Search

The co-occurrence of clear cell renal cell carcinoma (ccRCC) and bladder urothelial carcinoma (bUC) is rare, and owing to the lack of a unified treatment plan, the prognosis is poor. The present report describes the case of a 65-year-old male patient with a history of smoking and no history of malignant tumors who presented with hematuria at the Huanghe Sanmenxia Hospital Affiliated to Henan University of Science and Technology (Sanmenxia, China) in July 2021. Urinary system computed tomography urography revealed a right renal tumor, and cystoscopy revealed intravesical lesions. The patient underwent transurethral resection of a bladder tumor + laparoscopic partial nephrectomy + laparoscopic radical cystectomy and bilateral ureterostomy. Pathological examination revealed right-sided ccRCC (pT1aN0M0) and high-grade invasive bUC (pT2N0M0). After surgery, the patient underwent bilateral ureteral single J tube replacement in the outpatient clinic every 3 months. In September 2022, the patient presented with a mass on the right side of the neck. Further examination revealed a space-occupying lesion in the lower part of the left kidney and space-occupying lesions in the neck, axilla, mediastinal lymph nodes and liver. A neck lymph node puncture biopsy suggested UC, and the patient was diagnosed with metastatic UC (T4N0M1). The patient received tislelizumab (200 mg once every 3 weeks) + sunitinib (50 mg/day, administered for 4 weeks with a 2-week interval) for a total of 2 months and died of an advanced tumor in January 2023. In addition, the data of 36 patients with ccRCC and bUC from the literature were analyzed for the present report. The results showed that the median age at first onset was 56.5 years (range, 31-82 years) and the male-to-female ratio was 6:1. Smoking and male sex may be risk factors for this disease, which has a median survival time of 47.5 months. The survival analysis results showed that the pathological stage of bladder cancer may be associated with its prognosis. The present study reviews the potential risks, clinicopathological characteristics and treatment methods of co-occurrence of clear ccRCC and bUC. In conclusion, the high-risk factors for the co-occurrence of ccRCC and bUC were smoking and male sex, and the median survival time was 47.5 months. The pathological stage of bladder cancer may be related to the prognosis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Wu et al.)

Spindle oscillation is a waxing-and-waning neural oscillation observed in the brain, initiated at the thalamic reticular nucleus (TRN) and typically occurring at 7-15 Hz. Experiments have shown that in the adult brain, electrical synapses, rather than chemical synapses, dominate between TRN neurons, suggesting that the traditional view of spindle generation via chemical synapses may need reconsideration. Based on known experimental data, we develop a computational model of the TRN network, where heterogeneous neurons are connected by electrical synapses. The model shows that the interplay between synchronizing electrical synapses and desynchronizing heterogeneity leads to multiple synchronized clusters with slightly different oscillation frequencies whose summed-up activity produces spindle oscillation as seen in local field potentials. Our results suggest that during spindle oscillation, the network operates at the critical state, which is known for facilitating efficient information processing. This study provides insights into the underlying mechanism of spindle oscillation and its functional significance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: Bladder carcinosarcoma (BC) is a malignant tumor composed of a mixture of malignant epithelial and stromal components. Carcinosarcoma mostly occurs in the upper respiratory tract and upper gastrointestinal tract and is less common in the urinary system. The incidence of malignant tumors of the urinary system is <3%. It rarely occurs in the bladder and accounts for approximately 0.31% of all malignant bladder tumors. A literature review and this report will help to further improve our understanding, diagnosis, and treatment of bladder carcinosarcoma (BC)., Patient Concern: We describe the case of an 80-year-old female patient who was admitted to the hospital with a history of intermittent hematuria for 3 years. Furthermore, total cystectomy was refused when a BC was diagnosed. Palliative resection surgery was necessary because of the recurrent hematuria and abdominal pain., Diagnoses: Pathologically confirmed BC after surgery., Interventions: The patient's first transurethral resection of bladder tumor (TURBT) was diagnosed as BC. However, the patient refused a total cystectomy. Two months after intravesical treatment with epirubicin, bladder tumor recurrence was observed during follow-up cystoscopy. The patient underwent a second TURBT for hemostatic treatment due to persistent hematuria. Due to hematuria and abdominal pain, a third TURBT was performed to reduce tumor size and stop bleeding. Finally, tumor recurrence resulted in bilateral hydronephrosis, and the patient underwent bilateral renal catheter drainage guided by B-ultrasound., Outcomes: Bladder carcinosarcoma caused uremia, electrolyte imbalance, and sepsis. Approximately 19 months after the discovery of the tumor, the patient died., Lessons: Radical bladder resection is recommended once a BC is diagnosed. By reporting the cases and reviewing the literature in the database, we will summarize the epidemiology, origin, etiology, clinical features, existing treatments, and prognostic factors of BC, and propose new prospects for BC therapy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

In some patients, COVID-19 can trigger neurological symptoms with unclear pathogenesis. Here we describe a microphysiological system integrating alveolus and blood-brain barrier (BBB) tissue chips that recapitulates neuropathogenesis associated with infection by SARS-CoV-2. Direct exposure of the BBB chip to SARS-CoV-2 caused mild changes to the BBB, and infusion of medium from the infected alveolus chip led to more severe injuries on the BBB chip, including endothelial dysfunction, pericyte detachment and neuroinflammation. Transcriptomic analyses indicated downregulated expression of the actin cytoskeleton in brain endothelium and upregulated expression of inflammatory genes in glial cells. We also observed early cerebral microvascular damage following lung infection with a low viral load in the brains of transgenic mice expressing human angiotensin-converting enzyme 2. Our findings suggest that systemic inflammation is probably contributing to neuropathogenesis following SARS-CoV-2 infection, and that direct viral neural invasion might not be a prerequisite for this neuropathogenesis. Lung-brain microphysiological systems should aid the further understanding of the systemic effects and neurological complications of viral infection., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Recycling polluted water via different techniques has become one of the most feasible ways to solve the freshwater crisis. We describe a novel method to prepare reusable and efficient photothermal energy conversion materials for water purification. Using crosslinked xerogels as precursor, the porous and interconnected carboxymethylcellulose sodium-derived carbon aerogels (abbreviated as CCAs) with good hydrophilic performance and strong light absorption capability are firstly fabricated through pyrolysis. Photothermal measurement results show that CCA15 exhibit excellent solar steam generation rate of 2.31 kg m -2 h -1 with high light-to-vapor conversion efficiency of 95.9% under 1 sun illumination. In addition, the feasible application of CCA15 for efficient water purification under 1 sun irradiation using a homemade water treatment device has been demonstrated successfully. The as-prepared CCAs shown in here can be a continuable solution to mitigate the global freshwater crisis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (K D ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway., Competing Interests: Competing interests statement:The authors declare no competing interest.

