISA to detect changes in relevant inflammatory mediators and cytokines, studying the role of CCR3 mAb in inhibiting CCR3-related actions on the nasal mucosa of allergic rhinitis mice. Furthermore, In addition, the therapeutic effects of intraperitoneal injection (i.p.) and intranasal administration (i.n.) were studied on the basis of effective concentrations.

Detection of chlorophyll content based on optical properties of maize leaves.

The chlorophyll content reflects plants' photosynthetic capacity, growth stage, and nitrogen status. Maize is one of the three widely planted gain crops in the world. In order to offer useful information for the development of chlorophyll content detectors of maize leaves, a single integrating sphere system was used to measure the transmittance and reflectance spectra of maize leaves over the wavelength range of 500-950 nm. The linear relationships of transmittance and reflectance with chlorophyll content were investigated. The feature wavelengths (FWs) sensitive to chlorophyll content were extracted from the full transmittance and reflectance spectra using the successive projections algorithm (SPA). The partial least squares regression (PLSR) models for predicting the chlorophyll content were established using the full spectra and extracted FWs. The results showed that there were obvious linear relationships between transmittance and reflectance with chlorophyll content of maize leaves and the best linear relationships were found at 709 nm and 714 nm, respectively, with the linear correlation coefficients of 0.801 and 0.696, and the root-mean-squares error (RMSEP) of 0.321 mg·g-1 and 0.405 mg·g-1, respectively. Eight and 6 FWs were extracted from the transmittance and reflectance spectra, respectively. The PLSR model established using the selected FWs from transmittance spectra had better prediction performance with RMSEP of 0.208 mg·g-1 than using full transmittance spectra. The built PLSR models using the full reflectance spectra and extracted FWs had poor robustness. This research offers some theoretical basis for developing a maize leaf chlorophyll content detector based on transmittance or reflectance.

Revealing the "Yin-Jing" mystery veil of Platycodon grandiflorum by potentiating therapeutic effects and lung-oriented guidance property.

ETHNIC PHARMACOLOGICAL RELEVANCE: "Yin-Jing" medicine (YJM) has been widely used by both ancient and modern Chinese medicine practitioners during long-term clinical practice. However, it remains unclear how to best guide other medicines to the targeted organs in a traditional Chinese medicine (TCM) prescription. Here, in an attempt to explain the scientific connotation of the YJM property (YJMP) attributed to a basic TCM theory, Platycodon grandiflorum (PG) was chosen as a case study to reveal the mystery of YJMP theory. AIM OF THE STUDY: The main purpose of this study is to employ modern chemical and molecular biology methods to confirm the "Yin-Jing" effect of PG, and further clarify its material basis and related possible mechanism. MATERIALS AND METHODS: The ammonia-induced lung injury rat model was utilized to determine the optimal dosage of traditional prescription Hui Yan Zhu Yu decoction (HYZYD) using Wright Giemsa staining, HE staining, Masson staining, and TUNEL analysis. With the same way, PG was confirmed to have potentiating therapeutic effect (PTE) by comparison with HYZYD and [HYZYD-PG]. TMT proteomics was used to reveal the "Yin-Jing" mechanism of action. Western blot assay (WB) was employed for verification of differentially expressed proteins. Additionally, four non-crossing fragmentations (Fr. A-D) were characterized by RPLC/SEC-ELSD and HILIC-ESI--Q-OT-IT-MS techniques. The PTE and guidance property assays were utilized to evaluate "Yin-Jing" functions by a compatible combination of hydroxysafflor yellow A (HYA) using qPCR, FCM, WB, HPLC, high content cell imaging (HCI) and high-resolution live-cell imaging (HRLCI) techniques. RESULTS: The HYZYD-M (medium dose group) significantly improved the lung injury level in a pneumonia model of rats. PG enhanced the therapeutic effect of HYZYD ascribed to Yin-Jing PTE functions. TMT proteomics revealed a category of differentially expressed proteins ascribed to Golgi-ER between HYZYD and [HYZYD-PG]. Fr. C (i.e., saponins) and Fr. D (i.e., lipids) were determined as therapeutic fragmentations via the LPS-induced A549 cell injury model; however, Fr. B (fructooligosaccharides and small Mw fructans) had no therapeutic effect. Further compatibility PTE assays confirmed Fr. B significantly improved efficiency by a combination of HYA. The guidance assays showed Fr. B could significantly increase the uptake and distribution of HYA into lung cells and tissues. HCI assays showed that Fr. B increased uptake of HYA accompanied by significant activation of Golgi-ER. Unlike Fr. B, HRLCI showed that Fr. A, C and D were not only unobvious activations of Golgi-ER but also insignificant facilitation of colocalizations between HYA and Golgi-ER. CONCLUSIONS: Fr. B is believed to be a key YJMP material basis of PG attributed to Yin-Jing PTE with characteristic of lung-oriented guidance property, whereas another abound Fr. C was determined to have synergistic effects rather than Yin-Jing material basis.

