CsWRKY11 cooperates with CsNPR1 to regulate SA-triggered leaf de-greening and reactive oxygen species burst in cucumber.

Salicylic acid (SA) is a multi-functional phytohormone, regulating diverse processes of plant growth and development, especially triggering plant immune responses and initiating leaf senescence. However, the early SA signaling events remain elusive in most plant species apart from Arabidopsis, and even less is known about the multi-facet mechanism underlying SA-regulated processes. Here, we report the identification of a novel regulatory module in cucumber, CsNPR1-CsWRKY11, which mediates the regulation of SA-promoted leaf senescence and ROS burst. Our analyses demonstrate that under SA treatment, CsNPR1 recruits CsWRKY11 to bind to the promoter of CsWRKY11 to activate its expression, thus amplifying the primary SA signal. Then, CsWRKY11 cooperates with CsNPR1 to directly regulate the expression of both chlorophyll degradation and ROS biosynthesis related genes, thereby inducing leaf de-greening and ROS burst. Our study provides a solid line of evidence that CsNPR1 and CsWRKY11 constitute a key module in SA signaling pathway in cucumber, and gains an insight into the interconnected regulation of SA-triggered processes.

Association between blood chromium and hepatic steatosis assessed by liver ultrasound transient elastography: National Health and Nutrition Examination Survey 2017-2020.

Background: Hepatic steatosis is a significant pathological feature of fatty liver disease (FLD) which is widely spread with no effective treatment available. Previous studies suggest that chromium (Cr) intake reduces lipid deposition in the liver in animals. However, the connection between blood Cr and hepatic steatosis among humans remains inconclusive. Methods: Using the data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, we performed a cross-sectional analysis, including 4,926 participants. The controlled attenuation parameter (CAP) measured by the vibration controlled transient elastography (VCTE) was used to evaluate the degree of liver steatosis. Weighted univariate regression, multivariate linear regression, smooth fitting curves and subgroup analysis were used. In addition, we carried out trend tests, multiple interpolations, and interaction analyses to conduct sensitivity analyses. Results: After adjusting with various covariables, multivariate linear regression analysis demonstrated a significant negative correlation between blood Cr and CAP [ß (95% CI) = -5.62 (-11.02, -0.21)]. The negative correlation between blood Cr and CAP was more significant in the males, 50-59 years, overweight, hypercholesterolemia, HDL-C ≥ 65 mg/dL, HbA1c (5.70-6.10 %), HOMA-IR (0.12-2.76), total bilirubin (0.30-0.40 mg/dL), ever alcohol consumption subjects. Of note, the relationships between blood Cr and CAP followed a U-shaped curve in the smokers and non-smokers, with blood Cr thresholds of 0.48, 0.69 µg/L, respectively. Conclusions: There is an independently negative correlation between blood Cr and hepatic steatosis in American. Our study provides clinical researchers with a new insight into the prospective prevention of hepatic steatosis.

Identification of biomarkers and potential therapeutic targets for pancreatic cancer by proteomic analysis in two prospective cohorts.

Pancreatic cancer (PC) is the deadliest malignancy due to late diagnosis. Aberrant alterations in the blood proteome might serve as biomarkers to facilitate early detection of PC. We designed a nested case-control study of incident PC based on a prospective cohort of 38,295 elderly Chinese participants with ∼5.7 years' follow-up. Forty matched case-control pairs passed the quality controls for the proximity extension assay of 1,463 serum proteins. With a lenient threshold of p < 0.005, we discovered regenerating family member 1A (REG1A), REG1B, tumor necrosis factor (TNF), and phospholipase A2 group IB (PLA2G1B) in association with incident PC, among which the two REG1 proteins were replicated using the UK Biobank Pharma Proteomics Project, with effect sizes increasing steadily as diagnosis time approaches the baseline. Mendelian randomization analysis further supported the potential causal effects of REG1 proteins on PC. Taken together, circulating REG1A and REG1B are promising biomarkers and potential therapeutic targets for the early detection and prevention of PC.

Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae).

