Exposure to per- and polyfluoroalkyl substances in lung cancer patients and their associations with clinical health indicators.

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n = 282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80 % of samples and their total concentrations were 5.27-152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95% CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95% CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients.

The additive effect of metabolic syndrome on left ventricular impairment in patients with obstructive coronary artery disease assessed by 3.0 T cardiac magnetic resonance feature tracking.

BACKGROUND: Metabolic syndrome (MetS) can increase the risk of morbidity and mortality of cardiovascular disease and obstructive coronary artery disease (OCAD), which usually have a poor prognosis. This study aimed to explore the impact of MetS on left ventricular (LV) deformation and function in OCAD patients and investigate the independent factors of impaired LV function and deformation. MATERIALS AND METHODS: A total of 121 patients with OCAD and 52 sex- and age-matched controls who underwent cardiac magnetic resonance scanning were enrolled in the study. All OCAD patients were divided into two groups: OCAD with MetS [OCAD(MetS+), n = 83] and OCAD without MetS [OCAD(MetS-), n = 38]. LV functional and global strain parameters were measured and compared among the three groups. Multivariable linear regression analyses were constructed to investigate the independent factors of LV impairment in OCAD patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to test the prediction efficiency of MetS for LV impairment. RESULTS: From controls to the OCAD(MetS-) group to the OCAD(MetS+) group, LV mass (LVM) increased, and LV global function index (LVGFI) and LV global longitudinal peak strain (GLPS) decreased (all p < 0.05). Compared with the OCAD(MetS-) group, the LV GLPS declined significantly (p = 0.027), the LVM increased (p = 0.006), and the LVGFI decreased (p = 0.043) in the OCAD(MetS+) group. After adjustment for covariates in OCAD patients, MetS was an independent factor of decreased LV GLPS (ß = - 0.211, p = 0.002) and increased LVM (ß = 0.221, p = 0.003). The logistic multivariable regression analysis and ROC analysis showed that combined MetS improved the efficiency of predicting LV GLPS reduction (AUC = 0.88) and LVM (AUC = 0.89) increase. CONCLUSIONS: MetS aggravated the damage of LV deformation and function in OCAD patients and was independently associated with LV deformation and impaired LV strain. Additionally, MetS increased the prediction efficiency of increased LVM and decreased LV GLPS. Early detection and intervention of MetS in patients with OCAD is of great significance.

Experimental test and mechanism analysis of soil crust erosion resistance of rammed earth Great Wall in rainy season.

Rammed earth is a kind of cleaning material, widely used in all kinds of buildings in the world. The Great Wall of ancient China is a typical world cultural site built from rammed earth. The rammed earth Great Wall of Shanhaiguan is close to Bohai Bay, which has suffered from long-term erosion by rain, causing a series of problems such as soil loss, collapse and gully flushing. The protection materials of the rammed earth site have always puzzled scholars. However, during the rainy season, it was found that some of the walls at Xiaowan Gouge and Nantuzhuang Gouge in the Shanhaiguan Great Wall had unwashed traces, the soil surface of the walls was intact, and the anti-erosion ability of the walls was significantly higher than that of other places. In order to explore the reasons for its strong anti-erosion ability in the natural state of rammed earth wall, guide the protection of rammed earth Great Wall, and carry out different experimental tests to explore its anti-erosion reasons and internal mechanisms. Firstly, the characteristics of rammed soil were understood through the composition test of rammed soil, and the indoor and outdoor erosion test was carried out to determine that the anti-erosion reason was the protection of gray-green soil crust. The property and composition of soil crust were determined through the immersion test and genome sequencing. Finally, the protection mechanism of soil crust was analyzed by scanning electron microscopy.

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization.

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.

Palladium-catalyzed alkynylation of allylic gem-difluorides.

