Degeneration of the Olfactory System in a Murid Rodent that Evolved Diurnalism.

In mammalian research, it has been debated what can initiate an evolutionary tradeoff between different senses, and the phenomenon of sensory tradeoff in rodents, the most abundant mammalian clade, is not evident. The Nile rat (Arvicanthis niloticus), a murid rodent, recently adapted to a diurnal niche through an evolutionary acquisition of daylight vision with enhanced visual acuity. As such, this model provides an opportunity for a cross-species investigation where comparative morphological and multi-omic analyses of the Nile rat are made with its closely related nocturnal species, e.g. the mouse (Mus musculus) and the rat (Rattus norvegicus). Thus, morphological examinations were performed, and evolutionary reductions in relative sizes of turbinal bone surfaces, the cribriform plate, and the olfactory bulb were discovered in Nile rats. Subsequently, we compared multiple murid genomes, and profiled olfactory epithelium transcriptomes of mice and Nile rats at various ages with RNA sequencing. The results further demonstrate that, in comparison with mouse olfactory receptor (OR) genes, Nile rat OR genes have experienced less frequent gain, more frequent loss, and more frequent expression reduction during their evolution. Furthermore, functional degeneration of coding sequences in the Nile rat lineage was found in OR genes, yet not in other genes. Taken together, these results suggest that acquisition of improved vision in the Nile rat has been accompanied by degeneration of both olfaction-related anatomical structures and OR gene repertoires, consistent with the hypothesis of an olfaction-vision tradeoff initiated by the switch from a nocturnal to a diurnal lifestyle in mammals.

Prediction of recurrence-related factors for patients with early-stage cervical cancer following radical hysterectomy and adjuvant radiotherapy.

OBJECTIVE: To analyze recurrent factors in patients with clinical early-stage cervical cancer (ESCC) following hysterectomy and adjuvant radiotherapy. METHODS: We collected data from patients with ESCC, staged according to the 2009 Federation International of Gynecology and Obstetrics (FIGO) staging criteria, who underwent hysterectomy followed by adjuvant radiotherapy between 2012 and 2019. These patients were subsequently restaged using the 2018 FIGO criteria. Univariable and multivariable analyses, along with nomogram analyses, were conducted to explore factors associated with recurrence-free survival (RFS). RESULTS: A total of 310 patients met the inclusion criteria, with a median follow-up time of 46 months. Among them, 126 patients with ESCC were restaged to stage III C1 or III C2 after surgery due to lymph node metastasis (LNM) based on the 2018 FIGO staging criteria. Of these, 60 (19.3%) experienced relapse. The 1-, 3-, and 5-year RFS rates were 93.9%, 82.7%, and 79.3%, respectively. Multivariate analysis revealed that the number of positive lymph nodes (LNs), tumor diameter (TD) > 4 cm, and parametrial invasion (PI) were associated with recurrence. The nomogram indicated their predictive value for 3-year and 5-year RFS. Notably, the 5-year recurrence rate (RR) increased by 30.2% in patients with LNM, particularly those with ≥ 3 positive LNs (45.5%). Patients with stage III C2 exhibited a significantly higher RR than those with IIIC1 (56.5% vs. 24.3%, p < 0.001). The 5-year RFS for patients with TD > 4 cm was 65.8%, significantly lower than for those with TD ≤ 4 cm (88.2%). Subgroup analysis revealed higher 5-year RRs in patients with stage III C2 than that in patients with III-C1 (56.5% vs. 24.3%, p < 0.001), demonstrating a significant difference in the RFS survival curve. CONCLUSION: RR in patients with clinical ESCC after hysterectomy followed by adjuvant radiotherapy is correlated with the number of positive LNs, TD > 4 cm, and PI. Emphasis should be placed on the common high-risk factor of LNM association with recurrence after radical hysterectomy in ESCC.

