Pulsed laser deposition of a Ga2O3 thin film for an optoelectronic synaptic device.

With the rapid development of information era, the traditional von Neumann architecture faces the computing bottleneck, and integration of memory and perception is regarded as a potential solution. Herein, a Ga2O3/Si heterojunction based multi-modulated optoelectronic synaptic device is fabricated and demonstrated. As stimulated by ultraviolet (UV) optical spikes, the heterojunction device reveals typical synaptic functions of excitatory-postsynaptic current (EPSC), paired-pulse facilitation (PPF), spike-timing-dependent plasticity (STDP), and switch between short-term memory (STM) and long-term memory (LTM). In addition, stronger stimulations like higher reading voltage, stronger optical stimulated intensity, and longer pulse duration time can significantly prolong the attenuation of EPSC, which contributes to the improvement of the forgetting process. Our work provides a potential strategy for future neuromorphic computation through a UV light driven stimulation.

Social responsibility perspective in public response to the COVID-19 pandemic: a grounded theory approach.

BACKGROUND: Combating viral outbreaks extends beyond biomedical and clinical approaches; thus, public health prevention measures are equally important. Public engagement in preventive efforts can be viewed as the social responsibility of individuals in controlling an infectious disease and are subjected to change due to human behaviour. Understanding individuals' perception of social responsibility is crucial and is not yet explored extensively in the academic literature. We adopted the grounded theory method to develop an explanatory substantive theory to illustrate the process of how individual responded to the outbreak from a social responsibility perspective. METHODS: In-depth interviews were conducted among 23 Malaysians either through telephone or face-to-face depending on the participant's preference. Both purposive and theoretical sampling were used. Participants were invited to share their understanding, perceptions and activities during the COVID-19 pandemic. They were further probed about their perceptions on complying with the public health interventions imposed by the authorities. The interviews were audio-recorded and transcribed verbatim. Data was analysed via open coding, focus coding and theoretical coding, facilitated by memoing, sketching and modelling. RESULTS: Study findings showed that, social responsibility is perceived within its role, the perceived societal role responsibility. In a particular context, an individual assumed only one of the many expected social roles with their perceived circle of responsibility. Individuals negotiated their actions from this perspective, after considering the perceived risk during the outbreak. The four types of behaviour depicted in the matrix diagram facilitate the understanding of the abstract concept of negotiation in the human decision-making process, and provide the spectrum of different behaviour in relation to public response to the COVID-19 pandemic. CONCLUSIONS: Our study adopted the grounded theory approach to develop a theoretical model that illustrates how individual response to COVID-19 preventive measures is determined by the negotiation between perceived societal role responsibility and perceived infection risk. This substantive theoretical model is abstract, thus has relevance for adoption within similar context of an outbreak.

Elevated basal serum levels of calcitonin and simultaneous surgery of MEN2A-specific tumors.

Multiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome caused almost by germline RET mutation, and characterized by medullary thyroid carcinoma (MTC), in combination or not with pheochromocytoma (PHEO), hyperparathyroidism (HPTH), cutaneous lichen amyloidosis (CLA), and Hirschsprung's disease (HD). The basal serum calcitonin (Ctn)/carcinoembryonic antigen (CEA) levels are significantly correlated with the MTC stage. Metachronous surgery of MEN2A-specific tumors is a routine procedure. We aimed to explore the clinical significance of pro-gastrin-releasing peptide (proGRP) in MTC with elevated Ctn and simultaneous surgery of MEN2A-specific tumors. We retrospectively investigated 8 RET mutation carriers of 2 Chinese pedigrees with MEN2A. Clinical profiles, imaging examinations, preoperative and postoperative biochemical data, surgical procedures, and follow-up records were evaluated. Three patients showed levels of elevated Ctn but normal proGRP. Among them, one patient (FAIII-6) in Family A (one for RET C634R mutation), diagnosed with bilateral MTC, left PHEO, bilateral HPTH, and CLA, classified as MEN2A-related CLA subtype, underwent successfully simultaneous adrenal-sparing surgery (ASS), total thyroidectomy (TT), and parathyroidectomy, while TT of the other two patients (FBII-3 and FBIII-7) diagnosed with bilateral MTC in Family B (all for RET C618R mutation) were performed. Unexpectedly, the absence of neck lymph node MTC metastasis was indicated by histopathological examination. Postoperatively, all had consistently "undetectable" or normal levels of Ctn/CEA during follow-up. Patients with normal proGRP, despite high levels of Ctn, might have no regional lymph node MTC metastasis, and neck dissection should be avoided. Moreover, simultaneous surgery for coexistent PHEO and either MTC or HPTH is an approach of choice to use as an alternative treatment pattern. Recognition of MEN2A-related CLA and subsequently early screening of RET mutation may be favorable for timely management of MEN2A-specific tumors.

