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Background: Omitting axillary lymph node dissection (ALND) is recommended for early-stage breast cancer patients with 1-2 sentinel lymph nodes (SLNs) macro-metastases and breast-conserving therapy. However, it is not safe for part of patients, so it is significant to find risk factors and develop a predictive model of non-SLNs metastases in breast cancer patients with 1-2 SLNs macro-metastases and breast-conserving therapy., Methods: This retrospective study enrolled 228 breast cancer patients with 1-2 SLNs macro-metastases who underwent ALND and breast-conserving surgery between Jan 2012 and Dec 2017 at Cancer Hospital Chinese Academy of Medical Sciences. Chi-square test and backward stepwise binary logistic regression were used to find factors that influenced non-SLN metastases, then a predictive model was formulated and obtained its area under the curve., Results: Tumor pathologic invasion size, number of positive SLNs and ALN status on imaging was associated with non-SLNs metastases. The predictive model was also formulated based on these three factors to assess and the area under the curve of model was 0.708., Conclusion: We developed a predictive model to assess the high-risk cohort of patients of non-SLNs metastases which can be an auxiliary tool for doctors., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright© Iranian Public Health Association & Tehran University of Medical Sciences.)

Rich chemistry and surface functionalization provide MXenes enhanced electrochemical activity yet severely exacerbate their self-discharge behavior in supercapacitors. However, this self-discharge behavior and its related mechanism are still remaining issues. Herein, we propose a chemically interface-tailored regulation strategy to successfully unravel and efficiently alleviate the self-discharge behavior of Ti 3 C 2 T x MXene-based supercapacitors. As a result, Ti 3 C 2 T x MXenes with fewer F elements (∼0.65 atom %) show a positive self-discharge rate decline of ∼20% in comparison with MXenes with higher F elements (∼8.09 atom %). Such decline of the F elements can highly increase tight-bonding ions corresponding to an individual self-discharge process, naturally resulting in a dramatic 50% increase of the transition potential ( V T ). Therefore, the mixed self-discharge rate from both tight-bonding (contain fewer F elements) and loose-bonding ions (contain more F elements) is accordingly lowered. Through chemically interface-tailored engineering, the significantly changed average oxidation state and local coordination information on MXene affected the interaction of ion counterparts, which was evidently revealed by X-ray absorption fine structures. Theoretically, this greatly improved self-discharge performance was proven to be from higher adsorption energy between the interface of the electrode and the electrolyte by density functional theory. Therefore, this chemically interface-tailored regulation strategy can guide the design of high-performance MXene-based supercapacitors with low self-discharge behavior and will promote its wider commercial applications.

Background and Objective: Parathyroid carcinoma (PC) is a rare malignant neoplasm with a relatively poor prognosis. The loss of parafibromin expression or the presence of CDC73 mutation has been found to be remarkably associated with malignancy in parathyroid tumours. However, the prognostic role of them in PC has not yet been shown due to sampling limitations. We conducted a systematic review and meta-analysis based on individual patient data to clarify the performance of parafibromin immunohistochemical staining and CDC73 gene sequencing in predicting outcomes for patients PC., Methods: Published studies from PubMed/MEDLINE, EMBASE, Cochrane and Scopus Databases were searched using the terms 'parafibromin', 'CDC73', 'HRPT2' and 'parathyroid' to identify eligible studies. From the included studies, the survival data of patients with PC were extracted, and a Cox proportional hazards model was used to assess hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS)., Results: A total of 193 patients from 9 studies were included in this survival analysis. Negative immunohistochemical staining of parafibromin was shown to be a risk factor for recurrence/metastasis (HR 2.73, P = .002) and death (HR 2.54, P = .004). Patient age ≥ 50 years was significantly related to lower OS (HR 2.37, P = .004) but not to DFS. CDC73 mutation was not statistically related to DFS or OS., Conclusions: Negative parafibromin staining indicated a higher risk of recurrence/metastasis and mortality. The immunohistochemical staining of parafibromin seems to be more promising in predicting outcomes for patients with PC than the sequencing of CDC73., (© 2020 John Wiley & Sons Ltd.)

Solid-state composite polymer electrolytes (CPEs) usually suffer from intrinsic low ionic conductivity and a solid-solid interface, badly inhibiting their widespread commercial application in all-solid-state Li-metal battery (ASSLMB) energy storage. Herein, a synergetic strategy using strong Lewis acid-base and weak hydrogen bonds was employed for self-assembly in situ construction of three-dimensional (3D) network-structured poly(ethylene oxide) (PEO) and SiO 2 CPEs (PEO@SiO 2 ). Ascribed to this synergistically rigid-flexible coupling dynamic strategy, a harmonious incorporation of monodispersed SiO 2 nanoparticles into PEO could remarkably reduce crystallinity of PEO, significantly enhancing the ionic conductivity (∼1.1 × 10 -4 S cm -1 at 30 °C) and dramatically facilitating solid electrolyte interface stabilization (electrochemical stability window > 4.8 V at 90 °C). Moreover, the PEO@SiO 2 -based ASSLMBs possess excellent rate capability over a wide temperature range (∼105 mA h g -1 under 2 C at 90 °C), high temperature cycling capacity (retaining 90 mA h g -1 after 100 cycles at 90 °C), and high specific capacity (146 mA h g -1 under 0.3 C at 90 °C). Unambiguously, these high ionic conductivity CPEs along with excellent flexibility and safety can be one of the most promising candidates for high-performance ASSLMBs, evidently revealing that this synergistically rigid-flexible coupling dynamic strategy will open up a way to exploit the novel high ionic conductivity solid-state electrolytes.

