Positive role of plateau pika (Ochotona coronae) on environmental quality at low and moderate density on the Tibetan plateau: Evidence from a meta-analysis.

The roles of plateau pika (Ochotona coronae) in the Tibetan Plateau are often controversial, because it is often regarded as a destructive pest or an ecosystem engineer. Here a meta-analysis using 72 paired observations was conducted to examine whether the impacts of plateau pika on environmental quality (i.e., plant and soil properties) depend on population density in the Tibetan Plateau. Pika population density was used as a proxy for disturbance intensity. The pika disturbance intensity was divided into five groups based on the number of burrows, including low disturbance intensity (LD) (9-30 burrows per ha), medium disturbance intensity (MD) (31-100 burrows per ha), high disturbance intensity (HD) (101-170 burrows per ha), extreme disturbance intensity (ED) (171-240 burrows per ha) and uncontrolled (or excessive) disturbance intensity (UD) (>241 burrows per ha). Given that sample sizes in some of the groups are small (especially for the HD), we further pooled the disturbance groups including the LD-MD and HD-UD. Overall, relative to control (i.e., no disturbing), there was a great increase (80.3%) in aboveground biomass under the LD-MD, whereas a decrease of 41.1% occurred under the HD-UD. At the same time, plant coverage, species richness, height, and belowground biomass greatly decreased only in the HD-UD. Furthermore, the effect size of plant coverage, species richness, and aboveground biomass also declined with pika burrow density significantly. With regard to soil properties, there was a significant increase in soil organic carbon, ammonium nitrogen, and soil organic carbon stock under the LD-MD, whereas a decrease under the HD-UD. In addition, soil total nitrogen, total potassium, and nitrate nitrogen increased at the LD-MD and HD-UD. Nevertheless, the effect size of these soil properties (with >20 observations) was not related to pika burrow density. In summary, there is an implication that the low and moderate disturbance of pikas is beneficial to maintain and promote ecosystem functioning in the Tibetan grasslands. In the future pikas' eradication policy should be reconsidered in alpine grassland management.

A comprehensive study on the risk factors and pathogen analysis of postoperative wound infections following caesarean section procedures.

Postoperative wound infections (PWIs), a subtype of surgical site infections, are a significant concern for patients undergoing caesarean sections (C-sections). Understanding risk factors and pathogen profiles can greatly assist in early diagnosis and effective treatment. This study aimed to identify risk factors and analyse the pathogenic landscape contributing to PWIs in C-sections. A nested case-control study was carried out, utilising stringent criteria for case selection and control matching. Diagnostic criteria for surgical site infections included both clinical and microbiological parameters. Risk variables examined included patient age, Body Mass Index, duration of surgery and several other clinical indicators. Microbiological analysis was performed using the BD Phoenix-100 Automated Bacterial Identification System. Statistical analyses were conducted using SPSS version 26.0, and risk factors were evaluated through both univariate and multivariate analyses. A total of 50 patients, aged between 20 and 45 years (mean age 26.3 ± 5.6), developed PWIs following C-sections. The study revealed a temporal distribution and various clinical indicators of PWIs, including elevated white blood cell count and C-reactive protein levels. Gram-negative bacteria were found to be more prevalent at 57.4%. Notable pathogens included Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrobial resistance patterns were also identified, highlighting the need for a targeted antibiotic approach. Increased infection risks were linked to lack of prophylactic antibiotics, absence of preoperative povidone-iodine antisepsis, operations over an hour, anaemia, amniotic fluid contamination, diabetes, GTI, premature rupture of membranes and white blood cells counts above 10 × 109 /L. The study provides critical insights into the risk factors and microbial agents contributing to PWIs following C-sections. Our findings emphasise the importance of early diagnosis through clinical and laboratory parameters, as well as the need for constant surveillance and reassessment of antibiotic stewardship programs.

Downregulation of TCL6 protected human trophoblast cells from LPS-induced inflammation and ferroptosis.

