Trajectory patterns and cumulative burden of CEA during follow-up with non-small cell lung cancer outcomes: A retrospective longitudinal cohort study.

BACKGROUND: Previous studies of non-small cell lung cancer (NSCLC) focused on CEA measured at a single time point, ignoring serial CEA measurements. METHODS: This retrospective cohort included 2959 patients underwent surgery for stage I-III NSCLC. CEA trajectory patterns and long-term cumulative CEA burden were evaluated using the latent class growth mixture model. RESULTS: Four CEA trajectory groups were identified, named as low-stable, decreasing, early-rising and later-rising. Compared with the low-stable group, the adjusted hazard ratios associated with death were 1.27, 4.50, and 3.68 for the other groups. Cumulative CEA burden were positively associated with the risk of death in patients not belonging to the low-stable group. The 5-year overall survival (OS) rates decreased from 62.3% to 33.0% for the first and fourth quantile groups of cumulative CEA burden. Jointly, patients with decreasing CEA trajectory could be further divided into the decreasing & low and decreasing & high group, with 5-year OS rates to be 77.9% and 47.1%. Patients with rising CEA trajectory and high cumulative CEA were found to be more likely to develop bone metastasis. CONCLUSIONS: Longitudinal trajectory patterns and long-term cumulative burden of CEA were independent prognostic factors of NSCLC. We recommend CEA in postoperative surveillance of NSCLC.

Cumulative effect of metabolic risk factors on left ventricular geometry in those with versus without early-onset type 2 diabetes or prediabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIM: To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). METHODS: A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. RESULTS: One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (ß 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (ß 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (ß ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (ß ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. CONCLUSIONS: Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.

Prediction models of colorectal cancer prognosis incorporating perioperative longitudinal serum tumor markers: a retrospective longitudinal cohort study.

BACKGROUND: Current prognostic prediction models of colorectal cancer (CRC) include only the preoperative measurement of tumor markers, with their available repeated postoperative measurements underutilized. CRC prognostic prediction models were constructed in this study to clarify whether and to what extent the inclusion of perioperative longitudinal measurements of CEA, CA19-9, and CA125 can improve the model performance, and perform a dynamic prediction. METHODS: The training and validating cohort included 1453 and 444 CRC patients who underwent curative resection, with preoperative measurement and two or more measurements within 12 months after surgery, respectively. Prediction models to predict CRC overall survival were constructed with demographic and clinicopathological variables, by incorporating preoperative CEA, CA19-9, and CA125, as well as their perioperative longitudinal measurements. RESULTS: In internal validation, the model with preoperative CEA, CA19-9, and CA125 outperformed the model including CEA only, with the better area under the receiver operating characteristic curves (AUCs: 0.774 vs 0.716), brier scores (BSs: 0.057 vs 0.058), and net reclassification improvement (NRI = 33.5%, 95% CI: 12.3 ~ 54.8%) at 36 months after surgery. Furthermore, the prediction models, by incorporating longitudinal measurements of CEA, CA19-9, and CA125 within 12 months after surgery, had improved prediction accuracy, with higher AUC (0.849) and lower BS (0.049). Compared with preoperative models, the model incorporating longitudinal measurements of the three markers had significant NRI (40.8%, 95% CI: 19.6 to 62.1%) at 36 months after surgery. External validation showed similar results to internal validation. The proposed longitudinal prediction model can provide a personalized dynamic prediction for a new patient, with estimated survival probability updated when a new measurement is collected during 12 months after surgery. CONCLUSIONS: Prediction models including longitudinal measurements of CEA, CA19-9, and CA125 have improved accuracy in predicting the prognosis of CRC patients. We recommend repeated measurements of CEA, CA19-9, and CA125 in the surveillance of CRC prognosis.

Untargeted serum metabolomics reveals potential biomarkers and metabolic pathways associated with the progression of gastroesophageal cancer.

