Two-Step Competitive Hybridization Assay: A Method for Analyzing Cancer-Related microRNA Embedded in Extracellular Vesicles.

With an increased understanding of the role of microRNAs (miRNAs) in cancer evolution, there is a growing interest in the use of these non-coding nucleic acids in cancer diagnosis, prognosis, and treatment monitoring. miRNAs embedded in extracellular vesicles (EVs) are of particular interest given that circulating EVs carry cargo that are strongly correlated to their cells of origin such as tumor cells while protecting them from degradation. As such, there is a tremendous interest in new simple-to-operate vesicular microRNA analysis tools for widespread use in performing liquid biopsies. Herein, we present a two-step competitive hybridization assay that is rationally designed to translate low microRNA concentrations to large electrochemical signals as the measured signal is inversely proportional to the microRNA concentration. Using this assay, with a limit-of-detection of 122 aM, we successfully analyzed vesicular miRNA 200b from prostate cancer cell lines and human urine samples, demonstrating the expected lower expression levels of miRNA 200b in the EVs from prostate cancer cells and in the prostate cancer patient's urine samples compared to healthy patients and non-tumorigenic cell lines, validating the suitability of our approach for clinical analysis.

Enhancing the Sensitivity of Photoelectrochemical DNA Biosensing Using Plasmonic DNA Barcodes and Differential Signal Readout.

Photoelectrochemical biosensors hold great promise for sensitive bioanalysis; however, similar to their electrochemical analogues, they are highly affected by the variable backgrounds caused by biological matrices. We developed a new PEC biosensing strategy that uses differential signal generation, combining signals from two separate but correlated binding events on the biosensor, for improving the limit-of-detection, sensitivity, and specificity of PEC DNA biosensors in biological samples. In this assay, the binding of unlabeled target DNA is followed by the capture of a signal amplification barcode featuring a plasmonic nanoparticle. The interaction of the plasmonic barcode with the semiconductive building blocks of the biosensor results in significant signal amplification, and together with differential signal processing enhances the limit of detection and sensitivity of the assay by up to 15- and three-fold, respectively, compared to the previously-used PEC assays with a single binding event, demonstrating a limit of detection of 3 fM.

Correction: Solution-processed wrinkled electrodes enable the development of stretchable electrochemical biosensors.

Correction for 'Solution-processed wrinkled electrodes enable the development of stretchable electrochemical biosensors' by Yuting Chan et al., Analyst, 2019, 144, 172-179.

Solution-processed wrinkled electrodes enable the development of stretchable electrochemical biosensors.

Wearable biosensors are critical for enabling real-time and continuous health monitoring and disease management. Conductors that retain their conductivity under strain are an essential building block of these systems. Strategies based on stretchable materials or structures have enabled the development of electrodes that can withstand impressive strains before loss of conductivity. In spite of this, it remains challenging to develop three-dimensional and high surface area electrodes that combine stretchability with high analytical sensitivity. Here, we develop stretchable electrochemical biosensors using solution-processed wrinkled gold electrodes. Wrinkling enhances the surface area of the electrodes and allows glucose to be detected with a sensitivity of 750-810 µA M-1 cm-2. Furthermore, wrinkling enables electrodes to be strained by up to 230% without significant loss in conductivity.

Gatekeeper Tyrosine Phosphorylation of SYMRK Is Essential for Synchronizing the Epidermal and Cortical Responses in Root Nodule Symbiosis.

Symbiosis receptor kinase (SYMRK) is indispensable for activation of root nodule symbiosis (RNS) at both epidermal and cortical levels and is functionally conserved in legumes. Previously, we reported SYMRK to be phosphorylated on "gatekeeper" Tyr both in vitro as well as in planta. Since gatekeeper phosphorylation was not necessary for activity, the significance remained elusive. Herein, we show that substituting gatekeeper with nonphosphorylatable residues like Phe or Ala significantly affected autophosphorylation on selected targets on activation segment/αEF and ß3-αC loop of SYMRK. In addition, the same gatekeeper mutants failed to restore proper symbiotic features in a symrk null mutant where rhizobial invasion of the epidermis and nodule organogenesis was unaffected but rhizobia remain restricted to the epidermis in infection threads migrating parallel to the longitudinal axis of the root, resulting in extensive infection patches at the nodule apex. Thus, gatekeeper phosphorylation is critical for synchronizing epidermal/cortical responses in RNS.