Silver Nanoparticles Encapped by Dihydromyricetin: Optimization of Green Synthesis, Characterization, Toxicity, and Anti-MRSA Infection Activities for Zebrafish (Danio rerio).

To achieve the environmentally friendly and rapid green synthesis of efficient and stable AgNPs for drug-resistant bacterial infection, this study optimized the green synthesis process of silver nanoparticles (AgNPs) using Dihydromyricetin (DMY). Then, we assessed the impact of AgNPs on zebrafish embryo development, as well as their therapeutic efficacy on zebrafish infected with Methicillin-resistant Staphylococcus aureus (MRSA). Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) analyses revealed that AgNPs possessed an average size of 23.6 nm, a polymer dispersity index (PDI) of 0.197 ± 0.0196, and a zeta potential of -18.1 ± 1.18 mV. Compared to other published green synthesis products, the optimized DMY-AgNPs exhibited smaller sizes, narrower size distributions, and enhanced stability. Furthermore, the minimum concentration of DMY-AgNPs required to affect zebrafish hatching and survival was determined to be 25.0 µg/mL, indicating the low toxicity of DMY-AgNPs. Following a 5-day feeding regimen with DMY-AgNP-containing food, significant improvements were observed in the recovery of the gills, intestines, and livers in MRSA-infected zebrafish. These results suggested that optimized DMY-AgNPs hold promise for application in aquacultures and offer potential for further clinical use against drug-resistant bacteria.

Dual Proton/Silver-Catalyzed Serial (5 + 2)-Cycloaddition and Nazarov Cyclization of (E)-2-Arylidene-3-hydroxyindanones with Conjugated Eneynes: Synthesis of Indanone-Fused Benzo[cd]azulenes.

A one-pot step-economic tandem process involving (5 + 2)-cycloaddition and Nazarov cyclization reactions has been reported for the facile synthesis of indanone-fused benzo[cd]azulenes from (E)-2-arylidene-3-hydroxyindanones and conjugated eneynes. This highly regio- and stereoselective bisannulation reaction is enabled by dual silver and Brønsted acid catalysis and opens up a new avenue for the construction of important bicyclo[5.3.0]decane skeletons.

Manganese-induced apoptosis through the ROS-activated JNK/FOXO3a signaling pathway in CTX cells, a model of rat astrocytes.

Manganese (Mn) is an essential trace element that maintains many normal physiological functions. However, multi-system disorders would occur once overexposure to Mn, especially neurotoxicity. Despite evidence demonstrating the critical role of ROS-activated JNK/FOXO3a signaling pathway in neuronal survival, the specific mechanisms by which it contributes to Mn-induced neurotoxicity are still unclear. The objectives of this study was to examine the modulation of the JNK/FOXO3a signaling pathway, which is activated by ROS, in Mn-induced apoptosis, using a rat brain astrocyte cell line (CTX cells). This study found that a dose-dependent decrease in cell viability of CTX cells was observed with 150, 200, 250, 300 µmol/L Mn. The results of apoptosis-related protein assay showed that Mn decreased the expression of anti-apoptotic protein Bcl-2 and enhanced the expression of apoptosis-related proteins like Bax and Cleaved-Caspase3. In addition, treatment with Mn resulted in elevated ROS levels and increased phosphorylation levels of JNK. Conversely, phosphorylation of nuclear transcription factors FOXO3a, which regulates expression of transcription factors including Bim and PUMA, was decreased. Depletion of ROS by N-acetyl-L-cysteine (NAC) and inhibition of the JNK pathway by SP600125 prevented Mn-induced JNK/FOXO3a pathway activation and, more importantly, the level of apoptosis was also significantly reduced. Confirmation of Mn-induced apoptosis in CTX cells through ROS generation and activation of the JNK/FOXO3a signaling pathway was the outcome of this study. These findings offer fresh insights into the neurotoxic mechanisms of Mn and therapeutic targets following Mn exposure.

Efficacy of physical therapy interventions on quality of life and upper quadrant pain severity in women with post-mastectomy pain syndrome: a systematic review and meta-analysis.