Search for α3ß2/3γ2 subtype selective ligands that are stable on human liver microsomes.

Selective modulation of specific benzodiazepine receptor (BzR) gamma amino butyric acid-A (GABA(A)) receptor ion channels has been identified as an important method for separating out the variety of pharmacological effects elicited by BzR-related drugs. Importantly, it has been demonstrated that both α2ß(2/3)γ2 (α2BzR) and α3BzR (and/or α2/α3) BzR subtype selective ligands exhibit anxiolytic effects with little or no sedation. Previously we have identified several such ligands; however, three of our parent ligands exhibited significant metabolic liability in rodents in the form of a labile ester group. Here eight analogs are reported which were designed to circumvent this liability by utilizing a rational replacement of the ester moiety based on medicinal chemistry precedents. In a metabolic stability study using human liver microsomes, four compounds were found to undergo slower metabolic transformation, as compared to their corresponding ester analogs. These compounds were also evaluated in in vitro efficacy assays. Additionally, bioisostere 11 was evaluated in a rodent model of anxiety. It exhibited anxiolytic activity at doses of 10 and 100mg/kg and was devoid of sedative properties.

Xylem-Inspired Hydrous Manganese Dioxide/Aluminum Oxide/Polyethersulfone Mixed Matrix Membrane for Oily Wastewater Treatment.

Ultrafiltration membrane has been widely used for oily wastewater treatment application attributed to its cost-efficiency, ease of operation, and high separation performance. To achieve high membrane flux, the pores of the membrane need to be wetted, which can be attained by using hydrophilic membrane. Nevertheless, conventional hydrophilic membrane suffered from inhomogeneous dispersion of nanofillers, causing a bottleneck in the membrane flux performance. This called for the need to enhance the dispersion of nanofillers within the polymeric matrix. In this work, in-house-fabricated hydrous manganese dioxide-aluminum oxide (HMO-Al2O3) was added into polyethersulfone (PES) dope solution to enhance the membrane flux through a xylem-inspired water transport mechanism on capillary action aided by cohesion force. Binary fillers HMO-Al2O3 loading was optimized at 0.5:0.5 in achieving 169 nm membrane mean pore size. Membrane morphology confirmed the formation of macro-void in membrane structure, and this was probably caused by the hydrophilic nanofiller interfacial stress released in PES matrix during the phase inversion process. The superhydrophilic properties of PES 3 in achieving 0° water contact angle was supported by the energy-dispersive X-ray analysis, where it achieved high O element, Mn element, and Al elements of 39.68%, 0.94%, and 5.35%, respectively, indicating that the nanofillers were more homogeneously dispersed in PES matrix. The superhydrophilic property of PES 3 was further supported by high pure water flux at 245.95 L/m2.h.bar, which was 3428.70% higher than the pristine PES membrane, 197.1% higher than PES 1 incorporated with HMO nanofiller, and 854.00% higher than PES 5 incorporated with Al2O3 nanofillers. Moreover, the excellent membrane separation performance of PES 3 was achieved without compromising the oil rejection capability (98.27% rejection) with 12 g/L (12,000 ppm) oily wastewater.

A multicategory logit model detecting temporal changes in antimicrobial resistance.

