Development of a breast cancer prognostic model based on vesicle-mediated transport-related genes to predict immune landscape and clinical drug therapy.

BACKGROUND: Vesicle-mediated transport, vital for substance exchange and intercellular communication, is linked to tumor initiation and progression. This work was designed to study the role of vesicle-mediated transport-related genes (VMTRGs) in breast cancer (BC)prognosis. METHODS: Univariate Cox analysis was utilized to screen prognosis-related VMTRGs. BC samples underwent unsupervised clustering based on VMTRGs to analyze survival, clinical factors, and immune cell abundance across different subtypes. We constructed a risk model using univariate Cox and LASSO regression analysis, with validation conducted using GEO datasets. Subsequently, we performed tumor mutational burden analysis, and immune landscape analysis on both groups. Ultimately, we conducted immunophenoscore (IPS) scoring to forecast immunotherapy and performed drug sensitivity analysis. RESULTS: We identified 102 VMTRGs associated with BC prognosis. Using these 102 VMTRGs, BC patients were classified into 3 subtypes, with Cluster3 patients showing significantly better survival rates. We constructed a prognostic model for BC based on 12 VMTRGs that effectively predicted patient survival. Riskscore was an independent prognostic factor for BC patients. According to median risk score, high-risk group (HRG) had higher TMB values. The immune landscape of the HRG exhibited characteristics of cold tumor, with higher immune checkpoint expression levels and lower IPS scores, whereas Gemcitabine, Nilotinib, and Oxaliplatin were more suitable for treating low-risk group. CONCLUSION: We classified BC subtypes and built a prognostic model based on VMTRGs. The genes in the prognostic model may serve as potential targets for BC therapy.

Mechanical Robust GO/PVA Hydrogel for Strong and Recyclable Adhesion in Air, Underwater, and Underoil Environments.

Adhesive hydrogels are considered to be promising interfacial adhesive materials for various applications; however, their adhesive strength is significantly reduced when immersed in liquid environments (water and oil) due to obstruction of the liquid layer or swelling in liquid, and they could not always be reused when the failure of the adhesive performance occurred. Herein, a graphite oxide/poly(vinyl alcohol) (GO/PVA) hydrogel with strong adhesion in air and under liquid environments was developed by rationally regulating the interactions of water and dimethyl sulfoxide (DMSO) in the binary liquid system. The strong interaction between water and DMSO allowed the water layer of the GO/PVA hydrogel on the hydrogel surface to act as a shield to repel oil in air, under water, and even when immersed in oil, and it also endowed the obtained hydrogel with antiswelling property when immersed in water and oil. Importantly, the GO/PVA hydrogel could serve as an advanced adhesive to firmly bond different substrates in air, under water, and under oil, and interestingly, its dry and wet adhesive performance was repeatable and recyclable. This work is expected to be an important addition to the field of adhesive soft materials.

Versatile GO/ANFs Aerogel for Highly Efficient Solar-Powered Water Purification in Wide Environments.

Solar-driven interfacial evaporation is a very promising choice for producing clean water. Despite the considerable investigation of pure NaCl brine purification, solar-driven complex water purification, such as real-world seawater desalination as well as domestic and industrial wastewater treatment, has rarely been investigated, mainly due to its compositions being much more complicated than NaCl brine. Herein, we developed a graphene oxide/aramid nanofiber (GO/ANFs) aerogel by a freeze-drying process. The GO/ANFs aerogel combined opened porous microchannels, superhydrophilicity, anti-oil-fouling capacity, enhanced broad-spectrum light absorption (more than 92%), and good solar/heat management. These integrated properties enabled the GO/ANFs aerogel to be an advanced solar interfacial evaporator for efficient freshwater production with the characteristics of localized heat conversion, quick water transport, and salt crystallization inhibition, and the rate of steam production rate was as high as 2.25 kg m-2 h-1 upon exposure to 1 solar irradiation. Importantly, the high-water-vapor generation rate was maintained even under complicated conditions, including real-world seawater, dye water, emulsions, and corrosive liquid environments. Considering its promising adaptability to a wide range of environments, this work hopes to inspire the development of brine desalination, wastewater purification, clean water production, and solar energy utilization.

