Highly sensitive antibiotic sensing based on optical weak value amplification: A case study of chloramphenicol.

The public health concern of antibiotic residues in animal-origin food has been a long-standing issue. In this work, we present a novel method for antibiotic detection, leveraging optical weak value amplification and harnessing an indirect competitive inhibition assay, which significantly boosts the system's sensitivity in identifying small molecule antibiotics. We chose chloramphenicol as a model compound and mixed it with chloramphenicol-bovine serum albumin conjugates to bind to the chloramphenicol antibody competitively. We achieved a broad linear detection range of up to 3.24 ng/mL and a high concentration resolution of 33.20 pg/mL. To further validate the universality of our proposed detection methodology, we successfully applied it to testing gibberellin and tetracycline. Moreover, we conducted regeneration experiments and real-sample correlation studies. This study introduces a novel strategy for the label-free optical sensing of small molecule antibiotics, greatly expanding the range of applications for sensors utilizing optical weak value amplification.

MRI Assessment of Diastolic Dysfunction in People Living With the Human Immunodeficiency Virus: Correlation With Markers of Disease Activity.

BACKGROUND: Despite the advent of combination antiretroviral therapy, people living with human immunodeficiency virus (PLWH) are at an increased risk for cardiac disease. PURPOSE: To explore the presence and extent of diastolic atrial and left ventricular dysfunction in PLWH using cardiac MRI in correlation with clinical markers of disease activity. STUDY TYPE: Prospective. POPULATION: A total of 163 participants comprising 101 HIV-infected individuals (age: 52 years [42-62 years]; 92% male) and 62 age- and sex-matched healthy volunteers (age: 51 years [30-72 years]; 85% male). FIELD STRENGTH/SEQUENCE: 3.0 T, cardiac MRI including balanced steady-state free precession (SSFP) for the short-axis, two-, three-, and four-chamber views were performed. ASSESSMENT: Assessment of cardiac function and strain analysis were accomplished by CVI42 software. Blood samples for CD4+ T cells and cardiac risk factors were also collected before MRI. STATISTICAL TESTS: Independent t tests, Mann-Whitney U test, Pearson's correlation analysis, and multivariate linear analyses (significance level: P < 0.05). RESULTS: PLWH had a significantly larger left atrial volume maximum index (LAVImax: 32.6 ± 8.7 vs. 28.7 ± 8.1 mL/m2), minimum (LAVImin: 14.8 ± 5.5 vs. 11.5 ± 5.4 mL/m2,), and prior to atrial contraction (LAVIpre-a: 23.4 ± 6.7 vs. 19.7 ± 7.2 mL/m2) as compared to healthy volunteers. The LA reservoir (LAtEF: 55.0 ± 10.2 vs. 61.4 ± 10.4; Sls: 29.0 ± 8.1 vs. 33.8 ± 11.8), conduit (LApEF: 28.4 ± 8.2 vs. 32.3 ± 11.3, P = 0.01; Sle: 16.3 ± 6.5 vs. 18.9 ± 8.2), and booster pump function (LAaEF: 37.4 ± 12.4 vs. 42.7 ± 13.1, P = 0.01, Sla: 12.7 ± 5.1 vs. 14.9 ± 5.7) were all significant impaired in PLWH. Global circumferential left ventricular diastolic strain rate (LVGCS-d) was significantly lower in the HIV patients. Multivariate analysis results showed that Nadir CD4+ T cells had a significant adverse association with LVGCS-d (ß = 0.51). CONCLUSION: LA structure abnormalities and LV diastolic dysfunction were manifested in PLWH, with Nadir CD4+ T cell counts potentially serving as a risk factor for early cardiac diastolic dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Lasso-Cox interpretable model of AFP-negative hepatocellular carcinoma.