PURPOSE: To determine the efficacy of physical therapy interventions on quality of life (QoL) and pain severity in post-mastectomy pain syndrome (PMPS). METHODS: Multiple databases were searched from database inception to October 2020. Searches were limited to human studies published in either English or Chinese in peer-reviewed journals with full text available for randomized controlled trials conducted on females. Trials comparing the effectiveness of physical therapy interventions against control conditions on QoL and pain were included. RESULTS: Eighteen trials were included in the review. The pooled analysis of the four exercise trials revealed a significant effect of the intervention on general [standardized mean difference [SMD]: 0.87 (95%CI: 0.36, 1.37); p = 0.001], physical [SMD: 0.34 (95%CI: 0.01, 0.66); p = 0.044], and mental health components [SMD: 0.27 (95%CI: 0.03, 0.51); p = 0.027] of QoL compared with the control condition. Meta-analyses of six exercise trials, two myofascial release trials, and two acupuncture trials revealed a significant improvement in pain severity in the treatment group than in the control group. However, meta-analyses of two studies revealed a non-significant effect of compression therapy compared to control on pain severity. CONCLUSION: Our meta-analyses found that exercise is beneficial for improving the QoL and pain severity of women with PMPS. Future studies are needed to determine the optimal parameters for exercise interventions designed to improve QoL and pain severity in women with PMPS. The effect of acupuncture, myofascial release, and compression therapy remains inconclusive, and future research is required to validate the effect of these interventions on PMPS.

Enrichment of Tumor-Infiltrating B Cells in Group 4 Medulloblastoma in Children.

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is classified into core molecular subgroups (wingless activated (WNT), sonic hedgehog activated (SHH), Group 3 (G3), and Group 4 (G4)). In this study, we analyzed the tumor-infiltrating immune cells and cytokine profiles of 70 MB patients in Taiwan using transcriptome data. In parallel, immune cell composition in tumors from the SickKids cohort dataset was also analyzed to confirm the findings. The clinical cohort data showed the WNT and G4 MB patients had lower recurrence rates and better 5-year relapse-free survival (RFP) compared with the SHH and G3 MB patients, among the four subgroups of MB. We found tumor-infiltrating B cells (TIL-Bs) enriched in the G4 subgroups in the Taiwanese MB patients and the SickKids cohort dataset. In the G4 subgroups, the patients with a high level of TIL-Bs had better 5-year overall survival. Mast cells presented in G4 MB tumors were positively correlated with TIL-Bs. Higher levels of CXCL13, IL-36γ, and CCL27 were found compared to other subgroups or normal brains. These three cytokines, B cells and mast cells contributed to the unique immune microenvironment in G4 MB tumors. Therefore, B-cell enrichment is a G4-subgroup-specific immune signature and the presence of B cells may be an indicator of a better prognosis in G4 MB patients.

Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype.

Coronary artery disease (CAD) has been the leading cause of morbidity and mortality worldwide, and its pathogenesis is closely related with the proliferation and migration of vascular smooth muscle cell (VSMC). We previously reported a truncated GATA4 protein lacking C-terminus induced by p.S335X mutation in cardiomyocyte from ventricular septal defect (VSD) patients. However, it is still unclear whether GATA4 p.S335X mutation could influence the development of CAD. GATA4 wild-type (WT) and p.S335X mutant (MU) overexpression plasmids were constructed and transfected transiently into rat coronary artery smooth muscle cell (RCSMC) to observe the proliferative and migratory abilities by MTS and wound healing assay, respectively. PCR array was used to preliminarily detect the expression of phenotypic modulation-related genes, and QRT-PCR was then carried out to verify the screened differentially expressed genes (DEGs). The results showed that, when stimulated by fetal bovine serum (10%) for 24 h or tumor necrosis factor-α (10 or 30 ng/ml) for 10 or 24 h, deletion of GATA4 C-terminus by p.S335X mutation in GATA4 enhanced the proliferation of RCSMC, without alteration of the migration capability. Twelve DEGs, including Fas, Hbegf, Itga5, Aimp1, Cxcl1, Il15, Il2rg, Il7, Tnfsf10, Il1r1, Irak1, and Tlr3, were screened and identified as phenotypic modulation-related genes. Our data might be beneficial for further exploration regarding the mechanisms of GATA4 p.S335X mutation on the phenotypic modulation of coronary VSMC.

