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Abstract Background For patients with chronic hepatitis B and cirrhosis in less developed western regions in China, due to constraints of local economic conditions, the choice of treatment measures is often limited. However if patients recieved valid management and effective treatment, they were able to maintain their health and benign prognosis. Case presentation This study narrates the long-term treatment and careful follow-up of a patient with chronic hepatitis B and cirrhosis in a less developed western region in China, and analyzes the prognosis of the disease and countermeasures. Conclusions This would partly reflect the development of antiviral therapy for chronic hepatitis B and multidisciplinary comprehensive treatment for cirrhosis-related complications in remote region with limited resources in the past 20 years.

Objective: This study aimed to examine the differences of cognitive emotion regulation (CER) strategies between patients with gynecologic cancer and non-clinical individuals. Methods: A cohort of 329 female adults was recruited in this study. About 179 patients with gynecologic cancer were allocated to the clinical group and 150 healthy women were allocated to the non-clinical group. All the participants completed a demographic survey and the Chinese version of Cognitive Emotion Regulation Questionnaire (CERQ-C). Results: There were statistically significant group differences in the CER strategies used between the two groups. The most prevalent discrepancies of the CER strategies across the two samples were the self-blame, rumination, putting into perspective, catastrophizing, and blaming others. Further logistic regression analyzes indicated that these four strategies have significant and independent contributions to the prediction of group membership. In particular, a higher reported use of self-blame and blaming others, and a lower reported use of acceptance and putting into perspective, were observed for the clinical group. The CER strategies in the clinical group, which differentiated it from the non-clinical group, accounted for 23.9% of the variance, after controlling for the non-dominant variables. Conclusion: The implications of certain CER strategies may be a useful target for prevention and intervention of psychological distress on patients with gynecologic cancer.

Abstract Background High-grade spindle cell sarcomas are a subtype of rare, undifferentiated pleomorphic sarcomas (UPSs) for which diagnosis is difficult and no specific treatment strategies have been established. The limited published data on UPSs suggest an aggressive clinical course, high rates of local recurrence and distant metastasis, and poor prognosis. Case presentation Here we present the unusual case of a 45-year-old male patient with a lumbosacral UPS extending into the sacrum. An initial diagnosis of a low-grade malignant spindle cell tumor was based on a tumor core biopsy. After complete extensive resection, the diagnosis of an UPS of the lumbosacral region was confirmed by excluding other types of cancers. Despite treatment with neoadjuvant radiotherapy, extensive resection, and adjuvant chemotherapy, the patient presented with multiple pulmonary metastases 3 months after surgery. The patient then began treatment with crizotinib at an oral dose of 450 mg per day, based on the detection of a LMNA-NTRK1 fusion gene in the tumor by next-generation sequencing. Over 18 months of follow-up through July 2018, the patient maintained a near-complete clinical response to crizotinib. Conclusions The LMNA-NTRK1 fusion was likely the molecular driver of tumorigenesis and metastasis in this patient, and the observed effectiveness of crizotinib treatment provides clinical validation of this molecular target. Molecular and cytogenetic evaluations are critical to accurate prognosis and treatment planning in cases of UPS, especially when treatment options are limited or otherwise exhausted. Molecularly targeted therapy of these rare but aggressive lesions represents a novel treatment option that may lead to fewer toxic side effects and better clinical outcomes.

Emerging evidence has shown that circular RNAs (circRNAs) serve as a promising biomarker in different malignancies. Specifically, circ_001569 has been found to be upregulated in some types of human gastrointestinal cancer. In this study, we aimed to investigate clinical significances, diagnostic and prognostic values of circ_001569 in pancreatic cancer (PC), and identify its effects on the malignant behaviors of PC cells. The expression of circ_001569 was determined in 26 tissues samples and 97 plasma samples from PC patients by qRT-PCR. Relationship between circ_001569 expression and clinicopathological parameters was analyzed by Chi-square test. Diagnostic and prognostic values of circ_001569 were evaluated by ROC curves, Kaplan-Meier curves, and Cox regression analysis. The effects of circ_001569 on the proliferation, migration, invasion, and apoptosis of PC cells were assessed by MTT, wound healing, Transwell invasion assays, and flow cytometric analysis, respectively. Results showed that the expression of circ_001569 was upregulated in tissues and plasma of PC patients. High circ_001569 level was positively correlated with lymphatic metastasis, clinical stage, and venous invasion. Circ_001569 level was an independent prognostic indicator for overall survival rates of PC patients, and patients with high circ_001569 level had a poor prognosis. The AUC of circ_001569 was 0.716 (95% CI: 0.642-0.790) with a sensitivity and specificity of 62.76% and 74.29%, respectively. In vitro , circ_001569 silencing decreased cell proliferation, migration, and invasion, but promoted cell apoptosis of PC cells. Our data demonstrate that high circ_001569 level associates with tumor malignant behaviors, and may serve as a potential biomarker in the diagnosis and prognosis of PC.

Heart failure is a systemic syndrome caused by multiple pathological factors. Current treatments do not have satisfactory outcomes. Several basic studies have revealed the protective effect of trimetazidine on the heart, not only by metabolism modulation but also by relieving myocardial apoptosis, fibrosis, autophagy, and inflammation. Clinical studies have consistently indicated that trimetazidine acts as an adjunct to conventional treatments and improves the symptoms of heart failure. This review summarizes the basic pathological changes in the myocardium, with an emphasis on the alteration of cardiac metabolism in the development of heart failure. The clinical application of trimetazidine in heart failure and the mechanism of its protective effects on the myocardium are carefully discussed, as well as its main adverse effects. The intention of this review is to highlight this treatment as an effective alternative against heart failure and provide additional perspectives for future studies.

The aims of this study were (1) to quantify the intra-individual variation in the upper airway measurements on supine computed tomography (CT) scans at two different time points; and (2) to identify the most stable parameters of the upper airway measurements over time. Ten subjects with paired CT datasets (3–6 months interval) were studied, using computer software to segment and measure the upper airway. The minimum cross-sectional area of the total airway and all its segments (velopharynx, oropharynx, tongue base, and epiglottis) generally had the largest variation, while the length of the total airway had the lowest variation. Sphericity was the only parameter that was stable over time (relative difference

Chimeric antigen receptor (CAR) T cell is a promising method in cancer immunotherapy but faces many challenges in solid tumors. One of the major problems was immunosuppression caused by PD-1. In our study, the expression of c-Met in GC was analyzed from TCGA datasets, GC tissues, and cell lines. The c-Met CAR was a second-generation CAR with 4–1BB, cMet-PD1/CD28 CAR was c-Met CAR adding PD1/CD28 chimeric-switch receptor (CSR). In vitro, we measured the changes of different subgroups, phenotypes and PD-1 expression in CAR-T cells. We detected the secretion levels of different cytokines and the killing ability of CAR-Ts. In vivo, we established a xenograft GC model and observed the anti-tumor effect and off-target toxicity of different CAR-Ts. We find that the expression of c-Met was increased in GC. CD3+CD8+ T cells and CD62L+CCR7+ central memory T cells (TCM) were increased in two CAR-Ts. The stimulation of target cells could promote the expression of PD-1 in c-Met CAR-T. Compared with Mock T, the secretion of cytokines as IFN-γ, TNF-α, IL-6, IL-10 secreted by two CAR-Ts was increased, and the killing ability to c-Met positive GC cells was enhanced. The PD1/CD28 CSR could further enhance the killing ability, especially the long-term anti-tumor effect of c-Met CAR-T, and reduce the release level of IL-6. CAR-Ts target c-Met had no obvious off-target toxicity to normal organs. Thus, the PD1/CD28 CSR could further enhance the anti-tumor ability of c-Met CAR-T, and provides a promising design strategy to improve the efficacy of CAR-T in GC.