Herein, a palladium-catalyzed regioselective alkynylation, esterification, and amination of allylic gem-difluorides via C-F bond activation/transmetallation/ß-C elimination or nucleophilic attack has been achieved. This innovative protocol showcases an extensive substrate range and operates efficiently under mild reaction conditions, resulting in high product yields and Z-selectivity. Particularly noteworthy is its exceptional tolerance towards a wide array of functional groups. This developed methodology provides effective and convenient routes to access a diverse array of essential fluorinated enynes, esters and amines.

Biventricular Impairment and Ventricular Interdependence in Patients With Alcoholic Cardiomyopathy: Insights Through Cardiac Magnetic Resonance Imaging.

BACKGROUND: Alcoholic cardiomyopathy (ACM) can lead to progressive cardiac dysfunction and heart failure, but little is known about biventricular impairment and ventricular interdependence (VI) in ACM patients. PURPOSE: To use cardiac MRI to investigate biventricular impairment and VI in ACM patients. STUDY TYPE: Retrospective. POPULATION: Forty-one male patients with ACM and 45 sex- and age-matched controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence, inversion recovery prepared echo-planar imaging sequence and phase-sensitive inversion recovery sequence. ASSESSMENT: Biventricular structure, function, and global strain (encompassing peak strain [PS], peak systolic, and diastolic strain rate), PS of interventricular septal (IVS), microvascular perfusion (including upslope and time to maximum signal intensity [TTM]), late gadolinium enhancement (LGE), and baseline characteristics were compared between the controls and ACM patients. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, Pearson's correlation, and multivariable linear regression models with a stepwise selection procedure. A two-tailed P value <0.05 was deemed as statistically significant. RESULTS: Compared to control subjects, ACM patients showed significantly biventricular adverse remodeling, reduced left ventricle (LV) global upslope and prolonged global TTM, and the presence of LGE. ACM patients were characterized by a significant decline in all global strain within the LV, right ventricle (RV), and IVS compared with the controls. RV global PS was significantly associated with LV global PS and IVS PS in radial, circumferential, and longitudinal directions. Multivariable analyses demonstrated the longitudinal PS of IVS was significantly correlated with RV global radial PS (ß = 0.614) and circumferential PS (ß = 0.545). Additionally, RV global longitudinal PS (GLPS) was significantly associated with radial PS of IVS (ß = -0.631) and LV GLPS (ß = 1.096). DATA CONCLUSION: ACM patients exhibited biventricular adverse structural alterations and impaired systolic and diastolic function. This cohort also showed reduced LV microvascular perfusion, the presence of LGE, and unfavorable VI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Innovative insights: ITLN1 modulates renal injury in response to radiation.

Radiation-induced kidney injury is a common side effect of radiotherapy, as the pelvic region is in close proximity to the kidneys, posing a risk of inducing radiation-induced kidney injury when treating any pelvic malignancies with radiotherapy. This type of injury typically manifests as chronic kidney disease a few months after radiotherapy, with the potential to progress to end-stage renal disease. Radiation-induced damage involves various components of the kidney, including glomeruli, tubules, interstitium, and extracellular matrix. Therefore, investigating its molecular mechanisms is crucial. In this study, we extensively searched literature databases, selecting recent transcriptomic studies related to acute kidney injury (AKI) published in the past decade. We downloaded the raw RNA sequencing datasets GSE30718 and GSE66494 related to AKI from the GEO database and identified that intestinal-type lectin ITLN1 plays a significant role in regulating radiation-induced kidney injury in rats. Differential gene analysis was performed using chip data from the GEO database, and further bioinformatics analysis identified 13 genes that may be involved in regulating kidney injury, with ITLN1 being the most relevant to kidney damage, thus selected as the target gene for this study. Subsequently, a rat model of radiation-induced kidney injury was established for experimental validation, assessing kidney tissue morphology and injury extent through staining observation and immunohistochemical staining. The protective effect of ITLN1 on kidney function was evaluated by measuring changes in rat body weight and blood pressure, serum kidney injury markers, and kidney structure. The experimental results indicate that overexpression of ITLN1 can improve kidney function in rats with radiation-induced kidney injury by activating the Akt/GSK-3ß/Nrf2 signaling pathway, suppressing oxidative stress, cell apoptosis, inflammation, cellular senescence, and fibrosis. This study highlights the significant role of ITLN1 in regulating kidney injury, providing a novel target for future treatments of radiation-induced kidney injury.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Coupling dynamic response of saturated soil with anisotropic thermal conductivity under fractional order thermoelastic theory.