Conventional circuit elements are constrained by limitations in area and power efficiency at processing physical signals. Recently, researchers have delved into high-order dynamics and coupled oscillation dynamics utilizing Mott devices, revealing potent nonlinear computing capabilities. However, the intricate yet manageable population dynamics of multiple artificial sensory neurons with spatiotemporal coupling remain unexplored. Here, we present an experimental hardware demonstration featuring a capacitance-coupled VO 2 phase-change oscillatory network. This network serves as a continuous-time dynamic system for sensory pre-processing and encodes information in phase differences. Besides, a decision-making module for special post-processing through software simulation is designed to complete a bio-inspired dynamic sensory system. Our experiments provide compelling evidence that this transistor-free coupling network excels in sensory processing tasks such as touch recognition and gesture recognition, achieving significant advantages of fewer devices and lower energy-delay-product compared to conventional methods. This work paves the way towards an efficient and compact neuromorphic sensory system based on nano-scale nonlinear dynamics., (© 2024. The Author(s).)

Elucidating the intricate neural mechanisms underlying brain functions requires integrative brain dynamics modeling. To facilitate this process, it is crucial to develop a general-purpose programming framework that allows users to freely define neural models across multiple scales, efficiently simulate, train, and analyze model dynamics, and conveniently incorporate new modeling approaches. In response to this need, we present BrainPy. BrainPy leverages the advanced just-in-time (JIT) compilation capabilities of JAX and XLA to provide a powerful infrastructure tailored for brain dynamics programming. It offers an integrated platform for building, simulating, training, and analyzing brain dynamics models. Models defined in BrainPy can be JIT compiled into binary instructions for various devices, including Central Processing Unit, Graphics Processing Unit, and Tensor Processing Unit, which ensures high-running performance comparable to native C or CUDA. Additionally, BrainPy features an extensible architecture that allows for easy expansion of new infrastructure, utilities, and machine-learning approaches. This flexibility enables researchers to incorporate cutting-edge techniques and adapt the framework to their specific needs., Competing Interests: CW, TZ, XC, SH, SL, SW No competing interests declared, (© 2023, Wang et al.)

This work presents a novel strategy for the synthesis of a recyclable aerogel and its multifunctional application as effective adsorption material for organic pollutants and as a high-quality SERS substrate for on-site detection measurement. Silver nanoparticles (Ag NPs) were uniformly dispersed and adsorbed on the surface of an Fe 3 C-loaded carbon aerogel, resulting in the formation of a three-dimensional Ag-Fe 3 C-MCA (magnetic carbon aerogel) composite. The substrate preparation led to Ag-Fe 3 C-MCA with a mesoporous structure for high adsorption capacity, together with magnetic properties for easy separation capability. The Ag-Fe 3 C-MCA composite demonstrated an efficient removal ability for malachite green (MG), with an adsorption capacity of 296.7 mg g -1 . Moreover, Ag-Fe 3 C-MCA composite provided ultrasensitive surface-enhanced Raman scattering detection for MG molecules, obtaining a limit of detection (LOD) of 3 × 10 -10  M. Aquaculture water samples with spiked MG concentrations were used to simulate practical scenarios. The Ag-Fe 3 C-MCA presented has a significant potential for the removal of hazardous residues in wastewater, together with an efficient and sensitive method of quantification, all on the same substrate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Staphylococcus aureus ( S. aureus ) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on S. aureus infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of Hirudinaria manillensis ( H. manillensis ) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus , including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 μg/mL. The RK22 peptide rapidly killed S. aureus by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection.

When Poecilobdella manillensis attacks its prey, the prey bleeds profusely but feels little pain. We and other research teams have identified several anticoagulant molecules in the saliva of P. manillensis , but the substance that produces the paralyzing effect in P. manillensis is not known. In this study, we successfully isolated, purified, and identified a serine protease inhibitor containing an antistasin-like domain from the salivary secretions of P. manillensis . This peptide (named poeciguamerin) significantly inhibited elastase activity and slightly inhibited FXIIa and kallikrein activity, but had no effect on FXa, trypsin, or thrombin activity. Furthermore, poeciguamerin exhibited analgesic activity in the foot-licking and tail-withdrawal mouse models and anticoagulant activity in the FeCl 3 -induced carotid artery thrombosis mouse model. In this study, poeciguamerin was found to be a promising elastase inhibitor with potent analgesic and antithrombotic activity for the inhibition of pain and thrombosis after surgery or in inflammatory conditions.

Multidrug resistance (MDR) caused by ATP-Binding Cassette Subfamily B Member 1 (ABCB1, P-glycoprotein, P-gp) is a major barrier for the success of chemotherapy in clinics. In this study, we designed and synthesized a total of 19 Lissodendrins B analogues and tested their ABCB1-mediated MDR reversal activity in doxorubicin (DOX)-resistant K562/ADR and MCF-7/ADR cells. Among all derivatives, compounds D 1 , D 2 , and D 4 with a dimethoxy-substituted tetrahydroisoquinoline fragment possessed potent synergistic effects with DOX and reversed ABCB1-mediated drug resistance. Notably, the most potent compound D 1 merits multiple activities, including low cytotoxicity, the strongest synergistic effect, and effectively reversing ABCB1-mediated drug resistance of K562/ADR (RF = 1845.76) and MCF-7/ADR cells (RF = 207.86) to DOX. As a reference substance, compound D 1 allows for additional mechanistic studies on ABCB1 inhibition. The synergistic mechanisms were mainly related to the increased intracellular accumulation of DOX via inhibiting the efflux function of ABCB1 rather than from affecting the expression level of ABCB1. These studies suggest that compound D 1 and its derivatives might be potential MDR reversal agents acting as ABCB1 inhibitors in clinical therapeutics and provide insight into a design strategy for the development of ABCB1 inhibitors.