Spreading depolarization (SD) represents a neurological process characterized by a massive, self-sustaining wave of brain cell depolarization. Understanding its mechanism is important for treating ischemic or hemorrhagic stroke and migraine with aura. Many believed that ion fluxes through NMDA receptors (NMDARs) are responsible for neuronal transmembrane currents of SD. However, the explicit role of NMDARs remains ambiguous. This is in part due to the limitation of traditional pharmacological approaches in resolving the contribution of NMDARs in different intercellular and intracellular processes of SD. Here, we applied single-cell blockade and genetic deletion methods to remove functional NMDARs from individual hippocampal CA1 neurons in order to examine the role of NMDARs in the depolarization mechanism without affecting the propagation of SD. We analyzed neuronal membrane potential changes to demonstrate that NMDARs are not required for initiating the depolarization. Consistently, neuronal input resistance (RN) revealed a sharp decline at the start of SD, which was unaffected by blocking NMDARs. Instead, the recovery of both membrane potential and RN during the late phase of SD was facilitated by inhibition of NMDARs, indicating that NMDARs are responsible for sustaining the depolarization. Our results strongly indicate that NMDAR activation is not a determinant of the initiation of depolarization but is important for sustaining transmembrane ion fluxes during SD.

Background There has been significant controversy about the effects of pre‐hospitalization use of renin‐angiotensin system (RAS) inhibitors on the prognosis of patients with hypertension and coronavirus disease 2019. Methods and Results We retrospectively assessed 2297 hospitalized patients with coronavirus disease 2019 at Tongji Hospital in Wuhan, China, from January 10 to March 30, 2020; and identified 1182 patients with known hypertension on pre‐hospitalization therapy. We compared the baseline characteristics and in‐hospital mortality between patients with hypertension taking RAS inhibitors (n=355) versus non‐RAS inhibitors (n=827). Of the 1182 patients with hypertension (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group versus 95/827 (11.5%) patients in the non‐RAS inhibitors group (P

Chitinolyticbacter meiyuanensis SYBC-H1, a bacterium capable of hydrolyzing chitin and shrimp shell to N-acetyl glucosamine (GlcNAc) as the only product, was isolated previously. Here, the hydrolysis mechanism of this novel strain toward chitin was investigated. Sequencing and analysis of the complete genome of SYBC-H1 showed that it encodes 32 putatively chitinolytic enzymes including 30 chitinases affiliated with the glycoside hydrolase (GH) families 18 (26) and 19 (4), one GH family 20 β-N-acetylglucosaminidase (NAGase), and one Auxiliary Activities (AA) family 10 lytic polysaccharide monooxygenase (LPMO). However, only eight GH18 chitinases, one AA10 LPMO, and one GH20 NAGase were detected in the culture broth of the strain, according to peptide mass fingerprinting (PMF). Of these, genes encoding chitinolytic enzymes including five GH18 chitinases (Cm711, Cm3636, Cm3638, Cm3639, and Cm3769) and one GH20 NAGase (Cm3245) were successfully expressed in active form in Escherichia coli. The hydrolysis of chitinous substrates showed that Cm711, Cm3636, Cm3638, and Cm3769 were endo-chitinases and Cm3639 was exo-chitinase. Moreover, Cm3639 and Cm3769 can convert the GlcNAc dimer and colloidal chitin (CC) into GlcNAc, which showed that they also possess NAGase activity. In addition, NAGase Cm3245 possesses a very high exo-acting activity of hydrolyzing GlcNAc dimer. These results suggest that chitinases and NAGase from SYBC-H1 both play important roles in conversion of N-acetyl chitooligosaccharides to GlcNAc, resulting in the accumulation of the final product GlcNAc. To our knowledge, this is the first report of the complete genome sequence and chitinolytic enzyme genes discovery of this strain.

Chronic hypertension is a key risk factor for heart failure. However, the underlying molecular mechanisms are not fully understood. Our previous studies found that the valosin-containing protein (VCP), an ATPase-associated protein, was significantly decreased in the hypertensive heart tissues. In this study, we tested the hypothesis that restoration of VCP protected the heart against pressure overload-induced heart failure. With a cardiac-specific transgenic (TG) mouse model, we showed that a moderate increase of VCP was able to attenuate chronic pressure overload-induced maladaptive cardiac hypertrophy and dysfunction. RNA sequencing and a comprehensive bioinformatic analysis further demonstrated that overexpression of VCP in the heart normalized the pressure overload-stimulated hypertrophic signals and repressed the stress-induced inflammatory response. In addition, VCP overexpression promoted cell survival by enhancing the mitochondria resistance to the oxidative stress via activating the Rictor-mediated-gene networks. VCP was also found to be involved in the regulation of the alternative splicing and differential isoform expression for some genes that are related to ATP production and protein synthesis by interacting with long no-coding RNAs and histone deacetylases, indicating a novel epigenetic regulation of VCP in integrating coding and noncoding genomic network in the stressed heart. In summary, our study demonstrated that the rescuing of a deficient VCP in the heart could prevent pressure overload-induced heart failure by rectifying cardiac hypertrophic and inflammatory signaling and enhancing the cardiac resistance to oxidative stress, which brought in novel insights into the understanding of the mechanism of VCP in protecting patients from hypertensive heart failure.

In the past two decades, extensive efforts have been made to develop agents targeting prostate-specific membrane antigen (PSMA) for prostate cancer imaging and therapy. To date, represented by two recent approvals of [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL by the United States Food and Drug Administration (US-FDA) for positron emission tomography (PET) imaging to identify suspected metastases or recurrence in patients with prostate cancer, PSMA-targeting imaging and theranostic agents derived from small molecule PSMA inhibitors have advanced to clinical practice and trials of prostate cancer. The focus of current development of new PSMA-targeting agents has thus shifted to the improvement of in vivo pharmacokinetics and higher specific binding affinity with the aims to further increase the detection sensitivity and specificity and minimize the toxicity to non-target tissues, particularly the kidneys. The main strategies involve systematic chemical modifications of the linkage between the targeting moiety and imaging/therapy payloads. In addition to a summary of the development history of PSMA-targeting agents, this review provides an overview of current advances and future promise of PSMA-targeted imaging and theranostics with focuses on the structural determinants of the chemical modification towards the next generation of PSMA-targeting agents.