Microstructural Characterization and Magnetic, Dielectric, and Transport Properties of Hydrothermal La2FeCrO6 Double Perovskites.

Double perovskite La2FeCrO6 (LFCO) powders were synthesized via the hydrothermal method, which crystallized in an orthorhombic (Pnma) structure and exhibited a spherical morphology with an average particle size of 900 nm. Fourier transform infrared spectroscopy demonstrated the presence of fingerprints of vibrational modes of [FeO6] and [CrO6] octahedra in the powders. The XPS spectra revealed dual oxide states of Fe (Fe2+/Fe3+) and Cr (Cr3+/Cr4+) elements, and the oxygen element appeared as lattice oxygen and defect oxygen, respectively. The LFCO powders exhibited weak ferromagnetic behavior at 5 K with a Curie temperature of 200 K. Their saturation magnetization and coercive field were measured as 0.31 µB/f.u. and 8.0 kOe, respectively. The Griffiths phase was observed between 200 K and 223 K. A butterfly-like magnetoresistance (MR)-magnetic field (H) curve was observed in the LFCO ceramics at 5 K with an MR (5 K, 6 T) value of -4.07%. The temperature dependence of resistivity of the LFCO ceramics demonstrated their semiconducting nature. Electrical transport data were fitted by different conduction models. The dielectric behaviors of the LFCO ceramics exhibited a strong frequency dispersion, and a dielectric abnormality was observed around 260 K. That was ascribed to the jumping of electrons trapped at shallow levels created by oxygen vacancies. The dielectric loss showed relaxation behavior between 160 K and 260 K, which was attributed to the singly ionized oxygen vacancies.

Utilizing Mixed Training and Multi-Head Attention to Address Data Shift in AI-Based Electromagnetic Solvers for Nano-Structured Metamaterials.

When designing nano-structured metamaterials with an iterative optimization method, a fast deep learning solver is desirable to replace a time-consuming numerical solver, and the related issue of data shift is a subtle yet easily overlooked challenge. In this work, we explore the data shift challenge in an AI-based electromagnetic solver and present innovative solutions. Using a one-dimensional grating coupler as a case study, we demonstrate the presence of data shift through the probability density method and principal component analysis, and show the degradation of neural network performance through experiments dealing with data affected by data shift. We propose three effective strategies to mitigate the effects of data shift: mixed training, adding multi-head attention, and a comprehensive approach that combines both. The experimental results validate the efficacy of these approaches in addressing data shift. Specifically, the combination of mixed training and multi-head attention significantly reduces the mean absolute error, by approximately 36%, when applied to data affected by data shift. Our work provides crucial insights and guidance for AI-based electromagnetic solvers in the optimal design of nano-structured metamaterials.

CCR3 gene knockout inhibits proliferation, differentiation, and migration of eosinophils in allergic rhinitis model mice.

Allergic rhinitis (AR) is characterized by various bothersome clinical symptoms of the nasal mucosa that impaired the quality of daily life. Different chemokine receptors play a crucial role in the recruitment of inflammatory cells in AR. However, the effect of CC chemokine receptor (CCR) 3 on the function of eosinophils (EOS) is still unclear. We investigated the effect of CCR3 on EOS in a murine model of OVA-mediated allergic rhinitis using CCR3-deficient (CCR3-/-) mice. In vitro, bone marrow of CCR3-/- and wild-type (WT) mice were used to investigate the induction and development of EOS. In vivo, Allergic rhinitis was initiated in CCR3-/- and wild-type (WT) mice by passive transfer OVA, followed by detecting the eosinophil infiltration of the nasal mucosa and bone marrow. Then CD34+ progenitor cells in bone marrow and blood were evaluated by IHC analysis. Furthermore, the degranulation proteins of EOS in nasal mucosa, marrow, blood and NALF were determined by IHC, real-time PCR analysis and Western blot. We found that CCR3 gene can regulate the growth and development of primary cultured eosinophils. Knockout CCR3 gene can inhibit the proliferation and degranulation of EOS. The infiltration of eosinophils in the nasal mucosa following OVA-challenged, was significantly higher in WT mice compared with those stimulated with phosphate-buffered saline (PBS) for WT, but that was not seen in similarly treated CCR3-/- mice. Besides, the number of CD34+ progenitor cells in bone marrow and blood were also suppressed in CCR3-/- mice. The degranulation proteins of EOS expressed in nasal mucosa, marrow, blood and NALF were decreased in CCR3-/- AR mice compared with WT-AR mice. And the clinical symptoms were significantly alleviated. The expression of granulation proteins in NALF were not detected in both untreated CCR3-/- mice and WT mice. These results demonstrate a contribution of CCR3 to both the growth, migration, and degranulation of EOS during allergic rhinitis.