Peptide stapling is a strategy for improving the biological properties of peptides. Herein, we report a novel method for stapling peptides that utilizes bifunctional triazine moieties for two-component conjugation to the phenolic hydroxyl groups of tyrosine, which enables efficient stapling of unprotected peptides. In addition, we applied this strategy to the RGD peptide that can target integrins and demonstrated that the stapled RGD peptide had significantly improved plasma stability and integrin-targeting ability.

Herein, we discover the new reactivity of the 1,3,5-triazine moiety reacting with a phenol group and report the development of biocompatible and catalyst-free triazine-pyridine chemistry (TPC) for tyrosine labelling under physiological conditions and profiling in the whole proteome. TPC exhibited high tyrosine chemoselectivity in biological systems after cysteine blocking, displayed potential in tyrosine-guided protein labelling, and had bio-compatibility in live cells.

Strategically located between the thalamus and the cortex, the inhibitory thalamic reticular nucleus (TRN) is a hub to regulate selective attention during wakefulness and control the thalamic and cortical oscillations during sleep. A salient feature of TRN neurons contributing to these functions is their characteristic firing patterns, ranging in a continuum from tonic spiking to bursting spiking. However, the dynamical mechanism under these firing behaviors is not well understood. In this study, by applying a reduction method to a full conductance-based neuron model, we construct a reduced three-variable model to investigate the dynamics of TRN neurons. We show that the reduced model can effectively reproduce the spiking patterns of TRN neurons as observed in vivo and in vitro experiments, and meanwhile allow us to perform bifurcation analysis of the spiking dynamics. Specifically, we demonstrate that the rebound bursting of a TRN neuron is a type of "fold/homo-clinic" bifurcation, and the tonic spiking is the fold cycle bifurcation. Further one-parameter bifurcation analysis reveals that the transition between these discharge patterns can be controlled by the external current. We expect that this reduced neuron model will help us to further study the complicated dynamics and functions of the TRN network., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Li and Wu.)

A low-cost, collectable, and efficient material is essential for adsorbing water pollution, such as dyes and heavy metal ions pollution. In this work, we proposed a novel strategy for the preparation of an efficient and collectable magnetic aerogel as adsorbent for dye. The magnetic aerogels were prepared from sodium carboxymethylcellulose (CMC) hydrogel using citric acid (CA) as the crosslinker, followed by vacuum freeze-drying technique to obtain aerogels. The effects of magnetic Fe 3 O 4 nanoparticle contents on the adsorption properties of the aerogels were investigated. The results show that the as-prepared magnetic composite aerogels exhibit porous structure and display good adsorption and collectable performance for methylene blue (MB) in water with the removal rate of 97.5% in 6 h. The maximum compress strength and absorption capacity of the magnetic aerogel with 1 wt% Fe 3 O 4 nanoparticle loading for MB is 0.13 MPa and 83.6 mg/g, respectively. Aerogels with Fe 3 O 4 nanoparticles exhibited magnetism which enables the aerogels to easily collect. This excellent structure stability and collectability guarantees long-term integrity and floatability of the magnetic aerogels in water., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Host-pathogen interactions in the setting of chronic pulmonary inflammation remain unclear, and the occurrence of pneumonia is increased in patients with chronic obstructive pulmonary disease who use immunosuppressive drugs. We performed Acinetobacter baumannii infection in mice with chronic pulmonary inflammation after intranasal administration of SiO 2 and found SiO 2 treatment increased host defense against A. baumannii infection. Innate immune responses initiated by NF-κB, type 1 interferon, NLRP3 and AIM2 inflammasomes were dispensable for SiO 2 -mediated host defense. SiO 2 treatment activated the mTORC1 signaling, and mTORC1 was crucial for host defense against A. baumannii infection. Our study highlights the protective role of mTORC1 signaling in host defense against bacterial infection, offers novel insights into understanding the mechanisms of immunosuppressive drug-related pneumonia, and provides potential host-directed therapeutics to treat bacterial infections.

STAT1 is a master regulator that orchestrates type 1 and 2 interferon (IFN)-induced IFN-stimulated gene (ISG) expression. The mechanisms by which STAT1 is phosphorylated and activated upon IFN signaling remain elusive. Our work demonstrated that ubiquitination of STAT1 mediated by the E3 ligase RNF220 contributed significantly to STAT1 activation and innate immune responses. Rnf220 gene deficiency resulted in the downregulation of IFN signaling and decreased expression of ISGs in response to type 1 and 2 IFNs stimulation and Acinetobacter baumannii and HSV-1 infection. Mechanistically, RNF220 interacted with STAT1 and mediated the K63-linked polyubiquitination of STAT1 at residue K110, which promoted the interaction between STAT1 and the kinase JAK1. The expression of RNF220 was induced by pathogenic infection and IFN signaling. RNF220 promoted STAT1 ubiquitination and phosphorylation through a positive feedback loop. RNF220 haploinsufficiency impaired IFN signaling, and RNF220-defective mice were more susceptible to A. baumannii and HSV-1 infection than WT mice. Our work offers novel insights into the mechanisms of STAT1 modulation and provides potential therapeutic targets against bacterial and viral infection and inflammatory diseases.