Dysregulated ceRNA network modulated by copy number variation-driven lncRNAs in breast cancer: A comprehensive analysis.

Breast cancer is a malignancy harmful to physical and mental health in women, with quite high mortality. Copy number variations (CNVs) are vital factors affecting the progression of breast cancer. Detecting CNVs in breast cancer to predict the prognosis of patients has become a promising approach to accurate treatment in recent years. The differential analysis was performed on CNVs of long noncoding RNAs (lncRNAs) as well as the expression of lncRNAs, microRNAs (miRNAs) and mRNAs in normal tissue and breast tumor tissue based on The Cancer Genome Atlas (TCGA) database. The CNV-driven lncRNAs were identified by the Kruskal-Wallis test. Meanwhile, a competitive endogenous RNA (ceRNA) network regulated by CNV-driven lncRNA was constructed. As the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed, the mRNAs in the dysregulated ceRNA network were mainly enriched in the biological functions and signaling pathways, including the Focal Adhesion-PI3K-Akt-mTOR-signaling pathway, the neuronal system, metapathway biotransformation Phase I and II and blood circulation, etc. The relationship between the CNVs of five lncRNAs and their gene expression in the ceRNA network was analyzed via a chi-square test, which confirmed that except for LINC00243, the expression of four lncRNAs was notably correlated with the CNVs. The survival analysis revealed that only the copy number gain of LINC00536 was evidently related to the poor prognosis of patients. The CIBERSORT algorithm showed that five lncRNAs were correlated with the abundance of immune cell infiltration and immune checkpoints. In a word, by analyzing CNV-driven lncRNAs and the ceRNA network regulated by these lncRNAs, this study explored the mechanism of breast cancer and provided novel insights into new biomarkers.

Simple and Rapid Way to a Multifunctionally Conductive Hydrogel for Wearable Strain Sensors.

Conductive hydrogels have gained increasing attention in the field of wearable smart devices. However, it remains a big challenge to develop a multifunctionally conductive hydrogel in a rapid and facile way. Herein, a conductive tannic acid-iron/poly (acrylic acid) hydrogel was synthesized within 30 s at ambient temperature by the tannic acid-iron (TA@Fe3+)-mediated dynamic catalytic system. The TA@Fe3+ dynamic redox autocatalytic pair could efficiently activate the ammonium persulfate to initiate the free-radical polymerization, allowing the gelation to occur easily and rapidly. The resulting hydrogel exhibited enhanced stretchability (3560%), conductivity (33.58 S/m), and strain sensitivity (gauge factor = 2.11). When damaged, it could be self-healed through the dynamic and reversible coordination bonds between the Fe3+ and COO- groups in the hydrogel network. Interestingly, the resulting hydrogel could act as a strain sensor to monitor various human motions including the huge movement of deformations (knuckle, wrist) and subtle motions (smiling, breathing) in real time due to its enhanced self-adhesion, good conductivity, and improved strain sensitivity. Also, the obtained hydrogel exhibited efficient electromagnetic interference (EMI) shielding performance with an EMI shielding effectiveness value of 24.5 dB in the X-band (8.2-12.4 GHz). Additionally, it displayed antibacterial properties, with the help of the activity of TA.

Copper-Catalyzed Radical Enantioselective Synthesis of γ-Butyrolactones with Two Non-vicinal Carbon Stereocenters.

Chiral heterocycles with two or more carbon stereocenters are quite important skeletons in many fields. However, powerful strategies for the construction of such synthetically valuable heterocycles, especially with two or more remote carbon stereocenters, have largely lagged behind. We report here a powerful method for the synthesis of chiral γ-butyrolactones with two non-vicinal carbon stereocenters from readily available chemical feedstocks under mild conditions. Both of the two diastereoisomers can be obtained with good to excellent enantioselectivities. The well-designed copper/PyBox catalytic system overrides the intrinsic stereoinduction of the close chirality center generated by the previous innocent radical addition step. Nevertheless, this work has the power to selectively provide one single diastereoisomer by taking advantage of the epimerization effect but also to synthesize all four diastereoisomers with the pair of chiral ligands L2 and L2' having opposite chirality. The obtained useful chiral γ-butyrolactones can be synthetically transformed into acyclic or cyclic molecules with two non-vicinal carbon stereocenters. Mechanistic studies reveal that this radical reaction follows a linear relationship and can be well performed with a less loading amount of ligand compared to that of the copper catalyst.