BACKGROUND: Previous metabolic studies in upper digestive cancer have mostly been limited to cross-sectional study designs, which hinders the ability to effectively predict outcomes in the early stage of cancer. This study aims to identify key metabolites and metabolic pathways associated with the multistage progression of epithelial cancer and to explore their predictive value for gastroesophageal cancer (GEC) formation and for the early screening of esophageal squamous cell carcinoma (ESCC). METHODS: A case-cohort study within the 7-year prospective Esophageal Cancer Screening Cohort of Shandong Province included 77 GEC cases and 77 sub-cohort individuals. Untargeted metabolic analysis was performed in serum samples. Metabolites, with FDR q value < 0.05 and variable importance in projection (VIP) > 1, were selected as differential metabolites to predict GEC formation using Random Forest (RF) models. Subsequently, we evaluated the predictive performance of these differential metabolites for the early screening of ESCC. RESULTS: We found a distinct metabolic profile alteration in GEC cases compared to the sub-cohort, and identified eight differential metabolites. Pathway analyses showed dysregulation in D-glutamine and D-glutamate metabolism, nitrogen metabolism, primary bile acid biosynthesis, and steroid hormone biosynthesis in GEC patients. A panel of eight differential metabolites showed good predictive performance for GEC formation, with an area under the receiver operating characteristic curve (AUC) of 0.893 (95% CI = 0.816-0.951). Furthermore, four of the GEC pathological progression-related metabolites were validated in the early screening of ESCC, with an AUC of 0.761 (95% CI = 0.716-0.805). CONCLUSIONS: These findings indicated a panel of metabolites might be an alternative approach to predict GEC formation, and therefore have the potential to mitigate the risk of cancer progression at the early stage of GEC.

Gastric bacteria as potential biomarkers for the diagnosis of atrophic gastritis.

BACKGROUND: Identification of the risk factors for atrophic gastritis (AG) and prevention of further deterioration of the gastritis are effective approaches to reduce the incidence of gastric cancer. Previous studies found that dysbiosis has been implicated in a wide range of diseases, while the role of gastric bacteria as a biomarker for AG has not been explored. METHODS AND RESULTS: Gastric juices from cases with non-atrophic gastritis (NAG) and AG were collected for investigation of bacterial composition and function. The ß-diversity of microbiota exhibited a significant reduction in AG samples compared with that in NAG samples. Differential abundance analysis revealed that a total of 23 predicted species changed their distributions; meanwhile, all obligate anaerobic bacteria with a relatively high abundance lowered their contents in AG samples. Additionally, the correlation analysis indicated a clear shift in bacterial correlation pattern between the two groups. Functional interrogation of the gastric microbiota showed that bacterial metabolisms associated with enzyme families, digestive system, and endocrine system were downregulated in AG samples. The compositional dissection of "core microbiota" exhibited that oral pathogens, including Porphyromonas gingivalis, Campylobacter gracilis, and Granulicatella elegans, were magnified in AG samples, suggesting that oral diseases may be a trigger factor for early exacerbation of gastritis. Then, the differentially expressed bacteria were used as diagnostic biomarkers for the random forest classifier model for group prediction. CONCLUSIONS: The results showed that bacterial biomarkers could distinguish AG patients from NAG cases with an accuracy of 90% at the genus level.

Computational study of the photophysical properties and electronic structure of iridium(III) photosensitizer complexes with electron-withdrawing groups.

A series of novel [Ir(tpy)(btp)Cl]+ complexes (Ir1-Ir4) have been reported to show excellent performance as photosensitizers. The introduction of electron-withdrawing groups increases visible light absorption and the lifetime of triplet states. To improve the photophysical properties, we theoretically design Ir5-Ir9 with electron-withdrawing groups (Cl, F, COOH, CN and NO2). Surprisingly, our findings indicate that the photosensitizer performance does not strictly increase with the electron-withdrawing ability of the substituents. In this work, the geometric and electronic structures, transition features, and photophysical properties of Ir1-Ir9 are investigated. The natural transition orbital (NTO) analysis indicates that the T1 and T2 states play a role in the photochemical pathways. Ultraviolet-visible (UV-vis) absorption spectra and charge-transfer spectra (CTS) have been investigated to show that the introduction of electron-withdrawing groups not only improves the visible light absorbing ability, but also changes the nature of electron excitation, providing a future molecular design strategy for similar series of photosensitizers. The rates of (reverse) intersystem crossing and the Huang-Rhys factors are evaluated to interpret the experimental results within the framework of Marcus theory. For complexes Ir1-Ir7, the introduction of electron-withdrawing groups leads to a lower efficiency of reverse intersystem crossing and a strong non-radiative process T2 → T1, resulting in a long triplet lifetime and excellent performance as a photosensitizer. Furthermore, some newly designed complexes (Ir7-Ir9) show great potential as thermally activated delayed fluorescence emitters, contrary to our initial expectations.