Monitoring and investigating temporal trends in antimicrobial data is a high priority for human and animal health authorities. Timely detection of temporal changes in antimicrobial resistance (AMR) can rely not only on monitoring and analyzing the proportion of resistant isolates based on the use of a clinical or epidemiological cut-off value, but also on more subtle changes and trends in the full distribution of minimum inhibitory concentration (MIC) values. The nature of the MIC distribution is categorical and ordinal (discrete). In this contribution, we developed a particular family of multicategory logit models for estimating and modelling MIC distributions over time. It allows the detection of a multitude of temporal trends in the full discrete distribution, without any assumption on the underlying continuous distribution for the MIC values. The experimental ranges of the serial dilution experiments may vary across laboratories and over time. The proposed categorical model allows to estimate the MIC distribution over the maximal range of the observed experiments, and allows the observed ranges to vary across labs and over time. The use and performance of the model is illustrated with two datasets on AMR in Salmonella.

Prognostic Value of Coronary Sinus Flow Quantification by Cardiac Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction.

Background This study aimed to evaluate the prognostic value of hyperemic coronary sinus flow (h-CSF) and global coronary flow reserve (g-CFR) obtained by phase-contrast cine-magnetic resonance imaging in patients with acute myocardial infarction (MI). Methods and Results This retrospective study analyzed patients with acute MI (n=523) who underwent primary (ST-segment-elevation MI) or urgent (non-ST-segment-elevation MI) percutaneous coronary intervention. Absolute coronary sinus blood flow (CSF) at rest and during vasodilator stress hyperemia was quantified at 30 days (24-36 days) after the index infarct-related lesion percutaneous coronary intervention and revascularization of functionally significant non-infarct-related lesions. We used Cox proportional hazards regression modeling to examine the association between h-CSF, g-CFR, and major adverse cardiac events defined as all-cause death, nonfatal MI, hospitalization for congestive heart failure, and stroke. Finally, 325 patients with ST-segment-elevation MI (62.1%) and 198 patients with non-ST-segment-elevation MI (37.9%) were studied over a median follow-up of 2.5 years. The rest CSF, h-CSF, and g-CFR were 0.94 (0.68-1.26) mL/min per g, 2.05 (1.42-2.73) mL/min per g, and 2.17 (1.54-3.03), respectively. Major adverse cardiac events occurred in 62 patients, and Cox proportional hazards analysis showed that h-CSF and g-CFR were independent predictors of major adverse cardiac events (h-CSF: hazard ratio [HR], 0.64; 95% CI, 0.47-0.88; P=0.005; g-CFR: HR, 0.62; 95% CI, 0.47-0.82; P=0.001). When stratified by h-CSF and g-CFR, cardiac event-free survival was the worst in patients with concordantly impaired h-CSF (<1.6 mL/min per g) and g-CFR (<1.7) (P<0.001). Conclusions Global coronary sinus flow quantification using phase-contrast cine-magnetic resonance imaging provided significant prognostic information independent of infarction size and conventional risk factors in patients with acute MI undergoing revascularization.

Establishment of a patient-derived organoid model and living biobank for nasopharyngeal carcinoma.

Background: Recurrent nasopharyngeal carcinoma (NPC) remains a major challenge for clinicians and scientists. Tumor organoid is a revelational disease model that highly resembled the heterogeneity and histopathological characteristics of original tumors. This study aimed to optimize the modeling process of patient-derived NPC organoids (NPCOs), and establish a living-biobank of NPCs to study the mechanism and explore the more effective treatment of the disease. Methods: Sixty-two fresh NPC tissue samples and 15 normal mucosa samples were collected for 3-dimensional (3D) organoid culture. The organoids were confirmed using hematoxylin and eosin assays. The expression levels of CD133, CD44, BMI-1, and Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were detected by immunohistochemistry (IHC) and in situ hybridization (ISH). Recurrent NPCOs were frozen in liquid nitrogen for 6 months and then resuscitated and passaged. Results: We identified a novel two-step enzymatic strategy for the treatment of NPC and nasal mucosa specimens and an optimal medium for culturing NPCOs and nasal mucosa organoids (NMOs). Organoid cultures were generated from 34 primary NPC samples, 28 recurrent NPC samples, and 15 normal mucosa samples. The success rates for primary NPCO, recurrent NPCO, and NMO formation were 47.06%, 81.25%, and 86.5%, respectively. All the NPCOs were EBER positive and CK7 negative. Recurrent NPCOs had higher expressions of stem cell markers, including BMI-1, CD44, and CD133. Additionally, recurrent NPCOs could be cultured to passage 4 and frozen and revived repeatedly, while primary NPCOs were challenging to culture. Conclusions: In summary, we successfully established a living biobank using the NPCO model, which has enormous potential in basic and clinical research on NPC.