Dysregulation of noncoding RNAs has been reported to have a close correlation with preeclampsia(PE)development. TCL6 was upregulated in patients with PE. In this study, we examined the impacts of TCL6 on modulating HTR-8/SVneo cells induced by LPS. LPS (100 and 200 ng/ml) was applied to induce inflammation in trophoblast cells HTR-8/SVneo. Cell viability, apoptosis, and transwell experiments were conducted. The ELISA methods were used for pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. MDA, GSH, and GPX kits were employed. Transfection was performed for expression regulation of TCL6, miR-485-5p, and TFRC in cells. Bioinformatic online tools were used to predict the targeting sites. Luciferase and RNA immunoprecipitation-qPCR were done to verify the interactions of TCL6, miR-485-5p, and TFRC. RNA expression levels were measured using RT-qPCR, and protein expression of TFRC and GPX4 was detected using a western blot. The free Fe (II) contents were measured. LPS decreased viability, invasion, and migration but enhanced apoptosis, ferroptosis, and inflammation. TCL6 expression was enhanced by LPS induction. The knockdown of TCL6 increased HTR-8/SVneo cell viability and invasion but inhibited cell apoptosis, inflammation, and ferroptosis while inhibition of miR-485-5p could reverse this through TFRC regulation. Moreover, miR-485-5p was sponged by TCL6 and bound to TFRC. TCL6 protected trophoblast cells from LPS-induced injury through the TFRC pathway.

Reversible Chemical Protein Modification to Endogenous Glutathione and Its Utilities in the Manufacture of Transcellular Pro-Enzymes.

Proteins have been perceived as being an intriguing modality of therapeutics for the treatment of intractable diseases in view of their superlative precision and versatility. Nonetheless, proteins' intrinsic characters, particularly their being hydrophilic macromolecules with unmethodical charges, have imposed the exceeding challenge of seeking transcellular trafficking into cells' interiors. To circumvent this drawback, we have attempted to employ triple-functional amine-reactive 4-(2-((2-(((4-nitrophenoxy)carbonyl)oxy)ethyl)disulfaneyl)ethoxy)-4-oxobutanoic acid for the efficient incorporation of the anionic carboxyl moiety into amine-enriched enzymes, resulting in overall negatively charged pro-enzymes. The resulting pro-enzymes could be readily electrostatically assembled with cationic species [for instance: block copolymers of poly(ethylene glycol)-polylysine] into core-shell architectural delivery nanoparticles for their facilitated endocytosis into cells. Noteworthy is the aforementioned carboxylation chemistry designed to allow facile reversal of the pro-enzymes to the original amine groups due to the thiolysis of intermediate disulfide linkage for subsequent cascade reactions in response to the cytosol-enriched glutathione. Therefore, cytosol-selective structural disassembly for the liberation and activation of the pro-enzymes was accomplished. Our subsequent investigations utilizing ribonuclease A and catalase as the model enzymes demonstrated appreciable transcellular transportation of the active enzymes to the cell interiors, exerting overwhelming cytotoxic potencies and H2O2 scavenging capacities, respectively. Hence, we reported an unprecedented redox-stimulated charge reversal strategy in engineering cytosol-activatable pro-enzymes, manifesting a simple and efficient approach in the manufacture of transcellular proteinic therapeutics, which should be highlighted to promote their wide availability for use with diverse functional proteins as molecular biological tools and precision therapeutics.

Dynamic Asynchronous Anti Poisoning Federated Deep Learning with Blockchain-Based Reputation-Aware Solutions.

As promising privacy-preserving machine learning technology, federated learning enables multiple clients to train the joint global model via sharing model parameters. However, inefficiency and vulnerability to poisoning attacks significantly reduce federated learning performance. To solve the aforementioned issues, we propose a dynamic asynchronous anti poisoning federated deep learning framework to pursue both efficiency and security. This paper proposes a lightweight dynamic asynchronous algorithm considering the averaging frequency control and parameter selection for federated learning to speed up model averaging and improve efficiency, which enables federated learning to adaptively remove the stragglers with low computing power, bad channel conditions, or anomalous parameters. In addition, a novel local reliability mutual evaluation mechanism is presented to enhance the security of poisoning attacks, which enables federated learning to detect the anomalous parameter of poisoning attacks and adjust the weight proportion of in model aggregation based on evaluation score. The experiment results on three datasets illustrate that our design can reduce the training time by 30% and is robust to the representative poisoning attacks significantly, confirming the applicability of our scheme.

