Analysis of Spinal Pilocytic Astrocytoma in 12 Case Reports and Literature Review.

Spinal pilocytic astrocytoma (PA) is a rare disorder with atypical, clinical and imaging characteristics, and generally limited to case reports. We analysed the clinical manifestations, imaging findings, treatment and prognostic follow-up of 12 patients with spinal PA admitted from January 2010 to July 2021, and reviewed the relevant literature. Radiological assessment, especially magnetic resonance imaging, can help to provide effective diagnostic information. The diagnosis and differentiation of this disease is discussed in an attempt to contribute to a more comprehensive preoperative assessment.

Guided Heterostructure Growth of CoFe LDH on Ti3C2Tx MXene for Durably High Oxygen Evolution Activity.

Heterostructures of layered double hydroxides (LDHs) and MXenes have shown great promise for oxygen evolution reaction (OER) catalysts, owing to their complementary physical properties. Coupling LDHs with MXenes can potentially enhance their conductivity, stability, and OER activity. In this work, a scalable and straightforward in situ guided growth of CoFeLDH on Ti3C2Tx is introduced, where the surface chemistry of Ti3C2Tx dominates the resulting heterostructures, allowing tunable crystal domain sizes of LDHs. Combined simulation results of Monte Carlo and density functional theory (DFT) validate this guided growth mechanism. Through this way, the optimized heterostructures allow the highest OER activity of the overpotential = 301 mV and Tafel slope = 43 mV dec-1 at 10 mA cm-2, and a considerably durable stability of 0.1% decay over 200 h use, remarkably outperforming all reported LDHs-MXenes materials. DFT calculations indicate that the charge transfer in heterostructures can decrease the rate-limiting energy barrier for OER, facilitating OER activity. The combined experimental and theoretical efforts identify the participation role of MXene in heterostructures for OER reactions, providing insights into designing advanced heterostructures for robust OER electrocatalysis.

Establishing a model predicting Gleason grade group upgrading in prostate cancer.

Background: Gleason grade group (GG) upgrading is associated with increased biochemical recurrence (BCR), local progression, and decreased cancer-specific survival (CSS) in prostate cancer (PCa). However, descriptions of the risk factors of GG upgrading are scarce. The objective of this study was to identify risk factors and establish a model to predict GG upgrading. Methods: There were 361 patients with PCa who underwent radical prostatectomy between May 2011 and February 2022 enrolled. Univariate and multivariate logistic regression analyses were identified and nomogram further narrowed down the contributing factors in GG upgrading. The correction curve and decision curve were used to assess the model. Results: In the overall cohort, 141 patients had GG upgrading. But the subgroup cohort (GG ≤2) showed that 68 patients had GG upgrading. Multivariate logistic regression analysis showed that in the overall cohort, total prostate-specific antigen (tPSA) ≥10 ng/mL, systemic immune-inflammation index (SII) >379.50, neutrophil-lymphocyte ratio (NLR) >2.13, the GG of biopsy ≥3, the number of positive cores >3 were independent risk factors in GG upgrading. In the cohort of biopsy GG ≤2, multivariate logistic regression showed that the tPSA ≥10 ng/mL, SII >379.50 and the number of positive cores >3 were independent risk factors in GG upgrading. A novel model predicting GG upgrading was established based on these three parameters. The area under the curve (AUC) of the prediction model was 0.759. The C-index of the nomogram was 0.768. The calibration curves of the model showed good predictive performance. Clinical decision curves indicated clinical benefit in the interval of 20% to 90% of threshold probability and good clinical utility. Conclusions: Combined levels of tPSA, SII and the positive biopsy cores distinguish patients with high-risk GG upgrading in the group of biopsy GG ≤2 and are helpful in the decision of treatment plans.

Differential effect of tumor budding on the benefit of adjuvant chemotherapy in stage II colorectal cancer: a retrospective observational study.