BACKGROUND: Herpetospermum pedunculosum (Ser.) C. B. Clarke is a traditional Chinese herbal medicine that heavily relies on the lignans found in its dried ripe seeds (Herpetospermum caudigerum), which have antioxidant and hepatoprotective functions. However, little is known regarding the lignan biosynthesis in H. pedunculosum. In this study, we used metabolomic (non-targeted UHPLC-MS/MS) and transcriptome (RNA-Seq) analyses to identify key metabolites and genes (both structural and regulatory) associated with lignan production during the green mature (GM) and yellow mature (YM) stages of H. pedunculosum. RESULTS: The contents of 26 lignan-related metabolites and the expression of 30 genes involved in the lignan pathway differed considerably between the GM and YM stages; most of them were more highly expressed in YM than in GM. UPLC-Q-TOF/MS confirmed that three Herpetospermum-specific lignans (including herpetrione, herpetotriol, and herpetin) were found in YM, but were not detected in GM. In addition, we proposed a lignan biosynthesis pathway for H. pedunculosum based on the fundamental principles of chemistry and biosynthesis. An integrated study of the transcriptome and metabolome identified several transcription factors, including HpGAF1, HpHSFB3, and HpWOX1, that were highly correlated with the metabolism of lignan compounds during seed ripening. Furthermore, functional validation assays revealed that the enzyme 4-Coumarate: CoA ligase (4CL) catalyzes the synthesis of hydroxycinnamate CoA esters. CONCLUSION: These results will deepen our understanding of seed lignan biosynthesis and establish a theoretical basis for molecular breeding of H. pedunculosum.

Interleukin-12: Structure, Function, and Its Impact in Colorectal Cancer.

Interleukin 12 (IL-12) is a heterodimer consisting of 2 subunits, p35 and p40, with unique associations and interacting functions with its family members. IL-12 is one of the most important cytokines regulating the immune system response and is integral to adaptive immunity. IL-12 has shown marked therapeutic potential in a variety of tumor types. This review therefore summarizes the characteristics of IL-12 and its application in tumor treatment, focusing on its antitumor effects in colorectal cancer (CRC) and potential radiosensitization mechanisms. We aim to provide a current reference for IL-12 and other potential CRC treatment strategies.

Guaianolide sesquiterpenes and their activity from Artemisia mongolica.

Seven undescribed sesquiterpenes, including three dimeric guaianolide sesquiterpenes artemongolides G-I (1-3) and four sesquiterpene lactones artemanomalide D-G (16-19), along with seventeen known compounds isoabsinthin (4), absinthin (5), 11-eptabsinthin (6), 11, 11'-bis-epiabsinthin (7), 10', 11'- epiabsinthin (8), anabsinthin (9), isoanabsinthin (10), absinthin D (11), anabsin (12), caruifolin D (13), gnapholide (14), caruifolin C (15), 1ß(R),10ß(S)-dihydroxy-3-oxo-11ß (S)H-4,11(13)-guaien-6α(S),12-olide (20), 1α,6α,8α-trihydroxy-5α,7ßH-guaia-3,10(14),11(13)-trien-12-oic acid (21), 1α,6α,8α-trihydroxy-5α,7ßH-guaia-3,9,11(13)-trien-12-oic acid (22), argyinolide J (23), artabsinolide A (24) were isolated from the plant Artemisia mongolica. The structures were determined by interpreting NMR, HRESIMS and ECD data. The X-ray crystal structure of 4, 7 and 8 were reported for the first time. In the anti-vitiligo activity test, compounds 2, 7, 12, 23 and 24 demonstrated activity in promoting melanogenesis at a concentration of 50 µM in B16 cells, with 8-methoxypsoralan (8-MOP) as a positive control. Further research on the mechanism revealed that artemongolides H (2) enhance the expression of MITF and TRPs by upregulating p-Akt and p-GSK-3ß, leading to an increase in ß-catenin content in the cell cytoplasm. Subsequently, ß-catenin translocates into the nucleus, resulting in melanogenesis. The results supported the regulation of melanogenesis by artemongolide H (2) through the Akt/GSK3ß/ß-catenin signaling pathway. The anti-inflammatory results demonstrated that compounds 4, 5, 6, 9 and 14 can inhibit the upregulation of IL-6 mRNA and CCL2 mRNA expression. Compound 12 specifically inhibited the upregulation of IL-6 mRNA expression. These compounds exhibited significant anti-inflammatory activities. The activity results revealed that these sesquiterpene compounds have the potential to become lead compounds for the treatment of vitiligo and inflammatory diseases.