The mechanism by which inflammasome activation is modulated remains unclear. In this study, we identified an AIM2-interacting protein, the E3 ubiquitin ligase HUWE1, which was also found to interact with NLRP3 and NLRC4 through the HIN domain of AIM2 and the NACHT domains of NLRP3 and NLRC4. The BH3 domain of HUWE1 was important for its interaction with NLRP3, AIM2, and NLRC4. Caspase-1 maturation, IL-1β release, and pyroptosis were reduced in Huwe1-deficient bone marrow-derived macrophages (BMDMs) compared with WT BMDMs in response to stimuli to induce NLRP3, NLRC4, and AIM2 inflammasome activation. Furthermore, the activation of NLRP3, NLRC4, and AIM2 inflammasomes in both mouse and human cells was remarkably reduced by treatment with the HUWE1 inhibitor BI8622. HUWE1 mediated the K27-linked polyubiquitination of AIM2, NLRP3, and NLRC4, which led to inflammasome assembly, ASC speck formation, and sustained caspase-1 activation. Huwe1-deficient mice had an increased bacterial burden and decreased caspase-1 activation and IL-1β production upon Salmonella, Francisella, or Acinetobacter baumannii infection. Our study provides insights into the mechanisms of inflammasome activation as well as a potential therapeutic target against bacterial infection.

Visual information processing in the brain goes from global to local. A large volume of experimental studies has suggested that among global features, the brain perceives the topological information of an image first. Here, we propose a neural network model to elucidate the underlying computational mechanism. The model consists of two parts. The first part is a neural network in which neurons are coupled through gap junctions, mimicking the neural circuit formed by alpha ganglion cells in the retina. Gap junction plays a key role in the model, which, on one hand, facilitates the synchronized firing of a neuron group covering a connected region of an image, and on the other hand, staggers the firing moments of different neuron groups covering disconnected regions of the image. These two properties endow the network with the capacity of detecting the connectivity and closure of images. The second part of the model is a read-out neuron, which reads out the topological information that has been converted into the number of synchronized firings in the retina network. Our model provides a simple yet effective mechanism for the neural system to detect the topological information of images in ultra-speed., (Copyright © 2020 Wang, Lian, Dong, Mi and Wu.)

In this paper, a modified method for predicting surface effect parameters based on experimental data is developed using the surface effect theory. Polyacrylonitrile (PAN) nanowires with diameters in a range of 100 nm - 320 nm are manufactured by electrospinning. The data of the effective elastic moduli of PAN nanowire varying with diameters are obtained by experimenting with contact atomic-force microscopy (C-AFM). It was found that the effective Young's modulus of nanowires increased with the diameter of the nanowires decreases. The validity of the method in this paper are confirmed by comparing with the existing work. By taking into account the effect of surface energy on the bending, the deviation of the prediction of surface effect parameters in the existing work is solved. The current results will also be useful for predicting nanowire surface effect parameters and be helpful for the design of nanostructures and nanodevices related to nanowires.

Exposure to diesel exhaust particles (DEPs) is associated with acute inflammatory responses in the lung and exacerbation of respiratory diseases. However, the mechanism by which DEPs trigger the inflammatory responses remains unclear. Here, we demonstrated that the IFN response factors IRF3 and IRF7 played pivotal roles in DEP-induced pulmonary inflammation. DEPs could not directly induce inflammatory cytokine expression in mouse cells, whereas DEPs triggered autophagy both in vitro and in vivo. The DEP-induced autophagy was augmented in the absence of IRF3 and IRF7, but not in the absence of IFNAR. The expression of Raptor was induced by IRF3 and IRF7 in response to DEPs treatment. Furthermore, administration of the mechanistic target of rapamycin (mTOR) inhibitor alleviated the inflammatory responses in the lung during DEP exposure. Our findings define an IFNAR-independent role of increased autophagy in the absence of IRF3 and IRF7 during pulmonary DEP exposure, and provide the basis to develop new therapeutic approaches to counteract the adverse effects of DEPs and possibly other ambient particulate matters., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The potential screening effect of one-dimensional ZnO nanorods from carriers has been theoretically proved to severely limit its piezoelectricity, but its exact mechanism needs to be further revealed in experiments to guide the design of piezoelectric semiconductors. Here, a discretely structured design was proposed to prevent the free carriers from tunneling among adjacent ZnO nanorods for suppressing the screening effect. Piezoresponse force microscope and finite element analysis were employed in combination to uncover the underlying mechanism in experiment. Further, the output voltage of this discretely structured device was 1.62 times higher than that of the nondesigned device, which clearly authenticates this suppression behavior. Besides, this design prompts an unexpected improvement in flexibility, where the flexural modulus of this piezo-film was reduced by 35.74%. Notably, this work opens a new way to understand the potential screening effect, as expected, and to advance the development of piezo-electronics toward better piezoelectricity and more excellent flexibility.

Ginseng has been used as a popular herbal medicine in East Asia for at least two millennia. However, 20( R )-ginseng saponins, one class of important rare ginsenosides, are rare in natural products. 20( R )-ginseng saponins are generally prepared by chemical epimerization and microbial transformation from 20( S )-isomers. The C20 configuration of 20( R )-ginseng saponins are usually determined by 13 C NMR and X-ray single-crystal diffraction. 20( R )-ginseng saponins have antitumor, antioxidative, antifatigue, neuroprotective, and osteoclastogenesis inhibitory effects, among others. Owing to the chemical structure and pharmacological and stereoselective properties, 20( R )-ginseng saponins have attracted a great deal of attention in recent years. In this study, the discovery, identification, chemical epimerization, microbial transformation, pharmacological activities, and metabolism of 20( R )-ginseng saponins are summarized., (© 2019 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Ginseng is a perennial herb that contains various medicinal substances. The major active constituents of ginseng are ginsenosides, which have multifarious biological activities. Some pharmacological activities are closely dependent on the stereoisomers derived from the configuration at C20. In this study, the in vitro anti-inflammatory activity of C20 epimeric ocotillol-type triterpenes (2, 3, 9: , and 10: ) and protopanaxadiol [20( S / R )-protopanaxadiol] were investigated. Epimers 2: and 3: were prepared starting from 20( S )-protopanaxadiol. Epimers 9: and 10: were synthesized from 20( R )-3-acetylprotopanaxadiol (7: ). The anti-inflammatory activity of 2, 3, 9, 10: , 20( S )-protopanaxadiol, and 20( R )-protopanaxadiol was evaluated in cultured mouse macrophage RAW 264.7 cells. The MTT assay was used to measure the cytotoxicity. RAW 264.7 cells were stimulated by lipopolysaccharide to release the inflammatory mediators nitric oxide, prostaglandin E 2 , TNF- α , and interleukin-6 and anti-inflammatory mediator interleukin-10. The effect of the compounds on the overproduction of nitric oxide, prostaglandin E 2 , TNF- α , interleukin-6, and interleukin-10 was determined using Griess and ELISA methods. The results demonstrated that the in vitro anti-inflammatory activities of C20 epimeric ocotillol-type triterpenes and protopanaxadiol were different. Both the 20 S -epimers (2: and 3: ) and 20 R -epimers (9: and 10: ) inhibited the release of inflammatory mediator nitric oxide, while mainly the 20 S -epimers inhibited the release of inflammatory mediator prostaglandin E 2 , and the 20 R -epimers inhibited the release of inflammatory cytokine TNF- α . Both the 20 S -epimers [2, 3: , and 20( S )-protopanaxadiol] and 20 R -epimers [9, 10: , and 20( R )-protopanaxadiol] inhibited the release of inflammatory cytokine interleukin-6, but mainly the 20 S -epimers [2, 3: , and 20( S )-protopanaxadiol] increased the release of anti-inflammatory mediator interleukin-10., Competing Interests: The authors have no conflicts of interest to declare., (Georg Thieme Verlag KG Stuttgart · New York.)