MSCs Ameliorate Hepatic IR Injury by Modulating Phenotypic Transformation of Kupffer Cells Through Drp-1 Dependent Mitochondrial Dynamics.

BACKGROUND: Hepatic ischemia and reperfusion (IR) injury, characterized by reactive oxygen species (ROS) production and immune disorders, leads to exogenous antigen-independent local inflammation and hepatocellular death. Mesenchymal stem cells (MSCs) have been shown to be immunomodulatory, antioxidative and contribute to liver regeneration in fulminant hepatic failure. We aimed to investigate the underlying mechanisms by which MSCs protect against liver IR injury in a mouse model. METHODS: MSCs suspension was injected 30 min prior to hepatic warm IR. Primary kupffer cells (KCs) were isolated. Hepatic injury, inflammatory responses, innate immunity, KCs phenotypic polarization and mitochondrial dynamics were evaluated with or without KCs Drp-1 overexpression RESULTS: MSCs markedly ameliorated liver injury and attenuated inflammatory responses and innate immunity after liver IR injury. MSCs significantly restrained M1 phenotypic polarization but boosted M2 polarization of KCs extracted from ischemic liver, as demonstrated by lowered transcript levels of iNOS and IL-1ß but raised transcript levels of Mrc-1 and Arg-1 combined with p-STAT6 up-regulation and p-STAT1 down-regulation. Moreover, MSCs inhibited KCs mitochondrial fission, as evidenced by decreased Drp1 and Dnm2 levels. We overexpressed Drp-1 in KCs which promote mitochondrial fission during IR injury. the regulation of MSCs towards KCs M1/M2 polarization was abrogated by Drp-1 overexpression after IR injury. Ultimately, in vivo Drp-1 overexpression in KCs hampered the therapeutic effects of MSCs against hepatic IR injury CONCLUSIONS: We revealed that MSCs facilitated M1-M2 phenotypic polarization through inhibiting Drp-1 dependent mitochondrial fission and further attenuated liver IR injury. These results add a new insight into regulating mechanisms of mitochondrial dynamics during hepatic IR injury and may offer novel opportunities for developing therapeutic targets to combat hepatic IR injury.

Long Non Coding RNA FOXD3­AS1 Alleviates Allergic Rhinitis by Elevating the Th1/Th2 Ratio via the Regulation of Dendritic Cells.

This article aimed to explore whether the regulation of Th1/Th2 immune responses by FOXD3-AS1 is associated with dendritic cells (DCs) in allergic rhinitis (AR). HE staining was performed to assess the pathological changes in the nasal mucosa; ELISA was performed to measure the levels of Th1/Th2-related cytokines; flow cytometry was performed to analyze Th1/Th2 cells and MHC-II-, CD80-, and CD86-positive DCs; and qRT‒PCR and western blotting were performed to measure mRNA and protein expression levels, respectively. Our data revealed that LV-FOXD3-AS1 improved AR and increased the Th1/Th2 cell ratio in AR model mice. LV-FOXD3-AS1 further inhibited DC maturation both in vivo and in vitro. Moreover, the coculture system of DCs and CD4+ T cells demonstrated that LV-FOXD3-AS1 increased the Th1/Th2 cell ratio by inhibiting the maturation of DCs. In addition, LV-FOXD3-AS1 reduced the level of phosphorylated STAT6 in DCs derived from healthy mice, and STAT6 overexpression eliminated the inhibitory effect of LV-FOXD3-AS1 on the maturation of DCs. In summary, LV-FOXD3-AS1 ameliorated AR by increasing the Th1/Th2 cell ratio by inhibiting DC maturation via the inhibition of STAT6 phosphorylation. Our data confirmed the protective effect of FOXD3-AS1 in AR and provided a novel idea for the treatment of this disease.

