Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer.

BACKGROUND: Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2-BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2-BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. METHODS: In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2-BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2-BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan-Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2-BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. RESULTS: By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2-BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2-BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. CONCLUSION: In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.

Parecoxib inhibits tumorigenesis and angiogenesis in hepatocellular carcinoma through ERK-VEGF/MMPs signaling pathway.

Parecoxib, a well-recognized nonsteroidal anti-inflammatory drug, has been reported to possess anticancer properties in various tumor types. In this work, we aimed to investigate the potential anticancer effects of parecoxib on hepatocellular carcinoma (HCC) cells. To assess the impact of parecoxib on HCC cell proliferation, we employed Cell Counting Kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays. Hoechst/propidium iodide (PI) double staining and flow cytometry were performed to evaluate apoptosis and cell cycle analysis. Wound healing and transwell assays were utilized to assess cell migration and invasion. Tube formation assay was employed to analyze angiogenesis. Protein levels were determined using western blotting, and mRNA expression levels were assessed using quantitative real-time polymerase chain reaction (PCR). A xenograft mouse model was used to confirm the antitumor effects of parecoxib on HCC tumors in vivo. Our data demonstrated that parecoxib effectively inhibited the proliferation of HCC cells in a dose- and time-dependent manner. In addition, parecoxib induced cell cycle arrest in the G2 phase and promoted apoptosis. Moreover, parecoxib hindered tumor migration and invasion by impeding the epithelial-mesenchymal transition process. Further investigation showed that parecoxib could significantly suppress angiogenesis through the inhibition of extracellular signal-regulated kinase (ERK)-vascular endothelial growth factor (VEGF) axis. Notably, treatment with the ERK activator phorbol myristate acetate upregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF and reversed the function of parecoxib in HCC cells. Besides, parecoxib displayed its antitumor efficacy in vivo. Collectively, our results suggest that parecoxib ameliorates HCC progression by regulating proliferation, cell cycle, apoptosis, migration, invasion, and angiogenesis through the ERK-VEGF/MMPs signaling pathway.

Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury.

Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury. Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-κB [NF-κB], phospho-NF-κB [P-NF-κB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-18, in rat liver tissues. The level of P-NF-κB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-κB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury.

Using Redox-Switchable Polymerization Catalysis to Synthesize a Chemically Recyclable Thermoplastic Elastomer.

In an effort to synthesize chemically recyclable thermoplastic elastomers, a redox-switchable catalytic system was developed to synthesize triblock copolymers containing stiff poly(lactic acid) (PLA) end blocks and a flexible poly(tetrahydrofuran-co-cyclohexene oxide) (poly(THF-co-CHO) copolymer as the mid-block. The orthogonal reactivity induced by changing the oxidation state of the iron-based catalyst enabled the synthesis of the triblock copolymers in a single reaction flask from a mixture of monomers. The triblock copolymers demonstrated improved flexibility compared to poly(l-lactic acid) (PLLA) and thermomechanical properties that resemble thermoplastic elastomers, including a rubbery plateau in the range of -60 to 40 °C. The triblock copolymers containing a higher percentage of THF versus CHO were more flexible, and a blend of triblock copolymers containing PLLA and poly(d-lactic acid) (PDLA) end-blocks resulted in a stereocomplex that further increased polymer flexibility. Besides the low cost of lactide and THF, the sustainability of this new class of triblock copolymers was also supported by their depolymerization, which was achieved by exposing the copolymers sequentially to FeCl3 and ZnCl2 /PEG under reactive distillation conditions.

Anti-Inflammatory and Anti-Oxidative Effects of Isorhamnetin for Protection Against Lung Injury in a Rat Model of Heatstroke in a Dry-Heat Environment.