In this paper, a two-dimensional (2D) thermo-hydro-mechanical dynamic (THMD) coupling analysis in the presence of a half-space medium is studied using Ezzat's fractional order generalized theory of thermoelasticity. Using normal mode analysis (NMA), the influence of the anisotropy of the thermal conduction coefficient, fractional derivatives, and frequency on the THMD response of anisotropy, fully saturated, and poroelastic subgrade is then analyzed with a time-harmonic load including mechanical load and thermal source subjected to the surface. The general relationships among the dimensionless physical variables such as the vertical displacement, excess pore water pressure, vertical stress, and temperature distribution are graphically illustrated. The NMA method does not require the integration and inverse transformation, increases the decoupling speed, and eliminates the limitation of numerical inverse transformation. The obtained results can guide the geotechnical engineering construction according to different values of load frequency, fractional order coefficient, and anisotropy of thermal conduction coefficient. This improves the subgrade stability and enriches the theoretical studies on thermo-hydro-mechanical coupling.

Steering sp-Carbon Content in Graphdiynes for Enhanced Two-Electron Oxygen Reduction to Hydrogen Peroxide.

Compared to sp2-hybridized graphene, graphdiynes (GDYs) composed of sp and sp2 carbon are highly promising as efficient catalysts for electrocatalytic oxygen reduction into oxygen peroxide because of the high catalytic reactivity of the electron-rich sp-carbon atoms. The desired catalytic capacity of GDY, such as catalytic selectivity and efficiency, can theoretically be achieved by strategically steering the sp-carbon contents or the topological arrangement of the acetylenic linkages and aromatic bonds. Herein, we successfully tuned the electrocatalytic activity of GDYs by regulating the sp-to-sp2 carbon ratios with different organic monomer precursors. As the active sp-carbon atoms possess electron-sufficient π orbitals, they can donate electrons to the lowest unoccupied molecular orbital (LUMO) orbitals of O2 molecules and initiate subsequent O2 reduction, GDY with the high sp-carbon content of 50 at% exhibits excellent capability of catalyzing O2 reduction into H2O2. It demonstrates exceptional H2O2 selectivity of over 95.0% and impressive performance in practical H2O2 production, Faraday efficiency (FE) exceeding 99.0%, and a yield of 83.3 nmol s-1 cm-2. Our work holds significant importance in effectively steering the inherent properties of GDYs by purposefully adjusting the sp-to-sp2 carbon ratio and highlights their immense potential for research and applications in catalysis and other fields.

The CXCR4 might be a potential biomarker for esophageal squamous cell carcinoma: A meta-analysis.

OBJECTIVE: To evaluate the relationship between CXCL12/CXCR4 and the progress, prognosis of esophageal squamous cell carcinoma (ESCC), providing evidence for potential early diagnosis, clinical treatment, prognosis evaluation, and therapeutic target of ESCC. METHODS: Databases of PubMed, the Cochrane Library, Embase, and Web of Science were searched for the relationship between CXCL12/CXCR4 and clinicopathological characteristics and survival time of ESCC. Stata16.0 software was used to conduct meta-analysis. RESULTS: A total of 10 studies involving 1216 cases of patients with ESCC were included in our study. The results indicated that high-level expression of CXCR4 was significantly correlated with tumor differentiation [OR = 0.69, 95% confidence interval (CI): (0.50, 0.97)], tumor infiltration [OR = 0.39, 95% CI: (0.25, 0.61)], lymph node metastasis [OR = 0.36, 95% CI: (0.21, 0.61)], clinical stage [OR = 0.33, 95% CI: (0.24, 0.45)] of ESCC. The expression of CXCR4 was also significantly correlated with OS [HR = 2.00, 95% CI: (1.63, 2.45)] and disease-free survival [HR = 1.76, 95% CI: (1.44, 2.15)] in patients of ESCC after surgical resection. No significant relationship was observed between the expression of CXCL12 and the clinicopathological characteristics of ESCC. CONCLUSION: CXCR4 might be a potential biomarker for the progress and prognosis evaluation, and therapeutic target for ESCC.