Design and Evaluation of a Dual-Sensitive In Situ Gel for the Controlled Release of Pranoprofen.

Currently, the marketed ophthalmic preparations of pranoprofen (PF) are mainly eye drops, but due to the special clearance mechanism of the eye and corneal reflex, the contact time between the drug and the focal site is short, most of the drug is lost, and the bioavailability is less than 5%. In the present study, an in situ gel eye drop containing no bacteriostatic agent and sensitive to temperature and ions was designed for delivery of PF. It was demonstrated to meet the criteria for ophthalmic preparations by characterization such as appearance content sterility. Ocular irritation tests showed a favorable safety profile. In vivo ocular retention time experiments showed that the ocular retention time of the pranoprofen gel was 4.41 times longer than that of commercially available drops (Pranopulin®), and the nasal tear excretion of the pranoprofen gel was lower than that of Pranopulin®, which suggests that the drug loss was reduced relative to that of the drops. The efficacy of the pranoprofen gel against tincture of cayenne pepper-induced corneal and conjunctival inflammation was examined using Pranopulin® as a control and in conjunction with inflammation scores, H&E slice results, and levels of IL-1ß, IL-6, and TNF-α. The results showed that pranoprofen gel and Pranololin® had significant efficacy in the treatment of corneal and conjunctival inflammation, and the anti-inflammatory effect of pranoprofen gel was superior to that of Pranololin®. This study provides a new option for the treatment of corneal and conjunctival inflammation.

The interaction effects of zinc and polygenic risk score with benzo[a]pyrene exposure on lung cancer risk: A prospective case-cohort study among Chinese populations.

The relationship of exposure to benzo[a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-year median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer cases. The baseline concentrations of benzo[a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI)=0.77 (0.66, 0.91) per SD increment in ln-transformed Zn]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to the highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer.

EBUS-TBLC increase the diagnosis rate in different type of peripheral pulmonary lesions.

Background and objective: Recently, endobronchial ultrasonography with guide sheath-guided (EBUS-GS) has been increasingly used in the diagnosis of peripheral pulmonary lesions (PPLs) from human natural orifice. However, the diagnostic rate is still largely dependent on the location of the lesion and the probe. Here, we reported a new procedure to improve the diagnostic rate of EBUS-transbronchial lung cryobiopsy (EBUS-TBLC), which performed under general anesthesia with laryngeal mask airway (LMA) in all of the patients. This study retrospectively evaluated the diagnosis of PPLs with 'blind-ending' type (Type I) and 'pass-through' type procedures (Type II) of EBUS-GS-TBLB or EBUS-TBLC respectively. Methods: Retrospective review of 136 cases performed by EBUS-GS-TBLB or EBUS-TBLC for PPLs over 2 years. Results: A total of 126 cases EBUS-GS-TBLB or EBUS-TBLC were performed during the study period. Among them, 66 (52.4%) were performed Type I and 60 (47.6%) were performed Type II. Clinical baseline characteristics did not differ between two groups. The overall diagnosis rate of 126 patients with EBUS-GS-TBLB or EBUS-TBLC was 73% (92/126), and different method type have significant influence on the diagnostic yield (P = 0.012, x2 = 4.699). Among them, diagnostic yields for Type I with forceps biopsy (n=34), Type I with cryobiopsy (n=32), Type II with forceps biopsy (n=30), and Type II with cryobiopsy (n=30) were 72.5%, 64.5%, 70.4% and 74.2% respectively (Figure 2A). The study further compared the outcomes of different procedures in concentric and eccentric lesion. Diagnostic yields for Type I with eccentric (n=30), Type I with concentric (n=36), Type II with eccentric (n=34), and Type II with concentric (n=26) were 58.2%, 76.9%, 60.2% and 74.8%, respectively (P < 0.05). The incidence of complications in 126 patients was 2.6%. Conclusion: EBUS-GS-TBLB and EBUS-TBLC both are very safe and highly diagnostic technique; different method types have significant influence on the diagnostic yield. Moreover, Type II procedure has higher diagnostic yield. In addition, Type I with eccentric had the lowest diagnosis yield.