The Diagnostic and Therapeutic Value of NCAPG as a Proposed Biomarker Candidate in Acute Liver Failure.

BACKGROUND: Acute Liver Failure (ALF) is a difficult problem to solve in clinical practice. The presence of non-SMC condensin I complex subunit G (NCAPG) has previously been linked to vascular invasion of digestive system tumors, foreshadowing poor prognosis. Its role in ALF biology, however, remains unknown. This article explores the role of NCAPG as a potential biomarker candidate for the accurate diagnosis and targeted treatment of ALF. METHODS: The study included transcription data (GSE14668, GSE38941, GSE62029, GSE96851, and GSE120652) of ALF, normal tissues, and clinical samples, where NCAPG was selected as the differential gene by the "DESeq2" R package to analyze the immune cell functions and signal pathways. Furthermore, RT-qPCR and Western blot analyses were used to confirm the RNA and protein levels of NCAPG in ALF cell models, respectively. RESULTS: Bioinformatics analysis revealed that NACPG was up-regulated in ALF tissues, and the functional signaling pathway was primarily associated with immune infiltration. Based on the results of clinical samples, we suggest that NCAPG was overexpressed in ALF tissues. We also found that the expression of NCAPG increased with the degree of liver injury in vitro. Enrichment analysis suggested that NCAPG influenced ALF as a PI3K/AKT pathway activator. CONCLUSION: Our study suggests that NCAPG is a preliminary tool for the diagnosis of ALF. It can affect ALF via the PI3K/AKT pathway and is a potential therapeutic target to improve prognosis.

Hydration dominates dielectric spectroscopy-based high accuracy quantification of lactose content in cow's milk.

BACKGROUND: Lactose is a critical factor in the quality of milk and dairy products. Achieving high accuracy and rapid detection of lactose content in cow's milk remains a challenge. Dielectric spectroscopy has emerged as a promising tool for detecting food components. We explored the effect of lactose content on the dielectric spectra of cow's milk and we propose a rapid analytical method for the quantitative determination of lactose content in cow's milk with high accuracy based on dielectric spectra. RESULTS: We obtained the dielectric spectra of 316 cow's milk samples in the frequency range 20-4500 MHz and noticed a strong negative correlation between the lactose content and the value of the dielectric loss factor (ε″) below 1500 MHz. Lactose does not affect cow's milk dielectric properties by excluded volume effect, but dominates the effect on the dielectric properties of cow's milk by hydration. The support vector regression model based on the variable importance in projection has the best prediction performance for lactose content. Its root-mean-square error of prediction set and residual prediction deviation is 0.29 g kg-1 and 6.968, respectively, and its prediction performance is better than that of the currently reported near-infrared (NIR) method and other methods. CONCLUSION: Despite the weak polarity of lactose molecules, its hydration is a significant factor affecting the dielectric properties of milk. The present study provides a basis for high accuracy and rapid quantitative detection of lactose in cow's milk based on dielectric spectra. © 2023 Society of Chemical Industry.

Experimental observation of the effect of immunotherapy on CD4+ T cells and Th1/Th2 cytokines in mice with allergic rhinitis.

The present study aims to investigate the effect of immunotherapy in a mouse model of allergic rhinitis (AR) and to explore the possible molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with house dust mite (HDM) extract. The mice were injected subcutaneously with HDM for immunotherapy. AR nasal symptoms were evaluated according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The nasal mucosa and lung tissue architecture and inflammatory status by histological analysis; the infiltration of eosinophils in nasal lavage fluid (NALF) of mice was observed by Diff-Quik stain; ELISA-based quantification of serum HDM-specific IgE and TH1/TH2 cytokine concentration; and flow cytometry detected the number of serum CD4+/CD8+ cells to evaluate the mechanism of immunotherapy. It was found that after immunotherapy, the AR symptom score was reduced, the number of eosinophils in NALF was reduced, and the infiltration of inflammatory cells and tissue damage in the nasal mucosa and lung tissue were alleviated. Immunotherapy can increase the number of CD4+ T cells in the peripheral blood, increase the ratio of CD4+/CD8+ cells, increase the expression of Th1 cytokines such as IL-2 and IFN-γ, reduce the expression of Th2 cytokines such as IL-4 and IL-5. The results showed that repeated intraperitoneal injection of crude extract of HDM for sensitization, followed by nasal drops can effectively construct a mouse model of AR, and subcutaneous injection of immunotherapy in mice can reduce allergic inflammation in model mice and improve the inflammatory infiltration of the nasal cavity in allergic rhinitis. Immunotherapy can reduce the expression of inflammatory factors in AR, improve Th1/Th2 balance, and may play a role in the treatment of AR by improving the function of immune cells.