Objective: To estimate the long-term effect of the changing demography in China on blood supply and demand., Methods: We developed a predictive model to estimate blood supply and demand during 2017-2036 in mainland China and in 31 province-level regions. Model parameters were obtained from World Population Prospects, China statistical yearbook 2016 , China's report on blood safety and records from a large tertiary hospital. Our main assumptions were stable age-specific per capita blood supply and demand over time., Findings: We estimated that the change in demographic structure between 2016 (baseline year) and 2036 would result in a 16.0% decrease in blood supply (from 43.2 million units of 200 mL to 36.3 million units) and a 33.1% increase in demand (from 43.2 million units to 57.5 million units). In 2036, there would be an estimated shortage of 21.2 million units. An annual increase in supply between 0.9% and 1.8% is required to maintain a balance in blood supply and demand. This increase is not enough for every region as regional differences will increase, e.g. a blood demand/supply ratio ≥ 1.45 by 2036 is predicted in regions with large populations older than 65 years. Sensitivity analyses showed that increasing donations by 4.0% annually by people aged 18-34 years or decreasing the overall blood discard rate from 5.0% to 2.0% would not offset but help reduce the blood shortage., Conclusion: Multidimensional strategies and tailored, coordinated actions are needed to deal with growing pressures on blood services because of China's ageing population., ((c) 2020 The authors; licensee World Health Organization.)

Rational and Objectives: To compare thin-section computed tomography (CT) features of pulmonary cryptococcosis (PC) in immunocompetent and non-AIDS immunocompromised patients., Materials and Methods: We retrospectively reviewed CT findings of 18 immunocompetent and 24 non-AIDS immunocompromised patients with clinically proven PC. Different patterns of pulmonary abnormalities between the two groups of patients were compared by Fisher's exact test., Results: Pulmonary nodules were present in 37 of the 42 patients. Masses were detected in 16 patients and consolidation in 9. There were 12 patients with a solitary nodule or mass. Masses were associated with nodules in 12 patients. Consolidation was associated with nodules/masses in nine patients. The nodules/masses were associated with cavitations in 13 patients. Margination of nodules/masses was well defined in nine patients and ill-defined in 33. The abnormalities were predominantly distributed in the peripheral region of the lung (n = 29, 69.0%). The presence of cavitations in nodules/masses was significantly more frequent in non-AIDS immunocompromised than in immunocompetent patients (P = 0.001)., Conclusions: The most common thin-section CT feature of PC was pulmonary nodules/masses, which were ill-defined and located peripherally. Cavitations within nodules/masses were more commonly found in non-AIDS immunocompromised patients. PC should be considered in the differential diagnosis of pulmonary nodules/masses.

Developmentally regulated programmed cell death (PCD) is one of the key cellular events for precise controlling of neuronal population during postembryonic development of the central nervous system. Previously we have shown that a group of corazonin-producing peptidergic neurons (vCrz) undergo apoptosis in response to ecdysone signaling via ecdysone receptor (EcR)-B isoforms and Ultraspiracle during early phase of metamorphosis. Further utilizing genetic, transgenic, and mosaic analyses, we have found that TGF-β signaling mediated by a glia-produced ligand, Myoglianin, type-I receptor Baboon (particularly Babo-A isoform) and dSmad2, is also required autonomously for PCD of the vCrz neurons. Our studies show that TGF-β signaling is not acting epistatically to EcR or vice versa. We also show that ectopic expression of a constitutively active phosphomimetic form of dSmad2 (dSmad2 PM ) is capable of inducing premature death of vCrz neurons in larva but not other larval neurons. Intriguingly, the dSmad2 PM -mediated killing is completely suppressed by coexpression of a dominant-negative form of EcR (EcR DN ), suggesting that EcR function is required for the proapoptotic dSmad2 PM function. Based on these data, we suggest that TGF-β and ecdysone signaling pathways act cooperatively to induce vCrz neuronal PCD. We propose that this type of two-factor authentication is a key developmental strategy to ensure the timely PCD of specific larval neurons during metamorphosis.

Background and Objectives: A health industry standard recommending restrictive transfusion is to be in effect in China in April 2019. We aim to explore its potential economic and clinical impacts among surgical patients., Materials and Methods: A decision tree model was applied to compare cost-effectiveness of current routine transfusion in China, a restrictive (transfusion at Hb < 8 g/dl or ischaemic symptoms) and a liberal (transfusion at Hb < 10 g/dl) strategy. Parameters were estimated from empirical data of 25 227 surgical inpatients aged ≥30 years in a multicenter study and supplemented by meta-analysis when necessary. Results are shown for cardio-cerebral-vascular (CCV) surgery and non-CCV (orthopaedics, general, thoracic) surgery separately., Results: Per 10 000 patients in routine, restrictive, liberal transfusion scenarios, total spending (transfusion and length of stay related) was 7·67, 7·58 and 9·39 million CNY (1 CNY × 0.157 = 1 US dollar) for CCV surgery and 6·35, 6·70 and 8·09 million CNY for non-CCV surgery; infectious and severe complications numbered 354, 290, and 290 (CCV) and 315, 286, and 330 (non-CCV), respectively. Acceptability curves showed high probabilities for restrictive strategy to be cost-effective across a wide range of willingness-to-pay values. Such findings were mostly consistent in sensitivity and subgroup analyses except for patients with cardiac problems., Conclusion: We showed strong rationale, succeeding previous findings only in cardiac or joint procedures, to comply with the new standard as restrictive transfusion has high potential to save blood, secure safety, and is cost-effective for a wide spectrum of surgical patients. Experiences should be further summarized to pave the way towards individualized transfusion., (© 2019 International Society of Blood Transfusion.)

The development of a thermally activated delayed fluorescence (TADF) exciplex with high energy is of great significance in achieving highly efficient blue, green, and red organic light-emitting diodes (OLEDs) for use in full-color displays and white lighting. Highly efficient and stable blue and green phosphorescent OLEDs were demonstrated by employing a TADF exciplex (energy: 2.9 eV) based on 4-substituted aza-9,9'-spirobifluorenes (aza-SBFs). Blue PhOLEDs demonstrated a maximum current efficiency (CE) of 47.9 cd A -1 and an external quantum efficiency (EQE) of 22.5% at 1300 cd m -2 (2.5 times the values of aza-SBF-based systems), with the best blue PhOLED demonstrating a CE, power efficiency (PE) and EQE of 60.3 cd A -1 , 52.7 lm W -1 , and 26.2%, respectively. Green PhOLEDs exhibited a CE of 78.1 cd A -1 and EQE of 22.5% at 9360 cd m -2 , with the best green PhOLED exhibiting a maximum CE, PE, and EQE of 87.4 cd A -1 , 101.6 lm W -1 , and 24.5%, respectively. The device operational lifetime was improved over 17-fold compared to reference devices because of the high thermal stability of the materials and full utilization of the TADF exciplex energy, indicating their potential for application in commercial OLEDs., Competing Interests: There are no conflicts to declare, (This journal is © The Royal Society of Chemistry.)