Anti-inflammatory effect and mechanism of active parts of Artemisia mongolica in LPS-induced Raw264.7 cells based on network pharmacology analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia mongolica is well known for its use in folk medicine, it is commonly used to alleviate a variety of diseases associated with inflammation, such as laryngitis, tonsillitis, headaches and hepatitis in northwest China. However, its anti-inflammatory mechanism is still unknown. AIM OF THE STUDY: The most potential anti-inflammatory part (AMPA) was identified by screening individual parts of A. Mongolica. After the network pharmacological analysis, the anti-inflammation effects and molecular mechanisms of AMPA were evaluated in RAW264.7 cells induced by LPS. MATERIALS AND METHODS: AMPA was chosen as the most anti-inflammatory of the A. Mongolica, as measured by the effect of each part of the A. Mongolica on NO and COX-2. The chemical composition of AMPA was identified using HPLC-Q-TOF-MS/MS, and targets of bioactive chemicals and targets related to inflammation were found using open-source databases. The "Compound-targets" network and PPI network were established by combining compounds and overlapped targets, and targets in the PPI networks were analyzed by GO and KEGG enrichment. The RAW26.7 cells induced by LPS were used as a model of inflammation examination. MTT assay was performed to assess the cytotoxicity of AMPA on LPS-induced RAW264.7 cells. The level of NO was measured by the Griess method while the inflammatory factors were detected by ELISA. The protein expression levels of iNOS, COX-2, MAPK, NF-κB signaling pathway and AMPK/Nrf2-related proteins were determined by Western blot. The results of nuclear translocation of p65 and Nrf2 were analyzed by immunofluorescence assay. RESULTS: A total of 18 compounds with potential bioactivity were identified, and after intersecting 640 compound-predicted targets and 1608 inflammation targets, the compounds and intersected targets were utilized to structure "compound-target" and PPI networks. Among AMPA, AM6, AM7, AM11, AM8 and AM1 compounds were essential in the "compound-targets" network, meanwhile, TNF, RELA, MAPK1, NOS2, PRKAG, and PTGS2 targets play important roles in the PPI network. The top 10 terms and pathways were obtained based on GO and KEGG. The cell experiments show that 50 µg/mL was the maximum concentration of AMPA without cytotoxicity in the LPS-induced RAW264.7 cell model. When compared with the LPS group, AMPA treatment not only effectively suppressed the generation of NO, TNF-α, IL-6, PGE2, IL-1ß and MCP-1 in LPS-induced RAW264.7 cells, but also down-regulated the expression of COX-2, iNOS and the protein levels p-ERK, p-p38, p-IκB-α and p-p65, inhibited the nuclear translocation of p65. Furthermore, the expression levels of p-LKB1, p-AMPK, Nrf2 and HO-1 proteins were up-regulated and Nrf2 nuclear translocation was promoted. CONCLUSION: AMPA should be considered an anti-inflammatory agent for the results of network pharmacology and in vitro, which could inhibit the MAPK pathway and NF-κB pathway and activate the AMPK/Nrf2 pathway in LPS-stimulated RAW264.7 cells.

Glycyrol Prevents the Progression of Psoriasis-like Skin Inflammation via Immunosuppressive and Anti-Inflammatory Actions.

Glycyrol (GC) is one natural active product. Imiquimod-induced psoriasis-like Balb/c mouse models were established. The model mice were intraperitoneally injected with cyclosporine A (CsA) and GC for 8 days followed by a series of biological detections. GC had little toxicity according to the levels of peripheral blood cells, hemoglobin, blood urea nitrogen (BUN), and serum creatinine (CRE), while CsA significantly increased the levels of BUN and CRE. GC decreased the splenic index and reduced the expressions of IL-6, IL-23, and CXCL-3 in the model mice and IL-6, CXCL-1, and CXCL-2 in the inflammatory HaCaT cells. The half inhibition concentration (IC50) of GC on HaCaT cells was 29.72 µmol/L, resulting in improved apoptosis, enhanced expressions of p21, BAX, and BIK, and reduced expressions of BCL-2. GC is an immunosuppressive agent against psoriasis-like symptoms by anti-inflammatory effects, which provides a strategy for the discovery of anti-psoriatic natural products.