Long non-coding RNA ANRIL promotes tumorgenesis through regulation of FGFR1 expression by sponging miR-125a-3p in head and neck squamous cell carcinoma.

ANRIL (CDKN2B antisense RNA 1, CDKN2B-AS1) is involved in the progression of various cancers. However, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, we found that ANRIL expression was upregulated in HNSCC and correlated with tumor progression. Further functional analysis showed that knockdown of ANRIL significantly inhibited proliferation in vivo and in vitro. ANRIL functioned as a ceRNA (competing endogenous RNAs) for miR-125a-3p and upregulated FGFR1 (fibroblast growth factor receptor-1), which could promote tumor growth. Moreover, we confirmed that ANRIL promoted HNSCC activity via FGFR1 with a FGFR1 inhibitor in vivo and in vitro. Thus, it could be concluded that ANRIL promoted the progression of HNSCC via miR-125a-3p/FGFR1/MAPK signaling, which might provide a new target for the diagnosis and treatment of HNSCC.

Downregulation of SAFB Sustains the NF-κB Pathway by Targeting TAK1 during the Progression of Colorectal Cancer.

Purpose: To investigate the role and the underlying mechanism of scaffold attachment factor B (SAFB) in the progression of colorectal cancer (CRC).Experimental Design: SAFB expression was analyzed in the Cancer Outlier Profile Analysis of Oncomine and in 175 paraffin-embedded archived CRC tissues. Gene Ontology analyses were performed to explore the mechanism of SAFB in CRC progression. Western blot, RT-PCR, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to detect the regulation of transforming growth factor-ß-activated kinase 1 (TAK1) and NF-κB signaling by SAFB The role of SAFB in invasion, metastasis, and angiogenesis was investigated using in vitro and in vivo assays. The relationship between SAFB and TAK1 was analyzed in CRC tissues.Results: SAFB was downregulated in CRC tissues, and low expression of SAFB was significantly associated with an aggressive phenotype and poorer survival of CRC patients. The downregulation of SAFB activated NF-κB signaling by targeting the TAK1 promoter. Ectopic expression of SAFB inhibited the development of aggressive features and metastasis of CRC cells both in vitro and in vivo The overexpression of TAK1 could rescue the aggressive features in SAFB-overexpressed cells. Furthermore, the expression of SAFB in CRC tissues was negatively correlated with the expression of TAK1- and NF-κB-related genes.Conclusions: Our results show that SAFB regulated the activity of NF-κB signaling in CRC by targeting TAK1 This novel mechanism provides a comprehensive understanding of both SAFB and the NF-κB signaling pathway in the progression of CRC and indicates that the SAFB-TAK1-NF-κB axis is a potential target for early therapeutic intervention in CRC progression. Clin Cancer Res; 23(22); 7108-18. ©2017 AACR.

[A study on transfection of green fluorescence protein gene into human adipose stromal cells in vitro].