DNMT1 facilitates growth of breast cancer by inducing MEG3 hyper-methylation.

BACKGROUND: To understand the effect of DNMT1-mediated MEG3 promoter methylation on breast cancer progression. METHODS: Expression of DNMT1, MEG3 and miR-494-3p was assayed by qRT-PCR and western blot. Methylation-specific PCR was used to examine MEG3 promoter methylation level. ChIP, RNA binding protein immunoprecipitation assay and dual-luciferase reporter gene assay were applied to verify interaction between DNMT1 and MEG3, miR-494-3p and MEG3 and OTUD4. CCK-8, wound healing and Transwell assays were used to detect biological functions of breast cancer cells. Tumor growth was observed by tumor xenograft model. RESULTS: DNMT1 and miR-494-3p were highly expressed while MEG3 and OTUD4 were lowly expressed in breast cancer cells. Knockdown of DNMT1 inhibited progression of breast cancer cells by enhance MEG3 expression through demethylation. MEG3 could downregulate miR-494-3p expression, and OTUD4 was a target of miR-494-3p. Upregulation of MEG3 and downregulation of miR-494-3p both inhibited malignant behavior of cells in vitro. In addition, high MEG3 expression restrained growth of breast cancer in vivo. CONCLUSION: Briefly, our results demonstrated that, DNMT1 induced methylation of MEG3 promoter, and played a key role in breast cancer growth throughmiR-494-3p/OTUD4 axis. These findings provide new insights into molecular therapeutic targets for breast cancer.

Study on water resources carrying capacity in Zhuanglang River Basin.

With the rapid development of China's social economy, the phenomenon of unbalanced regional economic development is increasingly obvious. The shortage of water resources in northwest China is an important constraint to local development. The study on the water resources carrying capacity of the Zhuanglang River Basin plays an important role in the development of local economy; thus, we evaluate the water resources situation of Zhuanglang River Basin by using hydrology-related calculation method, combining with field investigation, visiting relevant departments, and referring to relevant data. Meanwhile, the water resources carrying capacity of 3 counties and 12 townships in the Zhuanglang River Basin in the current year are studied and analyzed based on methods such as fuzzy comprehensive evaluation model and quantitative calculation. Results indicate that the carrying capacity of water resources in Zhuanglang river basin can mostly meet the needs of township, but it is necessary to further optimize the water resources carrying capacity of the Zhuanglang River Basin from the four systems of water resources, society, economy, and ecology in the future. Besides, the results of quantitative calculation show that the maximum economic scale that water resources can withstand in most areas of the Zhuanglang River Basin is the overall well-off level, that is, the per capita domestic water is 80L/(d· person), and the per capita GDP is 10000 yuan/person. But there is still a certain gap to achieve the level, when the people are well-off in an all-round way, the two indexes are correspondently raised to 120L/(d· person), and the per capita GDP is 30,000 yuan/person.

Copper-Catalyzed Radical Enantioselective Carbo-Esterification of Styrenes Enabled by a Perfluoroalkylated-PyBox Ligand.

Chiral lactones are found in many natural products. The reaction of simple alkenes with iodoacetic acid is a powerful method to build lactones, but the enantioselective version of this reaction has not been implemented to date. Herein, we report the efficient catalytic radical enantioselective carbo-esterification of styrenes enabled by a newly developed CuI -perfluoroalkylated PyBox system. Simple styrenes have been converted to useful chiral lactones, whose synthetic applications are showcased. Mechanistic studies reveal that this reaction is a rare example of an efficient ligand-decelerated system, in which the ligand decelerates the reaction, but the reaction is still efficient with reduced amounts of ligand. This uncommon catalytic system may inspire further consideration of the effect of ligands in asymmetric catalysis.

Copper-Catalyzed Enantioselective Radical 1,4-Difunctionalization of 1,3-Enynes.