A combination of resistance genes confers high and durable resistance against stripe rust in wheat cultivar Lantian 26.

Lantian 26, a leading elite winter wheat cultivar in Gansu Province since its release in 2010, exhibits high resistance or immunization to stripe rust in adult-plant stage under a high disease pressure in Longnan (southeastern Gansu). Identifying the resistance genes in Lantian 26 could provide a basis for enhanced durability and high levels of resistance in wheat cultivars. Here, a segregating population was developed from a cross between a highly susceptible wheat cv. Mingxian 169 and the highly stripe rust-resistant cv. Lantian 26. The F2 and F2:3 progenies of the cross were inoculated with multiple prevalent virulent races of stripe rust for adult plant-stage resistance evaluation in two different environments. Exon sequence alignment analysis revealed that a stripe rust resistance gene on the 718.4-721.2 Mb region of chromosome 7BL, tentatively named as YrLT26, and a co-segregation STS marker GY17 was developed and validated using the F2:3 population and 103 wheat cultivars. The other two resistance genes, Yr9 and Yr30, were also identified in Lantian 26 using molecular markers. Therefore, the key to high and durable resistance to stripe rust at adult stage is the combination of Yr9, Yr30 and YrLT26 genes in Lantian 26. This could be a considerable strategy for improving the wheat cultivars with effective and durable resistance in the high-pressure region for stripe rust.

Tectorigenin protects against cardiac fibrosis in diabetic mice heart via activating the adiponectin receptor 1-mediated AMPK pathway.

Diabetic cardiomyopathy (DCM) is a common severe complication of diabetes that occurs independently of hypertension, coronary artery disease, and valvular cardiomyopathy, eventually leading to heart failure. Previous studies have reported that Tectorigenin (TEC) possesses extensive anti-inflammatory and anti-oxidative stress properties. In this present study, the impact of TEC on diabetic cardiomyopathy was examined. The model of DCM in mice was established with the combination of a high-fat diet and STZ treatment. Remarkably, TEC treatment significantly attenuated cardiac fibrosis and improved cardiac dysfunction. Concurrently, TEC was also found to mitigate hyperglycemia and hyperlipidemia in the DCM mouse. At the molecular level, TEC is involved in the activation of AMPK, both in vitro and in vivo, by enhancing its phosphorylation. This is achieved through the regulation of endothelial-mesenchymal transition via the AMPK/TGFß/Smad3 pathway. Furthermore, it was demonstrated that the level of ubiquitination of the adiponectin receptor 1 (AdipoR1) protein is associated with TEC-mediated improvement of cardiac dysfunction in DCM mice. Notably the substantial reduction of myocardial fibrosis. In conclusion, TEC improves cardiac fibrosis in DCM mice by modulating the AdipoR1/AMPK signaling pathway. These findings suggest that TEC could be an effective therapeutic agent for the treatment of diabetic cardiomyopathy.

Leveraging Bayesian network to reveal the importance of water level in a shallow lake ecosystem: A study based on Paleo-diatom and fish community.

