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Background: The biological activity and pharmacological effects of rare ginsenosides have been proven to be superior to those of the major ginsenosides, but they are rarely found in ginseng. Methods: Ginsenoside Rb1 was chemically transformed with the involvement of methanol molecules by a synthesized heterogeneous catalyst 12-HPW@MeSi, which was obtained by the immobilization of 12-phosphotungstic acid on a mesoporous silica framework. High-performance liquid chromatography coupled with mass spectrometry was used to identify the transformation products. Results: A total of 18 transformation products were obtained and identified. Methanol was found to be involved in the formation of 8 products formed by the addition of methanol molecules to the C-24 (25), C-20 (21) or C-20 (22) double bonds of the aglycone. The transformation pathways of ginsenoside Rb1 involved deglycosylation, addition, elimination, cycloaddition, and epimerization reactions. These pathways could be elucidated in terms of the stability of the generated carbenium ion. In addition, 12-HPW@MeSi was able to maintain a 60.5% conversion rate of Rb1 after 5 cycles. Conclusion: Tandem and high-resolution mass spectrometry analysis allowed rapid and accurate identification of the transformation products through the characteristic fragment ions and neutral loss. Rare ginsenosides with methoxyl groups grafted at the C-25 and C-20 positions were obtained for the first time by chemical transformation using the composite catalyst 12-HPW@MeSi, which also enabled cyclic heterogeneous transformation and facile centrifugal separation of ginsenosides. This work provides an efficient and recyclable strategy for the preparation of rare ginsenosides with the involvement of organic molecules.

Volatile organic compounds (VOCs) pose potential hazards to human health and contribute significantly to odor pollution. This study examined VOC emissions from a representative recycled rubber industry, evaluating the occupational health risks for frontline workers in various workshops. Variables such as gender and workshop-specific concentration variations were considered using Monte Carlo simulation methods. Employees in the five production workshops and office areas face noncarcinogenic health risks with hazard indices (HIs) greater than 1, with the rubber compounding phase presenting the highest risk. Acetaldehyde is identified as the primary noncarcinogenic health risk substance, with hazard quotient (HQ) values exceeding 1 in all workshops. Carcinogenic health risks vary by area, with the highest risks found in compounding and refining workshops. Formaldehyde poses the greatest risk in rubber grinding workshops and offices, with cumulative weights exceeding unacceptable levels of M80.58 % and W77.56 % in grinding and M94.98 % and W92.24 % in the office. Male workers face 4–7 % greater noncarcinogenic VOC health risks than females and 5–14 % greater carcinogenic risks from individual VOCs, increasing their susceptibility to health risks caused by VOCs. Additionally, our analysis of odor identification and intensity classification revealed that 53 VOCs are capable of causing odor pollution, with several substances reaching odor levels of 2 or higher. The predominant perceived odors, as reflected in the odor wheel, include categories such as ''solvent/aromatic'' and ''sweet/fruit,'' with aldehydes being the primary odor-causing substances. In summary, emissions of VOCs from rubber industrial processes not only pose substantial health risks to workers but also contribute significantly to odor pollution. Consequently, enterprises must prioritize optimizing workplace conditions to ensure the occupational health and well-being of their employees.

Objectives: SARS-CoV-2 infection could cause persistent lung injury or indicate potential genetic susceptibilities. Although infection-elicited hybrid immunity could protect against severe COVID-19, it remains unknown whether recent infection could reduce pneumonia risk during reinfection due to insufficient viral and chest computed tomography (CT) screening. Methods: A total of 15,598 patients, 96% fully vaccinated and 52% boosted, from Xiangyang, China, who had symptomatic COVID-19 and chest CT scans during the first Omicron BF.7 wave in December 2022 to January 2023, were followed through the second Omicron XBB.1.5 wave between May and August 2023. A total of 17,968 second-wave patients with COVID-19 with chest CT scans but without previous symptomatic COVID-19 were enrolled as first-time infection controls. Results: A total of 19.6% (3,061 of 15,598) first-wave patients were diagnosed with pneumonia. Among second-wave reinfected patients, only 0.2% (four of 2202) developed pneumonia, which was lower than the 1.7% (311 of 17,968) pneumonia prevalence among the second-wave first-time patients, with an adjusted relative risk of 0.11 (95% confidence interval: 0.04-0.29). A total of 1.3% (40 of 3,039) first-wave pneumonia survivors showed residual abnormal patterns in follow-up CT scans within 8 months after pneumonia diagnosis. Conclusions: In a highly vaccinated population, previous symptomatic Omicron infection within 8 months reduced pneumonia risk during reinfection. Uninfected individuals might need up-to-date vaccination to reduce pneumonia risk.

Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100β, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice.

Okara protein (OP) is a potential plant-based protein that is beneficial to human health. In this work, an alternating ultrasonic/alkali treatment method with non-continued cavitation and thermal energy output was used to extract protein (AUA-OP) from okara to enhance the functional properties of OP and improve the stability of OP-based emulsions. The purity of AUA-OP was greater than 80%. Compared with traditional (physical-assisted) alkali treatment, FTIR and SDS-PAGE revealed that AUA-OP retained the chemical structure of the protein, but the number of ultrasound-induced exposure sites increased, with increased fluorescence intensity, surface hydrophobicity, and absolute ζ-potential. After alternating ultrasonic/alkali treatment, the protein particles were looser and smaller. In addition, the water/oil holding capacity, EAI, and ESI of AUA-OP further increased. The viscosity of the AUA-OP-stabilized emulsion was also greater. Finally, a 28-day emulsion storage assay revealed that the AUA-OP-stabilized emulsion was stable with a relatively low droplet size and creaming index, indicating great potential for the development of stable protein-based emulsions.

Study region: Flood formation involves complex nonlinear processes and numerous variables, with data-driven models becoming a key non-engineering approach to flood prevention and mitigation. Yet, single machine learning models are insufficient to fully capture the complex dynamics of the flood process. Study focus: We propose an interpretable flood forecasting hybrid model based on Transformer, LSTM, and Adaptive Random Search Algorithm (AGRS), termed as AGRS-LSTM-Transformer. Investigating the predictive performance of the hybrid model, this study compares it against AGRS-LSTM, AGRS-Transformer, AGRS-BP, and AGRS-MLP models, utilizing flood data from 1971 to 2013 years in the Jingle watershed. New hydrological insights for the region: The AGRS-LSTM-Transformer model demonstrates superior performance over benchmark models, achieving accurate runoff forecasts with a lead time of 1–6 hours. It achieves a Nash-Sutcliffe Efficiency (NSE) greater than 0.905, and root mean squared error (RMSE), mean absolute error (MAE), Bias, and relative error (RE) values for the runoff process below 34.891 m³/s, 25.125 m³/s, 9.537 %, and 8.025 %, respectively. The coupling between the LSTM layers and the Transformer input components plays a crucial role in the architecture of the AGRS-LSTM-Transformer model. Rainfall from stations situated near the main river channel and downstream flow sections exerted a positive influence. Runoff from the preceding moment significantly impacts the predicted flow, with the contribution of runoff inputs exceeding that of rainfall. Inputs nearer to the forecast moment do not invariably improve forecasting accuracy, and historical rainfall and runoff volumes with extended lag times may detrimentally impact the model prediction. The study highlights the potential of hybrid data-driven models in enhancing the accuracy of flood forecasting, offering insights for reducing uncertainty in flood prediction and interpreting machine learning flood forecasting models. This provides a scientific basis for flood early warning systems and water resource management.

