Alginate oligosaccharides enhance gut microbiota and intestinal barrier function, alleviating host damage induced by deoxynivalenol in mice.

BACKGROUND: Alginate oligosaccharides (AOS) exhibits notable effects in terms of anti-inflammatory, antibacterial, and antioxidant properties. Deoxynivalenol (DON) has the potential to trigger intestinal inflammation by upregulating proinflammatory cytokines and apoptosis, thereby compromising the integrity of the intestinal barrier function and perturbing the balance of the gut microbiota. OBJECTIVES: We assessed the impact of AOS on mitigating DON-induced intestinal damage and systemic inflammation in mice. METHODS: After a one-week acclimatization period, the mice were divided into four groups. For three weeks, the AOS and AOS + DON groups were gavaged daily with 200 µl of AOS (200 mg/kg body weight (BW)), while the CON and DON groups received an equivalent volume of sterile Phosphate Buffered Saline (PBS). Subsequently, for one week, the DON and AOS + DON groups received 100 µl of DON (4.8 mg/kg BW) daily, whereas the CON and AOS groups continued receiving PBS. RESULTS: After administering DON via gavage to mice, there was a significant decrease (P < 0.05) in body weights compared to the control (CON) group. Interestingly, AOS exhibited a tendency to mitigate this weight loss in the AOS + DON group. In the feces of mice treated with both AOS and DON, the concentration of DON significantly increased (P < 0.05) compared to the DON group alone. Histological analysis revealed that DON exposure caused increased intestinal damage, including shortened villi and eroded epithelial cells, which was ameliorated by pre-supplementation with AOS, alleviating harm to the intestinal barrier function. In both jejunum and colon tissues, DON exposure significantly reduced (P < 0.05) the expression of tight junction proteins (Claudin and Occludin in the colon) and the mucin protein Mucin 2 (MUC2), compared to the CON group. Prophylactic administration of AOS alleviated these reductions, thereby improving the expression levels of these key proteins. Additionally, AOS supplementation protected DON-exposed mice by increasing the abundance of probiotics such as Bifidobacterium, Faecalibaculum, and Romboutsia. These gut microbes are known to enhance (P < 0.05) anti-inflammatory responses and the production of short-chain fatty acids (SCFAs), including total SCFAs, acetate, and valerate, compared to the DON group. CONCLUSIONS: This study unveils AOS not only enhance gut microbiota and intestinal barrier function but also significantly mitigate DON-induced intestinal damage.

Higher risk of patients after stent(s) insertion with vessel bifurcation treated in the association between PM2.5 and cardiovascular hospital readmission.

Stent(s) insertion is a common form of surgery for patients with cardiovascular diseases, and is associated with a high rate of hospital readmission. This study aims to investigate the acute association between PM2.5 exposure and hospital readmission for patients with cardiovascular disease and a history of stent(s) insertion. The records of hospital admission were collected from the Beijing Municipal Commission of Health and Family Planning Information Center between 1st January 2013 and 31st December 2017. Subsequent hospital readmission records for patients with a history of stent(s) insertion or without any surgery were extracted. The conditional logistic regression model was applied to investigate the association between PM2.5 concentration and cardiovascular disease readmission in patients who had undergone stent(s) insertion or without any surgery. A total of 81,468 patients who had a history of stent(s) insertion were included in this study. Of these, 17,224 patients (21.1 % of the total number of patients) were readmitted 27,749 times due to cardiovascular disease. The median daily PM2.5 concentration was 62.8 µg/m3 with an interquartile range (IQR) of 71.5 µg/m3. The excess risk (ER) associated 10 µg/m3 increase in PM2.5 concentration for readmission due to cardiovascular disease was 0.48 % (95 % CI: 0.09 %, 0.87 %) in patients with a history of stent(s) insertion. Patients who had stent(s) insertion at the vessel bifurcation site showed the highest risk of readmission for cardiovascular disease when exposed to PM2.5; the ER was 4.12 % (95 % CI: 1.60 %, 6.70 %). PM2.5 was significantly associated with angina pectoris and readmission for chronic ischemic heart disease in patients with a history of stent(s) insertion. PM2.5 had a significant association with cardiovascular readmission among patients with a history of insertion of stent(s). Patients who had vessel bifurcation treated showed the highest risk of readmission.