In situ surface regulation of 3D perovskite using diethylammonium iodide for highly efficient perovskite solar cells.

Surface passivation by constructing a 2D/3D structure is considered to be an effective strategy for suppressing non-radiative recombination and improving the device efficiency and stability. Herein, the 2D perovskite is formed in situ on the surface of a 3D perovskite via chemical interactions between diethylammonium iodide (DAI) and Pb-I octahedra, which greatly reduces the deep level defects and non-radiative recombination. Moreover, the 2D/3D structure can regulate the energy level alignment, enhance the charge extraction, and improve the open-circuit voltage. Finally, compared with the control device, the power conversion efficiency (PCE) of the DAI-treated device increases from 21.58 to 23.50%. The unencapsulated devices stored in air for more than 500 hours can still retain 97% of their initial PCE, revealing good long-term placement stability. This work provides a promising strategy to fabricate efficient PSCs through the in situ construction of 2D/3D perovskite heterojunctions.

Changes of serum metabolites levels during neoadjuvant chemoradiation and prediction of the pathological response in locally advanced rectal cancer.

INTRODUCTION: Previous studies have explored prediction value of serum metabolites in neoadjuvant chemoradiation therapy (NCRT) response for rectal cancer. To date, limited literature is available for serum metabolome changes dynamically through NCRT. OBJECTIVES: This study aimed to explore temporal change pattern of serum metabolites during NCRT, and potential metabolic biomarkers to predict the pathological response to NCRT in locally advanced rectal cancer (LARC) patients. METHODS: Based on dynamic UHPLC-QTOF-MS untargeted metabolomics design, this study included 106 LARC patients treated with NCRT. Biological samples of the enrolled patients were collected in five consecutive time-points. Untargeted metabolomics was used to profile serum metabolic signatures from LARC patients. Then, we used fuzzy C-means clustering (FCM) to explore temporal change patterns in metabolites cluster and identify monotonously changing metabolites during NCRT. Repeated measure analysis of variance (RM-ANOVA) and multilevel partial least-squares discriminant analysis (ML-PLS-DA) were performed to select metabolic biomarkers. Finally, a panel of dynamic differential metabolites was used to build logistic regression prediction models. RESULTS: Metabolite profiles showed a clearly tendency of separation between different follow-up panels. We identified two clusters of 155 serum metabolites with monotonously changing patterns during NCRT (74 decreased metabolites and 81 increased metabolites). Using RM-ANOVA and ML-PLS-DA, 8 metabolites (L-Norleucine, Betaine, Hypoxanthine, Acetylcholine, 1-Hexadecanoyl-sn-glycero-3-phosphocholine, Glycerophosphocholine, Alpha-ketoisovaleric acid, N-Acetyl-L-alanine) were further identified as dynamic differential biomarkers for predicting NCRT sensitivity. The area under the ROC curve (AUC) of prediction model combined with the baseline measurement was 0.54 (95%CI = 0.43 ~ 0.65). By incorporating the variability indexes of 8 dynamic differential metabolites, the prediction model showed better discrimination performance than baseline measurement, with AUC = 0.67 (95%CI 0.57 ~ 0.77), 0.64 (0.53 ~ 0.75), 0.60 (0.50 ~ 0.71), and 0.56 (0.45 ~ 0.67) for the variability index of difference, linear slope, ratio, and standard deviation, respectively. CONCLUSION: This study identified eight metabolites as dynamic differential biomarkers to discriminate NCRT-sensitive and resistant patients. The changes of metabolite level during NCRT show better performance in predicting NCRT sensitivity. These findings highlight the clinical significance of metabolites variabilities in metabolomics analysis.

Heavy Mn-doped CsPbBr3nanocrystals synthesized by high energy ball milling with high stability.