Background: Tumor budding (TB) has been shown to be a poor prognostic indicator after colorectal cancer (CRC) surgery. The aim of the present study is to evaluate the predictive role of morphological features (e.g., the number, structure, and location of tumor buds, and their reaction with the extracellular mesenchyme) in postoperative adjuvant chemotherapy in surgically resectable stage II CRC. Methods: Between 2016 and 2019, 336 patients with stage II CRC who underwent radical surgery were enrolled in this study. TB status was determined according to the criteria adopted at the 2016 International Tumor Budding Consensus Conference (ITBCC). We retrospectively recorded all the clinical and pathological data and assessed the effect of different types of TB status on patients' recurrence-free survival (RFS) and overall survival (OS). Results: Of the 336 patients, 173, 88, and 75 were budding grade 1 (BD1), BD2, and BD3, respectively. The 5-year RFS rates were 84.6%, 81.2%, and 68.0% (P=0.01), and the 5-year OS rates were 91.0%, 83.3%, and 76.2% (P=0.007) in BD1, BD2, and BD3, respectively. TB grade was strongly associated with vascular invasion status and mucinous adenocarcinoma, and BD3 was detected in 51.7% of patients with positive vascular invasion. The multivariate analysis showed that only age, perineural invasion, and TB grade [BD2 vs. BD1, hazard ratio (HR) =1.468, 95% confidence interval (CI): 0.703-3.063, P=0.30; BD3 vs. BD1, HR =2.310, 95% CI: 1.154-4.625, P=0.01] had an independent effect on RFS. In addition, the Kaplan-Meier curve analysis showed that BD3 patients had the worst RFS (P=0.01). The OS of the adjuvant chemotherapy group was significantly improved compared to that of the surgery-only group in the BD1/2 patients (HR =0.278, 95% CI: 0.114-0.676, P=0.005) but not in the BD3 patients with significant interaction (Pinteraction=0.03). Conclusions: Our results indicate that TB could play a subsidiary role in selecting stage II CRC patients who could achieve a favorable prognosis with chemotherapy.

Structural analysis and biological activity of cell wall polysaccharides and enzyme-extracted polysaccharides from pomelo (Citrus maxima (Burm.) Merr.).

Pomelo peel is a valuable source of pectin, but research on its cell wall polysaccharides is limited. This study compared the cell wall polysaccharides of pomelo peel, enzyme-extracted polysaccharides of pomelo peel, and enzyme-extracted polysaccharides of whole pomelo fruit. Cell wall polysaccharides, including water-soluble pectin (WSP), chelator-soluble pectin (CSP), sodium carbonate-soluble pectin (NSP), 1 mol/L KOH soluble hemicellulose (KSH-1), and 4 mol/L KOH soluble hemicellulose (KSH-2), were obtained by sequence-extraction method. Total polysaccharides from whole pomelo fruit (TP) and peel-polysaccharides from pomelo pericarps (PP) were obtained using enzyme-extraction method. The structural, thermal, rheological, antioxidant properties, and wound healing effect in vitro were described for each polysaccharide. WSP had a uniform molecular weight distribution and high uronic acid (UA) content, suitable for commercial pectin. NSP had the highest Rhamnose (Rha)/UA ratio and a rich side chain with highest viscosity and water retention. PP displayed the highest DPPH radical scavenging activity and reducing capacity at 0.1 to 2.0 mg/mL concentration range, with an IC50 of 1.05 mg/mL for DPPH free radicals. NSP also demonstrated the highest hydroxyl radical scavenging activity and promoted Human dermal keratinocyte proliferation and migration at 10 µg/mL, suggesting potential applications in daily chemical and pharmaceutical industries.

An updated and comprehensive review of the morphology, ethnomedicinal uses, phytochemistry, and pharmacological activity of Aster tataricus L. f.

Ethnopharmacological relevance: Aster tataricus L.f., an extensively used herb in traditional Chinese medicine for more than 2000 years, is known as "Zi wan" or "Fan huncao". Its dried root and rhizome hold great promise in the treatment of cough, asthma, tumor, inflammation, etc.Aim of the study: This literature review summarizes the morphology characteristics, ethnopharmacological use, phytochemical properties, pharmacological effects, and potential applications of Aster tataricus. Furthermore, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Using "Aster tataricus L.f.", "Traditional medicinal usage", "Phytochemistry", "Pharmacological effects" as the keywords and gathered relevant data on Aster tataricus L.f. using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. Result: A total of 186 compounds have been isolated and identified from Aster tataricus, including terpenes, organic acids, peptides, and flavonoids. And Aster tataricus has been widely used as a natural cough suppressant and has anti-oxidative, anti-inflammatory, anti-depressive, and anti-tumor effects. In addition, Aster tataricus has also been reported to have damaging effects on the liver as well as other toxicities were discussed in this review. Conclusions: Aster tataricus is an ancient herbal medicine with a broad spectrum of pharmaco logical activities that has been used for thousands of years in China, and has shown remarkable effectiveness in the treatment of various diseases, especially cough, asthma, inflammation. Although its rich chemical constituents have various pharmacological activities, the underlying mechanisms, as well as its toxicity and safety, remains unclear and warrant further investigation.