Highly microporous carbon material with nitrogen doping has been synthesized via a facile one-step approach by employing natural biowaste miscellaneous wood fibers derived hydrochar as precursor and melamine as nitrogen source respectively. The added melamine not only results in the incorporation of some nitrogen into the carbon framework but also increases the specific surface area of carbon material. Such resultant N-doped microporous carbon possesses the functionalized nitrogen doping (1.75 at. %), a large specific surface area (∼1807 m 2  g -1 ) and abundant highly interconnected micropores. Benefiting from the synergistic effect of high specific surface area, well-developed pore size distribution and functionalized groups, this carbon material delivers a high specific capacitance of 345 F g -1 at 0.5 A g -1 , an excellent capacitance retention with 270 F g -1 at up to 30 A g -1 , and a remarkable cycle ability with 91.3% retention after 10,000 cycles at 5.0 A g -1 . Based on it, the as-developed flexible symmetric solid-state supercapacitor delivers a high energy density of 7.92 W h kg -1 at the power density of 250 W kg -1 . Evidently, this work provides a facile and cost-effective route for functionalized natural biowaste-based carbon materials and further opens up a way for highly value-added recycling of biowaste-like materials., (Copyright © 2019. Published by Elsevier Inc.)

Surgery is still far from being completely safe and reliable. Surgical safety has, therefore, been the focus of considerable attention over the last few decades, and there are a growing number of national drives to improve it. There are also a number of large surgical complication reporting systems and system-based interventions, both of which have made remarkable progress in the past two decades. These systems, however, have either mainly focused on reporting complications and played a limited role in guiding practice or have provided nonselective interventions to all patients, perhaps imposing unnecessary burdens on frontline medical staff. We have, therefore, developed an evidence-based stratified surgical safety information system based on a multicenter surgical safety improvement program. This study discusses some critical issues in the process of developing this information system, including (1) decisions about data gathering, (2) establishing and sharing knowledge, (3) developing functions for the system, (4) system implementation, and (5) evaluation and continuous improvement. Using examples drawn from the surgical safety improvement program, we have shown how this type of system can be fitted into day-to-day clinical practice and how it can guide medical practice by incorporating inherent patient-related risk and providing tailored interventions for patients with different levels of risk. We concluded that multidisciplinary collaboration, involving experts in health care (including senior staff in surgery, nursing, and anesthesia), data science, health care management, and health information technology, can help build an evidence-based stratified surgical patient safety improvement system. This can provide an information-intensified surgical safety learning platform and, therefore, benefit surgical patients by delivering tailored interventions and an integrated workflow., (©Xiaochu Yu, Wei Han, Jingmei Jiang, Yipeng Wang, Shijie Xin, Shizheng Wu, Hong Sun, Zixing Wang, Yupei Zhao. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.06.2019.)

Objectives: To develop a risk-stratified intervention strategy and evaluate its effect on reducing surgical complications., Design: A multicentre prospective study with preintervention and postintervention stages: period I (January to June 2015) to develop the intervention strategy and period II (January to June 2016) to evaluate its effectiveness., Setting: Four academic/teaching hospitals representing major Chinese administrative and economic regions., Participants: All surgical (elective and emergent) inpatients aged ≥14 years with a minimum hospital stay of 24 hours, who underwent a surgical procedure requiring an anesthesiologist., Interventions: Targeted complications were grouped into three categories (common, specific, serious) according to their incidence pattern, severity and preventability. The corresponding expert consensus-generated interventions, which focused on both regulating medical practices and managing inherent patient-related risks, were implemented in a patient-tailored way via an electronic checklist system., Primary and Secondary Outcomes: Primary outcomes were (1) in-hospital death/confirmed death within 30 days after discharge and (2) complications during hospitalisation. Secondary outcome was length of stay (LOS)., Results: We included 51 030 patients in this analysis (eligibility rate 87.7%): 23 413 during period I, 27 617 during period II. Patients' characteristics were comparable during the two periods. After adjustment, the mean number of overall complications per 100 patients decreased from 8.84 to 7.56 (relative change 14.5%; P<0.0001). Specifically, complication rates decreased from 3.96 to 3.65 (7.8%) for common complications (P=0.0677), from 0.50 to 0.36 (28.0%) for specific complications (P=0.0153) and from 3.64 to 2.88 (20.9%) for serious complications (P<0.0001). From period I to period II, there was a decreasing trend for mortality (from 0.64 to 0.53; P=0.1031) and median LOS (by 1 day; P=0.8293), without statistical significance., Conclusions: Implementing a risk-stratified intervention strategy may be a target-sensitive, convenient means to improve surgical outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Profiling of both the genome and the transcriptome promises a comprehensive, functional readout of a tissue sample, yet analytical approaches are required to translate the increased data dimensionality, heterogeneity and complexity into patient benefits. We developed a statistical approach called Texomer ( https://github.com/KChen-lab/Texomer ) that performs allele-specific, tumor-deconvoluted transcriptome-exome integration of autologous bulk whole-exome and transcriptome sequencing data. Texomer results in substantially improved accuracy in sample categorization and functional variant prioritization.