Repeatability and agreement of two swept-source optical coherence tomographers and scheimpflug imaging for measurements of corneal curvature.

PURPOSE: To evaluate the repeatability and agreement of two swept-source optical coherence tomographers and Scheimpflug imaging for corneal curvature in healthy subjects to obtain data on the clinical application of a new device. METHODS: This prospective study was conducted in January and February 2021 with 100 healthy subjects at the Eye Hospital of Wenzhou Medical University. Simulated keratometry (Sim-K), posterior keratometry (Kp), total corneal power (TCP), and total corneal astigmatism (TCA) were measured with CASIA2, Anterion, and Pentacam. Within-subject standard deviation (Sw), repeatability coefficient (RC), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) were used to assess inter-device repeatability. Bland-Altman analysis was performed to determine inter-device agreement. RESULTS: The three devices showed good repeatability for Sim-K, Kp, and TCP with all ICC > 0.980. Pentacam showed the highest repeatability (ICC ≥ 0.993; ICC ≥ 0.993) while the CASIA2 demonstrated the lowest repeatability (ICC: ≥ 0.986; ICC: ≥ 0.985) for Sim-K and TCP. Anterion and CASIA2 revealed better repeatability (ICC ≥ 0.998; ICC ≥ 0.981) for Kp than Pentacam (ICC ≥ 0.980). Pentacam and Anterion showed good repeatability for TCA (ICC: 0.935 and 0.916), whereas the CASIA2 showed moderate repeatability (ICC: 0.836). Three instruments demonstrated good agreement with the maximum absolute 95% Limits of agreement (LoA) of 1.00 D for Sim-K, Kp, and TCP. Wide LoA were found for TCA with the maximum absolute 95% LoA ≥ 0.66 D between the three devices. CONCLUSIONS: In healthy subjects, the three devices (Pentacam, Anterion and CASIA2) displayed comparable repeatability and accuracy for SimK, Kp, and TCP, and could be used interchangeably for these parameters. However, TCA measured by the three devices was not interchangeable. TRIAL REGISTRATION: Chinese Clinical Trial Registry Center (10/10/2020, ChiCTR2000038959).

PICASSO: a universal brain phantom for positron emission tomography based on the activity painting technique.

Objective.This study presents a universal phantom for positron emission tomography (PET) that allows arbitrary static and dynamic activity distributions of various complexities to be generated using a single PET acquisition. Approach.We collected a high-statistics dataset (with a total of 22.4×109prompt coincidences and an event density of 2.75×106events/mm3) by raster-scanning a single plane with a22Na point source mounted on a robotic arm in the field-of-view of the uEXPLORER PET/CT scanner. The source position was determined from the reconstructed dynamic frames. Uniquely, true coincidences were separated from scattered and random events based on the distance between their line-of-response and the known source location. Finally, we randomly sampled the dataset to generate the desired activity distributions modeling several different phantoms. Main results.Overall, the target and the reconstructed phantom images had good agreement. The analysis of a simple geometric distribution showed high quantitative accuracy of the phantom, with mean error of <-3.0% relative to the ground truth for activity concentrations ranging from 5.3 to 47.7 kBq/ml. The model of a high-resolution18F-fluorodeoxyglucose distribution in the brain illustrates the usefulness of the technique in simulating realistic static neuroimaging studies. A dynamic18F-florbetaben study was modeled based on a time-activity curve of a human study and a segmented brain phantom with no coincidences repeating between frames. For all time points, the mean voxel-wise errors ranged from -4.4% to -0.7% in grey matter and from -3.9% to +2.8% in white matter. Significance.The proposed phantom technique is highly flexible and allows modeling of static and dynamic brain PET studies with high quantitative accuracy. It overcomes several key limitations of the existing phantoms and has many promising applications for the purposes of image reconstruction, data correction methods, and system performance evaluation, particularly for new high-performance dedicated brain PET scanners. .

Association between neutrophil-to-lymphocyte ratio and motor subtypes in idiopathic Parkinson's disease: a prospective observational study.