OBJECTIVE: To make a comparison on the efficiency of two methods for transfecting Green Fluorescence Protein gene into human adipose tissue-derived stromal cells, and to study the biological properties and multipotential differentiation of gene-transfected cells. METHODS: The human subcutaneous adipose tissue was obtained, digested with one volume of collagenase type I, and then cultured with BGJb medium. After subculture and expansion, the human adipose tissue-derived stromal cells infected with Ad-GFP or liposome were observed and analyzed with fluorescence microscopy and flow cytometry to assess transfection efficiency. The growth curve of transfected adipose tissue-derived stromal cells was protracted. The adipose tissue-derived storomal cells were induced to differentiate into osteoblasts, and non-transfected cells were set as control. RESULTS: 42.5% +/- 1.5 of the human adipose tissue-derived stomal cells infected with Ad-GFP were found to express GFP at a level higher than that of the control of liposome (11.40%). Infected adipose tissue-derived stromal cells were noted to form mineralized nodes by the use of Alizarin Red stain. CONCLUSION: The human adipose tissue-derived stromal cells infected with Ad-GFP can express higher level of GFP, and can maintain the ability of proliferation and differentiation as the non-infected human adipose tissue-derived stromal cells do. The infected adipose tissue-derived stromal cells with Ad-GFP can track the change of adipose tissue-derived stromal cells in the study of multipotential differentiation and can serve as cellular vehicles for systemic gene delivery.

TLE3 represses colorectal cancer proliferation by inhibiting MAPK and AKT signaling pathways.

BACKGROUND: Transducin-like enhancer of Split3 (TLE3) serves as a transcriptional corepressor during cell differentiation and shows multiple roles in different kinds of cancers. Recently, TLE3 together with many other genes involved in Wnt/ß-catenin pathway were detected hyper-methylated in colorectal cancer (CRC). However, the potential role and the underlying mechanism of TLE3 in CRC progression remain scarce. METHODS: Gene expression profiles were analyzed in The Cancer Genome Atlas (TCGA) microarray dataset of 41 normal colorectal intestine tissues and 465 CRC tissues. Western blot and Real-time Quantitative PCR (RT-qPCR) were respectively performed to detect protein and mRNA expression in 8 pairs of CRC tissue and matched adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to evaluate TLE3 protein expression in 105 paraffin-embedded, archived human CRC tissues from patients, whose survival data were analyzed with Kaplan-Meier method. In vitro experiments including MTT assay, colony formation assay, and soft agar formation assay were used to investigate the effects of TLE3 on CRC cell growth and proliferation. Additionally, subcutaneous tumorigenesis assay was performed in nude mice to confirm the effects of TLE3 in vivo. Furthermore, gene set enrichment analysis (GSEA) was run to explore potential mechanism of TLE3 in CRC, and then we measured the distribution of CRC cell cycle phases and apoptosis by flow cytometry, as well as the impacts of TLE3 on MAPK and AKT signaling pathways by Western blot and RT-qPCR. RESULTS: TLE3 was significantly down-regulated in 465 CRC tissues compared with 41 normal tissues. Both protein and mRNA expressions of TLE3 were down-regulated in CRC compared with matched adjacent normal mucosa. Lower expression of TLE3 was significantly associated with poorer survival of patients with CRC. Besides, knock down of TLE3 promoted CRC cell growth and proliferation, while overexpression of TLE3 showed suppressive effects. Furthermore, overexpression of TLE3 caused G1-S phase transition arrest, inhibition of MAPK and AKT pathways, and up-regulation of p21Cip1/WAF1 and p27Kip1. CONCLUSION: This study indicated that TLE3 repressed CRC proliferation partly through inhibition of MAPK and AKT signaling pathways, suggesting the possibility of TLE3 as a biomarker for CRC prognosis.

Types of Renal Calculi and Management Regimen for Chinese Minimally Invasive Percutaneous Nephrolithotomy.