BACKGROUND Isorhamnetin is a natural flavonoid compound with anti-inflammatory and antioxidant properties. However, its roles in alleviating lung injury associated with heatstroke remain unclear. Therefore, this study aimed to evaluate the protective effects of different isorhamnetin doses on lung injury in heatstroke rat models exposed to a dry-heat environment. MATERIAL AND METHODS Fifty Sprague-Dawley rats were randomly divided into 5 groups: normal control (0.9% saline), heatstroke (0.5% CMCNa), and isorhamnetin (25, 50, and 100 mg/kg) groups; treatments were administered by gavage daily for 7 days. All rats, except those in the control group, were exposed to a dry-heat environment (41±1°C, 10±2% relative humidity) for 150 min to induce heatstroke. Pathological changes, ultrastructure, edema, inflammation, and oxidative stress in the lungs were assessed. RESULTS Compared with the heatstroke group, rats treated with 100 mg/kg isorhamnetin showed amelioration of histopathological and ultrastructural changes in the lungs; decreased lung injury scores (P<0.05) and wet/dry weight ratios (P<0.01); lower levels of phospho-nuclear factor-kappaB (P<0.05), high-mobility group box 1 (P<0.01), tumor necrosis factor-alpha (P<0.01), interleukin (IL)-1ß (P<0.01), and IL-6 (P<0.01); lower malondialdehyde contents (P<0.01); and higher superoxide dismutase (P<0.01) and catalase activities (P<0.05). CONCLUSIONS In a dry-heat environment, isorhamnetin protected against lung injury in heatstroke rat models via anti-inflammatory and anti-oxidative mechanisms.

Graphene-Oxide-Based Fluoro- and Chromo-Genic Materials and Their Applications.

Composite materials and their applications constitute a hot field of research nowadays due to the fact that they comprise a combination of the unique properties of each component of which they consist. Very often, they exhibit better performance and properties compared to their combined building blocks. Graphene oxide (GO), as the most widely used derivative of graphene, has attracted widespread attention because of its excellent properties. Abundant oxygen-containing functional groups on GO can provide various reactive sites for chemical modification or functionalization of GO, which in turn can be used to develop novel GO-based composites. This review outlines the most recent advances in the field of novel dyes and pigments encompassing GO as a key ingredient or as an important cofactor. The interactions of graphene with other materials/compounds are highlighted. The special structure and unique properties of GO have a great effect on the performance of fabricated hybrid dyes and pigments by enhancing the color performance of dyes, the anticorrosion properties of pigments, the viscosity and rheology of inks, etc., which further expands the applications of dyes and pigments in dyeing, optical elements, solar-thermal energy storage, sensing, coatings, and microelectronics devices. Finally, challenges in the current development as well as the future prospects of GO-based dyes and pigments are also discussed. This review provides a reference for the further exploration of novel dyes and pigments.

Epidemiological survey to determine the prevalence of cholecystolithiasis in Uyghur, Kazakh, and Han Ethnic Groups in the Xinjiang Uyghur Autonomous Region of China: cross-sectional studies.

BACKGROUND: This study was performed to understand the prevalence of and possible risk factors for cholecystolithiasis in Uyghur, Kazakh, Han, and other ethnic groups in the Xinjiang Uyghur autonomous region of China. METHODS: Subjects were enrolled using typical case sampling and multistage stratified random sampling. We collected epidemiological data regarding cholecystolithiasis using a standard questionnaire of risk factors for gallbladder disease in Xinjiang. The subjects completed the questionnaire and underwent an abdominal ultrasound examination of the liver and gallbladder. RESULTS: This study included 5454 Xinjiang residents aged ≥ 18 years. The prevalence of cholecystolithiasis was 15% (11.3% in men and 17.1% in women), and the sex difference was statistically significant (male-to-female odds ratio [OR] 1.867; p < 0.001). The cholecystolithiasis prevalence was also significantly different among the Han, Uyghur, Kazakh, and other ethnic groups (13.1%, 20.8%, 11.5%, and 16.8%, respectively; p < 0.001). The prevalence of cholecystolithiasis in northern Xinjiang was 13.5% and that in southern Xinjiang was 17.5%; this difference was also statistically significant (OR 1.599; p < 0.001). Across all ethnic groups, the cholecystolithiasis prevalence significantly increased with age (all p < 0.01) and body mass index (BMI) (all p < 0.01). A multivariate logistic regression analysis indicated that cholecystolithiasis prevalence was associated with sex, age, BMI, smoking, diabetes, fatty liver disease, and geographical differences between northern and southern Xinjiang. CONCLUSIONS: The prevalence of cholecystolithiasis was significantly higher in the Uyghur ethnic group than in the Han, Kazakh, and other ethnic groups; in women than in men; in southern Xinjiang than in northern Xinjiang; in patients with fatty liver disease; and increased with age and BMI. Our findings could provide a theoretical basis for the formulation of control measures for cholecystolithiasis.