Mathematics anxiety (MA) is a widespread phenomenon that affects an individual's learning of mathematics. MA between different genders has been of great interest to researchers. Meta–analysis was used to examine the relationship between MA and gender in Chinese children, along with the influencing factors. After literature search and screening, 83 papers and 91 independent samples met the inclusion criteria. The results of the main effect test of the random effect model revealed a correlation of significant levels between MA and gender, r = −0.131, 95%CI [−0.158, −0.105], Z = –9.508, and p

A mild and eco-friendly protocol has been developed for the preparation of kaolin-decorated Au nanoparticles mediated by Ephedra root extract as a green reducing and stabilizing agents without any toxic substrates. Structural features of the prepared Au NPs/Kaolin were assessed through FE-SEM, TEM, and XRD techniques. TEM images show the good deposition of Au NPs over the surface of extract-modified kaolin without aggregation. Towards the medicinal application, its antioxidant efficacy was assessed by the DPPH method, and the corresponding IC50 value was obtained as 104 μg/mL. Cytotoxicity of the nanoformulated bio-composite was ascertained through MTT analysis against human ovarian carcinoma cells, i.e., PA-1 and SK-OV-3. The IC50 in those studies was 250 and 119 μg/mL against PA-1and SK-OV-3 cells, respectively. In the in vivo design, tamoxifen was used to induce the experimental adenomyosis model in mice. After treatment, the thymus, spleen, uterine, and body weights of all animals were measured. Then, inflammatory factor expression and myometrial infiltration were determined by qRT-PCR, ELISA, and histology examination in the uterus. Western blotting, qRT-PCR, and immune histochemical (IHC) staining were applied to analyze the MAPK/ERK signaling pathway protein expression. Au NPs/Kaolin bio-nanocomposite ameliorated the adenomyosis symptoms by raising the thymus and spleen index and decreasing the myometrial infiltration. The raised levels of TNF-α, IL-6, and IL-1β in adenomyosis model mice uterus and serum were also reduced after Au NPs/Kaolin bio-nanocomposite treatment. The adenomyosis amelioration of Au NPs/Kaolin bio-nanocomposite was gained by preventing the MAPK/ERK signaling pathway, including decreasing the expressions of protein and mRNA of p-p38/p38, p-JNK/JNK, and p-ERK/ERK.

Sorsby fundus dystrophy (SFD) is a rare autosomal dominant disorder with macular dystrophy and severe visual loss. Mutations in TIMP3 gene has been related to SFD with mechanisms unclear. We have successfully reprogrammed the peripheral blood mononuclear cells (PBMCs) from an SFD patient carrying c.484G>A mutation in TIMP3 gene to induced pluripotent stem cells (iPSCs) and characterized their pluripotency and genetic stability. This line may serve as a useful tool to explore the role of TIMP3 in SFD pathogenesis.

Background: The clinical characteristics and risk factors of all-cause mortality in young hospitalized patients with comorbid coronary heart disease and hypertension (CAD + HT) are not well-characterized. Method: A total of 2288 hospitalized CAD patients (age

Diabetic cardiomyopathy (DCM) is a metabolic disease and a leading cause of heart failure among people with diabetes. Mass spectrometry imaging (MSI) is a versatile technique capable of combining the molecular specificity of mass spectrometry (MS) with the spatial information of imaging. In this study, we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity. We optimized the air flow-assisted desorption electrospray ionization (AFADESI)-MSI platform to detect a wide range of metabolites, and then used matrix-assisted laser desorption ionization (MALDI)-MSI for increasing metabolic coverage and improving localization resolution. AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections, respectively, while MALDI-MSI detected 61 metabolites in negative analysis. Our study revealed the heterogenous metabolic profile of the heart in a DCM model, with over 105 region-specific changes in the levels of a wide range of metabolite classes, including carbohydrates, amino acids, nucleotides, and their derivatives, fatty acids, glycerol phospholipids, carnitines, and metal ions. The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model. Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.