Replacement of the bridging oxygen atom in rhodamine with phosphorus is one of the most efficient ways for bright near-infrared (NIR) fluorophores with wavelengths over 700 nm. However, the organophosphorus bridge is more versatile than just being a spectrum tuner, it is also a profound solubility booster and photostability enhancer, as proved by a series of phosphorus-substituted rhodamines (PRBs). A unique bridge-caging strategy for efficiently manipulating fluorescence has further been innovated in example PRB2. Consistent with theoretical calculations, the formation of organophosphinate by a caging group as a fluorescence-controller locks the spirolactone into a colorless and nonfluorescent form, whereas decaging, a process induced by a specific stimulus, results in a ring-opened form, which yields strong fluorescence. The bridge-caging strategy is feasible for the modular development of NIR probes. Efficient in vivo imaging of photoillumination, hydrogen peroxide, and enzyme have been achieved on the PRB2 scaffold as a photoactivatable fluorophore, PRB2-hν; fluorescent indicator, PRB2-H 2 O 2 ; and fluorogenic enzyme substrate, PRB2-NTR, respectively., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An unusual temperature-dependent autoinductive reversal of enantioselectivity (TARE) was discovered in an asymmetric palladium-mediated [3+3]-annulation of 4-hydroxycoumarin with Morita-Baylis-Hillman acetate. The absolute stereochemistry of the reaction product can be readily inversed by solely modifying the reaction temperature (from 10 °C to 60 °C), affording multicyclic adducts with the opposite configurations respectively in moderate to excellent enantiopurities. Furthermore, the first reported example of palladium-mediated bidirectional asymmetric autoinduction was identified to mainly contribute to the reversal of enantioselectivity, in which the corresponding adduct actively participated in the stereocontrol during the reaction. The correlation between reaction temperature and autoinduction was established, which might broaden the horizon of stereocontrol in asymmetric catalysis.

This article reports the observation of electrical modulation of localized surface plasmon around self-assembled monolayer (SAM)-modified gold nanoparticles and the establishment of a new spectroscopy technique, that is, dynamic electro-optical spectroscopy (DEOS). The gold nanoparticles are deposited onto a transparent conductive substrate, and an electrical bias applied on the conductive substrate can cause shift of resonance plasmon response, where the direction of peak shift is related to the polarity of applied bias. The peak shift observed at 2.4 V is approximately ten times larger than those reported in previous work. It is postulated that significant peak shift is the result of reorientation of adsorbed water on electrode, which can change local dielectric environment of nanoparticles. An energy barrier is identified when adsorbed water molecules are turned from oxygen-down to oxygen-up. Frequency-dependent peak shifts on surface-modified gold nanoparticles show that reorientation is a fast reversible process with rich dynamics.

A practical and straightforward synthetic route to construct a variety of 3-CF 2 /CF 3 -containing chromones via photoredox catalysis was developed. This novel protocol features a visible-light-induced radical-triggered tandem cyclization.

Millions of Americans suffer from nervous system injuries. Hydrogels have been investigated to (1) bridge nerve gaps; (2) act as scaffolds for bioactive molecule delivery or cell transplantation; and/or (3) promote axonal outgrowth. In this study, we use a rapid, one-step Michael addition click chemistry reaction to fabricate a hyaluronic acid (HA) scaffold for neural repair. Briefly, some of the primary hydroxyl groups on the HA backbone were modified with vinyl sulfone functional groups for (1) conjugation of thiol based bioactive molecules and (2) hydrogel crosslinking, which was confirmed by proton nuclear magnetic resonance ( 1 H-NMR) and Fourier transform infrared spectroscopy (FTIR). The degree of crosslinking creates a mechanically tunable hydrogel. Rheology confirmed that the storage modulus was within the order of magnitude to that of nervous tissue. Primary human dermal fibroblasts and primary mouse neural stem cells (NSCs) seeded in the HA hydrogel were viable and proliferative, thus demonstrating that the HA hydrogel is suitable as a scaffold for cell transplantation. The range of pore size demonstrated that the scaffold supports cell migration and neurite extension. Neurite outgrowth of cultured whole embryonic day 9 chick dorsal root ganglions signifies that the hydrogel supports axonal outgrowth. Reduction in immune and inflammatory cell viability was observed in the anti-Fas conjugated HA hydrogel, whereas the NSCs maintained viability in the anti-Fas HA hydrogel. Therefore, this one-step, rapid, controllable reaction is an efficient method for fabrication of tunable, biomolecule conjugated hydrogels for neural engineering applications.