Chiral allenes are important structural motifs frequently found in natural products, pharmaceuticals, and other organic compounds. Asymmetric 1,4-difunctionalization of 1,3-enynes is a promising strategy to construct axial chirality and produce substituted chiral allenes from achiral substrates. However, the previous state of the art in 1,4-difunctionalization of 1,3-enynes focused on the allenyl anion pathway. Because of this, only electrophiles can be introduced into the allene backbones in the second functionalization step, consequently limiting the reaction and allene product types. The development of asymmetric 1,4-difunctionalization of 1,3-enynes via a radical pathway would complement previous methods and support expansion of the toolbox for the synthesis of asymmetric allenes. Herein, we report the first radical enantioselective allene formation via a group transfer pathway in the context of copper-catalyzed radical 1,4-difunctionalization of 1,3-enynes. This method addresses a longstanding unsolved problem in asymmetric radical chemistry, provides an important strategy for stereocontrol with free allenyl radicals, and offers a novel approach to the valuable, but previously inaccessible, chiral allenes. This work should shed light on asymmetric radical reactions and may lead to other enantioselective group transfer reactions.

Tri-layer gradient and polarization-selective vertical couplers for interlayer transition.

We demonstrate and optimize a tri-layer vertical coupler for a silicon nitride (Si3N4) multilayer platform operating at a 2 µm band. The large spacing between the topmost and bottommost layers of a gradient structure enables ultra-low crossing loss and interlayer crosstalk without affecting the efficiency interlayer transition. We achieve a 0.31 dB transition loss, ultra-low multi-layer crosstalk of -59.3 dB at a crossing angle of 90° with an interlayer gap of 2300 nm at 1950nm. With width optimization of this structure, the fabrication tolerances toward lateral misalignment of two stages in this coupler have increased 61% and 56%, respectively. We also propose a vertical coupler, based on this design, with mode selectivity and achieve an extinction ratio of < 15 dB for wavelengths in the 1910-1990 range. Meanwhile, a multi-layer interlaced AWGs centered at 1950nm and based on vertical coupler has been demonstrated. The proposed vertical couplers exhibit potential for application in large-scale photonic-integrated circuits and broadly in photonic devices.

Copper-Catalyzed Radical 1,4-Difunctionalization of 1,3-Enynes with Alkyl Diacyl Peroxides and N-Fluorobenzenesulfonimide.

Many reactions involving allenyl ion species have been studied, but reactions involving allenyl radicals are less well understood, perhaps because of the inconvenience associated with the generation of short-lived allenyl radicals. We describe here a versatile method for the generation of allenyl radicals and their previously unreported applications in the intermolecular 1,4-carbocyanation and 1,4-sulfimidocyanation of 1,3-enynes. With the assistance of the trifunctional reagents, alkyl diacyl peroxides or N-fluorobenzenesulfonimide, a range of synthetically challenging multisubstituted allenes can be prepared with high regioselectivity. These multisubstituted allenes can be easily transformed into synthetically useful structures such as fluorinated vinyl cyanides, lactones, functionalized allenyl amides, 1-aminonaphthalenes, and pyridin-2(1 H)-ones, and several novel transformations are reported. The results of radical scavenger and radical clock experiments are consistent with the proposed allenyl radical pathway. Density functional theory (DFT) and IR spectroscopy studies suggest the formation of an isocyanocopper(II) species in the ligand exchange step. On the basis of the results of IR, DFT, and diastereoselectivity studies, an isocyanocopper(II)/copper(I) catalytic cycle is proposed, which differs from the previously considered Cu(III) mechanism in cyanation reactions.

Iron-Catalyzed Radical Decarboxylative Oxyalkylation of Terminal Alkynes with Alkyl Peroxides.

An iron-catalyzed oxyalkylation of alkynes with alkyl peroxides as the alkylating reagents has been investigated. Alkyl peroxides are readily available from aliphatic acids and serve simultaneously as the alkylating reagents and internal oxidants. Primary, secondary, and tertiary alkyl groups of aliphatic acids were readily incorporated into C-C triple bonds and diverse α-alkylated ketones were synthesized. Mechanism studies revealed that this reaction involves highly reactive alkyl free radicals. A unique equilibrium between lauric acid and water catalyzed by the iron(III) catalyst was observed.