Continuous positive airway pressure adherence and blood pressure lowering in patients with obstructive sleep apnoea syndrome and nocturnal hypertension.

PURPOSE: We investigated continuous positive airway pressure (CPAP) adherence and its association with the blood pressure (BP) and pulse rate changes in patients with obstructive sleep apnoea syndrome (OSAS) and hypertension. MATERIALS AND METHODS: In a single-blind trial, patients were randomly assigned to CPAP or sham CPAP treatment for 3 months. We performed clinic, ambulatory and home BP measurements at baseline and during follow-up. CPAP adherence was assessed as the CPAP frequency per week and time per night. Non-adherence was defined as a CPAP use for <5 days/week or <4 h/night. RESULTS: In the CPAP (n = 26) and sham CPAP groups (n = 21), the CPAP frequency was 5.5 and 4.8 days/week (p = 0.17), respectively, and the CPAP time was 5.0 and 4.1 h/night (p = 0.03), respectively. The corresponding prevalence of non-adherence was 46.2% and 66.7% (p = 0.16), respectively. The CPAP frequency but not time tended to be associated with the changes in BP and pulse rate at 3 months of follow-up, especially home systolic/diastolic BP in the CPAP group (3.2/1.3 mmHg greater reductions per 1 day increment, p ≤ 0.01). Adherent, compared with non-adherent patients, had greater reductions in BP or pulse rate at 3 months of follow-up. In the CPAP and sham CPAP groups combined, statistical significance was achieved for the adjusted between adherence and non-adherence differences in home systolic/diastolic BP (-5.0/-3.8 mmHg) and 24-h, daytime and night-time ambulatory pulse rate (-6.2, -7.8 and -4.4 beats/min, respectively, p ≤ 0.04). CONCLUSION: CPAP adherence was associated with the BP lowering and pulse rate slowing effects, especially the CPAP frequency.

[Molecular identification and efficacy analysis of herbs at Orussey Herbal Market, Phnom Penh, Cambodia].

Cambodia is rich in medicinal plant resources. One hundred and thirty-three medicinal material samples, including the hole herb, root, stem/branch, leaf, flower, fruit, seed, and resin, were collected from the Orussey Herbal Market in Phnom Penh, Cambodia, and then authenticated by ITS and psbA-trnH. A total of 46 samples were identified based on ITS sequences, belonging to 24 families, 40 genera, and 42 species. A total of 100 samples were identified by psbA-trnH sequences to belong to 42 families, 77 genera, and 84 species. A total of 103 samples were identified by two DNA barcodes. According to the morphological characteristics of the medicinal materials, 120 samples classified into 50 species, 86 genera, and 86 families were identified, and the majority of them were from Zingiberaceae, Fabaceae, and Acanthaceae. Such samples have been commonly used in traditional Cambodian medicine, Ayurvedic medicine, Unani medicine, traditional Chinese medicine, and ethnomedicine, but different medical systems focus on different functional aspects of the same medicinal material. The results of this study have demonstrated that DNA barcoding has a significant advantage in identifying herbal products, and this study has provided basic data for understanding the traditional medicinal materials used in Cambodia.

[Identification and characterization of DIR gene family in Schisandra chinensis].