BACKGROUND: Peripheral immunity and neuroinflammation interact with each other and they play important roles in the pathophysiology of idiopathic Parkinson's disease (IPD). There have been very few real-world reports on the relationship between peripheral immune inflammation and motor phenotypes of IPD. This study aimed to investigate the potential correlation between peripheral inflammatory indicators and motor subtypes in patients with IPD. METHODS: This observational, prospective case-control study examined patients with IPD and healthy controls (HC) matched for age and sex between September 2021 and July 2023 at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University. The levels of peripheral inflammatory indicators were collected from each patient with IPD and HCs. Differences in the levels of peripheral inflammatory indicators among groups were compared. Binary logistic regression analysis was used to explore the inflammatory mechanism underlying the motor subtype of IPD. RESULTS: A total number of 94 patients with IPD were recruited at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University between September 2021 and July 2023, including 49 males and 45 females, and 37 healthy volunteers matched for age and sex were also enrolled as the control group. Of the 94 patients with IPD, 42.6% performed as the TD motor subtype and 57.4% performed as the AR motor subtype. NLR and the plasma levels of IL-1ßand TNF-α in the IPD group were higher than those in the HC group (P < 0.05). The disease duration, Hoehn and Yahr (H-Y) stage, NLR, and the levels of IL-1ß in the AR group were higher than those in the TD group (P < 0.05). Additionally, IL-1ß plasma levels and NLR were positively correlated with disease duration, H-Y stage, movement disorder society-Unified Parkinson's Disease Rating Scale-III motor score, and AR subtype. The binary logistic regression model revealed that the plasma level of IL-1ß was mildly associated with the AR motor subtype and NLR was strongly associated with the AR motor subtype. The combination of NLR and IL-1ß showed better performance in identifying the AR motor subtype. CONCLUSION: NLR is strongly associated with the AR motor subtype in IPD, and peripheral immunity is probably involved in the pathogenesis of AR motor subtype in IPD.

SNAI2 as a Prognostic Biomarker Based on Cancer-Associated Fibroblasts in Patients With Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a common type of malignant tumor with therapeutic challenges. Cancer-associated fibroblasts (CAFs) promote LUAD growth and metastasis, regulate the tumor immune response, and influence tumor treatment responses and drug resistance. However, the molecular mechanisms through which CAFs control LUAD progression are largely unknown. In this study, we aimed to determine the correlations between CAF-related genes and overall survival (OS) in patients with LUAD. Methods: We acquired the gene expression data and clinical information of 522 patients with LUAD patients from The Cancer Genome Atlas (TCGA) and 442 patients with LUAD from the Gene Expression Omnibus (GEO) databases. CAF infiltration levels were assessed using the Microenvironment Cell Population (MCP) counter, the Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm, and Tumor Immune Dysfunction and Exclusion (TIDE) scores. A CAF-related gene network was constructed using the Weighted gene co-expression network analysis (WGCNA). Based on the CAF-related genes, univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were performed to identify prognostic genes. Gene expression levels within the prognostic model were validated using the Cancer Cell Line Encyclopedia (CCLE) databases and Western blotting. Results: Our results demonstrated that high CAF scores were associated with lower survival rates in patients with LUAD. Gene modules that were highly correlated with high CAF scores were closely associated with tissue characteristics and extracellular matrix structures in LUAD. In addition, correlations between CAF scores and responses to immunotherapy and chemotherapy were observed. Finally, we found that SNAI2 expression was higher in lung cancer tissues than in normal tissues. Conclusion: Deepening our understanding of the influence of CAFs on tumor progression and treatment response at the molecular level can aid the development of more effective therapeutic strategies. This study provides important insights into the functional mechanisms of action of CAFs in LUAD and highlights their clinical implications.

Exposome-Wide Ranking to Uncover Environmental Chemicals Associated with Dyslipidemia: A Panel Study in Healthy Older Chinese Adults from the BAPE Study.