Real-time three-dimensional echocardiography and two-dimensional speckle tracking imaging in the evaluation of left atrial function in patients with triple-vessel coronary artery disease without myocardial infarction.

OBJECTIVE: To evaluate left atrial function in patients with triple-vessel disease (TVD) without myocardial infarction by real-time three-dimensional echocardiography (RT-3DE) and two-dimensional speckle tracking imaging (2D-STE). METHODS: Sixty patients with coronary artery disease (CAD) without myocardial infarction were classified into two groups in accordance with the coronary angiography results: group B (all triple-vessel stenosis ≥ 50% and < 75%) and group C (all triple-vessel stenosis ≥ 75%). Thirty healthy individuals were selected as group A. LA volume related parameters including left atrial maximum volume index (LAVImax), LA passive and active ejection fraction (LAPEF, LAAEF) and LA total ejection fraction (LATEF) were measured by RT-3DE. The global peak atrial longitudinal systolic strain (LASRs), early and late diastolic LA strain (LASRe and LASRa) rates were measured by 2D-STE. RESULTS: We found statistically significant differences between 2D-STE and RT-3DE related parameters of these three groups. Furthermore, in groups B and C, N-terminal fragment brain natriuretic peptides (NT-pro-BNP) and left ventricular end-diastolic pressure (LVEDP) were found to be significantly correlated with LASRs and LASRa. And NT-pro-BNP had a moderate correlation with LVEDP. CONCLUSIONS: 2D-STE and RT-3DE can assess the LA function in patients with TVD without myocardial infarction. And LA strain values may provide additional information for predicting increased LVEDP and NT-pro-BNP.

Recent Advancements in Natural Plant Colorants Used for Hair Dye Applications: A Review.

There is an on-going demand in recent years for safer and "greener" hair coloring agents with the global consumer awareness of the adverse effects of synthetic hair dyes. The belief in sustainability and health benefits has focused the attention of the scientific community towards natural colorants that serve to replace their synthetic toxic counterparts. This review article encompasses the historical applications of a vast array of natural plant hair dyes and summarizes the possible coloration mechanisms (direct dyeing and mordant dyeing). Current information on phytochemicals (quinones, tannins, flavonoids, indigo, curcuminoids and carotenoids) used for hair dyeing are summarized, including their botanical sources, color chemistry and biological/toxicological activities. A particular focus is given on research into new natural hair dye sources along with eco-friendly, robust and cost-effective technologies for their processing and applications, such as the synthetic biology approach for colorant production, encapsulation techniques for stabilization and the development of inorganic nanocarriers. In addition, innovative in vitro approaches for the toxicological assessments of natural hair dye cosmetics are highlighted.

[Narrative evidence-based medicine:a strategy for evaluation of clinical efficacy of Chinese medicine].

Rich experience of clinical diagnosis and treatment has been accumulated in the developmental history of Chinese medicine, and the efficacy has been increasingly accepted by the public. However, the evaluation of clinical efficacy is currently based more on scientific evidence instead of merely the changes of patient symptoms. In Chinese medicine, the changes of major disease indicators, patient symptoms, and pathogenesis are the major criteria for the evaluation of clinical efficacy. The lack of well-accepted and uniform criteria and the uncertainty of subjective evaluation limit the development of clinical Chinese medicine. Evidence-based medicine combines clinical skills with the current best evidence. Narrative medicine, utilizing people's narratives in clinical practice, emphasizes patient feelings, willingness, and value orientation. The introduction of both evidence-based medicine and narrative medicine into the evaluation of clinical efficacy refers to the construction of the clinical efficacy evaluation system in a paradigm of participatory diagnosis and treatment. It can fully reflect the characteristics of Chinese medicine, respect the values of patients, and achieve universal clinical evidence. Therefore, it helps to improve the diagnosis and treatment, the relationship between doctors and patients, patients' life quality and decision-making awareness, and finally the new evaluation model of clinical efficacy of Chinese medicine.

Low Back Pain Assessment Based on Alpha Oscillation Changes in Spontaneous Electroencephalogram (EEG).