BACKGROUND: In AFP-negative hepatocellular carcinoma patients, markers for predicting tumor progression or prognosis are limited. Therefore, our objective is to establish an optimal predicet model for this subset of patients, utilizing interpretable methods to enhance the accuracy of HCC prognosis prediction. METHODS: We recruited a total of 508 AFP-negative HCC patients in this study, modeling with randomly divided training set and validated with validation set. At the same time, 86 patients treated in different time periods were used as internal validation. After comparing the cox model with the random forest model based on Lasso regression, we have chosen the former to build our model. This model has been interpreted with SHAP values and validated using ROC, DCA. Additionally, we have reconfirmed the model's effectiveness by employing an internal validation set of independent periods. Subsequently, we have established a risk stratification system. RESULTS: The AUC values of the Lasso-Cox model at 1, 2, and 3 years were 0.807, 0.846, and 0.803, and the AUC values of the Lasso-RSF model at 1, 2, and 3 years were 0.783, 0.829, and 0.776. Lasso-Cox model was finally used to predict the prognosis of AFP-negative HCC patients in this study. And BCLC stage, gamma-glutamyl transferase (GGT), diameter of tumor, lung metastases (LM), albumin (ALB), alkaline phosphatase (ALP), and the number of tumors were included in the model. The validation set and the separate internal validation set both indicate that the model is stable and accurate. Using risk factors to establish risk stratification, we observed that the survival time of the low-risk group, the middle-risk group, and the high-risk group decreased gradually, with significant differences among the three groups. CONCLUSION: The Lasso-Cox model based on AFP-negative HCC showed good predictive performance for liver cancer. SHAP explained the model for further clinical application.

Knowledge Mapping of Macrophages in Osteoporosis: A Bibliometric Analysis (1999-2023).

BACKGROUND: Osteoporosis is a common metabolic disorder that significantly impacts quality of life in the elderly population. Macrophages play a crucial role in the development of osteoporosis by regulating bone metabolism through cytokine secretion. However, there is a lack of scholarly literature in the field of bibliometrics on this topic. OBJECTIVE: This study provides a detailed analysis of the research focus and knowledge structure of macrophage studies in osteoporosis using bibliometrics. METHODS: The scientific literature on macrophage research in the context of osteoporosis, retrieved from the Web of Science Core Collection (WoSCC) database spanning from January 1999 to December 2023, has been incorporated for bibliometric examination. The data is methodically analyzed and visually represented using analytical and visualization tools including VOSviewer, CiteSpace, Scimago Graphica, the Bibliometrix R package, and Pajek. RESULTS AND CONCLUSIONS: In the last quarter-century, there has been a consistent rise in the quantity of scholarly publications focusing on the relationship between macrophages and osteoporosis, resulting in a total of 1499 research documents. These studies have originated from 45 different countries, with China, South Korea, and the United States being the most prominent contributors, and the United States having the highest frequency of citations. Noteworthy research institutions involved in this field include Shanghai Jiao Tong University, Wonkwang University, Huazhong University of Science and Technology, and Seoul National University. The Journal of Bone and Mineral Research is widely regarded as the premier and most frequently referenced publication in the field. These publications involve the collaboration of 8744 authors, with Lee Myeung Su contributing the most articles, and Takayanagi being the most co-cited author. Key emerging research focal points are encapsulated in keywords such as "mTOR," "BMSCs," "bone regeneration," and "exosome." The relationships between exosome from macrophage sources and those from BMSCs, along with the regulatory role of the mTOR signaling pathway on macrophages, represent crucial directions for future development in this field. This study represents the inaugural comprehensive bibliometric analysis detailing trends and advancements in macrophage research within the osteoporosis domain. It delineates recent frontiers and hotspots, providing valuable insights for researchers in this particular area of study.

A novel member of miR169 family negatively regulates maize resistance against Bipolaris maydis.

MicroRNAs (miRNAs) have been confirmed to play important roles in plant defense response. However, the key maize miRNAs involved in the defense response against Bipolaris maydis are very limited. In this study, a novel member of the miR169 family in response to B. maydis, named zma-miR169s, was discovered and investigated. The expression levels of pre-miR169s and zma-miR169s were significantly repressed during B. maydis infection. CRISPR/Cas9-induced zma-miR169s mutant exhibited more resistance against B. maydis, whereas overexpression zma-miR169s enhanced susceptibility, supporting that zma-miR169s might play a negative role in maize resistance. Moreover, RNA-seq and GO analysis showed that differentially expressed genes were highly enriched in the oxidation-reduction process and plant hormone pathway. Hence, reactive oxygen species (ROS) and plant hormone levels were further investigated. ROS detection confirmed that zma-miR169s mutant accumulated more ROS, while less ROS was detected in transgenic maize OE-miR169s. Furthermore, more remarkable changes in PR-1 expression levels and salicylic acid (SA) contents were detected in zma-miR169s mutant compared to wild-type and transgenic maize during B. maydis infection. Additionally, nuclear transcription factors (NF-YA1 and NF-YA13) were identified as targets regulated by zma-miR169s through the agrobacterium-mediated transient expression method. Overexpression of ZmNF-YA13 enhanced Arabidopsis resistance to Pseudomonas syringae pv. tomato DC3000. Taken together, our results suggest that zma-miR169s negatively regulate maize defense responses by influencing ROS accumulation and the SA-dependent signaling pathway.