CsPbX3(X = Cl, Br, I) semiconductor nanocrystals (NCs) have excellent optical and photoelectric properties, and are potential core materials for various photoelectric devices. However, the toxicity of Pb and instability have been the key limitations to application of NCs. Herein, using MnBr2and MnBr2·4H2O as manganese sources, heavy Mn-doped CsPbBr3(Mn:CsPbBr3) NCs are synthesized by high-energy ball grinding, which avoids high temperature, a large number of polar solvents and atmosphere protection required in traditional liquid phase methods. However, when MnBr2·4H2O is used as the raw material, infinite solid solution doping can be achieved, and the synthesized Mn:CsPbBr3NCs show smaller particle size, stronger PL intensity and stability. The reason is that presence of crystal water plays a similar role to wet milling in the ball milling process, and can promote the passivation effect of oleylamine (OAm) on nanocrystal defects and the connection between them. In addition, a simple, easy-operating and beneficial to commercial production method for the preparation of Mn:CsPbBr3NCs/EVA flexible films is proposed, which can effectively improve the stability of Mn:CsPbBr3NCs. This study is expected to provide an effective way for the synthesis and stability improvement of CsPbX3NCs doped with different ions.

Zero Lithium Miscibility Gap Enables High-Rate Equimolar Li(Mn,Fe)PO4 Solid Solution.

Forming olivine-structured Li(Mn,Fe)PO4 solid solution is theoretically a feasible way to improve the energy density of the solid solutions for lithium ion batteries. However, the Jahn-Teller active Mn3+ in the solid solution restricts their energy density and rate performance. Here, as demonstrated by operando X-ray diffraction, we show that equimolar LiMn0.5Fe0.5PO4 solid solution nanocrystals undergo a single-phase transition during the whole (de)lithiation process, with a feature of zero lithium miscibility gap, which endows the nanocrystals with excellent electrochemical properties. Specifically, the energy density of LiMn0.5Fe0.5PO4 reaches 625 Wh kg-1, which is 16% higher than that of LiFePO4. Moreover, the high-performance LiMn0.5Fe0.5PO4 nanocrystals are prepared by a microwave-assisted hydrothermal synthesis in pure water.

Intestinal bacteria are potential biomarkers and therapeutic targets for gastric cancer.

The diagnostic and therapeutic role of intestinal microbiota in gastric carcinogenesis remains unclear. In this study, feces from gastric cancer patients and healthy people were sequenced for microbiota analysis, and the correlation between fecal bacteria and the occurrence of gastric cancer was explored. The ß-diversity results showed that microbial compositions varied between gastric cancer patients and healthy people. Interestingly, the dissection of microbial structure revealed that all facultative anaerobic genera with relatively high abundances expanded significantly in gastric cancer patients. The succeeding correlation analysis demonstrated a distorted interaction of intestinal bacteria in gastric cancer. The application of some differential bacteria, Desulfovibrio, Escherichia, Faecalibacterium or Oscillospira, as biomarkers to predict gastric cancer could all reach an accuracy of 0.900 or above. The shift in Desulfovibrio was specifically verified by qPCR in newly collected fecal samples, and the patients with stage IV gastric cancer were identified to have significantly more Desulfovibrio than those with stage I, II and III gastric cancer. The possible role of Desulfovibrio in gastric cancer was assessed with H2S-treated HT-29 cells, and the results showed that H2S induced NO, IL-1ß and IL-18 production, which is important for inflammation promotion and can be delivered through the bloodstream. This study suggests a correlation of intestinal microbiota and the development of gastric cancer.

The mediation effect of serum metabolites on the relationship between long-term smoking exposure and esophageal squamous cell carcinoma.

BACKGROUND: Long-term smoking exposure will increase the risk of esophageal squamous cell carcinoma (ESCC), whereas the mechanism is still unclear. We conducted a cross-sectional study to explore whether serum metabolites mediate the occurrence of ESCC caused by cigarette smoking. METHODS: Serum metabolic profiles and lifestyle information of 464 participants were analyzed. Multiple logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of smoking exposure to ESCC risk. High-dimensional mediation analysis and univariate mediation analysis were performed to screen potential intermediate metabolites of smoking exposure for ESCC. RESULTS: Ever smoking was associated with a 3.11-fold increase of ESCC risk (OR = 3.11, 95% CI 1.63-6.05), and for each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR = 1.56, 95% CI 1.18-2.13). A total of 5 metabolites were screened as mediators by high-dimensional mediation analysis. In addition, glutamine, histidine, and cholic acid were further proved existing mediation effects according to univariate mediation analysis. And the proportions of mediation of histidine and glutamine were 40.47 and 30.00%, respectively. The mediation effect of cholic acid was 8.98% according to the analysis of smoking index. CONCLUSIONS: Our findings suggest that cigarette smoking contributed to incident ESCC, which may be mediated by glutamine, histidine and cholic acid.