Curcumin alleviates acute kidney injury in a dry-heat environment by reducing oxidative stress and inflammation in a rat model.

Curcumin exhibits anti-inflammatory and antioxidant activities. We investigated the protective effects of curcumin in a renal injury rat model under dry-heat conditions. We divided Sprague-Dawley rats into four groups: dry-heat 0- (normal temperature control group), 50-, 100-, and 150-minute groups. Each group was divided into five subgroups (n = 10): normal saline (NS), sodium carboxymethylcellulose (CMCNa), and curcumin pretreated low, medium, and high-dose (50, 100, and 200 mg/kg, respectively) groups. Compared to the normal temperature group, serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1, and neutrophil gelatinase-associated load changes in lipoprotein (NGAL) levels were significantly increased in the dry-heat environment group (P < .05); inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and malondialdehyde (MDA) and related inflammatory factor levels were increased in the kidney tissue. Superoxide dismutase (SOD) and catalase (CAT) levels were decreased. However, following all curcumin pretreatment, the serum levels of kidney injury indicators and NGAL were decreased in the urine compared to those in the NS and CMCNa groups (P < .05), whereas renal SOD and CAT activities were increased and MDA was decreased (P < .05). Renal tissues of the 150-minute group showed obvious pathological changes. Compared to the NS group, pathological changes in the renal tissues of the 100- and 200-mg/kg curcumin groups were significantly reduced. Furthermore, iNOS and COX-2 expression and inflammatory factor levels were decreased after curcumin treatment. Curcumin exerted renoprotective effects that were likely mediated by its antioxidant and anti-inflammatory effects in a dry-heat environment rat model.

Network analysis of potential risk genes for psoriasis.

BACKGROUND: Psoriasis is a complex chronic inflammatory skin disease. The aim of this study was to analyze potential risk genes and molecular mechanisms associated with psoriasis. METHODS: GSE54456, GSE114286, and GSE121212 were collected from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between psoriasis and controls were screened respectively in three datasets and common DEGs were obtained. The biological role of common DEGs were identified by enrichment analysis. Hub genes were identified using protein-protein interaction (PPI) networks and their risk for psoriasis was evaluated through logistic regression analysis. Moreover, differentially methylated positions (DMPs) between psoriasis and controls were obtained in the GSE115797 dataset. Methylation markers were identified after comparison with the common genes. RESULTS: A total of 118 common DEGs were identified, which were mainly involved in keratinocyte differentiation and IL-17 signaling pathway. Through PPI network, we identified top 10 degrees as hub genes. Among them, high expression of CXCL9 and SPRR1B may be risk factors for psoriasis. In addition, we selected 10 methylation-modified genes with the higher area under receiver operating characteristic curve (AUC) value as methylation markers. Nomogram showed that TGM6 and S100A9 may be associated with an increased risk of psoriasis. CONCLUSION: This suggests that immune and inflammatory responses are active in keratinocytes of psoriatic skin. CXCL9, SPRR1B, TGM6 and S100A9 may be potential targets for the diagnosis and treatment of psoriasis.

Charging effect induced by electron beam irradiation: a review.

Charging effect frequently occurs when characterizing nonconductive materials using electrons as probes and/or signals and can impede the acquisition of useful information about the material under investigation. It is not adequate to investigate it merely by experiments, but theoretical investigations, for which the Monte Carlo method is a suitable tool, are also necessary. In this paper we review Monte Carlo simulations and selected experiments, intending to provide general insight into the charging effects induced by electron beam irradiation. We will introduce categories of the charging effect, the theoretical framework that is adopted in Monte Carlo modeling of the charging effect and present some typical simulation results. At last, with the knowledge on charging effect imparted by the above contents, we will discuss the measures that can be used for minimizing it.

Design of the VRLA Battery Real-Time Monitoring System Based on Wireless Communication.

The VRLA (valve-regulated lead-acid) battery is an important part of a direct current (DC) power system. In order to resolve issues of large volume, complicated wiring, and single function for a battery monitoring system at present, we propose to build a novel intelligent-health-monitoring system. The system is based on the ZigBee wireless communication module for collecting voltage, temperature, internal resistance, and battery current in real-time. A general packet radio service (GPRS) network is employed for interacting data with the cloud-monitoring platform. The system can predict the remaining capacity of the battery combined with the software algorithm for realizing real-time monitoring of the battery's health status and fault-warning, providing a basis for ensuring the safe and reliable operation of the battery. In addition, the system effectively integrates most of the circuits of the battery status collector onto one chip, which greatly reduces the size and the power consumption of the collector and also provides a possibility for embedding each VRLA battery with a chip that can monitor the health status during the whole life. The test results indicate that the system has the characteristics of real-time monitoring, high precision, small-volume, and comprehensive functions.