Objectively and accurately assessing pain in clinical settings is challenging. Previous studies showed that alpha oscillations of electroencephalogram data are correlated with subjective perceived pain. Based on this finding, this study is aimed at assessing chronic low back pain based on alpha oscillations. Multichannel electroencephalogram data were recorded from 27 subjects with chronic low back pain under the simple conditions of closing eyes or opening eyes. Spectral analyses were conducted to extract the alpha band responses, and the alpha powers were calculated for the two conditions, respectively. Normalized alpha power was calculated by subtracting the alpha power in the eyes-open condition from that in the eyes-closed condition. The correlation between the alpha power and the subjective pain intensity was evaluated in frontal, central, and posterior regions. The normalized alpha power in the central region was negatively correlated with the subjective pain intensity (R = -0.50, P = 0.01), with the strongest correlation occurring at the Cz electrode (R = -0.59, P = 0.04). The correlation analysis results demonstrated the possibility of using the differences of alpha spectral power between eyes-closed and eyes-open conditions as a measure for assessing chronic low back pain. The findings suggest that the normalized alpha power in the central region may be used as a measurable and quantitative indicator of chronic pain for clinical applications.

Analgesic efficacy of ultrasound-guided transversus abdominis plane block after cesarean delivery: A systematic review and meta-analysis.

PURPOSE: The meta-analysis is aimed to further access the analgesic efficacy of ultrasound-guided transversus abdominis plane (USG-TAP) block after cesarean section (CS). METHODS: Electronic databases were searched for eligible studies. Primary objectives were pain-related outcomes. Weighted mean differences (WMDs) or standardized mean differences (SMDs), as well as risk ratios (RRs) with 95% confidence intervals (CIs), were used to calculate estimates. Subgroup analyses were done based on whether USG-TAP blocks were performed with long-acting intrathecal opioids (ITO). RESULTS: A total of 17 studies were included. When compared with control groups (placebo or no blocks), USG-TAP block resulted in lower cumulative opioid consumption at 6 h (WMD: -8.32; 95% CI: -14.86, -1.79), 12 h (WMD: -10.75; 95% CI: -20.93, -0.57), and 24 h (WMD: -12.71, 95% CI: -21.28, -4.14). No significant differences were demonstrated among dynamic or resting pain scores. Patients in USG-TAP groups needed longer time to request first analgesic (WMD: 3.56; 95% CI: 1.43, 5.68) and showed a lower requirement of opioid rescue analgesia for breakthrough severe pain during 24 h (RR: 0.40; 95% CI: 0.18, 0.86). Subgroup analyses showed USG-TAP blocks did not afford additional benefit in the presence of intrathecal morphine. Also, reduced need for antiemetics after CS and higher maternal satisfaction were provided by USG-TAP blocks. CONCLUSION: USG-TAP block can provide significantly effective analgesia for patients who underwent CS in the absence of long-acting ITO and therefore are worth promoting in the setting of long-acting ITO being unfeasible.

The risk factors and care measures of surgical site infection after cesarean section in China: a retrospective analysis.

BACKGROUND: Surgical site infections after cesarean section are very common clinically, it is necessary to evaluate the risk factors of surgical site infections after cesarean section, to provide evidences for the treatment and nursing care of cesarean section. METHODS: This study was a retrospective cohort study design. Patients undergone cesarean section in a tertiary hospital of China from May 2017 to May 2020 were identified, we collected the clinical data of the included patients, and we analyzed the infection rate, etiological characteristics and related risk factors of surgical site infection after caesarean section. RESULTS: A total of 206 patients with cesarean section were included, and the incidence of surgical site infection in patients with cesarean section was 23.30%. A total of 62 cases of pathogens were identified, Enterococcus faecalis (33.87%) and Escherichia coli (29.03%) were the most common pathogens. Both Enterococcus faecalis and Escherichia coli were highly sensitive to Cefoperazone, Meropenem, and Levofloxacin. Logistic regression analyses indicated that Age ≥ 30y (OR 4.18, 95%CI: 1.23-7.09), BMI ≥ 24 (OR 2.39, 95%CI: 1.02-4.55), duration of cesarean section ≥ 1.5 h (OR 3.90, 95%CI: 1.28-5.42), estimated blood loss ≥ 400 ml (OR 2.35, 95%CI: 1.10-4.37) and the duration of urinary catheter ≥ 24 h (OR 3.18, 95% CI: 1.21-5.71) were the independent risk factors of surgical site infection after cesarean section (all p < 0.05). CONCLUSIONS: Age, BMI, duration of surgery, blood loss and urinary catheter use were associated with higher risk of the surgical site infection after cesarean section. Clinical preventions and interventions are warranted for those population to reduce the occurrence of surgical site infection.