Effects of edge disorder on the stability of quantum oscillations in two-dimensional coupled systems.

This paper utilizes the theory of quantum diffusion to analyze the electron probability and spreading width of a wavepacket on each layer in a two-dimensional (2D) coupled system with edge disorder, aiming to clarify the effects of edge disorder on the stability of the electron periodic oscillations in 2D coupled systems. Using coupled 2D square lattices with edge disorder as an example, we show that, the electron probability and wavepacket spreading width exhibit periodic oscillations and damped oscillations, respectively, before and after the wavepacket reaches the boundary. Furthermore, these electron oscillations exhibit strong resistance against disorder perturbation with a longer decay time in the regime of large disorder, due to the combined influences of ordered and disordered site energies in the central and edge regions. Finally, we numerically verified the universality of the results through bilayer graphene, demonstrating that this anomalous quantum oscillatory behavior is independent of lattice geometry. Our findings are helpful in designing relevant quantum devices and understanding the influence of edge disorder on the stability of electron periodic oscillations in 2D coupled systems.

Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in adolescents and young adults (15-39 years): an analysis based on the global burden of disease study 2021.

BACKGROUND: Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. METHODS: Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15-39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). RESULT: In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. CONCLUSION: ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population.

CREB3 suppresses hepatocellular carcinoma progression by depressing AKT signaling through competitively binding with insulin receptor and transcriptionally activating RNA-binding motif protein 38.

cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA-binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.

Genome-wide Characterization of Small Secreted Peptides in Nicotiana tabacum and Functional Assessment of NtLTP25 in Plant Immunity.

Small secreted peptides (SSPs), serving as signaling molecules for intercellular communication, play significant regulatory roles in plant growth, development, pathogen immunity, and responses to abiotic stress. Despite several SSPs, such as PIP, PSK, and PSY having been identified to participate in plant immunity, the majority of SSPs remain understudied, necessitating the exploration and identification of SSPs regulating plant immunity from vast genomic resources. Here we systematically characterized 756 putative SSPs across the genome of Nicotiana tabacum. 173 SSPs were further annotated as established SSPs, such as nsLTP, CAPE, and CEP. Furthermore, we detected the expression of 484 putative SSP genes in five tissues, with 83 SSPs displaying tissue-specific expression. Transcriptomic analysis of tobacco roots under plant defense hormones revealed that 46 SSPs exhibited specific responsiveness to salicylic acid (SA), and such response was antagonistically regulated by methyl jasmonate. It's worth noting that among these 46 SSPs, 16 members belong to nsLTP family, and one of them, NtLTP25, was discovered to enhance tobacco's resistance against Phytophthora nicotianae. Overexpression of NtLTP25 in tobacco enhanced the expression of ICS1, subsequently stimulating the biosynthesis of SA and the expression of NPR1 and pathogenesis-related genes. Concurrently, NtLTP25 overexpression activated genes associated with ROS scavenging, consequently mitigating the accumulation of ROS during the subsequent phases of pathogenesis. These discoveries indicate that these 46 SSPs, especially the 16 nsLTPs, might have a vital role in governing plant immunity that relies on SA signaling. This offers a valuable source for pinpointing SSPs involved in regulating plant immunity.

[Evolution Trend of Water Quality in the Inner Mongolia Section of the Yellow River from 2003 to 2020].