Neuroendocrine prostate cancer (NEPC) is an aggressive and lethal variant of prostate cancer (PCa), and it remains a diagnostic challenge. Herein we report our findings of using synaptic vesicle glycoprotein 2 isoform A (SV2A) as a promising marker for positron emission tomography (PET) imaging of neuroendocrine differentiation (NED). The bioinformatic analyses revealed an amplified SV2A gene expression in clinical samples of NEPC versus castration-resistant PCa with adenocarcinoma characteristics (CRPC-Adeno). Importantly, significantly upregulated SV2A protein levels were found in both NEPC cell lines and tumor tissues. PET imaging studies were carried out in NEPC xenograft models with 18F-SynVesT-1. Although 18F-SynVesT-1 is not a cancer imaging agent, it showed a significant uptake level in the SV2A+ tumor (NCI-H660: 0.70 ± 0.14 %ID/g at 50–60 min p.i.). The SV2A blockade resulted in a significant reduction of tumor uptake (0.25 ± 0.03 %ID/g, p = 0.025), indicating the desired SV2A imaging specificity. Moreover, the comparative PET imaging study showed that the DU145 tumors could be clearly visualized by 18F-SynVesT-1 but not 68Ga-PSMA-11 nor 68Ga-DOTATATE, further validating the role of SV2A-targeted imaging for noninvasive assessment of NED in PCa. In conclusion, we demonstrated that SV2A, highly expressed in NEPC, can serve as a promising target for noninvasive imaging evaluation of NED.

Asymptomatic individuals with coronavirus disease (COVID-19) have been identified via nucleic acid testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the epidemiologic characteristics and viral shedding pattern of asymptomatic patients remain largely unknown. In this study, serological testing was applied when identifying nine asymptomatic cases of COVID-19 who showed persistent negative RT-PCR test results for SARS-CoV-2 nucleic acid and no symptoms of COVID-19. Two asymptomatic cases were presumed to be index patients who had cleared the virus when their close contacts developed symptoms of COVID-19. Three of the asymptomatic cases were local individuals who spontaneously recovered before their presumed index patients developed symptoms of COVID-19. This report presents the epidemiologic and clinical characteristics of asymptomatic individuals with SARS-CoV-2 infection that were undetected on RT-PCR tests in previous epidemiologic investigations probably due to the transient viral shedding duration.

Reverse cyclic lateral testing was undertaken to investigate the seismic behavior of 1/4 scale steel-plate concrete (SC) composite walls. The experimental program involved seven SC wall pier specimens. A new chamber structure is proposed, using steel diaphragms to connect the two steel faceplates to each other and to divide the SC wall pier into two parts. Conventional wall specimens failed mainly by tensile fracture of the concrete at the junction of the wall side and wall base, crushing of the concrete at the toe of the wall, or buckling of the steel faceplate. Tearing of the welded joints at the steel faceplates and steel diaphragm, buckling of steel, steel diaphragms being pulled out, tensile fracture and crushing of the concrete were the main failure modes of the chamber structure walls. A parametric numerical analysis in ABAQUS was developed to investigate the effects of the stiffening rib, steel web amount, material strength, shear-span ratio, and axial compression ratio on the seismic response of SC walls. The chamber structure of the SC wall piers can improve the peak load, ductility, and energy-dissipating capacity. The steel faceplate thickness and stiffening ribs can improve the behavior of SC wall piers.

Lysine decarboxylase (CadA) can directly convert L-lysine to cadaverine, which is an important platform chemical that can be used to produce polyamides. However, the non-recyclable and the poor pH tolerance of pure CadA hampered its practical application. Herein, a one-step purification and immobilization procedure of CadA was established to investigate the cadaverine production from L-lysine. Renewable biomass chitin was used as a carrier for lysine decarboxylase (CadA) immobilization via fusion of a chitin-binding domain (ChBD). Scanning electron microscopy, laser scanning confocal microscopy, fourier transform infrared spectra, elemental analysis, and thermal gravimetric analysis proved that the fusion protein ChBD-CadA can be adsorbed on chitin effectively. Furthermore, the fusion protein (ChBD-CadA) existed better pH stability compared to wild CadA, and kept over 73% of the highest activity at pH 8.0. Meanwhile, the ChBD-CadA showed high specificity toward chitin and reached 93% immobilization yield within 10 min under the optimum conditions. The immobilized ChBD-CadA (I-ChBD-CadA) could efficiently converted L-lysine at 200.0 g/L to cadaverine at 135.6 g/L in a batch conversion within 120 min, achieving a 97% molar yield of the substrate L-lysine. In addition, the I-ChBD-CadA was able to be reused under a high concentration of L-lysine and retained over 57% of its original activity after four cycles of use without acid addition to maintain pH. These results demonstrate that immobilization of CadA using chitin-binding domain has the potential in cadaverine production on an industrial scale.

Previous cochlear implant (CI) research has shown that at a pulse train with a long pulse phase duration (PPD) requires less current but greater charge to obtain the same loudness as a pulse train with a short PPD. This might result in different excitation patterns between long and short PPDs. At equal loudness, long PPDs might produce greater masking due to greater charge. However, because they require less current, long PPDs may produce a smaller spatial spread of excitation (SOE) compared to short PPDs by evoking a greater neural firing probability within the relatively small current field. To investigate the effects of PPD on excitation patterns, overall masking and SOE were compared for equally loud stimuli with short or long PPD in 10 adult CI ears. Forward masking patterns were measured at relatively soft, medium, and loud presentation levels. Threshold shifts were calculated in terms of percent dynamic range (DR) of the probe. The area under the curve (AUC) of the masking functions was significantly larger for the long PPD than for the short PPD masker. The difference in AUC was proportional to the difference in charge between the short and long PPD maskers. To estimate SOE, the masking patterns were first normalized to the peak masking, and then AUC was calculated. SOE was significantly larger for the short PPD than for the long PPD masker. Thus, at equal loudness, long PPDs produced greater overall masking (possibly due to greater charge) but less SOE (possibly due to less current spread) than did short PPDs. The effect of the interaction between masking and SOE by long PPD stimulation remains to be tested.

Background. Numerous studies have highlighted that long noncoding RNA (lncRNA) can indirectly regulate the expression of mRNAs by binding to microRNA (miRNA). LncRNA-associated ceRNA networks play a vital role in the initiation and progression of several pathological mechanisms. However, the lncRNA-miRNA-mRNA ceRNA network in endothelial cells under cyclic stretch is seldom studied. Methods. The miRNA, mRNA, and lncRNA expression profiles of 6 human umbilical vein endothelial cells (HUVECs) under circumferential stress were obtained by next-generation sequencing (NGS). We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the R software package GDCRNATools. Cytoscape was adopted to construct a lncRNA-miRNA-mRNA ceRNA network. In addition, through GO and KEGG pathway annotations, we analyzed gene functions and their related pathways. We also adopted ELISA and TUNEL to investigate the effect of si-NEAT1 on endothelial inflammation and apoptosis. Results. We recognized a total of 32978 lncRNAs, 1046 miRNAs, and 31958 mRNAs in 6 samples; among them, 155 different expressed lncRNAs, 74 different expressed miRNAs, and 960 different mRNAs were adopted. Based on the established theory, the ceRNA network was composed of 13 lncRNAs, 44 miRNAs, and 115 mRNAs. We constructed and visualized a lncRNA-miRNA-mRNA network, and the top 20 nodes are identified after calculating their degrees. The nodes with most degrees in three kinds of RNAs are hsa-miR-4739, NEAT1, and MAP3K2. Functional analysis showed that different biological processes enriched in biological regulation, response to stimulus and cell communication. Pathway analysis was mainly enriched in longevity regulating, cell cycle, mTOR, and FoxO signaling pathway. Circumferential stress can significantly downregulate NEAT1, and after transducing si-NEAT1 for 24 h, inflammatory cytokine IL-6 and MCP-1 were significantly increased; furthermore, fewer TUNEL-positive cells were found in the si-NEAT1 treated group. Conclusions. The establishing of a ceRNA network can help further understand the mechanism of vein graft failure. Our data demonstrated that NEAT1 may be a core factor among the mechanical stress factors and that cyclic stress can significantly reduce expression of NEAT1, give rise to inflammation in the early stage of endothelial dysfunction, and promote EC apoptosis, which may play an essential role in vein graft failure.