BACKGROUND: Environmental contaminants (ECs) are increasingly recognized as crucial drivers of dyslipidemia and cardiovascular disease (CVD), but the comprehensive impact spectrum and interlinking mechanisms remain uncertain. OBJECTIVES: We aimed to systematically evaluate the association between exposure to 80 ECs across seven divergent categories and markers of dyslipidemia and investigate their underpinning biomolecular mechanisms via an unbiased integrative approach of internal chemical exposome and multi-omics. METHODS: A longitudinal study involving 76 healthy older adults was conducted in Jinan, China, and participants were followed five times from 10 September 2018 to 19 January 2019 in 1-month intervals. A broad spectrum of seven chemical categories covering the prototypes and metabolites of 102 ECs in serum or urine as well as six serum dyslipidemia markers [total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein (Apo)A1, ApoB, and ApoE4] were measured. Multi-omics, including the blood transcriptome, serum/urine metabolome, and serum lipidome, were profiled concurrently. Exposome-wide association study and the deletion/substitution/addition algorithms were applied to explore the associations between 80 EC exposures detection frequency >50% and dyslipidemia markers. Weighted quantile sum regression was used to assess the mixture effects and relative contributions. Multi-omics profiling, causal inference model, and pathway analysis were conducted to interpret the mediating biomolecules and underlying mechanisms. Examination of cytokines and electrocardiograms was further conducted to validate the observed associations and biomolecular pathways. RESULTS: Eight main ECs [1-naphthalene, 1-pyrene, 2-fluorene, dibutyl phosphate, tri-phenyl phosphate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, chromium, and vanadium] were significantly associated with most dyslipidemia markers. Multi-omics indicated that the associations were mediated by endogenous biomolecules and pathways, primarily pertinent to CVD, inflammation, and metabolism. Clinical measures of cytokines and electrocardiograms further cross-validated the association of these exogenous ECs with systemic inflammation and cardiac function, demonstrating their potential mechanisms in driving dyslipidemia pathogenesis. DISCUSSION: It is imperative to prioritize mitigating exposure to these ECs in the primary prevention and control of the dyslipidemia epidemic. https://doi.org/10.1289/EHP13864.

Ambient fine particulate matter and its constituents may exacerbate the acceleration of aging in adults.

Both ambient fine particulate matter (PM2.5) and aging are important urban concerns. However, the associations between PM2.5 constituents and the acceleration of aging (AA) remain unclear. We included 16,051 adults (aged 25-80 years) with 19,252 medical observations in Taiwan during 2008-2017. 2-year average PM2.5 and its five major constituents were assessed using a two-stage machine learning model at a resolution of 1 km2. AA was determined by the difference between the Klemera-Doubal biological age and chronological age. A linear mixed model (LMM) with inverse probability weights was used to examine the associations between AA and air pollution. In a semi-randomized study design, we applied a post-matching LMM to assess the impacts of changes in air pollution exposure on AA. Each interquartile range increase in ambient PM2.5, SO4-2, NO3-, NH4+, organic matters (OM), and black carbon (BC) was associated with a 0.20 (95 %confidence interval [CI]: 0.17-0.24), 0.19 (0.15-0.23), 0.14 (0.11-0.18), 0.21 (0.17-0.24), 0.22 (0.19-0.26) and 0.25 (0.21-0.28) year increase in AA, respectively. BC was generally associated with the greatest increase in AA as compared to other constituents. We did not find evident thresholds in their concentration-response associations. Participants exposed to increased levels of PM2.5, SO4-2, NO3-, NH4+, OM, and BC experienced an increase in AA of 0.11 (-0.07-0.29), 0.20 (0.02-0.39), 0.15 (-0.02-0.33), 0.12 (-0.07-0.31), 0.24 (0.07-0.41), and 0.30 (0.07-0.52) years, respectively, compared to those exposed to decreased/unchanged levels. Long-term exposure to ambient PM2.5 and its constituents may accelerate biological aging among Chinese adults. Exposed to increased levels may further aggregate the aging process. This study suggests that reducing exposure to air pollution is beneficial, even for residents within moderately-to-highly polluted regions, such as Taiwan. Rigorous regulation of PM2.5 and its constituents may prevent the acceleration of biological age.

The imaging manifestations of persistent truncus arteriosus in children.