Dirigent(DIR) proteins are involved in the biosynthesis of lignin, lignans, and gossypol in plants and respond to biotic and abiotic stresses. Based on the full-length transcriptome of Schisandra chinensis, bioinformatics methods were used to preliminarily identify the DIR gene family and analyze the physico-chemical properties, subcellular localization, conserved motifs, phylogeny, and expression patterns of the proteins. The results showed that a total of 34 DIR genes were screened and the encoded proteins were 156-387 aa. The physico-chemical properties of the proteins were different and the secondary structure was mainly random coil. Half of the DIR proteins were located in chloroplast, while the others in extracellular region, endoplasmic reticulum, cytoplasm, etc. Phylogenetic analysis of DIR proteins from S. chinensis and the other 8 species such as Arabidopsis thaliana, Oryza sativa, and Glycine max demonstrated that all DIR proteins were clustered into 5 subfamilies and that DIR proteins from S. chinensis were in 4 subfamilies. DIR-a subfamily has the unique structure of 8 ß-sheets, as verified by multiple sequence alignment. Finally, through the analysis of the transcriptome of S. chinensis fruit at different development stages, the expression pattern of DIR was clarified. Combined with the accumulation of lignans in fruits at different stages, DIR might be related to the synthesis of lignans in S. chinensis. This study lays a theoretical basis for exploring the biological functions of DIR genes and elucidating the biosynthesis pathway of lignans in S. chinensis.

Age-specific associations of glycated haemoglobin variability with cardiovascular disease and mortality in patients with type 2 diabetes mellitus: A 10- year cohort study.

AIMS: To investigate the associations of increased variability in glycated haemoglobin (HbA1c) with cardiovascular disease (CVD) and mortality risk in patients with diabetes. MATERIALS AND METHODS: This prospective cohort study included 147 811 patients aged 45 to 84 years with type 2 diabetes mellitus, without CVD and with at least three HbA1c values recorded before baseline in the period 2008 to 2010. HbA1c variability was evaluated using a mixed effects model to reduce regression dilution bias. Age-specific associations (45- 54, 55- 64, 65- 74 and 75- 84 years) between HbA1c variability and risk of CVD and mortality were assessed by Cox regression, adjusted for patient characteristics and usual HbA1c. RESULTS: After a median follow-up of 7.4 years(1.02 million person-years), an overall incidence of 40 785 events including CVD (incidence 27 793) and all-cause mortalities (incidence 23 175) were identified. Positive log-linear associations between HbA1c variability and CVD and mortality were identified in all age groups. The hazard ratios (HRs) for the composite of CVD and all-cause mortality showed that age was inversely associated with HbA1c variability, with a 28% higher risk per 1% increase in HbA1c variability in the age group 45 to 54 years (all composite outcomes: HR 1.28, 95% confidence interval [CI] 1.21, 1.35), whereas only a 14% higher risk in the 75- 84 age group (all composite outcomes: HR 1.14, 95% CI 1.11, 1.17). Subgroup analysis showed the risk in patients with usual HbA1c <53mmol/mol was about eight times higher than in those with usual HbA1c ≥64mmol/mol. CONCLUSIONS: HbA1c variability was strongly related to CVD and mortality in patients with diabetes across all age groups. Whilst pursuing optimal HbA1c targets, attention should be given to patients with high HbA1c variability, especially younger patients with good HbA1c control.

Subtypes of masked hypertension and target organ damage in untreated outpatients.