Background: Extrahepatic cholangiocarcinoma (ECC) has become one of the most rapidly increasing malignancies in China during recent decades. The relationship between tobacco exposure and ECC epidemics is unclear; this study aimed to explore this relationship., Methods: We included 55,806 participants aged 30 years or older from the National Mortality and Smoking Survey of China. Smoking in participants and spouses was defined as 1 cigarette or more per day for up to 1 year. Spouses' smoking was taken as a measure of exposure to passive smoking. Smoking information in 1980 was ascertained and outcomes were defined as ECC mortality during 1986-1988., Results: We found that either passive or active smoking increased the risk of death from ECC by 20% (risk ratio [RR], 1.20; 95% confidence interval [CI], 0.99-1.47), compared with no exposure to any tobacco. This risk was a notable 98% (RR, 1.98; 95% CI, 1.49-2.64) for individuals exposed to passive plus active smoking. These findings were highly consistent among men and women. Pathology-based analyses showed dose-response relationships of ECC with pack-years for all types of smoking exposure (Ps for trend < 0.05); the RR reached 2.75 (95% CI, 1.20-6.30) in individuals exposed to combined smoking with the highest exposure dose. The findings were similar for non-pathology-based analysis., Conclusions: This study indicates that tobacco exposure increases ECC risk. Given the dramatic increase of exposure to secondhand smoke and patients with ECC, an inadequate provision of smoke-free environments could be contributing to ECC epidemics and could further challenge public health and medical services, based on the current disease spectrum.

Metal-semiconductor contact has been a critical topic in the semiconductor industry because it influences device performance remarkably. Conventional metals have served as the major contact material in electronic and optoelectronic devices, but such a selection becomes increasingly inadequate for emerging novel materials such as two-dimensional (2D) materials. Deposited metals on semiconducting 2D channels usually form large resistance contacts due to the high Schottky barrier. A few approaches have been reported to reduce the contact resistance but they are not suitable for large-scale application or they cannot create a clean and sharp interface. In this study, a chemical vapor deposition (CVD) technique is introduced to produce large-area semiconducting 2D material (2H MoTe 2 ) planarly contacted by its metallic phase (1T' MoTe 2 ). We demonstrate the phase-controllable synthesis and systematic characterization of large-area MoTe 2 films, including pure 2H phase or 1T' phase, and 2H/1T' in-plane heterostructure. Theoretical simulation shows a lower Schottky barrier in 2H/1T' junction than in Ti/2H contact, which is confirmed by electrical measurement. This one-step CVD method to synthesize large-area, seamless-bonding 2D lateral metal-semiconductor junction can improve the performance of 2D electronic and optoelectronic devices, paving the way for large-scale 2D integrated circuits.

In Drosophila melanogaster a significant number of heterogenous larval neurons in the central nervous system undergo metamorphosis-associated programmed cell death, termed metamorphoptosis. Interestingly distinct groups of doomed larval neurons are eliminated at different metamorphic phases. Although ecdysone hormonal signaling via nuclear ecdysone receptors (EcRs) is known to orchestrate the neuronal metamorphoptosis, little is known about how this signaling controls such diverse neuronal responses. Crustacean cardioactive peptide (CCAP)-producing neurons in the ventral nerve cord are developmentally programmed to die shortly after adult emergence. In this study, we show that disruption of endogenous EcR function by ectopic expression of dominant negative forms of EcRs (EcR DN ) causes premature death of larval CCAP neurons in a caspase-dependent manner. This event is rescued by co-expression of individual EcR isoforms. Furthermore, larval CCAP neurons are largely normal in ecr mutants lacking either EcR-A or EcR-B isoforms, suggesting that EcR isoforms redundantly function to protect larval CCAP neurons. Of surprise, a role of Ultraspiracle (Usp), a canonical partner of EcR, is dispensable in the protection of CCAP neurons, whereas both EcR and Usp are required for inducing metamorphoptosis of vCrz neurons shortly after prepupal formation. As a downstream, grim is an essential cell death gene for the EcR DN -mediated CCAP neuronal death, while either hid or rpr function is dispensable. Together, our results suggest that Usp-independent EcR actions protect CCAP neurons from their premature death by repressing grim expression until their normally scheduled apoptosis at post-emergence. Our studies highlight two opposite roles played by EcR function for metamorphoptosis of two different peptidergic neuronal groups, proapoptotic (vCrz) versus antiapoptotic (CCAP), and propose that distinct death timings of doomed larval neurons are determined by differential signaling mechanisms involving EcR.

Carbon doping can induce unique and interesting physical properties in hexagonal boron nitride (h-BN). Typically, isolated carbon atoms are doped into h-BN. Herein, however, the insertion of nanometer-scale graphene quantum dots (GQDs) is demonstrated as whole units into h-BN sheets to form h-CBN. The h-CBN is prepared by using GQDs as seed nucleations for the epitaxial growth of h-BN along the edges of GQDs without the assistance of metal catalysts. The resulting h-CBN sheets possess a uniform distrubution of GQDs in plane and a high porosity macroscopically. The h-CBN tends to form in small triangular sheets which suggests an enhanced crystallinity compared to the h-BN synthesized under the same conditions without GQDs. An enhanced ferromagnetism in the h-CBN emerges due to the spin polarization and charge asymmetry resulting from the high density of CN and CB bonds at the boundary between the GQDs and the h-BN domains. The saturation magnetic moment of h-CBN reaches 0.033 emu g -1 at 300 K, which is three times that of as-prepared single carbon-doped h-BN., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sensing devices with wearability would open the door to many advanced applications including soft robotics, artificial intelligence, and healthcare monitoring. Here, inspired by the configuration of the human epidermis, we present a flexible three-dimensional (3D) cellular sensor array (CSA) via a one-step thermally induced phase separation method. The CSA was framed by the 3D cellular electret with caged piezoelectric nanoparticles, which was ultrathin (80 μm), lightweight, and highly robust. For biomedical sensing, the 3D-CSA holds a decent pressure sensitivity up to 0.19 V kPa -1 with a response time of less than 16 ms. Owing to its rigid structural symmetry, the 3D-CSA could be identically operated from its both sides. It was demonstrated to successfully measure the human heartbeat, detect the eyeball motion for sleeping monitoring, and tactile imaging. Mimicking the functionalities of the human skin with a self-powered operation feature, the 3D-CSA was expected to represent a substantial advancement in wearable electronics for healthcare.

Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels. In examining 3,080 tumor samples from 8 cancer types in The Cancer Genome Atlas, rDriver predicted 1,389 driver mutations. Compared with existing tools, rDriver identified more low frequency mutations associated with lineage specific functional properties, timing of occurrence and patient survival. Evaluation of rDriver predictions using engineered cell-line models resulted in a positive predictive value of 0.94 in PIK3CA genes. Our study highlights the importance of integrating multi-omic data in predicting cancer driver mutations and provides a statistically rigorous solution for cancer target discovery and development.