The primary focus of this study was on exploring the optical soliton solutions and chaotic patterns in magneto-optic waveguides through the coupled stochastic Schrödinger–Hirota equation with multiplicative white noise. Firstly, by means of traveling wave transformations and homogeneous balance principle, the coupled stochastic Schrödinger–Hirota equation in magneto-optic waveguides is transformed into ordinary differential equation. By selecting some suitable parameters, phase diagrams are plotted with the help of the mathematical software Maple. Secondly, the optical soliton solutions of the coupled stochastic Schrödinger–Hirota equation corresponding to phase orbits can be easily deduced through the method of dynamical systems. In addition, chaotic behavior for the coupled stochastic Schrödinger–Hirota system with perturbation term has been discussed in detail. Finally, the two-dimensional and three-dimensional graphs of the stochastic Schrödinger–Hirota equation are drawn, which further explain the propagation of the coupled stochastic Schrödinger–Hirota equation in nonlinear optics.

Dihydroartemisinin (DHA) exerts an anti-tumor effect in multiple cancers, however, the molecular mechanism of DHA and whether DHA facilitates the anti-tumor efficacy of cisplatin in non-small cell lung cancer (NSCLC) are unclear. Here, we found that DHA potentiated the anti-tumor effects of cisplatin in NSCLC cells by stimulating reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, C-Jun-amino-terminal kinase (JNK) and p38 MAPK signaling pathways both in vitro and in vivo. Of note, we demonstrated for the first time that DHA inhibits prostaglandin G/H synthase 1 (PTGS1) expression, resulting in enhanced ROS production. Importantly, silencing PTGS1 sensitized DHA-induced cell death by increasing ROS production and activating ER-stress, JNK and p38 MAPK signaling pathways. In summary, our findings provided new experimental basis and therapeutic prospect for the combined therapy with DHA and cisplatin in some NSCLC patients.

Retinitis pigmentosa (RP) is the most common inherited retinal diseases, characterized by photoreceptor cell death and retinal pigment epithelial atrophy. Mutations in cyclic nucleotide gated channel subunit alpha 1 (CNGA1) have been reported to cause retinitis pigmentosa. Here, we established the human induced pluripotent stem cell line (iPSC) SJTUGHi002-A, generated from peripheral blood mononuclear cells of a 36-year-old male RP patient, who carried a homozygous frameshift variant in CNGA1 gene (c.265delC; p.L89Ffs*4). The cell line can serve as a patient-derived disease model for exploring the pathogenesis and drug development of CNGA1-RP.

The concept of sepsis has recently evolved from one of a ‘systemic inflammatory response syndrome caused by infection’ to a ‘severe, potentially fatal organic dysfunction caused by an inadequate or imbalanced host response to infection’. Organ dysfunction is closely related to sepsis. Multiple organ dysfunction syndrome (MODS) is the most serious outcome of sepsis, often leading to a poor prognosis. However, specific drugs for sepsis and MODS caused by sepsis remain undetermined, and the fatality rate is relatively high. Under the guidance of modern medicine, traditional Chinese medicine (TCM) has gained a wealth of experience in the prevention and treatment of sepsis and plays a key role via the effects of its numerous components, pathways and targets. This study used ‘Sepsis’, ‘Organ dysfunction’ and ‘Traditional Chinese medicine’ as strategies for searching the databases of Chinese National Knowledge Infrastructure, Wanfang, PubMed and The Web of Science. This paper presents an overview of the current status of TCM component formulations for preventing and treating sepsis with MODS to provide a theoretical basis for clinical treatment and drug development.