Microstructural Characterization of the Sol-Gel-Derived Sr2CrReO6 Powders and Their Magnetic and Electrical Transport Properties.

The double-perovskite (DP) Sr2CrReO6 (SCRO) oxide has gained much attention due to its high Curie temperature (∼635 K), high spin polarization, and strong spin-orbit coupling, which provides promising potential for room-temperature spintronic devices. In this work, we report on microstructures of a set of sol-gel-derived SCRO DP powders and their magnetic and electrical transport properties. The SCRO powders crystallize into a tetragonal crystal structure (space group of I4/m). X-ray photoemission spectroscopy spectra verify that the rhenium ions possess variable valences (Re4+ and Re6+) in the SFRO powders while chromium ions are presented as Cr3+. Ferrimagnetic behavior was observed in the SFRO powders at 2 K, and the saturation magnetization was evaluated to be 0.72 µB/f.u. and the coercive field to be 7.54 kOe. The Curie temperature was derived from susceptibility measurements to be 656 K at 1 kOe. Such ferrimagnetic behavior stems from the Cr3-Re4+(Re6+) super exchange interaction via intervening oxygen. Electrical transport measurements revealed that the SFRO ceramic grains were semiconducting and the electrical transport process was governed by the small polarons hopping with variable ranges. The hopping paths for these small polarons are provided by the hetero-valent Re ions in the SCRO ceramics. Negative magnetoresistance (MR) was observed in the SCRO ceramics, and the plot of MR vs magnetic field (H) exhibited a butterfly-like shape. The MR (2 K, 6 T) was measured to be -5.3%, due to the intergranular magneto-tunneling effect. The present results demonstrate a unique combination of high-temperature ferrimagnetism and intrinsic semiconducting nature of the sol-gel-derived SCRO oxides, which are highly attractive for oxide spintronics.

MiR-223-3p regulates the eosinophil degranulation and enhances the inflammation in allergic rhinitis by targeting FBXW7.

OBJECTIVES: MiR-223-3p is a multifunctional microRNA regulated by multiple transcription factors and plays a critical role in inflammation. This paper was designed to investigate the regulatory role and mechanism of miR-223-3p in eosinophils degranulation and allergic rhinitis (AR) inflammation. METHODS: OVA sensitized AR mouse model and EOL-1 cells model were established. RT-qPCR and FISH were performed to detect the miR-223-3p expression. ELISA and WB were utilized to evaluate mRNA and protein expression. HE staining and transmission electron microscopy were applied to observe the morphological changes in nasal mucosa. Flow cytometry and immunofluorescence staining were performed to measure the proportion of eosinophils and eosinophilic major basic protein expression. The targeting relationship between miR-223-3p and FBXW7 was verified by bioinformatic analysis and dual-luciferase reporter gene assay. The expression of FBXW7 was detected by immunohistochemistry. RESULTS: The level of miR-223-3p in nasal mucosa was significantly up-regulated in AR group. The expression of miR-223-3p, ECP, MBP, and EPO were increased in EOL-1 cells, further increasing the miR-223-3p level could promote the ECP and EPO mRNA expression. Upregulation of miR-223-3p increased eosinophils granule protein expression, aggravated mucosal destruction and enhanced AR inflammation. Luciferase assay verified miR-223-3p directly target the 3'-UTR of FBXW7. In vitro, overexpression of FBXW7 could reverse the increase in MBP expression caused by the up-regulation of miR-223-3p. In vivo, knockdown of FBXW7 could reverse the down-regulation in granule protein level caused by the down-regulation of miR-223-3p, thereby aggravating AR inflammation. CONCLUSION: Collected evidence elucidated that miR-223-3p could regulate the eosinophil degranulation and enhances the inflammation in AR by targeting FBXW7. The miR-223-3p/FBXW7 axis may provide a novel approach for AR treatment.

Sentiment analysis of hotel online reviews using the BERT model and ERNIE model-Data from China.