Optional Revascularization Strategies for Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Disease.

Percutaneous coronary intervention is the main strategy of revascularization and has been shown to improve outcomes in some patients with ST-segment elevation myocardial infarction (STEMI). However, multivessel disease (MVD), a common condition in these patients, is associated with worse clinical outcomes compared to single-vessel disease. Despite intervention being a standard treatment for coronary artery disease, optimal strategies and timings for patients with STEMI and MVD remain unclear. Numerous studies and meta-analyses have investigated this topic; however, many current conclusions are based on observational studies. Furthermore, clinical guidelines regarding the management of patients with STEMI and MVD contain conflicting recommendations. Therefore, we aimed to compile relevant studies and newly available evidence-based medicines to explore the most effective approach.

Development of a prognostic risk model of uveal melanoma based on N7-methylguanosine-related regulators.

BACKGROUND: Uveal melanoma (UVM) stands as the predominant type of primary intraocular malignancy among adults. The clinical significance of N7-methylguanosine (m7G), a prevalent RNA modifications, in UVM remains unclear. METHODS: Primary information from 80 UVM patients were analyzed as the training set, incorporating clinical information, mutation annotations and mRNA expression obtained from The Cancer Genome Atlas (TCGA) website. The validation set was carried out using Gene Expression Omnibus (GEO) database GSE22138 and GSE84976. Kaplan-Meier and Cox regression of univariate analyses were subjected to identify m7G-related regulators as prognostic genes. RESULT: A prognostic risk model comprising EIF4E2, NUDT16, SNUPN and WDR4 was established through Cox regression of LASSO. Evaluation of the model's predictability for UVM patients' prognosis by Receiver Operating Characteristic (ROC) curves in the training set, demonstrated excellent performance Area Under the Curve (AUC) > 0.75. The high-risk prognosis within the TCGA cohort exhibit a notable worse outcome. Additionally, an independent correlation between the risk score and overall survival (OS) among UVM patients were identified. External validation of this model was carried out using the validation sets (GSE22138 and GSE84976). Immune-related analysis revealed that patients with high score of m7G-related risk model exhibited elevated level of immune infiltration and immune checkpoint gene expression. CONCLUSION: We have developed a risk prediction model based on four m7G-related regulators, facilitating effective estimate UVM patients' survival by clinicians. Our findings shed novel light on essential role of m7G-related regulators in UVM and suggest potential novel targets for the diagnosis, prognosis and therapy of UVM.

Construction Au/FAPbI3 Schottky Heterojunction towards a High-Speed Electron Transfer Channel for High-Performance Perovskite Quantum Dot Solar Cells.

Formamidinium lead triiodide quantum dot (FAPbI3 QD) exhibits substantial potential in solar cells due to its suitable band gap, extended carrier lifetime, and superior phase stability. However, despite great attempts toward reconfiguring the surface chemical environment of FAPbI3 QDs, achieving the optimal efficiency of charge carrier extraction and transfer in cells remains a challenge. To circumvent this problem, we selectively introduced Au/FAPbI3 Schottky heterojunctions by reducing Au+ to Au0 and subsequently anchoring them on the surface of FAPbI3 QDs, which acts as a light-harvesting layer and establishes high-speed electron transfer channels (Au dot ↔ Au dot). As a result, the champion photoelectric conversion efficiency of solar cells reached 13.68%, a significant improvement over 11.19% of that of FAPbI3-based solar cells. The enhancement is attributed to efficient and directed electron transfer as well as a more aligned energy level arrangement. This work constructed Au/FAPbI3 QD Schottky heterojunctions, providing a viable strategy to enhance QD electron coupling for high-performance optoelectronic applications.

Radiological Features for Predicting the Status of CD8-Positive Lymphocytes in HER2 Positive Breast Cancer.