An Adaptive Routing Algorithm Based on Relation Tree in DTN.

It is found that nodes in Delay Tolerant Networks (DTN) exhibit stable social attributes similar to those of people. In this paper, an adaptive routing algorithm based on Relation Tree (AR-RT) for DTN is proposed. Each node constructs its own Relation Tree based on the historical encounter frequency, and will adopt different forwarding strategies based on the Relation Tree in the forwarding phase, so as to achieve more targeted forwarding. To further improve the scalability of the algorithm, the source node dynamically controls the initial maximum number of message copies according to its own cache occupancy, which enables the node to make negative feedback to network environment changes. Simulation results show that the AR-RT algorithm proposed in this paper has significant advantages over existing routing algorithms in terms of average delay, average hop count, and message delivery rate.

Correlation between change in pain, disability, and surface electromyography topographic parameters after interferential current treatment in patients with chronic low back pain.

[Purpose] Surface electromyography (SEMG) topography is used to objectively assess patients with low back pain (LBP). This study aimed to investigate the correlation between SEMG topographic variables, pain, and disability in patients with chronic LBP (CLBP) after interferential current (IFC) treatment, and to evaluate IFC treatment efficacy using SEMG topography. [Participants and Methods] Twenty nine patients with CLBP were recruited for a 6-week IFC treatment. Pain and disability scores, and the root-mean-square difference (RMSD) of SEMG topographic variables (relative areas [RAs] at flexion and extension) were compared before and after the intervention by repeated measures ANOVA; the correlation between variables was also explored and p-value was set at 0.001. [Results] Significant positive correlations between changes in pain score and the RMSD of RA at flexion (r(29)=0.593), and between changes in pain and disability scores (r(29)=0.426) were observed. All participants showed statistically significant improvements in the RMSD of RA at flexion, pain score, and disability score after IFC treatment. [Conclusion] SEMG topographic variables are closely associated with changes in pain score in patients with CLBP after IFC treatment. The RMSD of RA at flexion can be used as an objective marker in IFC treatment efficacy evaluation.

LncRNA-H19 regulates cell proliferation and invasion of ectopic endometrium by targeting ITGB3 via modulating miR-124-3p.

Endometriosis, a common gynecological disease, is associated with pelvic pain and infertility. Endometriosis affects approximately 10% of women, but that number increases to 30-50% in symptomatic premenopausal women. Despite the prevalence of endometriosis, the cause has yet to be fully elucidated. Recent study of the molecular pathways of endometrial cancer has brought the long non-coding RNA (lncRNA) H19 to our attention. In this paper, we explored the role of lncRNA-H19 in endometrial tissue proliferation. We found that ectopic endometrial cells taken from women with endometriosis showed elevated levels of lncRNA-H19, with expression levels correlating to disease progression. Knockdown of H19 in ectopic endometrial cells inhibited cell proliferation and invasion. Coinciding with this change was an increase in microRNA-124-3p (miR-124-3p) and a decrease in integrin beta-3 (ITGB3) levels. The addition of a miR-124-3p inhibitor mitigated this decrease in ITGB3. Up-regulation of miR-124-3p markedly suppressed ITGB3 expression by binding to the 3' untranslated region (3' UTR), while inhibition of miR-124-3p had the opposite effect. ITGB3 overexpression potently counteracted the effects of miR-124-3p mimics on ectopic endometrial cells. From these results, we can infer that in endometriosis both miR-124-3p and ITGB3 operate as downstream effector proteins in the H19-signaling pathway. Down-regulation of lncRNA-H19 could inhibit ectopic endometrial cell proliferation and invasion by modulating miR-124-3p and ITGB3, offering a novel target for treatment.