Microglia-mediated chronic neuroinflammation has been associated with cognitive decline induced by rotenone, a well-known neurotoxic pesticide used in agriculture. However, the mechanisms remain unclear. This work aimed to elucidate the role of complement receptor 3 (CR3), a highly expressed receptor in microglia, in cognitive deficits induced by rotenone. Rotenone up-regulated the expression of CR3 in the hippocampus and cortex area of mice. CR3 deficiency markedly ameliorated rotenone-induced cognitive impairments, neurodegeneration and phosphorylation (Ser129) of α-synuclein in mice. CR3 deficiency also attenuated rotenone-stimulated microglial M1 activation. In microglial cells, siRNA-mediated knockdown of CR3 impeded, while CR3 activation induced by LL-37 exacerbated, rotenone-induced microglial M1 activation. Mechanistically, CR3 deficiency blocked rotenone-induced activation of nuclear factor κB (NF-κB), signal transducer and activator of transcription 1 (STAT1) and STAT3 signaling pathways. Pharmacological inhibition of NF-κB or STAT3 but not STAT1 was confirmed to suppress microglial M1 activation elicited by rotenone. Further study revealed that CR3 deficiency or knockdown also reduced rotenone-induced expression of C3, an A1 astrocyte marker, and production of microglial C1q, TNFα and IL-1α, a cocktail for activated microglia to induce neurotoxic A1 astrocytes, via NF-κB and STAT3 pathways. Finally, a small molecule modulator of CR3 efficiently mitigated rotenone-elicited cognitive deficits in mice even administered after the establishment of cognitive dysfunction. Taken together, our findings demonstrated that CR3 is a key factor in mediating neurotoxic glial activation and subsequent cognitive impairments in rotenone-treated mice, giving novel insights into the immunopathogenesis of cognitive impairments in pesticide-related Parkinsonism.

Lung cancer is one of the leading causes of cancer-related death. Most advanced lung adenocarcinoma (LUAD) patients have poor survival because of drug resistance and relapse. Neglecting intratumoral heterogeneity might be one of the reasons for treatment insensitivity, while single-cell RNA sequencing (scRNA-seq) technologies can provide transcriptome information at the single-cell level. Herein, we combined scRNA-seq and bulk RNA-seq data of LUAD and identified a novel cluster of malignant epithelial cells - KRT81+ malignant epithelial cells - associated with worse prognoses. Further analysis revealed that the hypoxia and EMT pathways of these cells were activated to predispose them to differentiate into metastatic lung adenocarcinoma cells. Finally, we also studied the role of these tumor cells in the immune microenvironment and their role in the classification and prognosis prediction of lung adenocarcinoma patients.

Metasurfaces have emerged as crucial materials for optical information encryption and storage, lauded for their ease of operation and high programmability. However, the inherent inflexibility following metasurface fabrication leaves room for improvement in terms of information storage capacity. Incorporating multiplexed channels in metasurface boasts independent coding degrees of freedom, which bolsters the utility of metasurfaces for optical information storage and encryption. Most multiplexed metasurfaces conventionally rely on optical variables that can be controlled, such as wavelength, orbital angular momentum (OAM), forward/backward incidence of light, and polarization state, etc. However, there has been limited attention given to the inherent spatial properties of metasurfaces, let alone to combine these spatial properties with optical variables for multiplexing. To address this gap, we proposes a combined approach to develop a nanoprinting and meta-holography metasurface, which harnesses both metasurface-space and angular multiplexing to store seven independent holographic and nanoprinted images. This work not only unlocks new avenues for advanced optical information storage and encryption, but also pushes the boundaries of metasurface technology.

The stochastic coupled nonlinear Schrödinger systems are very important equations which can be wildly used in the fields of the optical-fiber communications, nonlinear optics, plasma physics, ecological system, statistical mechanics and so on. This work mainly focuses on dynamical behavior, phase portraits, chaotic behavior and multiple optical solitons for the (2+1)-dimensional stochastic coupled nonlinear Schrödinger system with multiplicative white noise. Here, we analytically deduced bright solitons, dark solitons and periodic solutions through the bifurcation theory. Additionally, some other bounded traveling wave solutions which include Jacobi elliptic function solutions, trigonometric function solutions, rational function solutions, hyperbolic function solutions and solitary wave solutions are also obtained by using the symbolic computation as well as the complete discriminant system method. It is worth noting that we give the classification of all single traveling wave solutions at the same time. Finally, in order to further explore the propagation of the (2+1)-dimensional stochastic coupled nonlinear Schrödinger system in nonlinear optics, three-dimensional, two-dimensional, density graphs and contour graphs are also given.