Background: The level of tumor-infiltrating lymphocytes (TILs) in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is positively correlated with pathological complete response. Aims: To investigate the relationship between ultrasound (US) and magnetic resonance imaging (MRI) features and the level of CD8-positive TILs (CD8+-TILs) in patients with HER2-positive BC. Study Design: Retrospective cohort study. Methods: This retrospective study included 155 consecutive women with HER2-positive BC. Patients were divided into two groups: CD8+-TILlow (< 35%) and CD8+-TILhigh (≥ 35%) groups. US and MRI features were evaluated using the BI-RADS lexicon, and the apparent diffusion coefficient (ADC) value was calculated using RadiAnt software. Univariate and multivariate analyses revealed the optimal US and MRI features for predicting CD8+-TIL levels. Receiver operating characteristic analysis and the Delong test were used to compare the diagnostic performance of US and MRI features. Furthermore, implementing a nomogram will increase clinical utility. Results: Univariate analysis of US features showed significant differences in shape, orientation, and posterior echo between the two groups; however, there were no significant differences in margins, internal echo, and microcalcification. Multifactorial analysis revealed that shape, orientation, and posterior echo were independent risk factors, with odds ratios of 11.62, 2.70, and 0.16, respectively. In terms of MRI features, ADC was an independent predictor of CD8+-TIL levels. These three US features and the ADC performed well, with area under the curve (AUC) values of 0.802 and 0.705, respectively. The combination of US and ADC values had higher predictive efficacy (AUC = 0.888) than either US or ADC alone (p = 0.009, US_ADC vs. US; p < 0.001, US_ADC vs. ADC). Conclusion: US features (shape, orientation, and posterior echo) and ADC value may be a valuable tool for estimating CD8+-TIL levels in HER2-positive BC. The nomogram may help clinicians in making decisions.

Development of a paper-based transcription aptasensor for convenient urinary uric acid self-testing.

The abnormal uric acid (UA) level in urine can serve as warning signals of many diseases, such as gout and metabolic cardiovascular diseases. The current methods for detecting UA face limitations of instrument dependence and the requirement for non-invasiveness, making it challenging to fulfill the need for home-based application. In this study, we designed an aptasensor that combined UA-specific transcriptional regulation and a fluorescent RNA aptamer for convenient urinary UA testing. The concentration of UA can be translated into the intensity of fluorescent signals. The aptasensor showed higher sensitivity and more robust anti-interference performance. UA levels in the urine of different volunteers could be accurately tested using this method. In addition, a paper-based aptasensor for UA self-testing was manufactured, in which the urinary UA levels could be determined using a smartphone-based colorimetric approach. This work not only demonstrates a new approach for the design of disease-associated aptasensor, but also offers promising ideas for home-based detection of UA.

3-aminopropyltriethoxysilane modified MXene on three-dimensional nonwoven fiber substrates for low-cost, stable, and efficient solar-driven interfacial evaporation desalination.

Recently, the solar-driven interfacial evaporation desalination has attracted more and more attentions due to the advantages of low cost, zero energy consumption, and high water purification rate, etc. One of the bottlenecks of this emerging technique lies in a lack of simple and low-cost ways to construct three-dimensional (3D) hierarchical microstructures for photothermal membranes. To this end, a two-step strategy is carried out by combining surface functionalization with substrate engineering. Firstly, a silane coupling agent 3-aminopropyltriethoxysilane (APTES) is grafted onto an ideal photothermal material of Ti3C2Tx MXene, to improve the nanochannel sizes and hydrophilicity, which are attributed to enlarged interspaces of MXene and introduced hydrophilic group e.g., -NH2 and -OH, respectively. Secondly, a low-cost and robust nonwoven fiber (NWF) substrate, which has a 3D micron-sized mesh structure with interlaced fiber stacks, is employed as the skeleton to load enough APTES-grafted MXene by a simple soaking method. Benefited from above design, the Ti3C2Tx-APTES/NWF composite membrane with a 3D hierarchical structure shows enhanced light scattering and utilization, water transport and vapor escape. A remarkable evaporation rate of 1.457 kg m-2 h-1 and an evaporation efficiency of 91.48 % are attained for a large-area (5 × 5 cm2) evaporator, and the evaporation rate is further increased to 1.672 kg m-2 h-1 for a small-area (2 × 2 cm2) device. The rejection rates of salt ions and heavy metal ions are higher than 99 % and 99.99 %, respectively, and the removal rates of organic dye molecules are nearly to 100 %. Besides, the composite photothermal membrane exhibits great stabilities in harsh conditions such as high salinities, long cycling, large light intensities, strong acid/alkali environments, and mechanical bending. Most importantly, the photothermal membrane shows a considerable cost-effectiveness of 89.4 g h-1/$. Hence, this study might promote the commercialization of solar-driven interfacial evaporation desalination by collaboratively considering surface modification and substrate engineering for MXene.