A challenge of X-ray radiation therapy is that high dose X-ray can damage normal cells and cause side effects. This paper describes a new nanoparticle-based method to reduce X-ray dose in radiation therapy by internalization of gold nanoparticles that are modified with cationic molecules into cancer cells. A cationic thiol molecule is synthesized and used to modify gold nanoparticles in a one-step reaction. The modified nanoparticles can penetrate cell membranes at high yield. By bring radio-sensitizing gold nanoparticles closer to nuclei where DNA is stored, the total X-ray dose needed to kill cancer cells has been reduced. The simulation of X-ray-gold nanoparticle interaction also indicates that Auger electrons contribute more than photoelectrons.

G protein-coupled receptors (GPCRs) represent the largest class of drug targets. Ligand-directed functional selectivity or biased agonism opens new possibility for discovering GPCR drugs with better efficacy and safety profiles. However, quantification of ligand bias is challenging. Herein, we present five different label-free dynamic mass redistribution (DMR) approaches to assess ligand bias acting at the β2-adrenergic receptor (β2AR). Multiparametric analysis of the DMR agonist profiles reveals divergent pharmacology of a panel of β2AR agonists. DMR profiling using catechol as a conformational probe detects the presence of multiple conformations of the β2AR. DMR assays under microfluidics, together with chemical biology tools, discover ligand-directed desensitization of the receptor. DMR antagonist reverse assays manifest biased antagonism. DMR profiling using distinct probe-modulated cells detects the biased agonism in the context of self-referenced pharmacological activity map.

A challenge of X-ray radiation therapy is that high dose X-ray under therapeutic conditions damages normal cells. This paper describes a nanoparticle-based method to enhance X-ray radiation therapy by delivering radio-sensitizing gold nanoparticles into cancer cells. The nanoparticles have been modified with cationic polyelectrolytes to allow internalization. Upon X-ray irradiation of nanoparticles, more photoelectrons and Auger electrons are generated to cause water ionization, leading to formation of free radicals that damage DNA of cancer cells. The X-ray dose required for DNA damage and cell killing is reduced by delivering gold nanoparticles inside cancer cells.

Ischemia-modified protein (IMA) is the most sensitive diagnostic biomarker of ischemic heart disease, but differentiation of IMA from human serum albumin (HSA), a ubiquitous serum protein, is still challenging owing to the shared antigenicity. In this investigation, we developed a rapid and interference-free approach for IMA determination using quantum dots-coupled X-ray Fluorescence Spectroscopy (Q-XRF). In a typical Q-XRF assay, serum total HSA is quantified using quantum dot-coupled sandwich immunoassay, and intact HSA (iHSA) is determined using a XRF spectroscopy, by measuring XRF intensity of Co (II) bonded to iHSA. IMA concentration is automatically determined within 30 min by calculating the difference between total HSA and iHSA. This strategy can effectively eliminate the interference from native HSA level. Results show that no significant influences have been observed from hemolysis or high levels of cholesterol (7 mg/L), triglyceride (5.2 mg/L), IgG (10 g/L), and fibrinogen (4 g/L). A linearity of 1-100mg/mL is obtained in iHSA determination using XRF (r(2)=0.979). The proposed Q-XRF assay demonstrates a lowest detection limit of 0.05 U/mL. Receiver-operating characteristic (ROC) curves reveal that Q-XRF assay provide an improved sensitivity than ACB assay (95.9% vs. 82.9%) in differentiating ischemic patients from health individuals, at an optimal cutoff point of 79.2U/mL. The proposed approach provides a new strategy for interference-free, simple and rapid evaluation of IMA concentration by combining sandwich immunoassay and XRF spectroscopy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A major issue of X-ray radiation therapy is that normal cells can be damaged, limiting the amount of X-rays that can be safely delivered to a tumor. This paper describes a new method based on graphene oxide (GO) to protect normal cells from oxidative damage by removing free radicals generated by X-ray radiation using grapheme oxide (GO). A variety of techniques such as cytotoxicity, genotoxicity, oxidative assay, apoptosis, γ-H2AX expression, and micro-nucleus assay have been used to assess the protective effect of GO in cultured fibroblast cells. It is found that although GO at higher concentration (100 and 500 μg/mL) can cause cell death and DNA damage, it can effectively remove oxygen free radicals at a lower concentration of 10 μg/mL. The level of DNA damage and cell death is reduced by 48%, and 39%, respectively. Thus, low concentration GO can be used as an effective radio-protective agent in occupational and therapeutic settings., Competing Interests: The authors declare no conflict of interest.

Novel organic photoCORMs based on micelle-encapsulated unsaturated cyclic α-diketones were designed and synthesized. These photoCORMs can be activated by visible light, have potentially low toxicity, allow the delivery of carbon monoxide to be monitored by fluorescence imaging techniques, and thus are useful tools for the study of the biological function of CO.

The canonical model of G protein-coupled receptor (GPCR) signalling states that it is solely initiated at the cell surface. In recent years, a handful of evidence has started emerging from high-resolution molecular assays that the internalized receptors can mediate the third wave of signalling, besides G protein- and β-arrestin-mediated signalling both initiating at the cell surface. However, little is known about the functional consequences of distinct waves of GPCR signalling, in particular, at the whole cell system level. We here report the development of label-free biosensor antagonist reverse assays and their use to differentiate the signalling waves of an endogenous β2-adrenergic receptor (β2-AR) in A431 cells. Results showed that the persistent agonist treatment activated the β2-ARs, leading to a long-term sustained dynamic mass redistribution (DMR) signal, a whole cell phenotypic response. Under the persistent treatment scheme in microplates, a panel of known β-blockers all dose-dependently and completely reversed the DMR signal of epinephrine at a relatively low dose (10 nM), except for sotalol which partially reversed the DMR. Under the perfusion conditions with microfluidics, the subsequent perfusion with sotalol only reversed the DMR induced by epinephrine or isoproterenol at 10 nM, but not at 10 μM. Furthermore, the degree of the DMR reversion by sotalol was found to be in an opposite relation with the duration of the initial agonist treatment. Together, these results suggest that the hydrophilic antagonist sotalol is constrained outside the cells throughout the assays, and the early signalling wave initiated at the cell surface dominates the DMR induced by epinephrine or isoproterenol at relatively low doses, while a secondary and late signalling wave is initiated once the receptors are internalized and contributes partially to the long-term sustainability of the DMR of epinephrine or isoproterenol at high doses.