Strict selection of patients for minimally invasive percutaneous nephrolithotomy could effectively improve the success rate of surgery. This study aimed to understand the required skills and the efficacy of mini-PCNL in the treatment of five types of upper ureteral calculi. Data collected after X-ray analysis and B mode ultrasound from 633 patients with upper ureteral and renal pelvis calculi who underwent B ultrasound-guided lithotomy was reviewed, including the following: type I, upper ureteral or renal pelvis calculi with moderate hydronephrosis (154 cases); type II, upper ureteral or renal pelvis calculi with severe hydronephrosis (157 cases); type III, upper ureteral or renal pelvis calculi without hydronephrosis (61 cases); type IV, renal pelvis calculi, one or two renal calyx calculi (206 cases); and type V, renal staghorn calculi (55 cases). Operations on 611 cases were successful. The treatment method for five patients was converted to open surgery. Twelve cases were treated by indwelling double-J tube retro-catheterization and extracorporeal shock wave lithotripsy. Five patients gave up the treatment. The rate of calculus clearance was 82.3 %, and the rate of residual calculus was 17.6 %. Selective renal artery embolization was performed in nine cases. Hydropneumothorax occurred in nine cases. No intestinal fistula occurred, and no patient had to undergo nephrectomy. The difficulty and the curative effect of the operation were different because the types of calculi varied. Selection of the procedure based on the different types of calculi could effectively improve the success rate of the procedure, reduce complications, and shorten the learning curve.

Erratum to: Types of Renal Calculi and Management Regimen for Chinese Minimally Invasive Percutaneous Nephrolithotomy.

[This corrects the article DOI: 10.1007/s12262-014-1043-4.].

[Modified cystectomy with preservation of erectile and ejaculatory functions in men with nonmalignant bladder disease].

OBJECTIVES: To evaluate modified cystectomy with preservation of erectile and ejaculatory functions in men with nonmalignant bladder disease. METHODS: Seven cases with average age of 27 years presented with bladder disease necessitating cystectomy, including 2 cases of tuberculous contractile bladder, 1 case of extensive polypoid cystitis glandularis, 4 cases of late stage of neurogenic bladder. All patients wished to maintain erectile and ejaculatory functions after the operation. We performed a modified simple cystectomy with preservation of the vasa deferens, seminal vesicles, prostate and neurovascular bundles, as well as construction of an Indiana pouch or ileal neobladder. RESULTS: Average operative time was 5 h 45 min without perioperative complications in this group. Follow-up ranged from 9 to 60 months. Erectile and ejaculatory functions were normal in all cases. All patients remained completely continent and no dysuria in neobladder, and there was no difficulty in inserting catheter to empty pouch. Upper urinary tract was in good condition 3 and 24 months after operation. CONCLUSIONS: Modified cystectomy with preservation of the vasa deferens, seminal vesicles, prostate and neurovascular bundles is an effective and reliable option for the patients who wish to maintain their fertility and erectile function after surgery.

Clinical effectiveness of the PolyScope™ endoscope system combined with holmium laser lithotripsy in the treatment of upper urinary calculi with a diameter of less than 2 cm.

The aim of this study was to evaluate the clinical value of the PolyScope™ endoscope system in the treatment of upper urinary calculi with a diameter of <2 cm. A total of 86 patients hospitalized with upper urinary tract calculi were included. The patients were placed under general or spinal anesthesia and in a lithotomy position. Following the dilation of the ureter, a guide wire was inserted under the direct vision of an F8/9.8 rigid ureteroscope, and an F12/14 flexible ureteral access sheath was positioned along the guide wire. Holmium laser lithotripsy was subsequently performed, using an F8.0 'PolyScope' modular flexible ureteroscope. Plain film of the kidney-ureter-bladder (KUB) was performed 1 day subsequent to the surgery, in order to determine the result of the lithotripsy and the position of the double-J stent which was inserted after after holmium laser lithotripsy. In addition, in certain patients, KUB radiography was performed 2-4 weeks subsequent to the surgery, and extracorporeal shockwave lithotripsy (ESWL) was performed if the diameter of the residual stones was >6 mm. Lithotripsy was successful in 77 patients and the duration of the surgery ranged between 25 and 80 min (mean duration, 42 min). Little bleeding was observed. Three patients presented with a slight fever following the surgery; however, no ureteral perforation, high fever or septicemia was observed among the patients following anti-inflammatory treatment. The stone-free rate (SFR) of the single-pass lithotripsy was 89.5% (77/86) and the SFR with ESWL was 96.5% (83/86). The study demonstrated that the F8 modular flexible ureteroscope was safe, convenient and effective for the lithotripsy of upper-tract calculi.