Lake ecological processes and nutrient patterns are increasingly affected by water level variation around the world. Still, the long-term effects of water level change on lake ecosystems and their implications for suitable lake level management have rarely been studied. Here, we studied the ecosystem dynamics of a mesotrophic lake located in the cold and arid region of northern China based on long-term paleo-diatom and fishery records. Utilizing a novel Copula-Bayesian Network model, possible hydrological-driven ecosystem evolution was discussed. Results show that increased nutrient concentration caused by the first water level drop in the early 1980s incurred a transition of sedimental diatoms towards pollution-resistant species, and the following water level rise in the mid-1980s brought about considerable external loading, which attributed to eutrophication and caused the miniaturization of fishery structure. In the 21st century, a continuous water level plummet further reduced the sediment diatom biomass and the fish biomass by altering nutrient concentration. However, with the implementation of the water diversion project in 2011, oligotrophic species increased, and the ecosystem developed for the better. From the perspective of water quality protection requirements and the ecological well-being of Lake Hulun, the appropriate water level should be around 542.42-544.15 m. In summary, our study highlights the coupling effect of water level and water quality on Lake Hulun ecosystem and gives shed to lake water level operation and management under future climate change and human activities.

Identification and characterization of the Remorin gene family in Saccharum and the involvement of ScREM1.5e-1/-2 in SCMV infection on sugarcane.

Introduction: Remorins (REMs) are plant-specific membrane-associated proteins that play important roles in plant-pathogen interactions and environmental adaptations. Group I REMs are extensively involved in virus infection. However, little is known about the REM gene family in sugarcane (Saccharum spp. hyrid), the most important sugar and energy crop around world. Methods: Comparative genomics were employed to analyze the REM gene family in Saccharum spontaneum. Transcriptomics or RT-qPCR were used to analyze their expression files in different development stages or tissues under different treatments. Yeast two hybrid, bimolecular fluorescence complementation and co-immunoprecipitation assays were applied to investigate the protein interaction. Results: In this study, 65 REMs were identified from Saccharum spontaneum genome and classified into six groups based on phylogenetic tree analysis. These REMs contain multiple cis-elements associated with growth, development, hormone and stress response. Expression profiling revealed that among different SsREMs with variable expression levels in different developmental stages or different tissues. A pair of alleles, ScREM1.5e-1/-2, were isolated from the sugarcane cultivar ROC22. ScREM1.5e-1/-2 were highly expressed in leaves, with the former expressed at significantly higher levels than the latter. Their expression was induced by treatment with H2O2, ABA, ethylene, brassinosteroid, SA or MeJA, and varied upon Sugarcane mosaic virus (SCMV) infection. ScREM1.5e-1 was localized to the plasma membrane (PM), while ScREM1.5e-2 was localized to the cytoplasm or nucleus. ScREM1.5e-1/-2 can self-interact and interact with each other, and interact with VPgs from SCMV, Sorghum mosaic virus, or Sugarcane streak mosaic virus. The interactions with VPgs relocated ScREM1.5e-1 from the PM to the cytoplasm. Discussion: These results reveal the origin, distribution and evolution of the REM gene family in sugarcane and may shed light on engineering sugarcane resistance against sugarcane mosaic pathogens.

A meta-analysis of predictive value of blood biomarkers in gestational trophoblastic neoplasia.

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to play a diagnostic and predictive role in gestational trophoblastic disease. However, the conclusions are still ambiguous. This meta-analysis aimed to evaluate the combined predictive value of NLR and PLR in the malignant progression of gestational trophoblastic disease. Method: Electronic databases including PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Wanfang and China Biomedical Literature Database were searched for the relevant literature published up to 1 October 2022. Study selection and data extraction were performed independently by two reviewers. All analyses were performed using Revman, MetaDisc and STATA software. Results: A total of 858 patients from five studies were included in this meta-analysis. The pooled sensitivity and specificity of NLR were 0.8 (95% CI: 0.71-0.88) and 0.73 (95% CI: 0.69-0.76), respectively, and the area under curve of the summary receiver operating curve was 0.81. The pooled sensitivity and specificity of PLR were 0.87 (95% CI: 0.75-0.95) and 0.49 (95% CI: 0.44-0.54), respectively, and the area under curve of the summary receiver operating curve was 0.88. I2 statistic and Deek's funnel plot showed no heterogeneity and publication bias. Conclusion: NLR can accurately predict the progression from hydatidiform mole to gestational trophoblastic neoplasia and is a promising biomarker in further follow-up.