Background & Aims: Metabolic reprogramming is recognized as a cancer hallmark intimately linked to tumor hypoxia, which supports rapid tumor growth and mitigates the consequential oxidative stress. Phosphofructokinase-fructose bisphosphatase (PFKFB) is a family of bidirectional glycolytic enzymes possessing both kinase and phosphatase functions and has emerged as important oncogene in multiple types of cancer. However, its clinical relevance, functional significance, and underlying mechanistic insights in hepatocellular carcinoma (HCC), the primary malignancy that develops in the most important metabolic organ, has never been addressed. Methods: PFKFB4 expression was examined by RNA sequencing in The Cancer Genome Atlas and our in-house HCC cohort. The up-regulation of PFKFB4 expression was confirmed further by quantitative polymerase chain reaction in an expanded hepatitis B virus–associated HCC cohort followed by clinicopathologic correlation analysis. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated PFKFB4 knockout cells were generated for functional characterization in vivo, targeted metabolomic profiling, as well as RNA sequencing analysis to comprehensively examine the impact of PFKFB4 loss in HCC. Results: PFKFB4 expression was up-regulated significantly in HCC and correlated positively with TP53 and TSC2 loss-of-function mutations. In silico transcriptome-based analysis further revealed PFKFB4 functions as a critical hypoxia-inducible gene. Clinically, PFKFB4 up-regulation was associated with more aggressive tumor behavior. Functionally, CRISPR/Cas9-mediated PFKFB4 knockout significantly impaired in vivo HCC development. Targeted metabolomic profiling revealed that PFKFB4 functions as a phosphatase in HCC and its ablation caused an accumulation of metabolites in downstream glycolysis and the pentose phosphate pathway. In addition, PFKFB4 loss induced hypoxia-responsive genes in glycolysis and reactive oxygen species detoxification. Conversely, ectopic PFKFB4 expression conferred sorafenib resistance. Conclusions: PFKFB4 up-regulation supports HCC development and shows therapeutic implications.

In recent years, large-scale and high-density operations have caused a dramatic increase in the energy consumption of metro systems. For overcrowded metro systems, the original energy-optimized timetable is no longer optimal after unexpected dwell disturbances occur. In this paper, we propose an actor–critic deep reinforcement learning (ACDRL) approach for solving the energy-aimed train schedule rescheduling (ETTR) problem in a real-time and energy-efficient manner. The proposed ACDRL approach can reduce metro systems’ net traction energy consumption by rearranging trains in millisecond time after the occurrence of unpredictable dwell disturbances. The simulation experimental results show that the average response time of ACDRL under unpredictable disturbances is only 0.0009 s and 0.0016 s in two-train and five-train metro systems, which can save energy by 4.73% and 6.95% on average, respectively. This means that a lot of energy can be saved.

Background: Allergen immunotherapy is the only etiological treatment for allergic rhinitis. Objective: To analyze the efficacy, safety, and mechanism of subcutaneous immunotherapy (SCIT). Methods: The efficacy, safety, and serum immunological changes of 3 modes of subcutaneous immunotherapy were compared. Peripheral blood mononuclear cells (PBMC) transcriptome changes were obtained on the Illumina sequencing platforms. We confirmed differentially expressed genes (DEGs) by quantitative real-time polymerase chain reaction (PCR). The DEGs were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks. The correlation between the common DEGs and clinical indicators was analyzed by Origin 2022. Results: The 3 SCITs were all effective after 1 year. The Combined Symptom and Medication Score (CSMS) and Visual Analog Score (VAS) in rush immunotherapy (RIT) are lowest after 24 and 48 weeks of treatment among the 3 groups. After treatment, the levels of sIgE, sIgE/tIgE, Th2 cytokines, Th17 cytokines, and percentage of peripheral eosinophils (EOS%) decreased significantly (P＜0.05), while the levels of Th1 type cytokines did not change significantly. Transcriptome analysis identified 24, 24, and 91 DEGs at W3 and 42, 52, 175 DEGs at W7 in conventional immunotherapy (CIT), cluster immunotherapy (CLIT), and RIT groups, respectively. The pathways and functions involved in SCIT include secretion of Th1/2 cytokines, immune cell differentiation. Unlike CIT and CLIT, DEGs are also involved in T cell tolerance induction, T cell anergy, and lymphocyte anergy in RIT. CXCR1, CXCR2, and IER3 had a specific effect on reflecting the improvement of symptoms in allergic rhinitis patients with SCIT. Conclusion: The clinical efficacy of RIT appeared earlier than CIT and CLIT. Clinicians can use the highly conserved gene expression profile to evaluate responses to immunotherapy.