There are a large number of photovoltaic (PV) arrays in large-scale PV power plants or regional distributed PV power plants, and the output of different arrays fluctuates with the external conditions. The deviation and evolution information of the array output are easily covered by the random fluctuations of the PV output, which makes the fault diagnosis of PV arrays difficult. In this paper, a fault diagnosis method based on the deviation characteristics of the PV array output is proposed. Based on the current of the PV array on the DC (direct current) side, the deviation characteristics of the PV array output under different arrays and time series are analyzed. Then, the deviation function is constructed to evaluate the output deviation of the PV array. Finally, the fault diagnosis of a PV array is realized by using the probabilistic neural network (PNN), and the effectiveness of the proposed method is verified. The main contributions of this paper are to propose the deviation function that can extract the fault characteristics of PV array and the fault diagnosis method just using the array current which can be easily applied in the PV plant.

Ice coating on overhead contact system (OCS) will affect the sliding of pantograph, and arc discharge phenomena will occur between pantograph and catenary, which will threaten the normal operation of train. This paper presents a comprehensive model to analyze the dynamics of icing on pantograph-catenary (PAC) system. The finite element model (FEM) is used for building the catenary, the pantograph is modeled as lumped-mass model, and the ice section of the cable is fan-shaped. The increased density method, uniform load method, and combinatorial material method of icing are used to analyze the icing problem of PAC system. The similarities and differences between the three simulation methods are compared. The influence of the ice thickness on the current collection quality between the pantograph and catenary at the different operating speeds calculated by the three methods is basically the same, which fully illustrates the effectiveness of the simulated ice coating method. In comparison, the combinatorial material method is a more reasonable method for calculating the icing of catenary systems. The research also shows that the influence of icing on the current collection quality of PAC system is different when the train runs at different speeds. Specifically, as the speed of trains increases, the effect of ice thickness on the current collection quality of the PAC system is becoming increasingly apparent.

Background It has been confirmed that mutations in solute carrier family 26 member 4 (SLC26A4) contribute to pendred syndrome. However, the role of SLC26A4 in cardiac hypertrophy and the signaling pathways remain unclear. Methods Cardiomyocytes were treated by 200 µM phenylephrine (PE) to induce cardiac hypertrophy. Also, the expression of SLC26A4, GSK3, cardiac hypertrophy markers including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was detected through real-time quantitative polymerase chain reaction (RT-qPCR). Flow cytometry assay was used to test the apoptosis of PE-induced cardiomyocytes transfected by small interfere RNA (siRNA)-SLC26A4. Furthermore, we detected the expression of autophagy-related markers including light chain 3 (LC3) and P62. Finally, we established a rat model of abdominal aortic constriction (AAC)-induced cardiac hypertrophy in vivo. Results RT-qPCR results showed that the mRNA expression of SLC26A4 was significantly up-regulated in PE-induced cardiac hypertrophy. After inhibiting SLC26A4, the release of ANP and BNP was significantly decreased and GSK3β was elevated in vivo and in vitro. Furthermore, inhibiting SLC26A4 promoted apoptosis of cardiac hypertrophy cells. In addition, LC3 was down-regulated and P62 was enhanced after transfection of siRNA-SLC26A4. Conclusion Our findings revealed that SLC26A4 increases cardiac hypertrophy, and inhibiting SLC26A4 could decrease the release of ANP/BNP and promote the expression of GSK-3β in vitro and in vivo. Moreover, SLC26A4 silencing inhibits autophagy of cardiomyocytes and induces apoptosis of cardiomyocytes. Therefore, SLC26A4 possesses potential value to be a therapeutic target of cardiac hypertrophy, and our study provides new insights into the mechanisms of cardiac hypertrophy.

Foreign body in urinary bladder is an unusual finding in urology emergency, which has always caused wide attention. In this case report, we presented a 28-year-old unmarried male who was admitted to the emergency room with magnetic balls in his bladder. An abdominal plain X ray showed metallic dense shadow in the pelvic region. The foreign body was removed under modified cystoscopy and 159 magnetic balls were detected. The patient was discharged without any surgical or postsurgical complications. Cystoscopy is a better option for dealing with a large number of magnetic balls in urinary bladder. Keywords: Magnetic balls, Foreign body, Urinary bladder, Cystoscopy

Long non-coding RNAs (lncRNAs) are emerging as important modulators of cancer progression, among which prostate cancer-associated transcript 1 (PCAT1) has been shown to be an oncogene in several tumors. However, the clinical significance and biological function of PCAT1 in endometrial carcinoma (EC) remain unclear. In this study, we used 89 EC tissues and HEC-1B, Ishikawa, RL95-2 and AN3CA EC cell lines. We found elevated expression levels of PCAT1 in EC tissues and cell lines using reverse transcription qPCR (RT-qPCR). The prognostic value of PCAT1 was determined using Kaplan–Meier survival and Cox regression analysis. The results showed that higher PCAT1 expression was positively correlated with FIGO stage, myometrial invasion, lymph node metastasis, and a shorter overall survival. A series of functional assays showed that the knockdown of PCAT1 by small interfering RNA (siRNA) targeting PCAT1 (siPCAT1) suppressed cell proliferation, migration and invasion, but promoted apoptosis. Western blot analysis further showed that B-cell lymphoma 2 (Bcl-2), vimentin and N-cadherin were downregulated, but E-cadherin and Bcl-2-associated death promoter (Bad) were upregulated in PCAT1-silenced EC cells. Taken together, our results underscore the oncogenic role of PCAT1 in EC and show that PCAT1 may be a potential therapeutic target in EC treatment.

Abstract Background RNA interference (RNAi) technology has been widely used to knockdown target genes via post-transcriptional silencing. In plants, RNAi is used as an effective tool with diverse applications being developed such as resistance against insects, fungi, viruses, and metabolism manipulation. To develop genetically modified (GM) RNAi traits for insect control, a transgene is created and composed of an inversely-repeated sequence of the target gene with a spacer region inserted between the repeats. The transgene design is subject to form a self-complementary hairpin RNA (hpRNA) and the active molecules are > 60 bp doubled-stranded RNA (dsRNA) derived from the hpRNA. However, in some cases, an undesirable intermediate such as single-stranded RNA (ssRNA) may be formed, which is not an active molecule. The aforementioned characteristics of RNAi traits lead to increase the challenges for RNAi-derived dsRNA quantitation. Results To quantify the dsRNA and distinguish it from the ssRNA in transgenic maize, an analytical tool is required to be able to effectively quantify dsRNA which contains a strong secondary structure. Herein, we develop a modified qRT-PCR method (abbreviated as RNase If -qPCR) coupled with a ssRNA preferred endonuclease (i.e., RNase If). This method enables the precise measurement of the active molecules (i.e., dsRNA) derived from RNAi traits of GM crops and separately quantifies the dsRNA from ssRNA. Notably, we also demonstrate that the RNase If -qPCR is comparable to a hybridization-based method (Quantigene Plex 2.0). Conclusions To our best knowledge, this is the first report of a method combining RNase If with modified qRT-PCR protocol. The method represents a reliable analytical tool to quantify dsRNA for GM RNAi crops. It provides a cost-effective and feasible analytical tool for general molecular laboratory without using additional equipment for other methods. The RNase If -qPCR method demonstrates high sensitivity (to 0.001 pg/ μL of dsRNA), precision and accuracy. In this report, we demonstrated the deployment of this method to characterize the RNAi events carrying v-ATPase C in maize during trait development process. The method can be utilized in any application which requires the dsRNA quantification such as double-stranded RNA virus or sprayable dsRNA as herbicide.