Associations among thyroid hormone levels and mean corpuscular volume in adults in the US: A cross-sectional examination of the NHANES 2007-2012 dataset.

Mean corpuscular volume (MCV) is an important indicator used to determine the etiology of anemia and is associated with a variety of diseases. However, the link between thyroid function and MCV has yet to be clarified. This study was thus developed to assess relationships between thyroid function and MCV in a population of adults in the US. Results from the National Health and Nutrition Examination Survey study performed from 2007 to 2012 were used to conduct a cross-sectional analysis. Key thyroid-related variables included in this analysis were thyroid-stimulating hormone, total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), antithyroglobulin, thyroglobulin, and antithyroid peroxidase levels. Generalized linear regression models were employed when estimating associations between MCV quartiles and thyroid parameters in 8104 adults 18 + years of age. In these participants, the weighted mean (SD) MCV was 89.36 (0.16) fL, with thyroid-stimulating hormone levels of 1.86 (0.03) mIU/mL, FT3 levels of 3.20 (0.01) pg/mL, FT4 levels of 0.80 (0.01) ng/dL, TT3 levels of 115.09 (0.64) ng/dL, and TT4 levels of 7.81 (0.04) µg/dL. When analyses were not adjusted, higher MCV values were related to reduced serum levels of FT3, TT3, or TT4. Following adjustment for possible confounding variables, this significant negative correlation between MCV and levels of FT3, TT3, and TT4 remained, and subgroup analysis revealed that this negative correlation was present in the male group and in the age group >50 years, but not in the female group and in the age group less than or equal to 50 years. These results suggest a significant negative correlation between MCV and FT3, TT3, and TT4, and this negative correlation originated more from the male population and those older than 50 years of age. The underlying mechanisms warrant additional investigation.

The association between the composite dietary antioxidant index and thyroid functionality among adults in the USA: NHANES 2007-2012.

Objective: Composite Dietary Antioxidant Index (CDAI) values serve as a summary of an individual's combined dietary antioxidant intake. Although specific antioxidants are known to reduce thyroid damage from oxidative stress, the relationship between the CDAI and thyroid function remains uncertain. The purpose of this study was thus to investigate this relationship in greater detail while focusing on a representative American adult population. Methods: A total of 6,860 subjects from the 2007-2012 NHANES cohort were included in this study. Associations between CDAI values and thyroid function were evaluated with weighted linear regression models and smoothed curve fitting. Subgroup analyses were also performed. Results: The weighted mean (SD) values for variables analyzed in this study included a CDAI of 0.13 (0.06), serum free T4 (FT4) levels of 0.80 (0.01) ng/dL, and serum total T4 (TT4) levels of 7.80 (0.03) ug/dL. Lower CDAI values were found to be associated with higher levels of FT4 and TT4 using both unadjusted and adjusted models that accounted for relevant confounders (adjusted model, FT4 ß = -0.003, p = 0.005; TT4 ß = -0.035, p < 0.001). This negative correlation persisted when CDAI was categorized into quartiles (FT4, p for trend = 0.014; TT4, p for trend = 0.003). Conclusion: These findings suggest that a diet rich in antioxidants, as reflected by higher CDAI scores, is associated with significant decreases in levels of free and total T4. Further analyses will be necessary to better clarify the underlying mechanisms behind these observations.

The Relationship between Nutritional Status and Thyroid Function among Adults in the USA: NHANES 2007-2012.

Controlled Nutritional Status (CONUT) scores have been developed as quantitative tools that can be employed to gauge the nutritional status of individual patients. However, there has been very little research investigating the association between these CONUT scores and the function of the thyroid. As such, the present study was designed to address this research gap through the evaluation of a representative cohort of American adults. National Health and Nutrition Examination Survey (NHANES) data were herein used to separate subjects into those with normal nutritional status (CONUT score: 0-1) from those who were malnourished (CONUT scores > 1). Associations between these CONUT scores and the function of the thyroid were investigated through linear regression modeling, employing weighted analytical strategies and subgroup analyses. Overall, 8,082 individuals from the NHANES 2007-2012 cohort were enrolled in this analysis. These individuals exhibited a weighted mean CONUT score of 0.72 (0.02). 6661 (weighted proportion: 83.12%) in the normal nutritional status group and 1421 (16.88%) in the malnourished group. In adjusted analyses, subjects who were malnourished were found to present with an increase in FT4 levels (ß = 0.033; p < 0.001 together with reduced TT3 levels (ß = -3.526; p = 0.01). The present data offer evidence in support of higher CONUT scores, which correspond to malnutrition, being related to increases in FT4 levels together with reductions in TT3 levels. More studies will be crucial to further probe the mechanistic drivers of these results.