Inhibition of microRNA-149 protects against recurrent miscarriage through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway.

AIM: Recently, microRNA-149 (miR-149) has been indicated to act as an oncogene or a tumor suppressor in various malignant tumors, while its inner mechanisms in recurrent miscarriage (RM) are still in infancy. Therein, this study intends to decode the mechanism of miR-149 in RM. METHODS: miR-149 and RUNX2 expression in the chorionic tissues of normal pregnant women and RM patients were first examined, and the correlation between miR-149 and RUNX2 was analyzed. Subsequently, miR-149 was upregulated in HTR-8 cells or downregulated in BEWO cells, and then the changes in biological functions of trophoblasts in RM were detected. Furthermore, the expression of PTEN/Akt signaling pathway-related factors in trophoblasts was detected by western blot analysis. RESULTS: miR-149 expression was increased while RUNX2 expression was suppressed in RM patients, and miR-149 was negatively correlated with RUNX2. Overexpressed miR-149 induced cell apoptosis and inhibited cell activity, while reduced miR-149 in trophoblasts contributed to opposite experimental results. Moreover, miR-149 promoted the expression of PTEN and inhibited Akt phosphorylation by targeting RUNX2, thereby inhibiting trophoblast activity and promoting their apoptosis. CONCLUSION: Our study demonstrates that miR-149 knockdown halted the RM development through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway.

Electrochemical characteristics of microelectrode designed for electrical stimulation.

BACKGROUND: Microelectrode arrays play an important role in prosthetic implants for neural signal recording or applying electrical pulses stimulation to target nerve system. Safety and long-term reliability are essential requirements for microelectrode arrays applied in electrical stimulation. In design and fabrication of the microelectrode array, soft materials are generally chosen to be the substrate for the aim of achieving better compliance with the surrounding tissue while maintaining minimal damage. By flexing of the array to the surface, the array is capable of keeping a more stable electrical contact resulting in a significantly improved signal detected. METHODS: In this study, we design and fabricate a flexible microelectrode array with gold as the electrode material and parylene-C as the substrate. The fabrication process of the array is presented. The in vitro electrochemical characteristics of the microelectrode are investigated by electrochemical impedance spectroscopy and cyclic voltammetry in a three-electrode electrochemical cell containing phosphate-buffered saline. Charge injection capacity measurements are carried out by multichannel systems and the CSC of the microarray is calculated. RESULTS: Electrochemical results showed that impedance decreased with frequency. The average impedance of the Au electrodes at 1 kHz was 36.54 ± 0.88 kΩ. The average phase angle at 1 kHz was - 73.52 ± 1.3°, and the CIC of the microelectrode was 22.3 µC/cm2. The results demonstrated that the microelectrode array performed as expected for neuronal signal recording or stimulation. CONCLUSIONS: With parylene-C as the substrate, the microarray has good flexibility. The electrochemical characteristics' results show that the array has the ability to resist any corrosion on metal-electrolyte interface and has good biocompatibility. This low-cost, flexible parylene-based, gold microelectrode array shows potential for use in implant neurological signal acquisition or neurostimulation applications.

Influence of early-life factors on the development of endometriosis.

Objective: Our aim was to study the association between early-life factors and the development of endometriosis. Methods: This case-control study included 440 women with surgically confirmed endometriosis (cases) and 880 women without endometriosis (controls). Information on early-life factors was ascertained retrospectively by in-person interviews with participants and their mothers. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between endometriosis and maternal and paternal characteristics and foetal and infant exposures were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Results: We observed that women who were not breastfed as infants had twice the risk of endometriosis compared with women who were breastfed (adjusted OR 2.0; 95% CI 1.6, 4.5). Our data suggested an increased endometriosis risk with neonatal vaginal bleeding (adjusted OR 1.9; 95% CI 1.2, 4.3) and paternal smoking (adjusted OR 1.8; 95% CI 1.1, 4.9). Although the CIs included the null hypothesis value, caesarean section (adjusted OR 1.7; 95% CI 1.0, 3.5) and prematurity (adjusted OR 1.4; 95% CI 0.8, 3.7) were probably associated with the incidence of endometriosis. Conclusions: Some early-life factors including breastfeeding, neonatal vaginal bleeding and paternal smoking were associated with subsequent, surgically confirmed endometriosis in this cohort of Chinese women.