Abstract The objective area in this paper is a complex fault-block reservoir, which is provided by China Petroleum Engineering Design Competition. Reservoir characteristics which comprise of stratigraphic features, vertical changes, and section properties (thickness, percentage sand, and percentage amalgamation) are documented. Through comprehensive analysis on structural architecture and reservoir characteristics, a three-dimensional quantitative reservoir modeling is taken at a regional scale of 69 × 97 × 37 m3 with the application of geostatistics as theoretical guidance. Then, a high-resolution hierarchical reservoir model of this field has been generated with a combination of hierarchical, structural, physical, and well trajectory data. The established three-dimensional geological model integrates all well and structural information, which can provide a basic model for subsequent sedimentary microfacies modeling and property modeling as well. Finally, a series of profiles are built successively, they are three-dimensional fence diagrams, connecting well sections and well group profiles, which can be a valuable tool for reflecting geologic body with great reality and thus achieve reservoir characterization of the complex fault-block reservoir.

Valosin-containing protein (VCP) was found to play a vital protective role against cardiac stresses. Genetic mutations of VCP are associated with human dilated cardiomyopathy. However, the essential role of VCP in the heart during the physiological condition remains unknown since the VCP knockout in mice is embryonically lethal. We generated a cardiac-specific dominant-negative VCP transgenic (DN-VCP TG) mouse to determine the effects of impaired VCP activity on the heart. Using echocardiography, we showed that cardiac-specific overexpression of DN-VCP induced a remarkable cardiac dilation and progressively declined cardiac function during the aging transition. Mechanistically, DN-VCP did not affect the endogenous VCP (EN-VCP) expression but significantly reduced cardiac ATPase activity in the DN-VCP TG mouse hearts, indicating a functional inhibition. DN-VCP significantly impaired the aging-related cytoplasmic/nuclear shuffling of EN-VCP and its co-factors in the heart tissues and interrupted the balance of the VCP-cofactors interaction between the activating co-factors, ubiquitin fusion degradation protein 1 (UFD-1)/nuclear protein localization protein 4 (NPL-4) complex, and its inhibiting co-factor P47, leading to the binding preference with the inhibitory co-factor, resulting in functional repression of VCP. This DN-VCP TG mouse provides a unique functional-inactivation model for investigating VCP in the heart in physiological and pathological conditions.

To investigate the evolution process of LNG (Liquefied Natural Gas) liquid pool and gas cloud diffusion, the Realizable k-ε model and Eluerian model were used to numerically simulate the liquid phase leakage and diffusion process of LNG storage tanks. The experimental results showed that some LNG flashed and vaporized rapidly to form a combustible cloud during the continuous leakage. The diffusion of the explosive cloud was divided into heavy gas accumulation, entrainment heat transfer, and light gas drift. The vapor cloud gradually separated into two parts from the whole “fan leaf shape”. One part was a heavy gas cloud; the other part was a light gas cloud that spread with the wind in the downwind direction. The change of leakage aperture had a greater impact on the whole spill and dispersion process of the storage tank. The increasing leakage aperture would lead to 10.3 times increase in liquid pool area, 78.5% increase in downwind dispersion of methane concentration at 0.5 LFL, 22.6% increase in crosswind dispersion of methane concentration at 0.5 LFL, and 249% increase in flammable vapor cloud volume. Within the variation range of the leakage aperture, the trend of the gas cloud diffusion remained consistent, but the time for the liquid pool to keep stable and the gas cloud to enter the next diffusion stage was delayed. The low-pressure cavity area within 200 m of the leeward surface of the storage tank would accumulate heavy gas for a long time, forming a local high concentration area, which should be an area of focus for alert prediction.

Background/Aims: Our previous studies demonstrated that intrinsic aortic smooth muscle cell (VSMC) stiffening plays a pivotal role in aortic stiffening in aging and hypertension. However, the underlying molecular mechanisms remain largely unknown. We here hypothesized that Rho kinase (ROCK) acts as a novel mediator that regulates intrinsic VSMC mechanical properties through the serum response factor (SRF) /myocardin pathway and consequently regulates aortic stiffness and blood pressure in hypertension. Methods: Four-month old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were studied. Aortic stiffness was measured by echography. Intrinsic mechanical properties of VSMCs were measured by atomic force microscopy (AFM) in vitro. Results: Compared to WKY rats, SHR showed a significant increase in aortic stiffness and blood pressure, which is accompanied by a remarkable cell stiffening and ROCK activation in thoracic aortic (TA) VSMCs. Theses alterations in SHR were abolished by Y-27632, a specific inhibitor of ROCK. Additionally, boosted filamentous/globular actin ratio was detected in TA VSMCs from SHR versus WKY rats, resulting in an up-regulation of SRF and myocardin expression and its downstream stiffness-associated genes including α-smooth muscle actin, SM22, smoothelin and myosin heavy chain 11. Reciprocally, these alterations in SHR TA VSMCs were also suppressed by Y-27632. Furthermore, a specific inhibitor of SRF/myocardin, CCG-100602, showed a similar effect to Y-27632 in SHR in both TA VSMCs stiffness in vitro and aorta wall stiffness in vivo. Conclusion: ROCK is a novel mediator modulating aortic VSMC stiffness through SRF/myocardin signaling which offers a therapeutic target to reduce aortic stiffening in hypertension.

Abstract Background Hand hygiene (HH) is an essential component for preventing and controlling of healthcare-associated infection (HAI), whereas compliance with HH among health care workers (HCWs) is frequently poor. This study aimed to assess compliance and correctness with HH before and after the implementation of a multimodal HH improvement strategy launched by the World Health Organization (WHO). Methods A quasi-experimental study design including questionnaire survey generalizing possible factors affecting HH behaviors of HCWs and direct observation method was used to evaluate the effectiveness of WHO multimodal HH strategy in a hospital of Traditional Chinese Medicine. Multimodal HH improvement strategy was drawn up according to the results of questionnaire survey. Compliance and correctness with HH among HCWs were compared before and after intervention. Also HH practices for different indications based on WHO “My Five Moments for Hand Hygiene” were recorded. Results In total, 553 HCWs participated in the questionnaire survey and multimodal HH improvement strategy was developed based on individual, environment and management levels. A total of 5044 observations in 23 wards were recorded in this investigation. The rate of compliance and correctness with HH improved from 66.27% and 47.75% at baseline to 80.53% and 88.35% after intervention. Doctors seemed to have better compliance with HH after intervention (84.04%) than nurses and other HCWs (81.07% and 69.42%, respectively). When stratified by indication, compliance with HH improved for all indications after intervention (P