Magnaporthe oryzae effector MoSPAB1 directly activates rice Bsr-d1 expression to facilitate pathogenesis.

Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.

CXCL chemokines-mediated communication between macrophages and BMSCs on titanium surface promotes osteogenesis via the actin cytoskeleton pathway.

The refined functional cell subtypes in the immune microenvironment of specific titanium (Ti) surface and their collaborative role in promoting bone marrow mesenchymal stem cells (BMSCs) driven bone integration need to be comprehensively characterized. This study employed a simplified co-culture system to investigate the dynamic, temporal crosstalk between macrophages and BMSCs on the Ti surface. The M2-like sub-phenotype of macrophages, characterized by secretion of CXCL chemokines, emerges as a crucial mediator for promoting BMSC osteogenic differentiation and bone integration in the Ti surface microenvironment. Importantly, these two cells maintain their distinct functional phenotypes through a mutually regulatory interplay. The secretion of CXCL3, CXCL6, and CXCL14 by M2-like macrophages plays a pivotal role. The process activates CXCR2 and CCR1 receptors, triggering downstream regulatory effects on the actin cytoskeleton pathway within BMSCs, ultimately fostering osteogenic differentiation. Reciprocally, BMSCs secrete pleiotrophin (PTN), a key player in regulating macrophage differentiation. This secretion maintains the M2-like phenotype via the Sdc3 receptor-mediated cell adhesion molecules pathway. Our findings provide a novel insight into the intricate communication and mutual regulatory mechanisms operating between BMSCs and macrophages on the Ti surface, highlight specific molecular events governing cell-cell interactions in the osteointegration, inform the surface design of orthopedic implants, and advance our understanding of osteointegration.

RBM25 regulates hypoxic cardiomyocyte apoptosis through CHOP-associated endoplasmic reticulum stress.

Ischemic heart failure (HF) is one of the leading causes of global morbidity and mortality; blocking the apoptotic cascade could help improve adverse outcomes of it. RNA-binding motif protein 25 (RBM25) is an RNA-binding protein related to apoptosis; however, its role remains unknown in ischemic HF. The main purpose of this study is to explore the mechanism of RBM25 in ischemic HF. Establishing an ischemic HF model and oxygen-glucose deprivation (OGD) model. ELISA was performed to evaluate the BNP level in the ischemic HF model. Echocardiography and histological analysis were performed to assess cardiac function and infarct size. Proteins were quantitatively and locationally analyzed by western blotting and immunofluorescence. The morphological changes of endoplasmic reticulum (ER) were observed with ER-tracker. Cardiac function and myocardial injury were observed in ischemic HF rats. RBM25 was elevated in cardiomyocytes of hypoxia injury hearts and localized in nucleus both in vitro and in vivo. In addition, cell apoptosis was significantly increased when overexpressed RBM25. Moreover, ER stress stimulated upregulation of RBM25 and promoted cell apoptosis through the CHOP related pathway. Finally, inhibiting the expression of RBM25 could ameliorate the apoptosis and improve cardiac function through blocking the activation of CHOP signaling pathway. RBM25 is significantly upregulated in ischemic HF rat heart and OGD model, which leads to apoptosis by modulating the ER stress through CHOP pathway. Knockdown of RBM25 could reverse apoptosis-mediated cardiac dysfunction. RBM25 may be a promising target for the treatment of ischemic HF.

Analysis of sputum microbial flora in chronic obstructive pulmonary disease patients with different phenotypes during acute exacerbations.