Detection of Arsenic(V) by Fluorescence Sensing Based on Chlorin e6-Copper Ion.

The high toxicity of arsenic (As) can cause irreversible harm to the environment and human health. In this study, the chlorin e6 (Ce6), which emits fluorescence in the infrared region, was introduced as the luminescence center, and the addition of copper ion (Cu2+) and As(V) provoked a regular change in fluorescence at 652 nm, whereas that of As(III) was 665 nm, which was used to optionally detect Cu2+, arsenic (As(III), and As(V)). The limit of detection (LOD) values were 0.212 µM, 0.089 ppm, and 1.375 ppb for Cu2+, As(III), and As(V), respectively. The developed method can be used to determine Cu2+ and arsenic in water and soil with good sensitivity and selectivity. The 1:1 stoichiometry of Ce6 with Cu2+ was obtained from the Job plot that was developed from UV-visible spectra. The binding constants for Cu2+ and As(V) were established to be 1.248 × 105 M-1 and 2.35 × 1012 M-2, respectively, using B-H (Benesi-Hildebrand) plots. Fluorescence lifetimes, B-H plots, FT-IR, and 1H-NMR were used to postulate the mechanism of Cu2+ fluorescence quenching and As(V) fluorescence restoration and the interactions of the two ions with the Ce6 molecule.

Downregulating miRNA-199a-5p exacerbates fluorouracil-induced cardiotoxicity by activating the ATF6 signaling pathway.

BACKGROUND: Fluorouracil (5-FU) might produce serious cardiac toxic reactions. miRNA-199a-5p is a miRNA primarily expressed in myocardial cells and has a protective effect on vascular endothelium. Under hypoxia stress, the expression level of miRNA-199a-5p was significantly downregulated and is closely related to cardiovascular events such as coronary heart disease, heart failure, and hypertension. We explored whether 5-FU activates the endoplasmic reticulum stress ATF6 pathway by regulating the expression of miRNA-199a-5p in cardiac toxicity. METHODS: This project established a model of primary cardiomyocytes derived from neonatal rats and treated them with 5-FU in vitro. The expression of miRNA-199a-5p and its regulation were explored in vitro and in vivo. RESULTS: 5-FU decreases the expression of miRNA-199a-5p in cardiomyocytes, activates the endoplasmic reticulum stress ATF6 pathway, and increases the expression of GRP78 and ATF6, affecting the function of cardiomyocytes, and induces cardiac toxicity. The rescue assay further confirmed that miRNA-199a-5p supplementation can reduce the cardiotoxicity caused by 5-FU, and its protective effect on cardiomyocytes depends on the downregulation of the endoplasmic reticulum ATF6 signaling pathway. CONCLUSIONS: 5-FU can down-regulate expression of miRNA-199a-5p, then activate the endoplasmic reticulum stress ATF6 pathway, increase the expression of GRP78 and ATF6, affect the function of cardiomyocytes, and induce cardiac toxicity.

Accessing Benzoazepine Derivatives via Photoinduced Radical Relay Formal [5 + 2] Reaction of Amide/Alkyne Enabled by Palladium Catalysis.

A novel class of alkyne-tethered amides facilitates an unprecedented photoinduced palladium-catalyzed radical relay formal [5 + 2] reaction. This innovative strategy allows for the rapid construction of diverse fused benzoazepine structures, yielding structurally novel and compelling compounds. With a broad substrate scope and excellent functional group tolerance, the methodology synthesizes biologically active compounds. Notably, the resulting tricyclic benzo[b]azepines offer diversification opportunities through simple transformations. DFT calculations elucidate a seven-membered ring closure mechanism involving the alkenyl radical and Pd(I) rebound alongside a concerted metalation-deprotonation (CMD) process.