Tree-Inspired Aerogel with a Radial and Centrosymmetric Structure for Efficient Solar-Powered Water Purification.

Solar-powered water purification is one of the promising choices for clean water production. However, it remains challenging to develop aerogel solar evaporators that simultaneously possess enhanced light-to-heat conversion, optimal thermal management, and salt crystal deposition inhibition. Herein, to address this challenge, we have developed a 3D chitosan-reduced graphene oxide/polypyrrole (CS-RGO/PPy) aerogel vaporizer with a vertical and radially aligned structure through a directional freezing process, inspired by the featured structure of conifers. The radially porous walls and vertically arranged channels within the 3D aerogel were able to facilitate high light absorption, localizing converted heat, rapid water transport, and self-salt discharge. Under 1 sun irradiation, the aerogel vaporizer displayed an improved light absorption characteristic of 95% and a high-rate evaporation (∼3.19 kg m-2 h-1) that achieved continuous freshwater from the saturated brine production without solid salt crystallization. Besides achieving seawater desalination, the obtained aerogel could purify organic wastewater and emulsions through solar distillation with high-rate continuous water production.

Ag/polydopamine-coated textile for enhanced liquid/liquid mixtures separation and dye removal.

Engineering a versatile platform that enables to separate both oil/water and oil/oil mixtures and remove dye from water is not easy. To address this challenge, we have developed an Ag/polydopamine-coated textile (Ag/PDA@textile) by chemically depositing Ag particles on the textile surface using polydopamine as the binder layer. The obtained Ag/PDA@textile attracts water but repels oil in the air, underwater, and when immersed into the oil. Exploiting its water-attracting and oil resistance, the Ag/PDA@textile is acted as a separation membrane to separate oil/water mixtures with enhanced separation efficiency. The Ag/PDA@textile also possesses opposite wetting behavior to oils with different polarities, allowing it to separate oil/oil mixtures efficiently. Thanks to the catalytic performance of the Ag particle, organic dyes can be decomposed effectively by our Ag/PDA@textile under UV illustration or in the presence of NaBH4. Our Ag/PDA@textile may be valuable for applications in water purification and oil sewage treatment.

Counterion exchange to achieve reversibly switchable hydrophobicity and oleophobicity on fabrics.

We describe a simple layer-by-layer (LbL) technology and counterion exchange procedure to tune the liquid wettability of commercially available cotton fabrics. A polyelectrolyte multilayer is deposited on the fabric surface by the LbL technology, and counterion exchange is used to control the surface composition and thereby to modulate the solid surface energy. The tunability of the solid surface energy, along with the inherent re-entrant texture of the cotton fabric, results in simultaneously switchable wettability between a nonwetting state and a fully wetted state for water and hexadecane. This switchable hydrophobicity and oleophobicity can be explained within a robustness factor, which is a quantitative criterion for the transition between the two states. The counterion exchange can be confirmed by X-ray photoelectron spectroscopy analysis.

Rapid control of switchable oil wettability and adhesion on the copper substrate.

We described a facile approach to rapidly achieve the reversible oil wettability and adhesion transition on the copper substrate. Plasma treatment and surface fluorination were used to tune the surface composition, and this tunability of the surface composition, along with the stable surface roughness, gave rise to the switchable wettability varying from superoleophobicity to superoleophilicity and reversible oil adhesion between sliding superoleophobicity and sticky superoleophobicity. It took only 1.25 min to realize the whole wettability transition and 5 min for the whole adhesion transition. Additionally, the application of a sticky superoleophobic surface was demonstrated. This study represents an important addition to the field of functional superoleophobic materials.