Relationship between S100A4 protein expression and pre-operative serum CA19.9 levels in pancreatic carcinoma and its prognostic significance.

BACKGROUND: Pancreatic carcinoma (PC) is one of the most lethal malignancies, and its poor prognosis is strongly associated with invasion and metastasis. CA19.9 is considered to be the most sensitive serum marker for PC in clinical practice; however, the detection of CA19.9 in PC has a certain false positive and false negative rate. The expression of the calcium-binding protein S100A4 has been reported to be associated with poor prognosis in various cancers. This study aimed to investigate the relationship between S100A4 and CA19.9 and its prognostic significance in PC. METHODS: We performed immunohistochemical staining for S100A4 in formalin-fixed, paraffin-embedded blocks of 128 PC tissues. The levels of S100A4 expression and pre-operative serum CA19.9 were correlated with clinicopathological parameters. The possible correlation between S100A4 protein expression and pre-operative serum CA19.9 levels were evaluated using the chi-square test and Spearman correlation. Survival was assessed by Kaplan-Meier analysis together with a single variable or multivariate Cox analysis. RESULTS: A significant positive correlation between S100A4 expression and pre-operative serum CA19.9 level was observed in PC tissues (ρ = 0.202, P = 0.022). The co-expression of both proteins correlated significantly with tumor differentiation (ρ = - 0.280, P = 0.001), TNM stage (ρ = - 0.389, P = 0.000), and lymph node metastasis (ρ = 0.254, P = 0.008). Upregulation of S100A4 was identified as a significant, independent predictor of poor overall survival (P = 0.000). Moreover, higher serum CA19.9 levels (≥ 35 U/mL) were also recognized as an independent predictor of inferior overall survival (P = 0.001). Additionally, upregulation of S100A4 and higher pre-operative serum CA19.9 levels (≥ 35 U/mL) in patients with PC contributed to a significant decrease in overall survival (P = 0.000). CONCLUSIONS: The expression levels of S100A4 in PC tissues were positively correlated with pre-operative serum CA19.9 levels. S100A4 expression and pre-operative serum CA19.9 levels were significant, independent prognostic factors for the overall survival of patients with PC. S100A4 expression/pre-operative serum CA19.9 levels may prove useful as dual prognostic biomarkers for PC. Analysis of CA19.9 in combination with S100A4 can better predict the prognosis of PC.

Nanoresolution patterning of hydrogenated graphene by electron beam induced C-H dissociation.

Direct writing of semi-conductive or insulative nanopatterns on graphene surfaces is one of the major challenges in the application of graphene in flexible and transparent electronic devices. Here, we demonstrate that nanoresolution patterning on hydrogenated graphene can be approached by using electron beam induced C-H dissociation when the electron accelerating voltage is beyond a critical voltage of 3 kV. The resolution of the patterning reaches 18 nm and remains constant as the accelerating voltage is beyond 15 kV. The origin of the nanoresolution pattering as well as the dependence of the resolution on voltage in this technique is well explained by studying the cross-section of the C-H bond under electron impact. This work constitutes a new approach to fabricate graphene-based electronic nanodevices, with the reduced hydrogenated graphene channel utilized as conductive or semi-conductive counterpart in the structure.

An Overview of High-k Oxides on Hydrogenated-Diamond for Metal-Oxide-Semiconductor Capacitors and Field-Effect Transistors.