(1) Background: The immune checkpoint blockade (ICB) has shown promising efficacy in non-small-cell lung cancer (NSCLC) patients with significant clinical benefits and durable responses, but the overall response rate to ICBs is only 20%. The lack of responsiveness to ICBs is currently a central problem in cancer immunotherapy. (2) Methods: Four public cohorts comprising 2986 patients with NSCLC were included in the study. We screened 158 patients with NSCLC with no durable clinical benefit (NDB) to ICBs in the Rizvi cohort and identified NDB-related gene mutations in these patients using univariate and multivariate Cox regression analyses. Programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), neoantigen load, tumor-infiltrating lymphocytes, and immune-related gene expression were analyzed for identifying gene mutations. A comprehensive predictive classifier model was also built to evaluate the efficacy of ICB therapy. (3) Results: Mutations in FAT1 and KEAP1 were found to correlate with NDB in patients with NSCLC to ICBs; however, the analysis suggested that only mutation in FAT1 was valuable in predicting the efficacy of ICB therapy, and that mutation in KEAP1 acted as a prognostic but not a predictive biomarker for NSCLC. Mutations in FAT1 were associated with a higher TMB and lower multiple lymphocyte infiltration, including CD8 (T-Cell Surface Glycoprotein CD8)+ T cells. We established a prognostic model according to PD-L1 expression, TMB, smoking status, treatment regimen, treatment type, and FAT1 mutation, which indicated good accuracy by receiver operating characteristic (ROC) analysis (area under the curve (AUC) for 6-months survival: 0.763; AUC for 12-months survival: 0.871). (4) Conclusions: Mutation in FAT1 may be a predictive biomarker in patients with NSCLC who exhibit NDB to ICBs. We proposed an FAT1 mutation-based model for screening more suitable NSCLC patients to receive ICBs that may contribute to individualized immunotherapy.

Background: Debate on treatment for young patients with coronary artery disease still exists. This study aimed to investigate the intermediate- and long-term outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients aged 18–45 years with diabetes mellitus (DM). Methods: Between January 2006 and March 2016, a total of 2018 DM patients aged 18–45 years including 517 cases of CABG and 1501 cases of PCI were enrolled in the study. Using propensity score matching (PSM), 406 patients were matched from each group. The intermediate- and long-term data were collected. The primary end point of this study was long-term death. The secondary end points included long-term major adverse cardiovascular and cerebrovascular events (MACCEs), stroke, angina, myocardial infarction (MI), and repeat revascularization. Results: Before PSM, the in-hospital mortality was 1.2% in the CABG group and 0.1% in the PCI group, with statistically significant difference (P < 0.0001). The 10-year follow-up outcomes including long-term survival rate and freedom from MACCEs were better in the CABG group than those in the PCI group (97.3% vs. 94.5%, P = 0.0072; 93.2% vs. 86.3%, P < 0.0001), but CABG group was associated with lower freedom from stoke compared to PCI group (94.2% vs. 97.5%, P = 0.0059). After propensity score-matched analysis, these findings at 10-year follow-up were also confirmed. Freedom from MACCEs was higher in CABG group compared to PCI group, but no significant difference was observed (93.1% vs. 89.2%, P = 0.0720). The freedom from recurrent MI was significantly higher in CABG patients compared with PCI patients (95.6% vs. 92.5%, P = 0.0260). Furthermore, CABG was associated with a higher rate of long-term survival rate than PCI (97.5% vs. 94.6%, P = 0.0403). There was no significant difference in the freedom from stroke between CABG and PCI groups (95.3% vs. 97.3%, P = 0.9385). The hospital cost was greater for CABG (13,936 ± 4480 US dollars vs. 10,926 ± 7376 US dollars, P < 0.0001). Conclusions: In DM patients aged 18–45 years, the cumulative survival rate, and freedom from MI and repeat revascularization for CABG were superior to those of PCI. However, a better trend to avoid stroke was observed with PCI.

Objective: The goal of this study is to evaluate pulmonary function and respiratory center drive in patients with early-stage idiopathic Parkinson's disease (IPD) to facilitate early diagnosis of Parkinson's Disease (PD).Methods: 43 IPD patients (Hoehn and Yahr scale of 1) and 41 matched healthy individuals (e.g., age, sex, height, weight, BMI) were enrolled in this study. Motor status was evaluated using the Movement Disorders Society-Unified PD Rating Scale (MDS-UPDRS). Pulmonary function and respiratory center drive were measured using pulmonary function tests (PFT). All IPD patients were also subjected to a series of neuropsychological tests, including Non-Motor Symptoms Questionnaire (NMSQ), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Beck Depression Inventory (BDI) and Mini Mental State Examination (MMSE).Results: IPD patients and healthy individuals have similar forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), forced expiratory volume in 1s/forced vital capacity (FEV1/FVC), peak expiratory flow (PEF), and carbon monoxide diffusion capacity (DLCOcSB). Reduced respiratory muscle strength, maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax) was seen in IPD patients (p = 0.000 and p = 0.002, respectively). Importantly, the airway occlusion pressure after 0.1 s (P0.1) and respiratory center output were notably higher in IPD patients (p = 0.000) with a remarkable separation of measured values compared to healthy controls.Conclusion: Our findings suggest that abnormal pulmonary function is present in early stage IPD patients as evidenced by significant changes in PImax, PEmax, and P0.1. Most importantly, P0.1 may have the potential to assist with the identification of IPD in the early stage.

Background: Immune checkpoint inhibitors (ICI) have shown promising prospects in gastroesophageal junction (G/GEJ) cancer immunotherapy, many clinical trials have been carried out. Objective: To evaluate the efficacy and safety of ICI in G/GEJ cancer. Methods: The published English articles of PubMed, Cochrane Library, Embase, Web of Science were searched up to 30/09/2018. The efficacy and safety of ICI were analyzed by meta-analysis. Results: A total of 2003 patients from nine clinical trials were included. Anti-PD-1 treatment improved the 12-month, 18-month overall survival (OS) rate (RR, 1.79 p = 0.013; 2.20 p = 0.011) and prolonged the duration of response (DOR) (MSR, 3.27 p < 0.001). The objective response rate (ORR) in PD-L1+ patients was greater than PD-L1− (RR, 4.31 p < 0.001). Microsatellite instability-high (MSI-H) patients had higher ORR and disease control rate (DCR) than microsatellite stability (MSS) (RR, 3.40 p< 0.001; 2.26 p= 0.001). The most common grade ≥3 treatment-related adverse events (TRAEs) were fatigue, aspartate aminotransferase increased, hepatitis, pneumonitis, colitis, hypopituitarism. The TRAE incidence of anti-PD-1/PD-L1 was less than chemotherapy (TRAE RR = 0.64 p< 0.001; ≥3 TRAE RR = 0.37 p < 0.001). The incidence of ≥3 TRAEs of anti-PD-1/PD-L1 treatment was less than that of anti-CTLA-4 (11.7% vs 43.9%). Conclusions: ICI treatment could improve some but not all survival endpoints to advanced or metastatic G/GEJ cancer patients suggesting modest benefit and less adverse reactions. Anti-PD-1/PD-L1 therapy was more effective to PD-L1+, MSI-H, EBV+, or high tumor mutational burden patients.

An experimental platform of gas cloud deflagration is built in this study, and the propane–air premixed gas blasting experiment was carried out in curved pipes with different lengths. The effect of pipe length on combustible gas explosion and the influence of explosion shock wave on thin-walled pipe loading were also studied. The experimental device included photoelectric, pressure, and strain sensors which were used to evaluate the explosion parameters and stress of the thin-walled pipe. The result was that the longer the pipeline, the higher the wall overpressure and the bigger the maximum tube wall. The pressure time curve was consistent with the thin-walled strain time–history curve. The pipe bend accelerates the flame propagation to a certain extent, and the pipe length influenced the law of flame ignition and explosion in pipe integrally; the longer the pipe, the greater the pressure and the speed of the flame. The maximum explosion pressure appears at the end of the pipe, and the loading of the shock wave on pipe wall belongs to dynamic response.