Distinct lateral hypothalamic CaMKIIα neuronal populations regulate wakefulness and locomotor activity.

For nearly a century, evidence has accumulated indicating that the lateral hypothalamus (LH) contains neurons essential to sustain wakefulness. While lesion or inactivation of LH neurons produces a profound increase in sleep, stimulation of inhibitory LH neurons promotes wakefulness. To date, the primary wake-promoting cells that have been identified in the LH are the hypocretin/orexin (Hcrt) neurons, yet these neurons have little impact on total sleep or wake duration across the 24-h period. Recently, we and others have identified other LH populations that increase wakefulness. In the present study, we conducted microendoscopic calcium imaging in the LH concomitant with EEG and locomotor activity (LMA) recordings and found that a subset of LH neurons that express Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) are preferentially active during wakefulness. Chemogenetic activation of these neurons induced sustained wakefulness and greatly increased LMA even in the absence of Hcrt signaling. Few LH CaMKIIα-expressing neurons are hypocretinergic or histaminergic while a small but significant proportion are GABAergic. Ablation of LH inhibitory neurons followed by activation of the remaining LH CaMKIIα neurons induced similar levels of wakefulness but blunted the LMA increase. Ablated animals showed no significant changes in sleep architecture but both spontaneous LMA and high theta (8 to 10 Hz) power during wakefulness were reduced. Together, these findings indicate the existence of two subpopulations of LH CaMKIIα neurons: an inhibitory population that promotes locomotion without affecting sleep architecture and an excitatory population that promotes prolonged wakefulness even in the absence of Hcrt signaling.

Toughening Hydrogels with Fibrillar Connected Double Networks.

Biological tissues, such as tendons or cartilage, possess high strength and toughness with very low plastic deformations. In contrast, current strategies to prepare tough hydrogels commonly utilize energy dissipation mechanisms based on physical bonds that lead to irreversible large plastic deformations, thus limiting their load-bearing applications. This article reports a strategy to toughen hydrogels using fibrillar connected double networks (fc-DN), which consist of two distinct but chemically interconnected polymer networks, that is, a polyacrylamide network and an acrylated agarose fibril network. The fc-DN design allows efficient stress transfer between the two networks and high fibril alignment during deformation, both contributing to high strength and toughness, while the chemical crosslinking ensures low plastic deformations after undergoing high strains. The mechanical properties of the fc-DN network can be readily tuned to reach an ultimate tensile strength of 8 MPa and a toughness of above 55 MJ m-3, which is 3 and 3.5 times more than that of fibrillar double network hydrogels without chemical connections, respectively. The application potential of the fc-DN hydrogel is demonstrated as load-bearing damping material for a jointed robotic lander. The fc-DN design provides a new toughening mechanism for hydrogels that can be used for soft robotics or bioelectronic applications.

Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity.

OBJECTIVES: The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress. METHODS: An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins. KEY FINDINGS: The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group. CONCLUSIONS: The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.

Visualizing Noncovalent Interactions and Property Prediction of Submicron-Sized Charge-Transfer Crystals from ab-initio Determined Structures.

The charge-transfer (CT) interactions between organic compounds are reflected in the (opto)electronic properties. Determining and visualizing crystal structures of CT complexes are essential for the design of functional materials with desirable properties. Complexes of pyranine (PYR), methyl viologen (MV), and their derivatives are the most studied water-based CT complexes. Nevertheless, very few crystal structures of CT complexes have been reported so far. In this study, the structures of two PYRs-MVs CT crystals and a map of the noncovalent interactions using 3D electron diffraction (3DED) are reported. Physical properties, e.g., band structure, conductivity, and electronic spectra of the CT complexes and their crystals are investigated and compared with a range of methods, including solid and liquid state spectroscopies and highly accurate quantum chemical calculations based on density functional theory (DFT). The combination of 3DED, spectroscopy, and DFT calculation can provide important insight into the structure-property relationship of crystalline CT materials, especially for submicrometer-sized crystals.

Protective effects of sodium humate and its zinc and selenium chelate on the oxidative stress, inflammatory, and intestinal barrier damage of Salmonella Typhimurium-challenged broiler chickens.