Increasing acidity is a promising method for bacterial inactivation by inhibiting the synthesis of intracellular proteins at low pH. However, conventional ways of pH control are not reversible, which can cause continuous changes in cellular and biological behaviours and are harmful to the host. Utilizing a photoacid that can reversibly alter pH over two units, we demonstrated a strong bacterial inhibition assisted by visible light. The pH value of the solution reverts back to the original level immediately after the irradiation is stopped. If a photoacid is combined with colistin, the minimum inhibitory concentration (MIC) of colistin on multidrug-resistant (MDR) Pseudomonas aeruginosa can be improved ∼32 times (from 8 to 0.25 μg mL -1 ), which significantly decreases the toxicity of colistin in clinics. Evidenced by the extremely low toxicity of the photoacid, this strategy is promising in MDR bacteria killing.

This paper describes a nanoparticle enhanced X-ray irradiation based strategy that can be used to kill multidrug resistant (MDR) bacteria. In the proof-of-concept experiment using MDR Pseudomonas aeruginosa (P. aeruginosa) as an example, polyclonal antibody modified bismuth nanoparticles are introduced into bacterial culture to specifically target P. aeruginosa. After washing off uncombined bismuth nanoparticles, the bacteria are irradiated with X-rays, using a setup that mimics a deeply buried wound in humans. Results show that up to 90% of MDR P. aeruginosa are killed in the presence of 200 μg ml(-1) bismuth nanoparticles, whereas only ∼6% are killed in the absence of bismuth nanoparticles when exposed to 40 kVp X-rays for 10 min. The 200 μg ml(-1) bismuth nanoparticles enhance localized X-ray dose by 35 times higher than the control with no nanoparticles. In addition, no significant harmful effects on human cells (HeLa and MG-63 cells) have been observed with 200 μg ml(-1) bismuth nanoparticles and 10 min 40 kVp X-ray irradiation exposures, rendering the potential for future clinical use. Since X-rays can easily penetrate human tissues, this bactericidal strategy has the potential to be used in effectively killing deeply buried MDR bacteria in vivo.

Binding kinetics of drugs is increasingly recognized to be important for their in vivo efficacy and safety profiles. However, little is known about the effect of drug binding kinetics on receptor signaling in native cells. Here we used label-free whole cell dynamic mass redistribution (DMR) assays under persistent and duration-controlled stimulation conditions to investigate the influence of the binding kinetics of four antagonists on the signaling of endogenous muscarinic M3 receptor in native HT-29 cells. Results showed that DMR assays under different conditions differentiated the biochemical mechanisms of action of distinct M3 antagonists. When co-stimulated with acetylcholine, tiotropium, a relatively slow binding antagonist, was found to selectively block the late signaling of the receptor, suggesting that acetylcholine attains its binding equilibrium faster than tiotropium does, thereby still being able to initiate its rapid response until the antagonist draws up and fully blocks the signaling. Furthermore, DMR assays under microfluidics allowed estimation of the residence times of these antagonists acting at the receptor in native cells, which were found to be the determining factor for the blockage efficiency of M3 receptor signaling under duration-controlled conditions. This study demonstrates that DMR assays can be used to elucidate the functional consequence of kinetics-driven antagonist occupancy in native cells.

This paper describes in vitro cytotoxicity of bismuth nanoparticles revealed by three complementary assays (MTT, G6PD, and calcein AM/EthD-1). The results show that bismuth nanoparticles are more toxic than most previously reported bismuth compounds. Concentration dependent cytotoxicities have been observed for bismuth nanoparticles and surface modified bismuth nanoparticles. The bismuth nanoparticles are non-toxic at concentration of 0.5 nM. Nanoparticles at high concentration (50 nM) kill 45, 52, 41, 34 % HeLa cells for bare nanoparticles, amine terminated bismuth nanoparticles, silica coated bismuth nanoparticles, and polyethylene glycol (PEG) modified bismuth nanoparticles, respectively; which indicates cytotoxicity in terms of cell viability is in the descending order of amine terminated bismuth nanoparticles, bare bismuth nanoparticles, silica coated bismuth nanoparticles, and PEG modified bismuth nanoparticles. HeLa cells are more susceptible to toxicity from bismuth nanoparticles than MG-63 cells. The simultaneous use of three toxicity assays provides information on how nanoparticles interact with cells. Silica coated bismuth nanoparticles can damage cellular membrane yet keep mitochondria less influenced; while amine terminated bismuth nanoparticles can affect the metabolic functions of cells. The findings have important implications for caution of nanoparticle exposure and evaluating toxicity of bismuth nanoparticles.

The early detection and eradication of circulating tumor cells (CTCs) play an important role in cancer metastasis management. This paper describes a new nanoparticle-enabled technique for integrated enrichment, detection and killing of CTCs by using magnetic nanoparticles and bismuth nanoparticles, X-ray fluorescence spectrometry, and X-ray radiation. The nanoparticles are modified with tumor targeting agents and conjugated with tumor cells through folate receptors over-expressed on cancer cells. A permanent micro-magnet is used to collect CTCs suspended inside a flowing medium that contains phosphate buffered saline (PBS) or whole blood. The characteristic X-ray emissions from collected bismuth nanoparticles, upon excitation with collimated X-rays, are used to detect CTCs. Results show that the method is capable of selectively detecting CTCs at concentrations ranging from 100-100,000 cells/mL in the buffer solution, with a detection limit of ≈ 100 CTCs/mL. Moreover, the dose of primary X-rays can be enhanced to kill the localized CTCs by radiation induced DNA damage, with minimal invasiveness, thus making in vivo personalized CTC management possible., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This paper reports an image-based, on-chip microtissue radiation biodosimeter that can simultaneously monitor radiation responses of multiple mammalian cell types. The microtissue chip is fabricated by molding molten agarose gel onto microfabricated patterns to form microwells, and seeding a variety of cell suspensions into different microwells inside the agarose gel. The camera of a mobile phone is used to collect images of an array of microtissues, and the color changes of microtissues upon X-ray irradiation allow accurate determination of cell death, which is related to radiation dose. The images can be transferred wirelessly, allowing the biodosimeter to be used for convenient and field deployable monitoring of radiation exposure.