Purpose: Masked hypertension (MHT) is characterised as an office normotension in the presence of out-of-office hypertension, and can be further categorised as isolated daytime (dMHT), night-time (nMHT) or day-night MHT (dnMHT) according to the time when hypertension is present. MHT is associated with adverse cardiovascular outcome. However, no previous studies contrasted these MHT subtypes in their associations with target organ damage (TOD).Materials and methods: Consecutive untreated patients referred for ambulatory blood pressure (BP) monitoring to our Hypertension Clinic were recruited. Office and ambulatory BPs were measured using the Omron 7051 and SpaceLabs 90217 monitors, respectively. The BP thresholds of daytime and night-time hypertension were of ≥135/85 mmHg and ≥120/70 mmHg, respectively. We performed various TOD measurements, including carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), left ventricular mass index (LVMI) and E/E', estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR).Results: The 1808 participants (mean age, 51 years; women, 52%) included 672 (37.2%) MHT subjects, among whom 123 (18.3%) had dMHT, 78 (11.6%) nMHT, and 471 (70.1%) dnMHT. In all participants as well as patients with office normotension (n = 1222), ambulatory daytime and night-time BPs were similarly associated with all TOD measurements (p ≥ 0.20) after multivariate adjustment. Compared to normotensive subjects (p < 0.05), patients with dMHT had faster cfPWV (7.81 vs. 7.58 m/s) and thicker cIMT (637.6 vs. 610.4 µm), patients with nMHT had thicker cIMT (641.8 vs. 610.4 µm) and increased UACR (0.79 vs. 0.59 mg/mmol), and patients with dnMHT had all worse TOD measures mentioned-above plus elevated eGFR (120.7 vs. 116.8 ml/min/1.73m2).Conclusion: MHT was associated with TOD irrespective of subtype, although TOD varied slightly across these subtypes. The study highlights the importance of controlling both daytime and night-time BP in hypertensive patients.

[Simultaneous determination of six major isosteroidal alkaloids in Beimu by UPLC-ELSD].

An UPLC method was established for the direct determination of six major bioactive isosteroidal alkaloids, namely peimisine, imperialine, sipeimine-3-D-glucoside, verticinone, verticine and hupehenine from the bulbus of Fritillaria(Beimu), a commonly used antitussive traditional Chinese medicinal(TCM) herb. An Acquity UPLC~(TM) CSH C_(18) column(2.1 mm×100 mm, 1.7 µm) was used for all analysis. The investigated six compounds were all separated with gradient mobile phase consisting of 0.02% diethylamine-water-methanol at a flow rate of 0.3 mL·min~(-1). The temperature of sample manager was set at 20 ℃. Drift tube temperature was 45 ℃, and spray parameter was 40% with injection volume of 1 µL. Then, the further quality assessment of Beimu was carried out by cluster analysis(CA) and principal component analysis(PCA). The investigated all had good linearity(r≥0.998 9) over the tested ranges. The method is simple, accurate and reproducible, and can be used for determining the content of six major bioactive isosteroidal alkaloids.

Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice.

OBJECTIVE: The gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance. DESIGN: A pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation. RESULTS: The OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT. CONCLUSION: The OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment. TRIAL REGISTRATION NUMBER: NCT02838732; Results.

Development of an inflammatory tissue-selective chimeric TNF receptor.

BACKGROUND: Inhibiting TNF-α is an effective therapy for inflammatory diseases such as rheumatoid arthritis. However, systemic, nondiscriminatory neutralization of TNF-α is associated with considerable adverse effects. METHODS: Here, we developed a trimeric chimeric TNF receptor by linking an N-terminal mouse Acrp30 trimerization domain and an MMP-2/9 substrate sequence to the mouse extracellular domain of TNF receptor 2 followed by a C-terminal mouse tetranectin coiled-coil domain (mouse Acrp-MMP-TNFR-Tn). RESULTS: Here, we show that the Acrp30 trimerization domain inhibited the binding activity of TNFR, possibly by closing the binding site of the trimeric receptor. Cleavage of the substrate sequence by MMP-9, an enzyme highly expressed in inflammatory sites, restored the binding activity of the mouse TNF receptor. We also constructed a recombinant human chimeric TNF receptor (human Acrp-MMP-TNFR-Tn) in which an MMP-13 substrate sequence was used to link the human Acrp and the human TNF receptor 2. Human Acrp-MMP-TNFR-Tn showed reduced binding activity, and MMP-13 digestion recovered its binding activity with TNF-α. CONCLUSION: Acrp-masked chimeric TNF receptors may be able to be used for inflammatory tissue-selective neutralization of TNF-α to reduce the adverse effects associated with systemic neutralization of TNF-α.