MXene-based hybrid system exhibits excellent synergistic antibiosis.

MXenes are a group of inorganic two-dimensional (2D) nanomaterial, and have raised significant interests in biomedical areas. Ti3C2Tx, as an important member of MXene family, is widely studied because of its biodegradability and low-cytotoxicity. However, their single antibacterial mechanism and poor stability in aqueous solution need to be improved, especially for the antimicrobial applications. In this work, a MXene-based hybrid antibacterial system (M-HAS) was developed and its synergistic antibacterial activity was investigated. In the M-HAS, 2D few-layer Ti3C2Tx(FL-Ti3C2Tx) was modified with hydrophilic polymers and thereby used as carriers for silver nanoparticles (Ag NPs). By assembling these two substrates, photodynamic performance of the prepared system is significantly improved with a large amount of reactive oxygen species produced under 660 nm laser. Antibacterial effects of the M-HAS are enhanced by over 4 times with irradiation. In another word, the developed hybrid system displays excellent photodynamic antibacterial synergistic properties. This work takes advantage of the photodynamic properties of each component in the M-HAS to achieve efficient antibacterial activity and proposes an innovative approach to develop the 2D FL-Ti3C2Tx-based antibacterial platform.

Z-scheme TiO2@Ti3C2/Cd0.5Zn0.5S nanocomposites with efficient photocatalytic performance via one-step hydrothermal route.

Photocatalytic degradation of pollutants has been proved to be an effective strategy for wastewater treatment. Herein, TiO2 nanoparticles were synthesized on a Ti3C2 matrix by in situ growth, forming Z-scheme TiO2@Ti3C2/Cd0.5Zn0.5S (TO/CZS) multilevel structured nanocomposites via one-step hydrothermal route. The effects of hydrothermal temperature and Cd0.5Zn0.5S content on microstructure and properties of composites were assessed. TO/CZS nanocomposites were probed into phase composition, morphological and optical properties with x-ray diffractometer, infrared radiation, scanning electron microscope and UV-vis reflective spectra. Following the hydrothermal reaction at 160 °C for 12 h, TiO2 nanoparticles of 30 nm in diameter were generated in situ on Ti3C2 lamina and Cd0.5Zn0.5S particles were evenly distributed on the Ti3C2 matrix. The photocatalytic activity of TO/CZS composites were evaluated, which found that degradation rate constant (k = 0.028 min-1) of TO/CZS-40 on Rhodamine B was 5.19 times that of pure TiO2 and 4.48 times that of Cd0.5Zn0.5S. Through anchoring Ti3C2 as an electron transition mediator and combination with TiO2 and Cd0.5Zn0.5S, the new Z-scheme between TiO2 oxidized by Ti3C2 and Cd0.5Zn0.5S establishes a multilevel structure of separating electron-hole pairs. This work demonstrates a valid way to control electrons and hole transfer directions efficiently through designing multilevel semiconductor structural designs.

A highly durable CoOx/N-doped graphitized-nano-diamond electrocatalyst for oxygen reduction reaction.

Oxygen reduction reaction (ORR) occupies a pivotal position in fuel cell applications, and it is a challenge to obtain highly durable ORR catalysts. Herein, porous cobalt oxide microsphere growing at the surface of on nitrogen-doped graphitized-nano-diamond (CoOx/N-GND) was prepared using hydrothermal and subsequent heat treatment process. Porous cobalt oxide of high specific surface area could expose more surface Co2+that act as active sites than bulk one does. The doping of nitrogen also promotes the catalytic activity. Besides, nano-diamond (ND) ofsp3hybrid structure was used as an electronic conduction carriers of ultrahigh stability to improve the durability of catalytic composite. Prepared CoOx/N-GND shows a satisfactory half-wave potential of 0.82 V (versus RHE), which is close to that of Pt/C (0.85 V), an excellent methanol tolerance and a lower activity loss after 5000 cycles. These merits inspire the application of CoOx/N-GND as the cathode of Zn-air battery and the battery performance was evaluated in this work. In general, this work highlights an innovate approach to design and prepare highly durable catalyst.