The aim of this study was to comprehensively understand the water environment quality status and its change trend in the Inner Mongolia section of the Yellow River Basin. To analyze the water quality in recent years,the water quality data in the Yellow River basin from 2003 to 2020 were firstly collected from five typical monitoring stations．Various data analysis methods, including principal component analysis, cluster analysis, and a long short-term memory model, were used along with an improved comprehensive water quality identification index to explore the spatiotemporal characteristics of water quality in the Yellow River Basin. The results showed that the overall water quality in the basin has improved and stabilized over time. In terms of temporal variation, there was a distinction between the wet season and dry season, with a better status observed during the wet season due to increased agricultural irrigation and higher water volume. Spatially, the five monitoring sections could be divided into three categories based on strong natural factors that maintained their temporal characteristics during the wet season； however, significant differences were observed during the dry season due to urban water usage patterns. Analysis using LSTM models revealed that ammonia nitrogen will continue to decline and have a decreasing impact on the comprehensive water quality. These findings provide valuable insights for the comprehensive management of water quality in Inner Mongolia's Yellow River Basin.

Long-term Trends of Dissolved Organic Carbon Dynamics in a Subtropical Forest Responding to Environmental Changes.

Dissolved organic carbon (DOC) dynamics are critical to carbon cycling in forest ecosystems and sensitive to global change. Our study, spanning from 2001 to 2020 in a headwater catchment in subtropical China, analyzed DOC and water chemistry of throughfall, litter leachate, soil waters at various depths, and streamwater. We focused on DOC transport through hydrological pathways and assessed the long-term trends in DOC dynamics amidst environmental and climatic changes. Our results showed that the annual DOC deposition via throughfall and stream outflow was 14.2 ± 2.2 and 1.87 ± 0.83 g C m-2 year-1, respectively. Notably, there was a long-term declining trend in DOC deposition via throughfall (-0.195 mg C L-1 year-1), attributed to reduced organic carbon emissions from clean air actions. Conversely, DOC concentrations in soil waters and stream waters showed increasing trends, primarily due to mitigated acid deposition. Moreover, elevated temperature and precipitation could partly explain the long-term rise in DOC leaching. These trends in DOC dynamics have significant implications for the stability of carbon sink in terrestrial, aquatic, and even oceanic ecosystems at regional scales.

Design, synthesis and biological evaluation of piperine derivatives as potent antitumor agents.

A series of piperine derivatives were designed and successfully synthesized. The antitumor activities of these compounds against 293 T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines, were assessed through the MTT assay. Notably, compound H7 exhibited moderate activity, displaying reduced toxicity towards non-tumor 293 T cells while potently enhancing the antiproliferative effects in Hela and MDA-MB-231 cells. The IC50 values were determined to be 147.45 ± 6.05 µM, 11.86 ± 0.32 µM, and 10.50 ± 3.74 µM for the respective cell lines. In subsequent mechanistic investigations, compound H7 demonstrated a dose-dependent inhibition of clone formation, migration, and adhesion in Hela cells. At a concentration of 15 µM, its inhibitory effect on Hela cell function surpassed that of both piperine and 5-Fu. Furthermore, compound H7 exhibited promising antitumor activity in vivo, as evidenced by significant inhibition of tumor angiogenesis and reduction in tumor weight in a chicken embryo model. These findings provide a valuable scientific foundation for the development of novel and efficacious antitumor agents, particularly highlighting the potential of compound H7 as a therapeutic candidate for cervical cancer and breast cancer.

S3T-Net: A novel electroencephalogram signals-oriented emotion recognition model.

In this paper, a novel skipping spatial-spectral-temporal network (S3T-Net) is developed to handle intra-individual differences in electroencephalogram (EEG) signals for accurate, robust, and generalized emotion recognition. In particular, aiming at the 4D features extracted from the raw EEG signals, a multi-branch architecture is proposed to learn spatial-spectral cross-domain representations, which benefits enhancing the model generalization ability. Time dependency among different spatial-spectral features is further captured via a bi-directional long-short term memory module, which employs an attention mechanism to integrate context information. Moreover, a skip-change unit is designed to add another auxiliary pathway for updating model parameters, which alleviates the vanishing gradient problem in complex spatial-temporal network. Evaluation results show that the proposed S3T-Net outperforms other advanced models in terms of the emotion recognition accuracy, which yields an performance improvement of 0.23% , 0.13%, and 0.43% as compared to the sub-optimal model in three test scenes, respectively. In addition, the effectiveness and superiority of the key components of S3T-Net are demonstrated from various experiments. As a reliable and competent emotion recognition model, the proposed S3T-Net contributes to the development of intelligent sentiment analysis in human-computer interaction (HCI) realm.