BACKGROUND: Increasing studies have shown that the imbalance of the respiratory microbial flora is related to the occurrence of COPD, the severity and frequency of exacerbations and mortality.However, it remains unclear how the sputum microbial flora differs during exacerbations in COPD patients manifesting emphysema phenotype, chronic bronchitis with emphysema phenotype and asthma-COPD overlap phenotype. METHODS: Sputum samples were obtained from 29 COPD patients experiencing acute exacerbations who had not received antibiotics or systemic corticosteroids within the past four weeks.Patients were divided into three groups;emphysema phenotype(E);chronic bronchitis with emphysema phenotype(B+E) and asthma-COPD overlap phenotype(ACO).We utilized metagenomic Next Generation Sequencing (mNGS) technology to analyze the sputum microbial flora in COPD patients with different phenotypes during exacerbations. RESULTS: There was no significant difference in alpha diversity and beta diversity among three groups.The microbial flora composition was similar in all three groups during exacerbations except for a significant increase in Streptococcus mitis in ACO.Through network analysis,we found Candidatus Saccharibacteria oral taxon TM7x and Fusobacterium necrophorum were the core nodes of the co-occurrence network in ACO and E respectively.They were positively correlated with some species and play a synergistic role.In B+E,Haemophilus pittmaniae and Klebsiella pneumoniae had a synergistic effect.Besides,some species among the three groups play a synergistic or antagonistic role.Through Spearman analysis,we found the relative abundance of Streptococcus mitis was negatively correlated with the number of hospitalizations in the past year(r = -0.410,P = 0.027).We also observed that the relative abundance of Prevotella and Prevotella melaninogenica was negatively correlated with age(r = -0.534,P = 0.003;r = -0.567,P = 0.001),while the relative abundance of Streptococcus oralis and Actinomyces odontolyticus was positively correlated with age(r = 0.570,P = 0.001;r = 0.480,P = 0.008).In addition,the relative abundance of Prevotella melaninogenica was negatively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio(r = -0.479,P = 0.009;r = -0.555,P = 0.002),while the relative abundance of Streptococcus sanguinis was positively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio (r = 0.450,P = 0.014;r = 0.501,P = 0.006).There was also a significant positive correlation between Oribacterium and blood eosinophil counts(r = 0.491,P = 0.007). CONCLUSION: Overall,we analyzed the sputum microbiota of COPD patients with different phenotypes and its relationship with clinical indicators, and explored the relationships between microbiota and inflammation in COPD.We hope to alter the prognosis of patients by inhibiting specific bacterial taxa related to inflammation and using guide individualized treatment in the future research.

Metalens enhanced ray optics: an end-to-end wave-ray co-optimization framework.

We present a fully differentiable framework for seamlessly integrating wave optical components with geometrical lenses, offering an approach to enhance the performance of large-scale end-to-end optical systems. In this study, we focus on the integration of a metalens, a geometrical lens, and image data. Through the use of gradient-based optimization techniques, we demonstrate the design of nonparaxial imaging systems and the correction of aberrations inherent in geometrical optics. Our framework enables efficient and effective optimization of the entire optical system, leading to improved overall performance.

The Distribution Characteristics and Ecological Risks of Alkylphenols and the Relationships between Alkylphenols and Different Types of Land Use.

In this study, the spatial distribution characteristics of nine alkylphenols (APs) in the Yongding River and Beiyun River were analyzed. The differences in the concentrations and spatial distribution patterns of nine APs were systematically evaluated using principal component analysis (PCA). The relationships between the concentration distribution patterns and the risks associated with nine APs were investigated under various categories of land use conditions in the region. The results demonstrated that the APs were widely present in both rivers, and the pollution risks associated with the APs were more severe in the Yongding River than in the Beiyun River. The results show that the contamination risks associated with 4-NP were the most serious in the two rivers, with detection percentages of 100% and 96.3%, respectively. In the Yongding River, the APs showed a tendency of low concentration levels in the upper reaches and high levels in the middle and lower regions. Meanwhile, the overall concentration levels of the APs in the Beiyun River were relatively high. However, despite the differences between the upper and middle regions of the Yongding River, the distribution pattern of the APs in the Beiyun River was basically stable. The concentration levels and risk quotient of the APs were negatively correlated with the vegetation cover land use type and positively correlated with the cropland and unused land use types within 500 m, 1 km, and 2 km. The purpose of this study was to provide theoretical data support and a basis for AP pollution risk evaluations in the Yongding River and Beiyun River.