Cyclin D dependent kinase 4 and 6 (CDK 4/6) inhibitors are novel anticancer drugs used in therapeutic combinations with endocrine therapy for breast cancer treatment. Their determination in patient plasma is of high interest as a prerequisite for possible therapeutic drug monitoring. Dispersive liquid-liquid microextraction (DLLME) shows great potential in bioanalytical sample preparation. Its simplicity and speed, along with the suitability for using small amounts of sample and hazardous solvents are some of its main advantages. However, its application on plasma samples is scarce and requires further development. The aim of this work was to explore the applicability of DLLME in the simultaneous extraction of six drugs of interest from human plasma, with an emphasis placed on achieving high extraction recoveries with low sample and solvent consumption. To tackle the low availability and amount of the plasma sample, as well as the complexity of the biological matrix, three novel DLLME modes are proposed: organic sample DLLME (OrS-DLLME), aqueous sample DLLME (AqS-DLLME), and a modified air-assisted DLLME (AA-DLLME). The extractant and disperser type and volume, volume ratios of all the components in the ternary system, effect of pH and salting out were optimised for all three proposed modes of DLLME. Optimised representative DLLME-HPLC-DAD-FLD method was validated and shown to be linear (R > 0.994), precise (RSD ≤13.8%, interday), accurate (bias −13.1–13.1%, interday) and robust (relative effect −3.34–6.08%). Simultaneous extraction of all six drugs with high recoveries (81.65–95.58%) was achieved. Sample volumes used were as low as 50–100 μL, with necessary organic solvent volumes in μL ranges. Greenness scores obtained using the AGREE software were between 0.63 and 0.66, demonstrating compliance with green analytical chemistry principles. Finally, the validated method was successfully applied on breast cancer patient plasma samples.

Background: Ovarian serous cystadenocarcinoma (OSC) is the most prevalent histological subtype of ovarian cancer (OV) and presents a serious threat to women's health. Anoikis is an essential component of metastasis, and tumor cells can get beyond it to become viable. The impact of anoikis on OSC, however, has only been the topic of a few studies. Methods: The mRNA sequencing and clinical information of OSC came from The Cancer Genome Atlas Target Genotype-Tissue Expression (TCGA TARGET GTEx) dataset. Anoikis-related genes (ARGs) were collected by Harmonizome and GeneCards websites. Centered on these ARGs, we used unsupervised consensus clustering to explore potential tumor typing and filtered hub ARGs to create a model of predictive signature for OSC patients. Furthermore, we presented clinical specialists with a novel nomogram based on ARGs, revealing the underlying clinical relevance of this signature. Finally, we explored the immune microenvironment among various risk groups. Results: We identified 24 ARGs associated with the prognosis of OSC and classified OSC patients into three subtypes, and the subtype with the best prognosis was more enriched in immune-related pathways. Seven ARGs (ARHGEF7, NOTCH4, CASP2, SKP2, PAK4, LCK, CCDC80) were chosen to establish a risk model and a nomogram that can provide practical clinical decision support. Risk scores were found to be an independent and significant prognostic factor in OSC patients. The CIBERSORTx result revealed an inflammatory microenvironment is different for risk groups, and the proportion of immune infiltrates of Macrophages M1 is negatively correlated with risk score (rs = −0.21, P

In this paper, the stochastic Schrödinger–Hirota equation in birefringent fibers with spatiotemporal dispersion and parabolic law nonlinearity is studied, which is usually used to describe the mathematical model of optical soliton propagation in dispersive optical fibers from the field of nonlinear optics. Firstly, the stochastic Schrödinger–Hirota equation is converted into two-dimensional planar dynamic system by using the traveling wave transformation. Secondly, the qualitative analysis of the stochastic Schrödinger–Hirota equation is discussed by using the theory of planar dynamical systems. Finally, the chaos pattern of the stochastic Schrödinger–Hirota equation with perturbed system is considered. What is more, phase portraits and sensitivity analysis of the perturbed system are plotted by using the Maple software.