Celecoxib Conjugated Fluorescent Probe for Identification and Discrimination of Cyclooxygenase-2 Enzyme in Cancer Cells.

Cyclooxygenase-2 (COX-2) is an enzyme overexpressed in most types of cancers and has been used for an excellent targetable biomarker. Celecoxib is an effective inhibitor of COX-2, used in anti-inflammation. Herein we report a one and two-photon fluorescence probe (NP-C6-CXB) for COX-2, based on the conjugation of naphthalamide with Celecoxib, by using flexible hexylene linker. NP-C6-CXB is nonfluorescent in buffer solution and normal cells, while it shows bright fluorescence in solutions and cancer cells in the presence of COX-2 with an excellent selectivity. Interestingly, NP-C6-CXB can discriminate cancer cells (MCF-7) from normal cells (COS-7) in the single culture medium under confocal microscopy. Due to the selective binding affinity of NP-C6-CXB with a COX-2 enzyme, the intensity is proportional to the level of COX-2 enzyme in cancer cells. In vivo and in vitro experiments proved that NP-C6-CXB is a potential tool for identification of tumor and might be used in surgical resection of COX-2 expressed tumors.

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14.

BACKGROUND/AIMS: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. METHODS: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo. Apoptosis was analysed by Hoechst staining and western blotting. A tissue microarray including 129 samples from breast cancer patients was used for immunohistochemistry (IHC) assays. RESULTS: Overexpression of Osx decreased the chemosensitivity of breast cancer cells, while knockdown of Osx increased the chemosensitivity of breast cancer cells. In particular, we found that the decreased chemosensitivity effect was significantly associated with elevated expression of the polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14). Silencing of GALNT14 in Osx-overexpressed cells restored the decreased chemosensitivity. Conversely, overexpression of GALNT14 in Osx-knockdown cells abrogated the increased chemosensitivity in breast cancer cells. In addition, we revealed that Osx decreased GALNT14-dependent chemosensitivity by enhancing anti-apoptosis. GALNT14 expression exhibited a significant association with breast cancer stages as well as the disease-free survival (DFS) rate. CONCLUSION: Osx plays an important role in the chemosensitivity and inhibition of Osx expression may represent a therapeutic strategy to enhance the chemosensitivity of breast cancer.

Early assessment of the left ventricular function by epirubicin-induced cardiotoxicity in postoperative breast cancer patients.

OBJECTIVE: Epirubicin (Epi) is a potent and effective drug for many malignant cancers with serious cardiotoxicity. Therefore, layer-specific two-dimensional speckle tracking echocardiography (2D-STE) was used to evaluate the longitudinal and circumferential systolic function of the left ventricular for the early detection of cardiotoxicity in this retrospective work. METHODS: Overall, 130 female patients with postoperative breast cancer who did not receive radiotherapy were classified into three groups: Group A (control group, n = 40) without any chemotherapy; Group B (n = 44) administered Epi at 180 ~ 240 mg/m2 ; and Group C (n = 46) administered Epi at ≥360 mg/m2 . Peak and global systolic longitudinal strains (GLS) in the total and endocardium, mid-myocardium, and epicardium were measured and calculated from apical four-chamber, apical two-chamber, and left ventricular long-axis views, respectively. Peak and global circumferential strains (GCS) in the total and endocardium, mid-myocardium, and epicardium were measured and calculated from mitral annulus, papillary muscle, and apical levels of the short-axis view, respectively. RESULTS: The total GLS and GLS of the endocardium in every view were significantly reduced in group C compared with both groups A and B (P < .05), but there was no significant difference between groups A and B (P > .05). The GLS of the epicardium and mid-myocardium in groups B and C were not significantly reduced (P > .05). There were no significant differences in the total GCS and layer-specific GCS of endocardium, mid-myocardium, and epicardium among the three groups (P > .05). CONCLUSIONS: Left ventricular longitudinal systolic dysfunction was detected. Moreover, an impaired endocardium was also detected in an early assessment by layer-specific 2DSTE.