Persistent truncus arteriosus (PTA) is a rare congenital heart malformation. A 4-year-old girl was diagnosed with type I PTA through echocardiography and confirmed by cardiac CTA.

Cerium oxide mimetic enzyme based colorimetric detection of potential oesophageal cancer biomarkers.

Oesophageal cancer (OC) is a prevalent malignant tumor that poses a significant threat to individuals. Current mainstream detection method is endoscopy, which requires professional operators and expensive instruments. Therefore, it is crucial to develop a rapid, easy-to-operate, and low-cost detection method. In this study, an RNA colorimetric biosensor was successfully constructed using cerium oxide mimetic enzyme. The sensor is constructed on 96-well plates, which are immobilized with DNA-RNA-DNA complexes in microtiter wells when target RNA is present. This immobilization is based on the principle of base complementary pairing. The CeO2 immobilized has the unique advantage of catalyzing the bluing of 3,3',5,5'-tetramethylbenzidine (TMB) directly without the need any additional oxidant in microtiter wells. This property allows for the detection of RNA and enables the visualization of multiple sample assays. Furthermore, the RNA colorimetric sensor demonstrates good selectivity, immunity to interference, and high stability. Under optimal conditions, the sensor exhibited linearity in the range of 10-13 to 10-9 M with a detection limit of 33.26 fM. Therefore, this study presents a new detection method for oesophageal cancer screening.

Oral administration of Lactobacillus plantarum expressing aCD11c modulates cellular immunity alleviating inflammatory injury due to Klebsiella pneumoniae infection.

BACKGROUND: Klebsiella pneumoniae (KP), responsible for acute lung injury (ALI) and inflammation of the gastrointestinal tract, is a zoonotic pathogen that poses a threat to livestock farming worldwide. Nevertheless, there is currently no validated vaccine to prevent KP infection. The development of mucosal vaccines against KP using Lactobacillus plantarum (L. plantarum) is an effective strategy. RESULTS: Firstly, the L. plantarum strains NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c were constructed via homologous recombination to express the aCD11c protein either inducibly or constitutively. Both NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c strains could enhance the adhesion and invasion of L. plantarum on bone marrow-derived dendritic cells (BMDCs), and stimulate the activation of BMDCs compared to the control strain NC8-pSIP409 in vitro. Following oral immunization of mice with NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c, the cellular, humoral, and mucosal immunity were significantly improved, as evidenced by the increased expression of CD4+ IL-4+ T cells in the spleen, IgG in serum, and secretory IgA (sIgA) in the intestinal lavage fluid (ILF). Furthermore, the protective effects of L. plantarum against inflammatory damage caused by KP infection were confirmed by assessing the bacterial loads in various tissues, lung wet/dry ratio (W/D), levels of inflammatory cytokines, and histological evaluation, which influenced T helper 17 (Th17) and regulatory T (Treg) cells in peripheral blood and lung. CONCLUSIONS: Both the inducible and constitutive L. plantarum strains NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c have been found to stimulate cellular and humoral immunity levels and alleviate the inflammatory response caused by KP infection. These findings have provided a basis for the development of a novel vaccine against KP.

The potential of flavonoids to mitigate cellular senescence in cardiovascular disease.

Aging is one of the most significant factors affecting cardiovascular health, with cellular senescence being a central hallmark. Senescent cells (SCs) secrete a specific set of signaling molecules known as the senescence-associated secretory phenotype (SASP). The SASP has a remarkable impact on age-associated diseases, particularly cardiovascular diseases (CVD). Targeting SCs through anti-aging therapies represents a novel strategy to effectively retard senescence and attenuate disease progression. Accumulating evidence demonstrates that the flavonoids, widely presented in fruits and vegetables worldwide, can delay or treat CVD via selectively eliminating SCs (senolytics) and modulating SASPs (senomorphics). Nevertheless, only sporadic research has illustrated the application of flavonoids in targeting SCs for CVD, which requires further exploration. This review recapitulates the hallmarks and key molecular mechanisms involved in cellular senescence, then summarizes senescence of different types of cardiac cells and describes the mechanisms by which cellular senescence affects CVD development. The discussion culminates with the potential use of flavonoids via exerting their biological effects on cellular senescence to reduce CVD incidence. This summary will provide valuable insights for cardiovascular drug design, development and clinical applications leveraging flavonoids.