Effects of Inoculating Autochthonous Starter Cultures on Changes of N-Nitrosamines and Their Precursors in Chinese Traditional Fermented Fish during In Vitro Human Digestion.

The objective of this research was to investigate the impact of inoculating autochthonous starter cultures on the alterations in microorganisms, biogenic amines, nitrite, and N-nitrosamines in Chinese traditional fermented fish products (CTFPs) during in vitro human digestion. The results revealed that gastric digestion significantly (p < 0.05) inhibited the proliferation of lactic acid bacteria, yeast, Staphylococcus, and Enterobacteriaceae, whereas various microorganisms proliferated extensively during small intestine digestion. Meanwhile, small intestine digestion could significantly increase (p < 0.05) levels of putrescine, cadaverine, and tyramine. The reduced content observed in inoculated fermentation groups suggests that starter cultures may have the ability to deplete biogenic amines in this digestion stage. Gastric digestion significantly (p < 0.05) inhibited nitrite accumulation in all CTFPs samples. Conversely, the nitrite content increased significantly (p < 0.05) in all groups during subsequent small intestine digestion. However, the rise in the inoculated fermentation groups was smaller than that observed in the spontaneous fermentation group, indicating a potentially positive role of inoculated fermentation in inhibiting nitrite accumulation during this phase. Additionally, gastric digestion significantly (p < 0.05) elevated the levels of N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine in CTFPs. Inoculation with L. plantarum 120, S. cerevisiae 2018, and mixed starter cultures (L. plantarum 120, S. cerevisiae 2018, and S. xylosus 135 [1:1:1]) effectively increased the degree of depletion of NDMA during this digestion process.

S-glutathionylation in hepatocytes is involved in arsenic-induced liver fibrosis through activation of the NLRP3 inflammasome, an effect alleviated by NAC.

Arsenic, a toxicant widely distributed in the environment, is considered as a risk factor for liver fibrosis. At present, the underlying mechanism still needs to be explored. In the present study, we found that, for mice, chronic exposure to arsenic induced liver fibrosis, activated the NLRP3 inflammasome, and increased the levels of reactive oxygen species (ROS). After hepatocytes were co-cultured with hepatic stellate cells (HSCs), we observed the arsenic-activated NLRP3 inflammasome in hepatocytes, and the co-cultured HSCs were activated. Further, we found that, in livers of mice, arsenic disturbed GSH metabolism and promoted protein S-glutathionylation. A 3D molecular docking simulation suggested that NLRP3 binds with GSH, which was confirmed by immunoprecipitation experiments. N-acetylcysteine (NAC) increased the levels of GSH in hepatocytes, which suppressed the S-glutathionylation of NLRP3 and blocked arsenic-induced activation of the NLRP3 inflammasome. Mechanistically, an imbalance of the redox state induced by arsenic promotes the S-glutathionylation of NLRP3, which regulates activation of the NLRP3 inflammasome, leading into the activation of HSCs. Moreover, NAC increases the levels of GSH to block arsenic-induced S-glutathionylation of NLRP3, thereby blocking arsenic-induced liver fibrosis. Thus, via activating HSCs, the S-glutathionylation of NLRP3 in hepatocytes is involved in arsenic-induced liver fibrosis, and, for hepatocytes, NAC alleviates these effects by increasing the levels of GSH. These results reveal a new mechanism and provide a possible therapeutic target for the liver fibrosis induced by environmental factors.

Comprehensive analysis and identification of subtypes and hub genes of high immune response in lung adenocarcinoma.