Emerging 2D MXenes for supercapacitors: status, challenges and prospects.

MXenes refer to a family of 2D transition metal carbides/nitrides that are rich in chemistry. The first member of the family, Ti3C2Tx, was reported in 2011. Since then MXenes have opened up an exciting new field in 2D inorganic functional materials by virtue of their intrinsic electronic conductivity, superior hydrophilicity, rich surface chemistry and layered structure, as evidenced by the fact that the number of papers on MXenes has increased exponentially. The unique properties and ease of processing have positioned them as promising materials for a variety of applications including energy storage, especially for supercapacitors. In this review, we aim to summarize the current advances in MXene research on supercapacitors. We begin by reviewing various fabrication routes and their influence on the structure and surface chemistry of MXenes. The structure, properties, stability, and species of layered MXenes are then introduced. The focus then turns to the capacitive energy-storage mechanisms and the factors determining the electrochemical behavior and performance in supercapacitors. Besides, various types of MXene-based supercapacitors are summarized to highlight the significance of MXenes in constructing energy storage devices. Finally, challenges and prospects in this booming field are proposed to promote further development of MXenes in supercapacitors.

HOX transcript antisense RNA is elevated in gastric carcinogenesis and regulated by the NF-κB pathway.

The expression pattern of HOX transcript antisense RNA (HOTAIR) in the progression of gastric cancer and the regulation of its expression are still unclear. In the current study, HOTAIR expressions in gastric tissues collected from patients with superficial gastritis, atrophic gastritis, atypical hyperplasia, and gastric cancer as well as normal controls was quantitatively examined. The results showed that the expression of HOTAIR was higher in gastric cancer than in normal tissues, but reached the highest level in atrophic gastritis, suggesting that HOTAIR may be involved in the molecular process of nonresolving inflammation. Then tumor necrosis factor-α-induced protein-8 like-2 (TIPE2), a known gene associated with nonresolving inflammation, was overexpressed and the results showed that the promotion in TIPE2 expression triggered HOTAIR reduction, this result was further verified by microarray analysis and TIPE2 knockout mice. Subsequently, the data obtained from HOTAIR knockdown experiment showed that it significantly enhanced colony forming capability and inhibited p27 expression in AGS cells. Furthermore, deletion constructs and luciferase-based activity assays indicated that the -475 to -443bp region of HOTAIR promoter contained a crucial regulatory element. Transcription factor prediction with software TRANSFAC revealed that nuclear factor-κB signaling protein p65 had a binding site in this region and might have roles in HOTAIR expression. The binding of phosphor-p65 to HOTAIR promoter was verified by chromatin immunoprecipitation, and succeeding experiment results demonstrated that p65 reduction by p65 small interfering RNA and TIPE2 overexpression also decreased HOTAIR expression. Conclusively, our results suggest that HOTAIR was associated with nonresolving inflammation, and its expression is regulated by p65.

Interleukin-1 Receptor Associated Kinase 1 Mediates the Maintenance of Neuropathic Pain after Chronic Constriction Injury in Rats.

Neuropathic pain (NP) has complicated pathogenesis as it mainly involves a lesion or dysfunction of the somatosensory nervous system and its clinical treatment remains challenging. Chronic constriction injury (CCI) model is a widely used neuropathic pain model and involved in mechanisms including both nerve inflammatory and injury. Cytokines and their receptors play essential roles in the occurrence and persistence of neuropathic pain, but the underlying mechanisms have not well been understood. Therefore, Interleukin-1 receptor-associated kinase 1 (IRAK1) is chosen to explore the possible mechanisms of NP. In the present study, IRAK1 was found to persistently increase in the dorsal root ganglion (DRG) and spinal cord (SC) during CCI detected by western blot. The staining further confirmed that IRAK1 was mainly co-located in the DRG astrocytes or SC neurons, but less in the DRG microglia or SC astrocytes. Moreover, the region of increased IRAK1 expression was observed in superficial laminae of the spinal dorsal horn, which was the nociceptive neuronal expression domain, suggesting that IRAK1 may mediated CCI-induced pain by nociceptive primary afferent. In addition, intrathecal injection of Toll-like receptor 4 (TLR4) inhibitor or IRAK1 siRNA decreased the expression of IRAK1 accompanied with the alleviation of CCI-induced neuropathic pain. The upregulation of p-NF-κB expression was reversed by IRAK1 siRNA in SC, and intrathecal injection of p-NF-κB inhibitor relieved neuropathic pain. Taking together, targeting IRAK1 may be a potential treatment for chronic neuropathic pain.