Intracellular catalytic domain of symbiosis receptor kinase hyperactivates spontaneous nodulation in absence of rhizobia.

Symbiosis Receptor Kinase (SYMRK), a member of the Nod factor signaling pathway, is indispensible for both nodule organogenesis and intracellular colonization of symbionts in rhizobia-legume symbiosis. Here, we show that the intracellular kinase domain of a SYMRK (SYMRK-kd) but not its inactive or full-length version leads to hyperactivation of the nodule organogenic program in Medicago truncatula TR25 (symrk knockout mutant) in the absence of rhizobia. Spontaneous nodulation in TR25/SYMRK-kd was 6-fold higher than rhizobia-induced nodulation in TR25/SYMRK roots. The merged clusters of spontaneous nodules indicated that TR25 roots in the presence of SYMRK-kd have overcome the control over both nodule numbers and their spatial position. In the presence of rhizobia, SYMRK-kd could rescue the epidermal infection processes in TR25, but colonization of symbionts in the nodule interior was significantly compromised. In summary, ligand-independent deregulated activation of SYMRK hyperactivates nodule organogenesis in the absence of rhizobia, but its ectodomain is required for proper symbiont colonization.

Hybrid pn-junction solar cells based on layers of inorganic nanocrystals and organic semiconductors: optimization of layer thickness by considering the width of the depletion region.

We report the formation and characterization of hybrid pn-junction solar cells based on a layer of copper diffused silver indium disulfide (AgInS2@Cu) nanoparticles and another layer of copper phthalocyanine (CuPc) molecules. With copper diffusion in the nanocrystals, their optical absorption and hence the activity of the hybrid pn-junction solar cells was extended towards the near-IR region. To decrease the particle-to-particle separation for improved carrier transport through the inorganic layer, we replaced the long-chain ligands of copper-diffused nanocrystals in each monolayer with short-ones. Under illumination, the hybrid pn-junctions yielded a higher short-circuit current as compared to the combined contribution of the Schottky junctions based on the components. A wider depletion region at the interface between the two active layers in the pn-junction device as compared to that of the Schottky junctions has been considered to analyze the results. Capacitance-voltage characteristics under a dark condition supported such a hypothesis. We also determined the width of the depletion region in the two layers separately so that a pn-junction could be formed with a tailored thickness of the two materials. Such a "fully-depleted" device resulted in an improved photovoltaic performance, primarily due to lessening of the internal resistance of the hybrid pn-junction solar cells.

Substrate-controlled band positions in CH3NH3PbI3 perovskite films.

Using X-ray and ultraviolet photoelectron spectroscopy, the surface band positions of solution-processed CH3NH3PbI3 perovskite thin films deposited on an insulating substrate (Al2O3), various n-type (TiO2, ZrO2, ZnO, and F:SnO2 (FTO)) substrates, and various p-type (PEDOT:PSS, NiO, and Cu2O) substrates are studied. Many-body GW calculations of the valence band density of states, with spin-orbit interactions included, show a clear correspondence with our experimental spectra and are used to confirm our assignment of the valence band maximum. These surface-sensitive photoelectron spectroscopy measurements result in shifting of the CH3NH3PbI3 valence band position relative to the Fermi energy as a function of substrate type, where the valence band to Fermi energy difference reflects the substrate type (insulating-, n-, or p-type). Specifically, the insulating- and n-type substrates increase the CH3NH3PbI3 valence band to Fermi energy difference to the extent of pinning the conduction band to the Fermi level; whereas, the p-type substrates decrease the valence band to Fermi energy difference. This observation implies that the substrate's properties enable control over the band alignment of CH3NH3PbI3 perovskite thin-film devices, potentially allowing for new device architectures as well as more efficient devices.

An approach to evaluate the efficacy of vaginal misoprostol administered for a rapid management of first trimester spontaneous onset incomplete abortion, in comparison to surgical curettage.