BACKGROUND: The advent of immunotherapy targeting immune checkpoints has conferred significant clinical advantages to patients with lung adenocarcinoma (LUAD); However, only a limited subset of patients exhibit responsiveness to this treatment. Consequently, there is an imperative need to stratify LUAD patients based on their response to immunotherapy and enhance the therapeutic efficacy of these treatments. METHODS: The differentially co-expressed genes associated with CD8 + T cells were identified through weighted gene co-expression network analysis (WGCNA) and the Search Tool for the Retrieval of Interacting Genes (STRING) database. These gene signatures facilitated consensus clustering for TCGA-LUAD and GEO cohorts, categorizing them into distinct immune subtypes (C1, C2, C3, and C4). The Tumor Immune Dysfunction and Exclusion (TIDE) model and Immunophenoscore (IPS) analysis were employed to assess the immunotherapy response of these subtypes. Additionally, the impact of inhibitors targeting five hub genes on the interaction between CD8 + T cells and LUAD cells was evaluated using CCK8 and EDU assays. To ascertain the effects of these inhibitors on immune checkpoint genes and the cytotoxicity mediated by CD8 + T cells, flow cytometry, qPCR, and ELISA methods were utilized. RESULTS: Among the identified immune subtypes, subtypes C1 and C3 were characterized by an abundance of immune components and enhanced immunogenicity. Notably, both C1 and C3 exhibited higher T cell dysfunction scores and elevated expression of immune checkpoint genes. Multi-cohort analysis of Lung Adenocarcinoma (LUAD) suggested that these subtypes might elicit superior responses to immunotherapy and chemotherapy. In vitro experiments involved co-culturing LUAD cells with CD8 + T cells and implementing the inhibition of five pivotal genes to assess their function. The inhibition of these genes mitigated the immunosuppression on CD8 + T cells, reduced the levels of PD1 and PD-L1, and promoted the secretion of IFN-γ and IL-2. CONCLUSIONS: Collectively, this study delineated LUAD into four distinct subtypes and identified five hub genes correlated with CD8 + T cell activity. It lays the groundwork for refining personalized therapy and immunotherapy strategies for patients with LUAD.

Dioscin attenuates lupus nephritis in NZB/W F1 mice by decreasing NF-κB activation and NLRP3 inflammasome.

INTRODUCTION: . Dioscin, a natural steroid saponin, has anticancer, anti-inflammatory, anti-hyperlipidemic, and glycemic capabilities. This study focused on dioscin roles and its related mechanisms in experimental lupus nephritis. MATERIALS AND METHODS: . Lupus-prone NZB/W F1 mice were intragastrically administered with dioscin, prednisone or vehicle, and kidney, urine and blood samples were harvested after the mice were sacrificed. Proteinuria, blood urea nitrogen (BUN), creatinine, anti-dsDNA, IL-1ß, and IL-18 levels in serum as well as IFN-γ, IL-6, IL-17 and TNF-α levels in kidney tissues were assessed. Renal histopathology was examined through hematoxylin-eosin staining. IgG and C3 expression in kidney was evaluated using immunofluorescence staining. The number of glomerular F4/80-positive cells and NLRP3-positive cells was determined by immunohistochemical staining. The protein expression was examined by western blotting. RESULTS: . Dioscin alleviated lupus nephritis in NZB/W F1 mice. Dioscin declined serum anti-dsDNA level, prevented deposition of immune complexes in renal glomeruli, and inhibited the inflammatory response and infiltration of macrophages into mouse kidneys. Dioscin inhibited NF-κB and NLRP3 inflammasome in NZB/W F1 mice. CONCLUSIONS: . Dioscin ameliorates lupus nephritis through inhibition of NLRP3 inflammasome and NF-κB signaling.

Apoplast-Extraction Based Method to Improve the Purity of Plant Produced Recombinant Protein.

Plants are a newly developing eukaryotic expression system being explored to produce therapeutic proteins. Purification of recombinant proteins from plants is one of the most critical steps in the production process. Typically, proteins were purified from total soluble proteins (TSP), and the presence of miscellaneous intracellular proteins and cytochromes poses challenges for subsequent protein purification steps. Moreover, most therapeutic proteins like antigens and antibodies are secreted to obtain proper glycosylation, and the presence of incompletely modified proteins leads to inconsistent antigen or antibody structures. This work introduces a more effective method to obtain highly purified recombinant proteins from the plant apoplastic space. The recombinant Green fluorescent protein (GFP) is engineered to be secreted into the apoplast of Nicotiana benthamiana and is then extracted using an infiltration-centrifugation method. The GFP-His from the extracted apoplast is then purified by nickel affinity chromatography. In contrast to the traditional methods from TSP, purification from the apoplast produces highly purified recombinant proteins. This represents an important technological improvement for plant production systems.