The functional impact of the vast majority of cancer somatic mutations remains unknown, representing a critical knowledge gap for implementing precision oncology. Here, we report the development of a moderate-throughput functional genomic platform consisting of efficient mutant generation, sensitive viability assays using two growth factor-dependent cell models, and functional proteomic profiling of signaling effects for select aberrations. We apply the platform to annotate >1,000 genomic aberrations, including gene amplifications, point mutations, indels, and gene fusions, potentially doubling the number of driver mutations characterized in clinically actionable genes. Further, the platform is sufficiently sensitive to identify weak drivers. Our data are accessible through a user-friendly, public data portal. Our study will facilitate biomarker discovery, prediction algorithm improvement, and drug development., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity. Experimental Design: We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of nonsarcomatoid RCC (RCC). We evaluated whole-exome sequencing, single-nucleotide polymorphism, and RNA sequencing data from patients with SRCC ( n = 65) and RCC ( n = 598) across different parent RCC subtypes, including clear-cell RCC, papillary RCC, and chromophobe RCC subtypes. Results: SRCC was molecularly discrete from RCC and clustered according to its parent RCC subtype, though with upregulation of TGFβ signaling across all subtypes. The epithelioid (E-) and spindled (S-) histologic components of SRCC did not show differences in mutational load among cancer-related genes despite a higher mutational burden in S-. Notably, sarcomatoid clear-cell RCC (SccRCC) showed significantly fewer deletions at 3p21-25, a lower rate of two-hit loss for VHL and PBRM1 , and more mutations in PTEN , TP53 , and RELN compared with ccRCC. A two-hit loss involving VHL predicted for ccRCC and a better prognosis, whereas mutations in PTEN , TP53 , or RELN predicted for SccRCC and worse prognosis. Conclusions: SRCC segregates by parent subtype, and SccRCC has a fundamentally different early molecular pathogenesis, usually lacking the classic 3p21-25 deletion and showing distinctive mutational and transcriptional profiles. These features prompt a more precise molecular classification of RCC, with diagnostic, prognostic, and therapeutic implications. Clin Cancer Res; 23(21); 6686-96. ©2017 AACR See related commentary by Bergerot et al., p. 6381 ., (©2017 American Association for Cancer Research.)

Ultrathin ceramic coatings are of high interest as protective coatings from aviation to biomedical applications. Here, a generic approach of making scalable ultrathin transition metal-carbide/boride/nitride using immiscibility of two metals is demonstrated. Ultrathin tantalum carbide, nitride, and boride are grown using chemical vapor deposition by heating a tantalum-copper bilayer with corresponding precursor (C 2 H 2 , B powder, and NH 3 ). The ultrathin crystals are found on the copper surface (opposite of the metal-metal junction). A detailed microscopy analysis followed by density functional theory based calculation demonstrates the migration mechanism, where Ta atoms prefer to stay in clusters in the Cu matrix. These ultrathin materials have good interface attachment with Cu, improving the scratch resistance and oxidation resistance of Cu. This metal-metal immiscibility system can be extended to other metals to synthesize metal carbide, boride, and nitride coatings., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Mortality outcomes in trials of low-dose computed tomography (CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung cancer mortality and to investigate the factors that associate with the screening effect., Methods: A decision tree model with three scenarios (low-dose CT screening, chest X-ray screening, and no screening) was developed to compare screening results in a simulated Chinese urban cohort (100,000 smokers aged 45-80 years). Data of participant characteristics were obtained from national registries and epidemiological surveys for estimating lung cancer prevalence. The selection of other tree variables such as sensitivities and specificities of low-dose CT and chest X-ray screening were based on literature research. Differences in lung cancer mortality (primary outcome), false diagnoses, and deaths due to false diagnosis were calculated. Sensitivity analyses were performed to identify the factors that associate with the screening results and to ascertain worst and optimal screening effects considering possible ranges of the variables., Results: Among the 100,000 subjects, there were 448, 541, and 591 lung cancer deaths in the low-dose CT, chest X-ray, and no screening scenarios, respectively (17.2% reduction in low-dose CT screening over chest X-ray screening and 24.2% over no screening). The costs of the two screening scenarios were 9387 and 2497 false diagnoses and 7 and 2 deaths due to false diagnosis among the 100,000 persons, respectively. The factors that most influenced death reduction with low-dose CT screening over no screening were lung cancer prevalence in the screened cohort, low-dose CT sensitivity, and proportion of early-stage cancers among low-dose CT detected lung cancers. Considering all possibilities, reduction in deaths (relative numbers) with low-dose CT screening in the worst and optimal cases were 16 (5.4%) and 288 (40.2%) over no screening, respectively., Conclusions: In terms of mortality outcomes, our findings favor conducting low-dose CT screening in urban China. However, approaches to reducing false diagnoses and optimizing important screening conditions such as enrollment criteria for screening are highly needed.

The application of exciplex energy has become a unique way to achieve organic light-emitting diodes (OLEDs) with high efficiencies, low turn-on voltage, and low roll-off. Novel δ-carboline derivatives with high triplet energy (T 1 ≈ 2.92 eV) and high glass transition temperature (T g ≈ 153 °C) were employed to manipulate exciplex emissions in this paper. Deep blue (peak at 436 nm) and pure blue (peak at 468 nm) thermally activated delayed fluorescence (TADF) of exciplex OLEDs were demonstrated by utilizing them as emitters with the maximum current efficiency (CE) of 4.64 cd A -1 , power efficiency (PE) of 2.91 lm W -1 , and external quantum efficiency (EQE) of 2.36%. Highly efficient blue phosphorescent OLEDs doped with FIrpic showed a maximum CE of 55.6 cd A -1 , PE of 52.9 lm W -1 , and EQE of 24.6% respectively with very low turn on voltage at 2.7 V. The devices still remain high CE of 46.5 cd A -1 at 100 cd m -2 , 45.4 cd A -1 at 1000 cd m -2 and 42.3 cd A -1 at 5000 cd m -2 with EQE close to 20% indicating low roll-off. Manipulating blue exciplex emissions by chemical structure gives an ideal strategy to fully utilize all exciton energies for lighting of OLEDs.