Short-term reproducibility of the 24-h ambulatory monitoring of brachial and central hemodynamics in untreated Chinese.

Objective: Advanced technology allows non-invasive monitoring of the 24-h brachial and central hemodynamics simultaneously. However, related reproducibility data was limited in White patients. We therefore explored if the novel measurements would be reproducible in Chinese. Methods: From February 2017 to January 2018, 152 untreated patients who were suspected of hypertension and referred for ambulatory blood pressure (BP) monitoring were recruited. Ambulatory BP monitoring was repeated within one month (median, 12.5 days) using the Mobil-O-Graph monitors (IEM, Germany). Reproducibility was assessed as the intra-class correlation coefficient (ICC), coefficient of variation (CV), and repeatability coefficient (RC). Results: The 152 participants (average age, 58.6 years) included 54 men and 98 women. The first and second means of the ambulatory brachial and central BPs, pulse wave velocity (PWV), augmentation pressure, augmentation index (AIx) and AIx at a heart rate of 75 beats per minute (AIx@75) were all similar (p ≥ 0.065), except that the repeated daytime and 24-h brachial and central systolic BPs and pulse pressure slightly differed by approximately 1-2 mmHg (p ≤ 0.011). ICC ranged from 0.70 to 0.94 for all ambulatory BPs and ≥0.91 for the arterial measurements. CV was in the range from 5.0% to 10.3% for all BPs and PWV measurements, and from 15.5% to 22.3% for AIx and AIx@75. RC expressed as percentages of maximal variation was <15% for the PWVs and ranged from 25.5% to 54.7% for BPs, AIx and AIx@75. Conclusions: The 24-h ambulatory brachial and central BPs and arterial measurements were reproducible within a short time period in Chinese, and could therefore be used in clinical practice and research settings.

Echocardiographic strain in hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy.

BACKGROUND: The myocardial structure differs between secondary left ventricular hypertrophy (LVH) and hypertrophic cardiomyopathy (HCM). We investigated left ventricular function of these two types of hypertrophy using multilayer strain analysis with two-dimensional echocardiography. METHODS: Transthoracic echocardiography (Vivid-E9) was performed in 240 patients with preserved left ventricular ejection fraction (LVEF ≥50%) and with either HCM (n = 80, 63 men, age 49.8 ± 14.1 years), hypertensive LVH (n = 80, 63 men, age 51.4 ± 13.3 years) or normal blood pressure and left ventricular structure (n = 80, 63 men, 50.8 ± 12.4 years). Quantitative multilayer longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) were analyzed. The ratio of endo-/epi-myocardial strain was calculated. RESULTS: Longitudinal strain was significantly (P < 0.001) lower in HCM patients than normal controls (15.2 ± 4.2% vs 23.1 ± 2.7%), especially in hypertrophic segments (14.5 ± 4.4% vs 17.2 ± 3.2% in nonhypertrophic segments, P < 0.01). LS was lower in patients with hypertensive LVH, similarly in all left ventricular segments (20.7 ± 3.7%, P < 0.001 vs controls). CS was lower in the mid- and epicardium (P < 0.01), but not endocardium in HCM (P = 0.4), and preserved in all myocardial layers in hypertensive LVH. The endo-/epi-myocardial ratios of both LS and CS were higher in HCM than hypertensive LVH (P < 0.01). RS was higher (P < 0.01) in HCM than hypertensive LVH and controls. Endocardial CS and global RS were correlated with LVEF (r ≥ 0.32, P < 0.01). CONCLUSIONS: Hypertrophic cardiomyopathy patients had marked reductions in LS and CS, whereas patients with hypertensive LVH had less reduction in LS and preserved CS. The increased endo-/epi-myocardial ratios of LS and CS may be useful in differentiating HCM from hypertensive LVH.

Preincubation and vermicomposting of divergent biosolids exhibit vice versa multielements stoichiometry and earthworm physiology.