Exploration of Geographical Environmental Factors Influencing Regional Population Mortality Patterns in China.

OBJECTIVES: The regional population mortality patterns in China exhibit substantial geographical distribution characteristics. This paper aims to explore the impact and mechanisms of geographical environmental factors on regional population mortality patterns. METHODS: This study first utilized the data from China's Seventh Population Census to obtain mortality patterns for the 31 provincial-level administrative regions. Subsequently, a functional regression method was employed to explore the geographical environmental driving factors of regional mortality patterns. RESULTS: The study provides a detailed explanation of the mechanisms and marginal contributions of key geographical environmental factors at different age groups. CONCLUSIONS: (1) The impact of geographical environmental factors on mortality patterns shows distinct phased characteristics. Mortality patterns before the age of 40 years are hardly influenced by geographical environmental factors, with a noticeable impact beginning at ages 40-69 years and reaching the maximum influence after the age of 70 years. (2) In mortality patterns at ages 40-69 years, average altitude have the most substantial impact, followed by extreme low-temperature days and PM2.5 concentration. In mortality patterns at ages 70-94 years, high-temperature days have the greatest influence, followed by the impact of SO2 concentration. (3) In comparisons based on gender, socioeconomic factors, and geographical environmental factors, gender and urban-rural differences have the most significant impact on regional population mortality patterns, followed by the influence of other socioeconomic factors, with geographical environmental factors having a relatively smaller impact.

A study on maglev force and vibration attenuation characteristics of quasi-zero stiffness cruciform maglev isolator.

This paper aims to study the maglev force and vibration attenuation characteristics of quasi-zero stiffness cruciform maglev isolators (CMIs). The maglev force and stiffness of CMIs were analytically computed based on equivalent charge theory, and the transfer function of the system was conducted. The effects of magnet geometry parameters and air gap on the maglev force, stiffness, and vibration transmission characteristics of the CMI system were revealed through parametric analyses. With the increase in magnet length and width, the maximum value of maglev force increases, but the displacement range of near-zero stiffness, amplitude, and phase of the system gradually decrease. With the increase in magnet height, the displacement range of near-zero stiffness increases, while the variation in the amplitude and phase of the system has minimal impact. Meanwhile, in the Halbach array, the height variation of the magnet at different positions has different impacts on the magnetic force. As the air gap increases, the maximum value of maglev force decreases, but the amplitude and phase gradually increase, and the displacement range of near-zero stiffness first rises and then decreases. Finally, an experimental study was carried out to test the vibration attenuation characteristics of CMIs, in which sinusoidal excitation, hammer strike excitation, and random excitation were applied.

Double-orifice mitral valve associated with mild mitral stenosis and coarctation of the aortic isthmus: A rare case of incomplete form of Shone's syndrome.

Shone's syndrome (SS) is a rare congenital cardiac anomaly characterized by a spectrum of developmental abnormalities. It predominantly presents as consisting of a variety of left ventricular inflow and outflow tract lesions, with inflow tract lesions typically including parachute mitral valve and supravalvular mitral ring. However, reports of SS involving double-orifice mitral valve are scarce.

Role of Csdc2 in Regulating Secondary Hair Follicle Growth in Cashmere Goats.

Cashmere goats possess two types of hair follicles, with the secondary hair follicles producing valuable cashmere fiber used for textiles. The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. Transcription factors play crucial roles during this process. The transcription factor, cold-shock domain, containing C2 (Csdc2) plays a crucial role in modulating cell proliferation and differentiation. Our preceding research indicated that the expression of Csdc2 changes periodically during anagen to telogen. However, the mechanisms of Csdc2 in regulating SHF growth remain unclear. Here, we found that the knockdown of Csdc2 inhibits the proliferation of dermal papilla cells. ChIP-Seq analysis showed that Csdc2 had a unique DNA binding motif in SHFs. Through conjoint analysis of ChIP-Seq and RNA-Seq, we revealed a total of 25 candidate target genes of Csdc2. Notably, we discovered a putative Csdc2 binding site within roundabout guidance receptor 2 (Robo2) on chromosome 1 of the goat genome. Furthermore, qRT-PCR and dual-luciferase reporter assay confirmed Csdc2's positive regulatory influence on Robo2. These findings expand the research field of hair follicle transcriptional regulatory networks, offering insights into molecular breeding strategies to enhance cashmere production in goats.