Thanks to its excellent intrinsic properties, diamond is promising for applications of high-power electronic devices, ultraviolet detectors, biosensors, high-temperature tolerant gas sensors, etc. Here, an overview of high-k oxides on hydrogenated-diamond (H-diamond) for metal-oxide-semiconductor (MOS) capacitors and MOS field-effect transistors (MOSFETs) is demonstrated. Fabrication routines for the H-diamond MOS capacitors and MOSFETs, band configurations of oxide/H-diamond heterointerfaces, and electrical properties of the MOS and MOSFETs are summarized and discussed. High-k oxide insulators are deposited using atomic layer deposition (ALD) and sputtering deposition (SD) techniques. Electrical properties of the H-diamond MOS capacitors with high-k oxides of ALD-Al2O3, ALD-HfO2, ALD-HfO2/ALD-Al2O3 multilayer, SD-HfO2/ALD-HfO2 bilayer, SD-TiO2/ALD-Al2O3 bilayer, and ALD-TiO2/ALD-Al2O3 bilayer are discussed. Analyses for capacitance-voltage characteristics of them show that there are low fixed and trapped charge densities for the ALD-Al2O3/H-diamond and SD-HfO2/ALD-HfO2/H-diamond MOS capacitors. The k value of 27.2 for the ALD-TiO2/ALD-Al2O3 bilayer is larger than those of the other oxide insulators. Drain-source current versus voltage curves show distinct pitch-off and p-type channel characteristics for the ALD-Al2O3/H-diamond, SD-HfO2/ALD-HfO2/H-diamond, and ALD-TiO2/ALD-Al2O3/H-diamond MOSFETs. Understanding of fabrication routines and electrical properties for the high-k oxide/H-diamond MOS electronic devices is meaningful for the fabrication of high-performance H-diamond MOS capacitor and MOSFET gas sensors.

A Tunable Plasmonic Refractive Index Sensor with Nanoring-Strip Graphene Arrays.

In the present study, we design a tunable plasmonic refractive index sensor with nanoring-strip graphene arrays. The calculations prove that the nanoring-strip have two transmission dips. By changing the strip length L of the present structure, we find that the nanoring-strip graphene arrays have a wide range of resonances (resonance wavelength increases from 17.73 µm to 28.15 µm). When changing the sensing medium refractive index nmed, the sensitivity of mode A and B can reach 2.97 µm/RIU and 5.20 µm/RIU. By changing the doping level ng, we notice that the transmission characteristics can be tuned flexibly. Finally, the proposed sensor also shows good angle tolerance for both transverse magnetic (TM) and transverse electric (TE) polarizations. The proposed nanoring-strip graphene arrays along with the numerical results could open a new avenue to realize various tunable plasmon devices and have a great application prospect in biosensing, detection, and imaging.

Amorphous Phosphorus/Nitrogen-Doped Graphene Paper for Ultrastable Sodium-Ion Batteries.

As the most promising anode material for sodium-ion batteries (SIBs), elemental phosphorus (P) has recently gained a lot of interest due to its extraordinary theoretical capacity of 2596 mAh/g. The main drawback of a P anode is its low conductivity and rapid structural degradation caused by the enormous volume expansion (>490%) during cycling. Here, we redesigned the anode structure by using an innovative methodology to fabricate flexible paper made of nitrogen-doped graphene and amorphous phosphorus that effectively tackles this problem. The restructured anode exhibits an ultrastable cyclic performance and excellent rate capability (809 mAh/g at 1500 mA/g). The excellent structural integrity of the novel anode was further visualized during cycling by using in situ experiments inside a high-resolution transmission electron microscope (HRTEM), and the associated sodiation/desodiation mechanism was also thoroughly investigated. Finally, density functional theory (DFT) calculations confirmed that the N-doped graphene not only contributes to an increase in capacity for sodium storage but also is beneficial in regards to improved rate performance of the anode.

Self-assembling diacetylene molecules on atomically flat insulators.

Single crystal sapphire and diamond surfaces are used as planar, atomically flat insulating surfaces, for the deposition of the diacetylene compound 10,12-nonacosadiynoic acid. The surface assembly is compared with results on hexagonal boron nitride (h-BN), highly oriented pyrolytic graphite (HOPG) and MoS2 surfaces. A perfectly flat-lying monolayer of 10,12-nonacosadiynoic acid self-assembles on h-BN like on HOPG and MoS2. On sapphire and oxidized diamond surfaces, we observed assemblies of standing-up molecular layers. Surface assembly is driven by surface electrostatic dipoles. Surface polarity is partially controlled using a hydrogenated diamond surface or totally screened by the deposition of a graphene layer on the sapphire surface. This results in a perfectly flat and organized SAM on graphene, which is ready for on-surface polymerization of long and isolated molecular wires under ambient conditions.