Timely detecting disturbances and locating their sources are critical to the reliable operation of power grids. This capability enables operators to effectively diagnose disturbances over wide areas and earns time for remedial reactions. In this study, a travelling-wave based scheme, namely data-driven online distributed disturbance location (DODDL), is proposed to quickly detect disturbances and determine their geographic location in large-scale power grids when the grids’ topology is not available. The proposed DODDL scheme consists of two function blocks: (i) a singular spectrum analysis-based change-point detection method, which can quickly detect disturbances and determine their arrival time at distributed sensors, and (ii) a novel temporal scanning algorithm, which can accurately determine the geographic location of the disturbance source point. Utilising field measurement data sets recorded by the frequency disturbance recorders from the frequency monitoring network, it is shown that the DODDL scheme is not only quicker and more robust to grid non-homogeneity than existing approaches, but also can capture and locate more subtle and concealed disturbances.

In recent years, the length of electrified railway systems has increased along with the number of railway vehicles in China. For the pantograph-catenary system, as one of the key components of the vehicle system, an urgent problem includes diagnosing faults and proposing a safety monitoring system to assure safe operation, improve the level of detection, and decrease the cost of maintenance and repairs. For the monitoring system based on the pantograph, the design process, whole architecture, function module, fault diagnosis method, and monitoring scheme have been investigated. Two specified faults were introduced to describe how to develop such a monitoring scheme based on the pantograph condition-based recognition.

According to the glutamate hypothesis of schizophrenia, the abnormality of glutamate transmission induced by hypofunction of NMDA receptors (NMDARs) is causally associated with the positive and negative symptoms of schizophrenia. However, the underlying mechanisms responsible for the changes in glutamate transmission in schizophrenia are not fully understood. Astrocytes, the major regulatory glia in the brain, modulate not only glutamate metabolism but also glutamate transmission. Here we review the recent progress in understanding the role of astrocytes in schizophrenia. We focus on the astrocytic mechanisms of (i) glutamate synthesis via the glutamate-glutamine cycle, (ii) glutamate clearance by excitatory amino acid transporters (EAATs), (iii) D-serine release to activate NMDARs, and (iv) glutamatergic target engagement biomarkers. Abnormality in these processes is highly correlated with schizophrenia phenotypes. These findings will shed light upon further investigation of pathogenesis as well as improvement of biomarkers and therapies for schizophrenia.

In indoor target tracking based on wireless sensor networks, the particle filtering algorithm has been widely used because of its outstanding performance in coping with highly non-linear problems. Resampling is generally required to address the inherent particle degeneracy problem in the particle filter. However, traditional resampling methods cause the problem of particle impoverishment. This problem degrades positioning accuracy and robustness and sometimes may even result in filtering divergence and tracking failure. In order to mitigate the particle impoverishment and improve positioning accuracy, this paper proposes an improved genetic optimization based resampling method. This resampling method optimizes the distribution of resampled particles by the five operators, i.e., selection, roughening, classification, crossover, and mutation. The proposed resampling method is then integrated into the particle filtering framework to form a genetic optimization resampling based particle filtering (GORPF) algorithm. The performance of the GORPF algorithm is tested by a one-dimensional tracking simulation and a three-dimensional indoor tracking experiment. Both test results show that with the aid of the proposed resampling method, the GORPF has better robustness against particle impoverishment and achieves better positioning accuracy than several existing target tracking algorithms. Moreover, the GORPF algorithm owns an affordable computation load for real-time applications.

Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%–2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission.

This article reports the synthesis of a new class of conjugates containing a nucleobase, a peptidic epitope, and a saccharide and the evalution of their gelation, biostability, and cell compatibility. We demonstrate a facile synthetic process, based on solid-phase peptide synthesis of nucleopeptides, to connect a saccharide with the nucleopeptides for producing the target conjugates. All the conjugates themselves (1–8) display excellent solubility in water without forming hydrogels. However, a mixture of 5 and 8 self-assembles to form nanofibers and results in a supramolecular hydrogel. The proteolytic stabilities of the conjugates depend on the functional peptidic epitopes. We found that TTPV is proteolytic resistant and LGFNI is susceptible to proteolysis. In addition, all the conjugates are compatible to the mammalian cells tested.

Background/Aims: Angiotensin II (AngII) type 1 receptor (AT1R) could be activated by mechanical stress without the involvement of AngII during the development of cardiac hypertrophy. We aimed to identify sensing sites of AT1R for activation by mechanical stretch. Methods: We constructed several site-directed mutations of AT1R (AT1RK199Q, AT1RL212F, AT1RQ257A and AT1RC289A), transfected them respectively into COS7 cells or angiotensinogen knockout cardiomyocytes (ATG−/−-CMs), and observed cellular events after mechanical stretch. Results: AngII-induced phosphorylation of ERKs and Jak2, and redistribution of Gαq11 in AT1RWT- COS7 or -ATG−/−-CMs were dramatically decreased in AT1RK199Q- or AT1RQ257A- COS7 cells or -ATG−/−-CMs, while those effects induced by mechanical stretch were greatly suppressed in COS7 cells or ATG−/−-CMs expressing AT1RL212F, AT1RQ257A or AT1RC289A compared with these cells expressing AT1RWT. AngII-induced hypertrophic responses (the increase in hypertrophic genes expression and cross-sectional area) in AT1RWT- ATG−/−-CMs were partly abolished in AT1RK199Q-ATG−/−-CMs or AT1RQ257A-ATG−/−-CMs, while these responses induced by mechanical stretch were greatly inhibited in ATG−/−-CMs overexpressing AT1RL212F, AT1RQ257A or AT1RC289A. Conclusion: These results indicated that Leu212, Gln257 and Cys289 in AT1R are not only sensing sites for mechanical stretch but also functional amino residues for activation of the receptor and cardiomyocytes hypertrophy induced by mechanical stretch.

A reflective intensity-modulated fiber-optic sensor based on microelectromechanical systems (MEMS) for pressure measurements is proposed and experimentally demonstrated. The sensor consists of two multimode optical fibers with a spherical end, a quartz tube with dual holes, a silicon sensitive diaphragm, and a high borosilicate glass substrate (HBGS). The integrated sensor has a high sensitivity due to the MEMS technique and the spherical end of the fiber. The results show that the sensor achieves a pressure sensitivity of approximately 0.139 mV/kPa. The temperature coefficient of the proposed sensor is about 0.87 mV/°C over the range of 20 °C to 150 °C. Furthermore, due to the intensity mechanism, the sensor has a relatively simple demodulation system and can respond to high-frequency pressure in real time. The dynamic response of the sensor was verified in a 1 kHz sinusoidal pressure environment at room temperature.