CCL18 promotes endometriosis by increasing endometrial cell migration and neuroangiogenesis.

Endometriosis is an estrogen-dependent inflammatory gynecological disease whose pathogenesis is unclear. C-C motif chemokine ligand 18 (CCL18), a chemokine, is involved in several inflammatory diseases. In this study, we aimed to investigate the role of CCL18 in endometriosis and its underlying mechanisms. Human endometrium and peritoneal fluid were obtained from women with and without endometriosis for molecular studies. The expression level of CCL18 in each tissue sample was examined by RNA sequencing analysis, quantitative PCR analysis and immunohistochemistry staining. The effects of CCL18 on cell migration, tube formation and neurite growth were investigated in vitro using primary endometrial cells, human umbilical vein endothelial cells (HUVECs) and dorsal root ganglion (DRG) neurons, respectively. Moreover, the development of endometriosis in mice was studied in vivo by blocking CCL18. CCL18 was shown to be overexpressed in endometrial foci and peritoneal fluid in women with endometriosis and was positively correlated with endometriosis pain. In vitro, CCL18 promoted the migration of ectopic endometrial cells, tube formation of HUVECs, and nerve outgrowth of DRG neurons. More importantly, inhibition of CCL18 significantly suppressed lesion development, angiogenesis, and nerve infiltration in a mouse model of endometriosis. In conclusion, CCL18 may play a role in the progression of endometriosis by increasing endometrial cell migration and promoting neuroangiogenesis.

Identification and Validation of Aging Related Genes Signature in Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) is regarded as an accelerated aging disease. Aging-related genes in COPD are still poorly understood. METHOD: Data set GSE76925 was obtained from the Gene Expression Omnibus (GEO) database. The "limma" package identified the differentially expressed genes. The weighted gene co-expression network analysis (WGCNA) constructes co-expression modules and detect COPD-related modules. The least absolute shrinkage and selection operator (LASSO) and the support vector machine recursive feature elimination (SVM-RFE) algorithms were chosen to identify the hub genes and the diagnostic ability. Three external datasets were used to identify differences in the expression of hub genes. Real-time reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the expression of hub genes. RESULT: We identified 15 differentially expressed genes associated with aging (ARDEGs). The SVM-RFE and LASSO algorithms pinpointed four potential diagnostic biomarkers. Analysis of external datasets confirmed significant differences in PIK3R1 expression. RT-qPCR results indicated decreased expression of hub genes. The ROC curve demonstrated that PIK3R1 exhibited strong diagnostic capability for COPD. CONCLUSION: We identified 15 differentially expressed genes associated with aging. Among them, PIK3R1 showed differences in external data sets and RT-qPCR results. Therefore, PIK3R1 may play an essential role in regulating aging involved in COPD.

Local Excitation of Kagome Spin Ice Magnetism Seen by Scanning Tunneling Microscopy.

The kagome spin ice can host frustrated magnetic excitations by flipping its local spin. Under an inelastic tunneling condition, the tip in a scanning tunneling microscope can flip the local spin, and we apply this technique to kagome metal HoAgGe with a long-range ordered spin ice ground state. Away from defects, we discover a pair of pronounced dips in the local tunneling spectrum at symmetrical bias voltages with negative intensity values, serving as a striking inelastic tunneling signal. This signal disappears above the spin ice formation temperature and has a dependence on the magnetic fields, demonstrating its intimate relation with the spin ice magnetism. We provide a two-level spin-flip model to explain the tunneling dips considering the spin ice magnetism under spin-orbit coupling. Our results uncover a local emergent excitation of spin ice magnetism in a kagome metal, suggesting that local electrical field induced spin flip climbs over a barrier caused by spin-orbital locking.