Association of immune cell composition with the risk factors and incidence of acute coronary syndrome.

BACKGROUND: Although immune cells are involved in acute coronary syndrome (ACS), few studies have explored the association of incident ACS with the relative immune cell proportions. We aimed to investigate the association of immune cell proportions with the incidence and risk factors of ACS in the Dongfeng-Tongji cohort. METHODS: We conducted the analyses with 38,295 subjects from the first follow-up of the Dongfeng-Tongji cohort, including DNA methylation profiles for 1570 individuals. The proportions of immune cell types were observed from routine blood tests or estimated from DNA methylation profiles. For both observed and estimated immune cell proportions, we tested their associations with risk factors of ACS by multivariable linear regression models. In addition, the association of each immune cell proportion with incident ACS was assessed by the Cox regression model and conditional logistic regression model, respectively, adjusting for the risk factors of ACS. FINDINGS: The proportions of lymphocytes, monocytes, and neutrophils showed strong associations with sex, followed by diabetes. Moreover, sex and current smoking were the two factors with strongest association with the proportions of lymphocyte subtypes. The hazard ratio (HR) and 95% confidence interval (CI) of incident ACS per standard deviation (SD) increase in proportions of lymphocytes and neutrophils were 0.91 (0.85-0.96) and 1.10 (1.03-1.16), respectively. Furthermore, the OR (95% CI) of incident ACS per SD increase in proportions of NK cells, CD4+ T cells, and B cells were 0.88 (0.78-0.99), 1.15 (1.03-1.30), and 1.13 (1.00-1.26), respectively. INTERPRETATION: The proportions of immune cells were associated with several risk factors of ACS, including sex, diabetes, and current smoking. In addition, proportion of neutrophils had a risk effect, while proportion of lymphocytes had a protective effect on the incidence of ACS. The protective effect of lymphocytes was probably driven by NK cells.

MMP14 is a diagnostic gene of intrahepatic cholangiocarcinoma associated with immune cell infiltration.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor of the hepatobiliary system with concealed onset, strong invasiveness and poor prognosis. AIM: To explore the disease characteristic genes that may be helpful in the diagnosis of ICC and affect immune cell infiltration. METHODS: We downloaded two ICC-related human gene expression profiles from GEO database as the training group (GSE26566 and GSE32958 datasets) for difference analysis, and performed enrichment analysis on differential genes. The least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), three machine learning algorithms, were used to screen the characteristic genes. Double verification was carried out on GSE107943 and The Cancer Genome Atlas, two verification groups. Receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of genes for ICC. CIBERSORT and ssGSEA algorithms were used to evaluate the effect of characteristic genes on immune infiltration pattern. Human Protein Atlas (HPA) was used to analyze the protein expression level of the target gene. RESULTS: A total of 1091 differential genes were obtained in the training group. Enrichment analysis showed that the above genes were mainly enriched in small molecular catabolism, complement and coagulation cascade, bile secretion and other functions and pathways. Twenty-five characteristic genes were screened by LASSO regression, 19 by SVM-RFE algorithm, and 30 by RF algorithm. Three algorithms were used in combination to determine the characteristic gene of ICC: MMP14. The verification group confirmed that the genes had a high diagnostic accuracy (AUC values of the training group and the verification group were 0.960, 0.999, and 0.977, respectively). Comprehensive analysis of immune infiltration showed that MMP14 could affect the infiltration of monocytes, activated memory CD4 T cells, resting memory CD4 T cells, and other immune cells, and was closely related to the expression of CD200, cytotoxic T-lymphocyte-associated antigen 4, CD14, CD44, and other immune checkpoints. The results of immunohistochemistry in HPA database showed was indeed overexpressed in ICC. CONCLUSION: MMP14 can be used as a disease characteristic gene of ICC, and may regulate the distribution of immune-infiltrating cells in the ICC tumor microenvironment, which provides a new method for the determination of ICC diagnostic markers and screening of therapeutic targets.