Traditional in vitro nanotoxicity researches are conducted on cultured two-dimensional (2D) monolayer cells and thereby cannot reflect organism response to nanoparticle toxicities at tissue levels. This paper describes a new, high-throughput approach to test in vitro nanotoxicity in three-dimensional (3D) microtissue array, where microtissues are formed by seeding cells in nonsticky microwells, and cells are allowed to aggregate and grow into microtissues with defined size and shape. Nanoparticles attach and diffuse into microtissues gradually, causing radial cytotoxicity among cells, with more cells being killed on the outer layers of the microtissue than inside. Three classical toxicity assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT), glucose-6-phosphate dehydrogenase (G6DP), and calcein AM and ethidium homodimer (calcein AM/EthD-1)] have been adopted to verify the feasibility of the proposed approach. Results show that the nanotoxicities derived from this method are significantly lower than that from traditional 2D cultured monolayer cells (p < 0.05). Equipped with a microplate reader or a microscope, the nanotoxicity assay could be completed automatically without transferring the microtissue, ensuring the reliability of toxicity assay. The proposed approach provides a new strategy for high-throughput, simple, and accurate evaluation of nanoparticle toxicities by combining 3D microtissue array with a panel of classical toxicity assays.

This paper describes a new type of silica microspheres that contain a panel of phase change nanoparticles (Field's alloy, indium, tin or lead-tin eutectic alloy). The thermophysical properties of solid-liquid phase change nanoparticles, i.e., composition-dependent melting temperatures, sharp melting peaks, and large thermal scan range, allow construction of a large number of silica microspheres that have thermally distinguishable patterns of melting temperatures.

The molecular level damage to DNA is important due to DNA's susceptibility to free radical attacks and crucial roles in maintaining cell functions. Although a panel of techniques can be used to detect DNA damages, most of them are limited due to low sensitivity, low throughput, incompatibility for automated data analysis, and labor-intensive operations. We have developed a cell array based DNA damage assay in which mammalian cells are attached on an array of microfabricated patterns through electrostatic interactions. After trapping patterned cells inside gels, damaged DNA fragment can diffuse out of the nucleus and form a halo around each cell inside gels. The halo array can be observed fluorescently after labeling DNA with ethidium bromide. DNA damages can be determined sensitively at the single cell level, accurately due to the symmetric shape of the halo, and automatically due to the spatial registry of each cell and the nonoverlapping halos surrounding cells. The HaloChip can be used to detect DNA damages caused by chemicals and ultraviolet and X-ray irradiations with high efficiency. A major advantage of HaloChip is the ability to increase throughout by spatially encoding multiple dosing conditions on the same chip. Most importantly, the method can be used to measure variations in response to DNA damaging agents within the same cell population. Compared with halo assay or comet assay alone, this method allows automated analysis of a million cells without an overlapping issue. Compared with the microwell array based comet assay, this method can selectively capture and analyze cells, and the results can be easily analyzed to provide precise information on DNA damage. This method can be used in a broad range of clinical, epidemiological, and experimental settings.

A big challenge for multiplexed detection of cancer biomarkers is that biomarker concentrations in body fluid differs several orders of magnitude. Existing techniques are not suitable to detect low- and high-concentration biomarkers (protein and DNA) at the same time, and liquid chromatography or electrophoresis is used to separate or purify target biomarkers before analysis. This paper describes a new broad-range biomarker assay using solid to liquid phase change nanoparticles, where a panel of metallic nanoparticles (i.e., metals and eutectic alloys) are modified with a panel of ligands to establish a one-to-one correspondence and attached onto ligand-modified substrates by forming sandwiched complexes. The melting peak and fusion enthalpy of phase change nanoparticles during thermal analysis reflect the type and concentration of biomarkers, respectively. The thermal readout condition can be adjusted in such a way that multiple biomarkers with concentration difference over 3 orders of magnitude have been simultaneously detected under the same condition.

This paper describes a novel thermal biosensing technique for the highly sensitive and selective detection of thrombin using RNA aptamer-functionalized phase change nanoparticles as thermal probes. The presence of thrombin in solution leads to attachment of nanoparticles onto a substrate modified with the same aptamer by forming sandwiched complexes. The phase changes of nanoparticles from solid to liquid adsorb heat energy and generate sharp melting peaks during linear temperature scans, where the positions and areas of the melting peaks reflect the presence and the amount of thrombin, respectively. A detection sensitivity of 22 nM is achieved on flat aluminum surfaces, and the sensitivity can be enhanced by four times using silicon nanopillar substrates that have higher surface area. The thermal detection is immune to colored species in solution and has been used directly to detect thrombin in serum samples. By combining the high specificity of aptamers and the large surface area of silicon nanostructures, the thermal signals obtained during phase change of nanoparticles provide a highly sensitive, selective and low-cost method for thrombin detection., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Most of the existing techniques cannot be used to detect molecular biomarkers contained in complex fluids due to issues such as enzyme inhibition or signal interference. We have developed a nanoparticle-based scanning calorimetric method for the highly sensitive detections of multiple DNA biomarkers contained in cell lysate and milk by using solid-liquid phase change nanoparticles as thermal barcodes. The detection is based on the principle that the temperature of solid will not rise above the melting temperature unless all solid is molten, thus nanoparticles have sharp melting peaks during the thermal scan process. A one-to-one correspondence can thus be created between one type of nanoparticles and one type of biomarker, i.e., multiple biomarkers can be detected at the same time using a combination of nanoparticles. The melting temperature and the heat flow reflect the type and the concentration of the biomarker, respectively. The target oligonucleotides at low concentration in cell lysate (80 pM) have been detected through thermal signal transduction. The melting temperature of nanoparticles can be designed to avoid interference from coexisting species contained in the fluids, bringing simultaneously high sensitivity and multiplicity, as well as sample preparation benefits to biomarker detections.