Introduction: Surgical safety has emerged as a crucial global health issue in the past two decades. Although several safety-enhancing tools are available, the pace of large-scale improvement remains slow, especially in developing countries such as China. The present project (Modern Surgery and Anesthesia Safety Management System Construction and Promotion) aims to develop and validate system-based integrated approaches for reducing perioperative deaths and complications using a multicentre, multistage design., Methods and Analysis: The project involves collection of clinical and outcome information for 1 20 000 surgical inpatients at four regionally representative academic/teaching general hospitals in China during three sequential stages: preparation and development, effectiveness validation and improvement of implementation for promotion. These big data will provide the evidence base for the formulation, validation and improvement processes of a system-based stratified safety intervention package covering the entire surgical pathway. Attention will be directed to managing inherent patient risks and regulating medical safety behaviour. Information technology will facilitate data collection and intervention implementation, provide supervision mechanisms and guarantee transfer of key patient safety messages between departments and personnel. Changes in rates of deaths, surgical complications during hospitalisation, length of stay, system adoption and implementation rates will be analysed to evaluate effectiveness and efficiency., Ethics and Dissemination: This study was approved by the institutional review boards of Peking Union Medical College Hospital, First Hospital of China Medical University, Qinghai Provincial People's Hospital, Xiangya Hospital Central South University and the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. Study findings will be disseminated via peer-reviewed journals, conference presentations and patent papers., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To explore the effect of interaction between ACE genotype and salt intake on hypertension among Chinese Kazakhs, and to compare applications of interactions between logistic model and generalised partially linear tree-based regression (GPLTR) model., Design: Population-based cross-sectional study., Setting: Hong Dun, North Xinjiang, China., Participants: Non-consanguineous Chinese Kazakh participants (n=916, 342 men and 574 women) aged ≥30 years., Main Outcome Measures: Association between ACE genotype and hypertension, association between salt intake and hypertension, and interaction of ACE genotype and salt intake on hypertension in two models., Results: Associations between salt intake and hypertension were different in ACE genotype of II and ID+DD. Under the logistic models, main and interaction effects were not observed for men, but effects were present in opposite directions for women (main effect of ACE: OR=0.20, p=0.003; interaction effect: OR=1.07, p=0.027). Under the GPLTR model, Bayesian information criterion trees included both salt intake and ACE genotype as split variables. Individuals with a salt intake ≥19.5 g/day and ID+DD genotypes had a 3.99-fold (p=0.004) higher risk of hypertension compared with the II genotype for men, whereas salt intake <20.1 g/day and ID+DD genotypes had an OR=0.55 (p=0.014) compared with the II genotype for women., Conclusions: An interaction of ACE genotype and salt intake on hypertension was observed among Chinese Kazakhs but in different ways according to sex. The GPLTR model appears to be more suitable for an exploration of interactions in complex diseases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Mice and rats are the most commonly used animals for preclinical stroke studies, but it is unclear whether targets and mechanisms are always the same across different species. Here, we mapped the baseline expression of a chemokine/cytokine subnetwork and compared responses after oxygen-glucose deprivation in primary neurons, astrocytes, and microglia from mouse, rat, and human. Baseline profiles of chemokines (CX3CL1, CXCL12, CCL2, CCL3, and CXCL10) and cytokines (IL-1α, IL-1β, IL-6, IL-10, and TNFα) showed significant differences between human and rodents. The response of chemokines/cytokines to oxygen-glucose deprivation was also significantly different between species. After 4 h oxygen-glucose deprivation and 4 h reoxygenation, human and rat neurons showed similar changes with a downregulation in many chemokines, whereas mouse neurons showed a mixed response with up- and down-regulated genes. For astrocytes, subnetwork response patterns were more similar in rats and mice compared to humans. For microglia, rat cells showed an upregulation in all chemokines/cytokines, mouse cells had many down-regulated genes, and human cells showed a mixed response with up- and down-regulated genes. This study provides proof-of-concept that species differences exist in chemokine/cytokine subnetworks in brain cells that may be relevant to stroke pathophysiology. Further investigation of differential gene pathways across species is warranted.

Hypertension is a leading cause of death worldwide; data on hypertension among ethnic minorities in China are sparse. This study aimed to estimate hypertension prevalence, awareness, treatment, and control in a Kazakh population, and to assess the association between salt intake and the above measures. A cross-sectional survey was conducted among Kazakh adults (≥30 years old) in the town of Hongdun, Altay, Xinjiang. Survey procedures included a questionnaire, physical measurement, and laboratory tests. Of 1805 eligible individuals, 1668 (92.4%) were included in the analysis. After adjustment for gender, age, and occupation, prevalence of hypertension was 45.5%. The proportions with awareness, treatment, control, or medication-control were 61.0%, 28.8%, 2.9% and 10.1%, respectively. Higher prevalence was seen among nomads and farmers (50.7% and 44.6%, respectively). However, the proportions with treatment or control were lower than seen among urban citizens. Hypertension prevalence was higher in those with higher salt intake (p = 0.0008). In contrast, the proportions with awareness (p = 0.0389), treatment (p = 0.0010), control (p = 0.0503), and medication-control (p = 0.2012) reduced as salt intake increased. In conclusion, hypertension prevalence is high in this population, but the proportions with awareness, treatment, or control are sub-optimal. Public health interventions that improve hypertension prevention and control, particularly among nomads, is needed.