Hyperoside (quercetin 3-o-β-d-galactopyranoside) is one of the flavonoid glycosides with anti-inflammatory, antidepressant, and anti-cancer effects. But it remains unknown whether it had effects on breast cancer. Here, different concentrations of hyperoside were used to explore its therapeutic potential in both breast cancer cells and subcutaneous homotransplant mouse model. CCK-8 and wound healing assays showed that the viability and migration capability of Michigan Cancer Foundation-7 (MCF-7) and 4T1 cells were inhibited by hyperoside, while the apoptosis of cells were increased. Real-time quantitative PCR (qRT-PCR) and western blot analysis were used to detect mRNA and the protein level, respectively, which showed decreased levels of B cell lymphoma-2 (Bcl-2) and X-linked inhibitor of apoptosis (XIAP), and increased levels of Bax and cleaved caspase-3. After exploration of the potential mechanism, we found that reactive oxygen species (ROS) production was reduced by the administration of hyperoside, which subsequently inhibited the activation of NF-κB signaling pathway. Tumor volume was significantly decreased in subcutaneous homotransplant mouse model in hyperoside-treated group, which was consistent with our study in vitro. These results indicated that hyperoside acted as an anticancer drug through ROS-related apoptosis and its mechanism included activation of the Bax−caspase-3 axis and the inhibition of the NF-κB signaling pathway.

The hearing loss criterion for cochlear implant candidacy in mainland China is extremely stringent (bilateral severe to profound hearing loss), resulting in few patients with substantial residual hearing in the nonimplanted ear. The main objective of the current study was to examine the benefit of bimodal hearing in typical Mandarin-speaking implant users who have poorer residual hearing in the nonimplanted ear relative to those used in the English-speaking studies. Seventeen Mandarin-speaking bimodal users with pure-tone averages of ∼80 dB HL participated in the study. Sentence recognition in quiet and in noise as well as tone and word recognition in quiet were measured in monaural and bilateral conditions. There was no significant bimodal effect for word and sentence recognition in quiet. Small bimodal effects were observed for sentence recognition in noise (6%) and tone recognition (4%). The magnitude of both effects was correlated with unaided thresholds at frequencies near voice fundamental frequencies (F0s). A weak correlation between the bimodal effect for word recognition and unaided thresholds at frequencies higher than F0s was identified. These results were consistent with previous findings that showed more robust bimodal benefits for speech recognition tasks that require higher spectral resolution than speech recognition in quiet. The significant but small F0-related bimodal benefit was also consistent with the limited acoustic hearing in the nonimplanted ear of the current subject sample, who are representative of the bimodal users in mainland China. These results advocate for a more relaxed implant candidacy criterion to be used in mainland China.

Background. The key gene sets involved in the progression of acute liver failure (ALF), which has a high mortality rate, remain unclear. This study aims to gain a deeper understanding of the transcriptional response of peripheral blood mononuclear cells (PBMCs) following ALF. Methods. ALF was induced by D-galactosamine (D-gal) in a porcine model. PBMCs were separated at time zero (baseline group), 36 h (failure group), and 60 h (dying group) after D-gal injection. Transcriptional profiling was performed using RNA sequencing and analysed using DAVID bioinformatics resources. Results. Compared with the baseline group, 816 and 1,845 differentially expressed genes (DEGs) were identified in the failure and dying groups, respectively. A total of five and two gene ontology (GO) term clusters were enriched in 107 GO terms in the failure group and 154 GO terms in the dying group. These GO clusters were primarily immune-related, including genes regulating the inflammasome complex and toll-like receptor signalling pathways. Specifically, GO terms related to cell death, including apoptosis, pyroptosis, and autophagy, and those related to fibrosis, coagulation dysfunction, and hepatic encephalopathy were enriched. Seven Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, cytokine-cytokine receptor interaction, hematopoietic cell lineage, lysosome, rheumatoid arthritis, malaria, and phagosome and pertussis pathways were mapped for DEGs in the failure group. All of these seven KEGG pathways were involved in the 19 KEGG pathways mapped in the dying group. Conclusion. We found that the dramatic PBMC transcriptome changes triggered by ALF progression was predominantly related to immune responses. The enriched GO terms related to cell death, fibrosis, and so on, as indicated by PBMC transcriptome analysis, seem to be useful in elucidating potential key gene sets in the progression of ALF. A better understanding of these gene sets might be of preventive or therapeutic interest.

Background: Work in voiding (WIV) of the bladder may be used to evaluate bladder status throughout urination rather than at a single time point. Few studies, however, have assessed WIV owing to the complexity of its calculations. We have developed a method of calculating work capacity of the bladder while voiding and analyzed the associations of bladder work parameters with bladder contractile function and bladder outlet obstruction (BOO). Methods: The study retrospectively evaluated 160 men and 23 women, aged >40 years and with a detrusor pressure at maximal flow rate (P det Q max) of ≥40 cmH 2 O in men, who underwent urodynamic testing. The bladder power integration method was used to calculate WIV; WIV per second (WIV/t) and WIV per liter of urine voided (WIV/v) were also calculated. In men, the relationships between these work capacity parameters and P det Q max and Abrams-Griffiths (AG) number were determined using linear-by-linear association tests, and relationships between work capacity parameters and BOO grade were investigated using Spearman′s association test. Results: The mean WIV was 1.15 ± 0.78 J and 1.30 ± 0.88 J, mean WIV/t was 22.95 ± 14.45 mW and 23.78 ± 17.02 mW, and mean WIV/v was 5.59 ± 2.32 J/L and 2.83 ± 1.87 J/L in men and women, respectively. In men, WIV/v showed significant positive associations with P det Q max (r = 0.845, P = 0.000), AG number (r = 0.814, P = 0.000), and Schafer class (r = 0.726, P = 0.000). Conversely, WIV and WIV/t showed no associations with P det Q max or AG number. In patients with BOO (Schafer class > II), WIV/v correlated positively with increasing BOO grade. Conclusions: WIV can be calculated from simple urodynamic parameters using the bladder power integration method. WIV/v may be a marker of BOO grade, and the bladder contractile function can be evaluated by WIV and WIV/t.

This article reports the synthesis of a novel type of conjugate of three fundamental biological build blocks (i.e., saccharide, amino acids, and nucleobase) and their cell compatibility. The facile synthesis starts with the synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide synthesis (SPPS) to build the peptide segment (Phe-Arg-Gly-Asp or naphthAla-Phe-Arg-Gly-Asp with fully protected groups), and later, an amidation reaction in liquid phase connects these three parts together. The overall yield of these multiple step synthesis is about 34%. Besides exhibiting excellent solubility, these conjugates of saccharide–amino acids–nucleobase (SAN), like the previously reported conjugates of nucleobase–amino acids–saccharide (NAS) and nucleobase–saccharide–amino acids (NSA), are mammalian cell compatible.

Background This study was performed to compare changes in urinary incontinence (UI) symptoms and pelvic floor structure during pregnancy between nulliparous and multiparous women. Methods A cross-sectional survey was performed among pregnant women from July 2016 to January 2017. In total, 358 pregnant women from two hospitals underwent an interview and pelvic floor transperineal ultrasound assessment. A questionnaire regarding sociodemographic, gynecological, obstetric features and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) were used for the interview. Imaging data sets were analyzed offline to assess the bladder neck vertical position (BNVP), urethral angles (α, β, and γ angles), and hiatal area (HA) at rest and at maximal Valsalva maneuver (VM). Results After excluding 16 women with invalid data, 342 women were included. The prevalence (χ2 = 9.15, P = 0.002), frequency (t = 2.52, P = 0.014), usual amount of UI (t = 2.23, P = 0.029) and scores of interference with daily life (t = 2.03, P = 0.045) during pregnancy were higher in multiparous than nulliparous women. A larger bladder neck descent (BND) (F = 4.398, P