[Effects of Rhodiola on the Expression of iNOS mRNA in Severe Acute Pancreatitis Associated Re- nal Injury Rats].

OBJECTIVE: To explore the effect of Rhodiola on the expression of iNOS mRNA in severe acute pancreatitis (SAP) associated renal injury rats. METHODS: A total of 72 healthy rats were randomly divided into the sham-operated group (S), the SAP associated renal injury group (M), and the Rhodiola-treated group (RHO), 24 in each group. Rats in S and M groups were peritoneally injected with 10 mL/kg saline 3h before modeling, while rats in the RHO group were peritoneally injected with 10 mL/kg Rhodiola Injection 3 h before modeling. The peripheral ligament of pancreas was bluntly dissociated in rats of M and RHO groups. The head of pancreas was occlused by nontraumatic blood vessel forceps 3 h later to establish the model. Eight rats were randomly selected from each group at 12, 24, and 36 h after modeling to detect levels of serum amylase, creatinine, and blood urea nitrogen. Serum levels of interleukin 1ß (IL-1ß) and interleukin 10 (IL-10) were detected by enzyme-linked immunosorbent assay (ELISA). Pathological changes of the left kidney were observed under light microscope. The expression of inducible nitric oxide synthase (iNOS) mRNA in the right kidney was detected with real time polymerase chain reaction (RT-PCR). RESULTS: Compared with the S group, serum levels of amylase, creatinine (Cr), blood urea nitrogen (BUN), IL-1ß, IL-10, and iNOS mRNA expression significantly increased in the M group (P < 0.01). The function of kidney and pancreas were obviously improved in the RHO group than in the M group. Levels of IL-1ß and iNOS significantly decreased, but IL-10 levels significantly increased in the RHO group with statistical difference (P < 0.05). CONCLUSION: Rhodiola had better protective effect on SAP associated renal injury, which might be achieved through inhibiting the expression of IL-1ß, stimulating the expression of IL-10, down-regulating iNOS mRNA expression, reducing the generation of oxygen free radicals and NO damage to cells, and improving hypoxia tolerance capabilities of the kidney.

Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response.

Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P < 0.05). These index values in the L-AS, M-AS, and H-AS groups were significantly lower than those in the DHC group (P < 0.05). The index values decreased significantly with an increase in the concentration of isorhamnetin (P < 0.05), while the index values of CAT and SOD showed the opposite tendency (P < 0.05). The expression of liver tissue nuclear factor kappa B (NF-κB), caspase-3, and heat shock protein (HSP-70) was higher in the DHC group than in the NC group (P < 0.05). Comparison between the isorhamnetin and DHC groups revealed that the expression of NF-кB and caspase-3 was decreased, while that of HSP-70 continued to increase (P < 0.05). The difference was significant for HSP-70 among all the isorhamnetin groups (P < 0.05); however, the NF-кB and caspase-3 values in the L-AS and H-AS groups did not differ. In summary, isorhamnetin has protective effects against liver injury in heat-stroke-affected rats. This protective effect may be related to its activities concerning antioxidative stress, anti-inflammatory response, inhibition of NF-кB and caspase-3 expression, and enhancement of HSP-70 expression.

Immune cell signatures and causal association with irritable bowel syndrome: A mendelian randomization study.

BACKGROUND: The mucosal barrier's immune-brain interactions, pivotal for neural development and function, are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome (IBS). Prior studies linking immune inflammation with IBS have been inconsistent. To further elucidate this relationship, we conducted a Mendelian randomization (MR) analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS. Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets. AIM: To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS. We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies. METHODS: We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS. By utilizing genetic data from public databases, we examined the causal associations between 731 immune cell markers, encompassing median fluorescence intensity, relative cell abundance, absolute cell count, and morphological parameters, with IBS susceptibility. Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy. RESULTS: Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes. However, our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes (P < 0.05). Nine immune phenotypes demonstrated a protective effect against IBS [inverse variance weighting (IVW) < 0.05, odd ratio (OR) < 1], while 21 others were associated with an increased risk of IBS onset (IVW ≥ 0.05, OR ≥ 1). CONCLUSION: Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS, providing valuable insights into the pathophysiology of the condition. These results pave the way for the development of more precise biomarkers and targeted therapies for IBS. Furthermore, this research enriches our comprehension of immune cell roles in IBS pathogenesis, offering a foundation for more effective, personalized treatment approaches. These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.