Background: The purpose of this study was to investigate whether ultra-low-dose chest computed tomography (CT) can be used for visual assessment of CT features in patients with pulmonary alveolar proteinosis (PAP) and to evaluate the relationship between the quantitative analysis of the ultra-low-dose CT scans and the pulmonary function tests (PFTs)., Methods: Thirty-eight patients (mean [SD] age, 44.47 [12.28] years; 29 males, 9 females) with PAP were enrolled and subjected to two scans each with low-dose CT (reference parameters: 120 kV and 50 mAs) and ultra-low-dose CT (reference parameters, 80 kV, 25 mAs). Images were reconstructed via filtered back projection (FBP) for low-dose CT and iterative reconstruction (IR) for ultra-low-dose CT. All patients underwent PFT. The Visual analysis for ground glass opacity (GGO) is performed. The quantitative CT and PFT results were analyzed by canonical correlations., Results: The mean body mass index (BMI) was 25.37±3.26 kg/m2. The effective radiation doses were 2.30±0.46 and 0.24±0.05 mSv for low-dose and ultra-low-dose CT, respectively. The size-specific dose estimates were 5.81±0.81 and 0.62±0.09 mSv for low-dose and ultra-low-dose CT. GGOs and interlobular septal thickening were observed bilaterally in all patients. The average visual GGO score was lower in the upper field (2.67±1.24) but higher in the middle and lower fields (3.08±1.32 and 3.08±0.97, respectively). The average score for the whole lung was 2.94±1.19. There is a significant correlation between PFTs and quantitative of ultra-low-dose CT (canonical loading = 0.78)., Conclusions: Ultra-low-dose CT has the potential to quantify the lung parenchyma changes of PAP. This technique could provide a sensitive and objective assessment of PAP and has good relation with PFTs. In addition, the radiation dose of ultra-low-dose CT was very low.

MicroRNAs (miRNAs) are small RNA molecules that play key regulatory roles in general biological processes and disease pathogenesis. These small RNA molecules interact with their target mRNAs to induce mRNA degradation and/or inhibit the translation of mRNAs into proteins. Therefore, identifying miRNA targets is an essential step to fully understand the regulatory effects of miRNAs. Here, we describe a regularized regression approach that integrates the sequence information with the miRNA and mRNA expression profiles for detecting miRNA targets. This method takes into account the full spectrum of gene sequence features of miRNA targets, including the thermodynamic stability, the accessibility energy, and the context features of the target sites,. Given these sequence features for each putative miRNA-mRNA interaction and their expression values, this model is able to quantify the down-regulation effect of each miRNA on its targets while simultaneously estimating the contribution of each sequence feature for predicting functional miRNA-mRNA interactions.

Background: Smoking increases the risk of numerous cancers; however, an association of smoking with adult gliomas has not been found in a population., Methods: This case-control study included 4556 glioma cases (ICD-9 code 191.0-191.9) aged ≥ 30 years and 9112 controls from a national survey of smoking and mortality in China in 1989-1991. Controls from 325 255 surviving spouses of all-cause deaths were randomly assigned to cases in each of 103 areas according to sex and age groups at a ratio of 2:1. Smoking information was ascertained retrospectively by interviewing surviving spouses., Results: After adjustment for confounders, smoking increased the risk of glioma deaths by 11% (odds ratio [OR] = 1.11; 95% confidence interval [CI]: 1.03-1.21). Compared with non-smokers; the increased risk was 9% (OR = 1.09; 95% CI: 0.99-1.20) in men and 16% (OR = 1.16; 95% CI: 1.00-1.36) in women. The risk increased with age and doses. For individuals aged ≥ 50 years, smoking was associated with higher risk of glioma death by 25% (OR = 1.25; 95% CI: 1.15-1.38); this increased risk for smokers who smoked ≥ 20 cigarettes daily for ≥ 30 years was 53% (OR = 1.53; 95% CI: 1.34-1.74). There were similar findings in both men and women and with either pathology-based or non-pathology-based comparisons., Conclusions: This study indicates that smoking is associated with glioma deaths in the Chinese population. Long-term heavy smoking could be a factor for risk stratification in individuals attending brain tumor clinics., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Motivation: MicroRNAs (miRNAs) play important roles in general biological processes and diseases pathogenesis. Identifying miRNA target genes is an essential step to fully understand the regulatory effects of miRNAs. Many computational methods based on the sequence complementary rules and the miRNA and mRNA expression profiles have been developed for this purpose. It is noted that there have been many sequence features of miRNA targets available, including the context features of the target sites, the thermodynamic stability and the accessibility energy for miRNA-mRNA interaction. However, most of current computational methods that combine sequence and expression information do not effectively integrate full spectrum of these features; instead, they perceive putative miRNA-mRNA interactions from sequence-based prediction as equally meaningful. Therefore, these sequence features have not been fully utilized for improving miRNA target prediction., Results: We propose a novel regularized regression approach that is based on the adaptive Lasso procedure for detecting functional miRNA-mRNA interactions. Our method fully takes into account the gene sequence features and the miRNA and mRNA expression profiles. Given a set of sequence features for each putative miRNA-mRNA interaction and their expression values, our model quantifies the down-regulation effect of each miRNA on its targets while simultaneously estimating the contribution of each sequence feature to predicting functional miRNA-mRNA interactions. By applying our model to the expression datasets from two cancer studies, we have demonstrated our prediction results have achieved better sensitivity and specificity and are more biologically meaningful compared with those based on other methods., Availability and Implementation: The source code is available at: http://nba.uth.tmc.edu/homepage/liu/miRNALasso., Supplementary Information: Supplementary data are available at Bioinformatics online., Contact: Yin.Liu@uth.tmc.edu., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Motivation: A major goal in genomic research is to identify genes that may jointly influence a biological response. From many years of intensive biomedical research, a large body of biological knowledge, or pathway information, has accumulated in available databases. There is a strong interest in leveraging these pathways to improve the statistical power and interpretability in studying gene networks associated with complex phenotypes. This prior information is a valuable complement to large-scale genomic data such as gene expression data generated from microarrays. However, it is a non-trivial task to effectively integrate available biological knowledge into gene expression data when reconstructing gene networks., Results: In this article, we developed and applied a Lasso method from a Bayesian perspective, a method we call prior Lasso (pLasso), for the reconstruction of gene networks. In this method, we partition edges between genes into two subsets: one subset of edges is present in known pathways, whereas the other has no prior information associated. Our method assigns different prior distributions to each subset according to a modified Bayesian information criterion that incorporates prior knowledge on both the network structure and the pathway information. Simulation studies have indicated that the method is more effective in recovering the underlying network than a traditional Lasso method that does not use the prior information. We applied pLasso to microarray gene expression datasets, where we used information from the Pathway Commons (PC) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as prior information for the network reconstruction, and successfully identified network hub genes associated with clinical outcome in cancer patients., Availability: The source code is available at http://nba.uth.tmc.edu/homepage/liu/pLasso.