Plant MYB transcription factors (TFs) play crucial roles in regulating the biosynthesis of flavonoids but current analysis on their role in Zanthoxylum bungeanum Maxim. (ZBM) is far from comprehensive. In this study, we identified 270 MYB genes in ZBM and divided them into four subfamilies. The R2R3-MYB (ZbMYB) category contained 251 genes and was classified into 33 subfamilies according to their phylogenetic results and sequence similarity. These subfamilies included 24 subgroups containing both MYBs of ZBM plants and AtMYBs, and nine subgroups containing only ZBM MYBs or AtMYBs. ZbMYBs with similar functions clustered into the same subgroup, indicating functional conservation. The subcellular localization analysis predicted that most ZbMYB genes were found in the nucleus. The transposed duplications appeared to play a major role in the expansion of the MYB gene family in ZBM. Through phylogenetic analysis and transcriptome profiling, it was found that 28 ZbMYB genes may regulate the biosynthesis of flavonoids in ZBM, and these genes expression presented distinct temporal and spatial expression patterns. In different fruit development stages of ZBM, the expression patterns of EVM0042160 and EVM0033809 genes obtained by qRT-PCR analysis are very similar to the flavonoid and anthocyanin content curves in ZBM. Further correlation analysis showed that the content of flavonoids in different fruit development stages and the transcript abundance levels of 28 ZbMYB genes have different degrees of correlation relationship. These results indicated that the ZbMYB genes might be involved in the flavonoid metabolic pathway. This comprehensive and systematic analysis of MYB family genes provided a solid foundation for further functional analysis of MYB TFs in ZBM.

Influences of Glycyrrhetinic acid on expression of inflammatory factors in interleukin (IL)-1β-induced SW982 cells and its anti-inflammatory effects were discussed in this study. MTT results showed that Glycyrrhetinic acid (≤80 μmol·L−1) almost has no toxicity on SW982 cells. The results of ELISA and real-time PCR showed that Glycyrrhetinic acid (10, 20 and 40 μmol · L-1) can significantly inhibit the expression of inflammatory factors such as IL-6, IL-8 and matrix metalloproteinase-1 (MMP-1). Western blot analysis showed that Glycyrrhetinic acid remarkably blocked the NF-κB signaling pathway in vitro. Molecule docking showed that Glycyrrhetinic acid could bind to the active site (NLS Polypeptide) of NF-κB p65. Furthermore, observation of rat foot swelling proved that Glycyrrhetinic acid had a significant therapeutic effect on adjuvant-induced arthritis (AIA) in rats in vivo. Collectively, all these findings suggested that Glycyrrhetinic acid might be a promising lead compound worthy of further pursuit as anti-inflammation agent.

Lung cancer is one of the most commonly diagnosed cancers worldwide. Although cisplatin-based chemotherapy regimens serve a pivotal role in non-small cell lung cancer (NSCLC) treatment, drug resistance and serious side effects limited its further clinical application. Regorafenib, a small-molecule multi-kinase inhibitor, was demonstrated to have promising anti-tumor activity in various solid tumors. In the present study, we found that regorafenib markedly enhanced cisplatin-induced cytotoxicity in lung cancer cells by activating reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ER Stress), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Regorafenib increased ROS generation by promoting NADPH oxidase 5 (NOX5) expression, and knocking down NOX5 attenuated ROS-mediated cytotoxicity of regorafenib in lung cancer cells. Additionally, mice xenograft model validated that synergistic anti-tumor effects of combined treatment with regorafenib and cisplatin. Our results suggested that combination therapy with regorafenib and cisplatin may serve as a potential therapeutic strategy for some NSCLC patients.