The objective of this study was to investigate the protective effects and mechanisms of dietary administration of sodium humate (HNa) and its zinc and selenium chelate (Zn/Se-HNa) in mitigating Salmonella Typhimurium (S. Typhi) induced intestinal injury in broiler chickens. Following the gavage of 109 CFU S. Typhi to 240 broilers from 21-d to 23-d aged, various growth performance parameters such as body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed ratio (FCR) were measured before and after infection. Intestinal morphology was assessed to determine the villus height, crypt depth, and chorionic cryptologic ratio. To evaluate intestinal barrier integrity, levels of serum diamine oxidase (DAO), D-lactic acid, tight junction proteins, and the related genes were measured in each group of broilers. An analysis was conducted on inflammatory-related cytokines, oxidase activity, and Nuclear Factor Kappa B (NF-κB) and Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related proteins and mRNA expression. The results revealed a significant decrease in BW, ADG, and FCR in S. typhi-infected broilers. HNa tended to increase FCR (P = 0.056) while the supplementation of Zn/Se-HNa significantly restored BW and ADG (P < 0.05). HNa and Zn/Se-HNa exhibit favorable and comparable effects in enhancing the levels of serum DAO, D-lactate, and mRNA and protein expression of jejunum and ileal tight junction. In comparison to HNa, Zn/Se-HNa demonstrates a greater reduction in S. Typhi shedding in feces, as well as superior efficacy in enhancing the intestinal morphology, increasing serum catalase (CAT) activity, inhibiting pro-inflammatory cytokines, and suppressing the activation of the NF-κB pathway. Collectively, Zn/Se-HNa was a more effective treatment than HNa to alleviate adverse impact of S. Typhi infection in broiler chickens.

Upregulation of CIRP by its agonist prevents the development of heart failure in myocardial infarction rats.

BACKGROUND: Downregulated expression of cold-inducible RNA binding protein (CIRP), a stress-response protein, has been demonstrated in the hearts of patients with heart failure (HF). However, whether CIRP plays a critical role in the pathogenesis of HF remains unknown. Zr17-2 is a recently identified CIRP agonist, which can enhance the expression of CIRP in hearts. Herein, we evaluated the effects of zr17-2 on the development of HF in a rat model of myocardial infarction (MI). METHODS: Male SD rats were pretreated with CIRP agonist zr17-2 or vehicle saline for 6 consecutive days, followed by MI induction. 1-week post-MI, cardiac function, and structural and molecular changes were determined by echocardiography and molecular biology methods. RESULTS: Excitingly, we found that pretreatment with zr17-2 significantly attenuated MI-induced cardiac dysfunction and dilation, coupled with reduced infarction size and cardiac remodeling. In addition, increased inflammatory response in the peri-infarcted heart including macrophage infiltration and the expression of inflammatory genes were all significantly decreased by zr17-2 pretreatment, suggesting an anti-inflammatory effect of zr17-2. Moreover, zr17-2 pretreatment also upregulated the antioxidant genes (e.g. NQO-1, Nrf2, and HO-1) level in the hearts. In isolated cultured cardiomyocytes, pretreatment with zr17-2 markedly attenuated cell injury and apoptosis induced by oxidative injury, along with elevation of Nrf2-related antioxidant genes and CIRP. However, silencing CIRP abolished zr17-2's antioxidant effects against oxidative injury, confirming that zr17-2's role is dependent on CIRP. CONCLUSION: Collectively, our study suggests CIRP plays a crucial role in the development of HF and a beneficial effect of CIRP agonist in preventing MI-induced HF, possibly via anti-inflammatory and anti-oxidant pathways.

The emerging roles of histone demethylases in cancers.

Modulation of histone methylation status is regarded as an important mechanism of epigenetic regulation and has substantial clinical potential for the therapy of diseases, including cancer and other disorders. The present study aimed to provide a comprehensive introduction to the enzymology of histone demethylases, as well as their cancerous roles, molecular mechanisms, therapeutic possibilities, and challenges for targeting them, in order to advance drug design for clinical therapy and highlight new insight into the mechanisms of these enzymes in cancer. A series of clinical trials have been performed to explore potential roles of histone demethylases in several cancer types. Numerous targeted inhibitors associated with immunotherapy, chemotherapy, radiotherapy, and targeted therapy have been used to exert anticancer functions. Future studies should evaluate the dynamic transformation of histone demethylases leading to carcinogenesis and explore individual therapy.