As a typical industrial wastewater, coal gasification wastewater has poor biodegradability and high toxicity. In this paper, a laboratory-scale anaerobic-anoxic-oxic membrane reactor (A(2)O-MBR) system was developed to investigate the treatment ability of coal gasification wastewater. The removal capacity of each pollutants used in this system were determined at different hydraulic residence times (HRT) and mixed liquor recycle ratios (R). The experimental results showed that this system could effectively deal with COD and phenol removal and remain in a stable level when the operational parameters altered, while the nitrification was sensitive to operational conditions. The best performance was obtained at HRT of 48 h and R of 3. The maximum removal efficiencies of COD, NH(4)(+)-N and phenols were 97.4%, 92.8% and 99.7%, with final concentrations in the effluent of 71 mg/L, 9.6 mg/L and 3 mg/L, respectively. Organics degradation and transformation were analyzed by GC/MS and it was found that anaerobic process played an important role in degradation of refractory compounds., (Copyright © 2012. Published by Elsevier B.V.)

A great number of obsolete larval neurons in the Drosophila central nervous system are eliminated by developmentally programmed cell death (PCD) during early metamorphosis. To elucidate the mechanisms of neuronal PCD occurring during this period, we undertook genetic dissection of seven currently known Drosophila caspases in the PCD of a group of interneurons (vCrz) that produce corazonin (Crz) neuropeptide in the ventral nerve cord. The molecular death program in the vCrz neurons initiates within 1 hour after pupariation, as demonstrated by the cytological signs of cell death and caspase activation. PCD was significantly suppressed in dronc-null mutants, but not in null mutants of either dredd or strica. A double mutation lacking both dronc and strica impaired PCD phenotype more severely than did a dronc mutation alone, but comparably to a triple dredd/strica/dronc mutation, indicating that dronc is a main initiator caspase, while strica plays a minor role that overlaps with dronc's. As for effector caspases, vCrz PCD requires both ice and dcp-1 functions, as they work cooperatively for a timely removal of the vCrz neurons. Interestingly, the activation of the Ice and Dcp-1 is not solely dependent on Dronc and Strica, implying an alternative pathway to activate the effectors. Two remaining effector caspase genes, decay and damm, found no apparent functions in the neuronal PCD, at least during early metamorphosis. Overall, our work revealed that vCrz PCD utilizes dronc, strica, dcp-1, and ice wherein the activation of Ice and Dcp-1 requires a novel pathway in addition to the initiator caspases.

Two parallel membrane bioreactors (MBRs) were operated under different calcium dosages (168.5, 27 mg/L) to gain a better understanding of the mechanism of retarding membrane fouling by adding calcium. The results showed that the particle size of sludge flocs increased and the particle size distribution tended to be narrow at the optimum dosage (168.5 mg/L). Calcium was effective in decreasing loosely bound extracellular polymeric substances (LB-EPS) in microbial flocs and soluble microbial products (SMP) in the supernatant at the dosage of 168.5 mg/L by strengthening the neutralization and bridging of EPS with flocs. Furthermore, the amount of CODs and CODc decreased in both the mixed liquor and the fouling cake layer on the membrane surface. In order to compare the filtration characteristics of cake layers from the MBRs with the two calcium dosages, the specific cake resistance and the compressibility coefficient were measured. The specific cake resistance from the MBR with optimum dosage (168.5 mg/L) was distinctly lower than that with low dosage (27 mg/L). The compressibility coefficient of the cake layers under two dosages were respectively attained as 0.65, 0.91. Scanning electron microscopy (SEM) and three-dimensional confocal scanning laser microscope analysis (CLSM) images were utilized to observe the gel layer directly.

Although the corazonin gene (Crz) has been molecularly characterized, little is known concerning the function of this neuropeptide in Drosophila melanogaster. To gain insight into Crz function in Drosophila, we have investigated the developmental regulation of Crz expression and the morphology of corazonergic neurons. From late embryo to larva, Crz expression is consistently detected in three neuronal groups: dorso-lateral Crz neurons (DL), dorso-medial Crz neurons (DM), and Crz neurons in the ventral nerve cord (vCrz). Both the vCrz and DM groups die via programmed cell death during metamorphosis, whereas the DL neurons persist to adulthood. In adults, Crz is expressed in a cluster of six to eight neurons per lobe in the pars lateralis (DLP), in numerous neuronal cells in the optic lobes, and in a novel group of four abdominal ganglionic neurons present only in males (ms-aCrz). The DLP group consists of two subsets of cells having different developmental origins: embryo and pupa. In the optic lobes, we have detected both Crz transcripts and Crz promoter activity, but no Crz-immunoreactive products, suggesting a post-transcriptional regulation of Crz mRNA. Projections of the ms-aCrz neurons terminate within the ventral nerve cord, implying a role as interneurons. Terminals of the DLP neurons are found in the retrocerebral complex that produces juvenile hormone and adipokinetic hormone. Significant reduction of trehalose levels in adults lacking DLP neurons suggests that DLP neurons are involved in the regulation of trehalose metabolism. Thus, the tissue-, stage-, and sex-specific expression of Crz and the association of Crz with the function of the retrocerebral complex suggest diverse roles for this neuropeptide in Drosophila.

A dual-fluorescent donor-acceptor (D-A) dyad with tercarbazole (donor) and 2,3-dithienylmaleimide (acceptor) was synthesized and characterized. The emission intensity of long wavelength could be regulated by either bistable structures of the dyad or the polarities of solvents. By mimicking the function of an integrated logic gate, a 2-input AND logic operation is established. [reaction: see text].

A series of 9-(cycloheptatrienylidene)fluorene derivatives were synthesized in good yields through the Suzuki or Sonogashira cross-coupling reactions. Fluorescence "off-on" behaviors of these compounds were investigated on the basis of variable acid concentrations. These compounds were shown to be acid-sensing fluorophores with utility as indicators in acidic environments.