The emotion analysis of hotel online reviews is discussed by using the neural network model BERT, which proves that this method can not only help hotel network platforms fully understand customer needs but also help customers find suitable hotels according to their needs and affordability and help hotel recommendations be more intelligent. Therefore, using the pretraining BERT model, a number of emotion analytical experiments were carried out through fine-tuning, and a model with high classification accuracy was obtained by frequently adjusting the parameters during the experiment. The BERT layer was taken as a word vector layer, and the input text sequence was used as the input to the BERT layer for vector transformation. The output vectors of BERT passed through the corresponding neural network and were then classified by the softmax activation function. ERNIE is an enhancement of the BERT layer. Both models can lead to good classification results, but the latter performs better. ERNIE exhibits stronger classification and stability than BERT, which provides a promising research direction for the field of tourism and hotels.

First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC).

BACKGROUND: This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR). METHODS: For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both subcutaneous). For dose expansion, patients with mCRPC received recommended phase 2 dose (RP2D) of PrCa VBIR plus tremelimumab 80 mg and sasanlimab 300 mg; patients with BCR received PrCa VBIR plus tremelimumab 80 mg (Cohort 1B-BCR) or tremelimumab 80 mg plus sasanlimab 130 mg (Cohort 5B-BCR) without androgen deprivation therapy (ADT). The primary endpoint was safety. RESULTS: Ninety-one patients were treated in dose escalation (mCRPC=38) and expansion (BCR=35, mCRPC=18). Overall, treatment-related and immune-related adverse events occurred in 64 (70.3%) and 39 (42.9%) patients, with fatigue (40.7%), influenza-like illness (30.8%), diarrhea (23.1%), and immune-related thyroid dysfunction (19.8%) and rash (15.4%), as the most common. In patients with mCRPC, the objective response rate (ORR, 95% CI) was 5.6% (1.2% to 15.4%) and the median radiographic progression-free survival (rPFS) was 5.6 (3.5 to not estimable) months for all; the ORR was 16.7% (3.6% to 41.4%) and 6-month rPFS rate was 45.5% (24.9% to 64.1%) for those who received RP2D with measurable disease (n=18). 7.4% of patients with mCRPC achieved a ≥50% decline in baseline PSA (PSA-50), with a median duration of 4.6 (1.2-45.2) months. In patients with BCR, 9 (25.7%) achieved PSA-50; the median duration of PSA response was 3.9 (1.9-4.2) and 10.1 (6.9-28.8) months for Cohorts 5B-BCR and 1B-BCR. Overall, antigen specific T-cell response was 88.0% to PSMA, 84.0% to PSA, and 80.0% to PSCA. CONCLUSIONS: PrCa VBIR overall demonstrated safety signals similar to other ICI combination trials; significant side effects were seen in some patients with BCR. It stimulated antigen-specific immunity across all cohorts and resulted in modest antitumor activity in patients with BCR without using ADT. TRIAL REGISTRATION NUMBER: NCT02616185.

A Retrospective Study of the Effect of Metformin on Patients with Metastatic Prostate Cancer.

Introduction: Previous studies demonstrated that metformin could lead to an inhibition of proliferation of cancer cells through a shift from anabolic to catabolic metabolism. In this study, we seek to investigate the effect of metformin in metastatic prostate cancer. Methods: Patients followed at Northwell Health Zuckerberg Cancer Center during 2014-2018 were included if they were diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) or metastatic castration-resistant prostate cancer (mCRPC), with ⩾6 months follow-up with and without metformin treatment. The primary outcomes, 6-month prostate-specific antigen (PSA) response, overall survival (OS), and radiographic progression free survival (rPFS), were evaluated. Results: There were 267 patients included in the final analysis; 196 patients had mHSPC (73.2%) and 71 had mCRPC (26.8%). Within the mHSPC subjects, there was a significant difference in OS between metformin vs nonmetformin groups (148.5 vs 85.6 months; P < .046) in a univariate analysis; patients who took metformin had a significantly longer OS than subjects who did not (median OS: 148.5 vs 86 months; P < .046). There was no significant difference between the 2 groups with respect to either PSA response rate at 6 months or rPFS or OS in patients with mHSPC in both univariate and multivariate analysis. Within the mCRPC subjects, there was no significant difference between metformin and nonmetformin groups with respect to OS (43.3 vs 51.5 months; P < 0.160) or PSA response at 6 months (38.5% vs 57.1%; p < 0.24); however, patients on metformin had a significantly shorter rPFS in both the univariate analysis (7.3 vs 17.4; P < .0002) and in the multivariate analysis (HR = 2.52; 95% CI: 1.24m 5.11; P < .0109). Conclusions: Among patients with mHSPC, use of metformin was not significantly associated with improved OS in the multivariate analysis.