Enhancement of photocatalytic activity of g-C3N4 by hydrochloric acid treatment of melamine.

Modified g-C3N4 samples (g-X, where X corresponds to the number of hours of acid treatment of the melamine) with outstanding photocatalytic performance were prepared by using hydrochloric acid-treated melamine as a precursor and calcining at 550 °C for 2 h. An x-ray diffractometer, field-emission scanning electron microscope, infrared spectrometer, N2 adsorption-desorption test, x-ray photoelectron spectroscopy, and ultraviolet-visible diffuse-reflectance spectroscopy analysis were carried out to characterize the phase composition, microstructure, chemical structure, specific surface area (SSA), chemical states, elemental composition and optical properties of the samples, respectively. The photocatalytic performance of the samples was evaluated by degrading the Rhodamine B (RhB) aqueous solution. The results showed that the crystal structure and vibration bands of melamine changed due to the reaction with hydrochloric acid. The crystallinity and grain size of g-C3N4 in g-X (X = 1, 2, 4, 6, 8, 10) reduced, and the SSA values of g-X increased compared to that of the g-0 sample, which was synthesized from pristine melamine. The g-X samples exhibited excellent photocatalytic activity towards degradation of RhB compared to g-0. The photocatalytic activity of the g-X samples increased gradually as the acid treatment time of the melamine increased from 1 h to 2 h, and then decreased gradually with the extension of the acid treatment time. The rate constant (k) values of g-X are higher than that of g-0. g-2 presented the highest rate constant (k = 0.052 min-1), which was 5.5 times higher than that of g-0. The improved photocatalytic activity of the g-X samples was attributed to the higher SSA value, the appearance of surface defects, the outstanding photo-carrier separation efficiency and stronger light harvesting ability of g-X, with the last two factors being more significant. Acid treatment of melamine is helpful in the preparation of high performance g-C3N4 photocatalyst, and the microstructure and photocatalytic performance of g-C3N4 were affected significantly by the acid treatment time.

Trajectories of Haemoglobin and incident stroke risk: a longitudinal cohort study.

BACKGROUND: Studies have demonstrated that high or low haemoglobin increases the risk of stroke. Previous studies, however, performed only a limited number of haemoglobin measurements, while there are dynamic haemoglobin changes over the course of a lifetime. This longitudinal cohort study aimed to classify the long-term trajectory of haemoglobin and examine its association with stroke incidence. METHODS: The cohort consisted of 11,431 participants (6549 men) aged 20 to 50 years whose haemoglobin was repeatedly measured 3-9 times during 2004-2015. A latent class growth mixture model (LCGMM) was used to classify the long-term trajectory of haemoglobin concentrations, and hazard ratios (HRs) and 95% confidence intervals (95% CI) according to the Cox proportional hazard model were used to investigate the association of haemoglobin trajectory types with the risk of stroke. RESULTS: Three distinct trajectory types, high-stable (n = 5395), normal-stable (n = 5310), and decreasing (n = 726), were identified, with stroke incidence rates of 2.7, 1.9 and 3.2 per 1000 person-years, respectively. Compared to the normal-stable group, after adjusting for the baseline covariates, the decreasing group had a 2.94-fold (95% CI 1.22 to 7.06) increased risk of developing stroke. Strong evidence was observed in men, with an HR (95% CI) of 4.12 (1.50, 11.28), but not in women (HR = 1.66, 95% CI 0.34, 8.19). Individuals in the high-stable group had increased values of baseline covariates, but the adjusted HR (95% CI), at 1.23 (0.77, 1.97), was not significant for the study cohort or for men and women separately. CONCLUSIONS: This study revealed that a decreasing haemoglobin trajectory was associated with an increased risk of stroke in men. These findings suggest that long-term decreasing haemoglobin levels might increase the risk of stroke.