Sewage sludge and kitchen refuse are ubiquitously mounting wastes with high organic load, which if reprocessed they could salvage the environment. Reckoned with this certitude, an incubating study was initiated on sequential preincubation of sewage sludge with kitchen waste in 100:0, 70:30, 50:50, and 30:70 ratios for 16 days ensued by vermicomposting of 30 days using Eisenia fetida. Concentration of heavy metals (Cd, Cr, Cu, Mn, Pb, and Zn) in the biosolid mixtures increased during preincubation but reduced progressively through vermicomposting due to bioaccumulation of these metals in the earthworm tissues. Earthworm growth parameters data reflected that sewage sludge and kitchen waste mixture with 70:30 ratio increased the number of cocoons (10.6%), biomass (8.2%), growth rate (8.3%), reproduction rate (12.2%), and decreased their mean mortality rate (80.1%) as compared to that in sole sewage sludge (control). Results of chemical analysis and SEM/EDS imaging, showed that alkalinity, organic carbon, C/N ratio, organic matter and concentration of trace elements (Cd, Cr, Cu, Mn, Pb, and Zn) reduced while macronutrients (N, P, K, Ca and Mg) increased in the final vermicompost as compared to that in initial mixtures. The FT-IR analysis also revealed that various biochemical functional groups underwent biodegradation during combined preincubation-vermicomposting. Bioaccumulation factor (BAF) of all trace elements in the earthworm tissues was higher with 70:30 ratio of substrates, with the trend of Cd > Zn > Cu > Mn > Pb > Cr. Hence, this study concludes that combined preincubation-vermicomposting is the most efficient and ecofriendly technique for biodegradation, stabilization, and conversion of sewage sludge and kitchen waste into organic fertilizer. The nutrient rich vermicompost can be safely used as horticultural substrate and soil conditioner for efficient management of degraded soils. Finally, combined preincubation-vermicomposting is a sustainable system of recycling the sewage sludge along with kitchen waste.

Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer.

BACKGROUND: Gastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration. Integrin α2ß1 is over-expressed on a variety of cancer cells, but is low or absent in most normal organs and resting endothelial cells. RESULTS: In this report, we assessed the ITGA2 as the potential therapeutic target with the bioinformatics tools from the TCGA dataset in which composed of 375 gastric cancer tissues and 32 gastric normal tissues. According to the information from the Cancer Cell Line Encyclopedia (CCLE) database, the AGS cell line with ITGA2 high expression and the SUN-1 cell line with low expression were chosen for the further investigation. Interestingly, the anti-ITGA2 antibody (at 3 µg/ml) inhibited approximately 50% survival of the AGS cells (over-expressed ITGA2), but had no effect in SNU-1 cells (ITGA2 negative). The extents of antibody-mediated cancer inhibition positively correlated with the expression levels of the ITGA2. We further showed that the anti-ITGA2 antibody induced apoptosis by up-regulating the RhoA-p38 MAPK signaling to promote the expressions of Bim, Apaf-1 and Caspase-9, whereas the expressions of Ras and Bax/Bcl-2 were not affected. Moreover, blocking ITGA2 by the specific antibody at lower doses also inhibited cell migration of gastric cancer cells. Blockade of ITGA2 by a specific antibody down-regulated the expression of N-WASP, PAK and LIMK to impede actin organization and cell migration of gastric cancer cells. CONCLUSIONS: Here, we showed that the mRNA expression levels of ITGA2 comparing to normal tissues significantly increased. In addition, the results revealed that targeting integrin alpha 2 subunit by antibodies did not only inhibit cell migration, but also induce apoptosis effect on gastric cancer cells. Interestingly, higher expression level of ITGA2 led to significant effects on apoptosis progression during anti-ITGA2 antibody treatment, which indicated that ITGA2 expression levels directly correlate with their functionality. Our findings suggest that ITGA2 is a potential therapeutic target for gastric cancer.