PURPOSE: The purpose of this study is to evaluate the efficacy and safety of the medical method in the management of first trimester spontaneous onset incomplete abortion, by using misoprostol vaginal tablets, in comparison to surgical evacuation, with an intention of completing the procedure within 24 h. METHODS: In this prospective, randomised study of 100 women admitted with features suggestive of incomplete abortion, 50 women received misoprostol vaginal tablets, while another 50 underwent suction curettage of products of conceptus. They were followed up after 24 h of last dosage of misoprostol or surgical intervention. Statistical analysis was done with respect to efficacy, safety and procedure-related side effects. RESULTS: In this study, when analysed after 24 h of treatment allocation, the efficacy of misoprostol was 91.3%, and the efficacy of the surgical method was 96%, with the statistical difference being insignificant. Procedure-related blood loss and pain perception between the two groups were statistically insignificant. However, the incidence of fever in the misoprostol group statistically appeared higher. CONCLUSIONS: Misoprostol could be a safe and easily accessible alternative to surgical evacuation, in cases of first trimester spontaneous onset incomplete miscarriage, and could be administered by the patient herself at home.

A universal bacterial sensor created by integrating a light modulating aptamer complex with photoelectrochemical signal readout.

Photoelectrochemical (PEC) signal transduction is of great interest for ultrasensitive biosensing; however, signal-on PEC assays that do not require target labeling remain elusive. In this work, we developed a signal-on biosensor that uses nucleic acids to modulate PEC currents upon target capture. Target presence removes a biorecognition probe from a DNA duplex carrying a gold nanoparticle, bringing the gold nanoparticle in direct contact to the photoelectrode and increasing the PEC current. This assay was used to develop a universal bacterial detector by targeting peptidoglycan using an aptamer, demonstrating a limit-of-detection of 82 pg/mL (13 pM) in buffer and 239 pg/mL (37 pM) in urine for peptidoglycan and 1913 CFU/mL forEscherichia coliin urine. When challenged with a panel of unknown targets, the sensor identified samples with bacterial contamination versus fungi. The versatility of the assay was further demonstrated by analyzing DNA targets, which yielded a limit-of-detection of 372 fM.

Factors that predict compliance in a virtual cardiac rehabilitation program.

BACKGROUND: Despite the well-established benefits of cardiac rehabilitation (CR) for patients with cardiovascular disease (CVD), participation in CR remain low. Virtual CR programs present a unique opportunity to promote utilization. To date, few virtual CR cohorts have been analyzed for compliance. This study aims to determine factors that predict compliance within a large virtual CR program in the United States. METHODS: We analyzed 1409 patients enrolled in the Kaiser Permanente Mid-Atlantic States Virtual CR program that consists of 12 CR sessions via telephone. Demographic characteristics, as well as body weight, blood pressure, HbA1c level, and smoking status were collected at admission. Patients were further classified by CVD diagnosis codes. Compliance was defined as at least 75% (9/12 sessions) attendance. Data was analyzed using simple and multiple regression models with significance defined as P < 0.05. RESULTS: Age was the single strongest predictor for virtual CR compliance (adjusted R2 = 0.58; P < 0.001), and non-compliant patients were younger. HbA1C level, CVD diagnosis codes, and smoking status each moderately predicted compliance (adjusted R2 = 0.48, 0.42, and 0.31, respectively; P < 0.001). Smoking and HbA1C level combined in a multiple regression model significantly improved prediction of compliance (adjusted R2 = 0.79, P < 0.01). Sex, baseline weight or hypertension were not significant predictors of CR compliance. CONCLUSIONS: Age, diabetes, CVD diagnoses, smoking status at admission are independent predictors of compliance in a large virtual CR program. Targeted intervention could be designed accordingly to improve CR compliance.

Cu2ZnSnS4 (CZTS) nanoparticle based nontoxic and earth-abundant hybrid pn-junction solar cells.

A heterojunction between a layer of CZTS nanoparticles and a layer of fullerene derivatives forms a pn-junction. We have used such an inorganic-organic hybrid pn-junction device for solar cell applications. As routes to optimize device performance, interdot separation has been reduced by replacing long-chain ligands of the quantum dots with short-chain ligands and thickness of the CZTS layer has been varied. We have shown that the CZTS-fullerene interface could dissociate photogenerated excitons due to the depletion region formed at the pn-junction. From capacitance-voltage characteristics, we have determined the width of the depletion region, and compared it with the parameters of devices based on the components of the heterojunction. The results demonstrate solar cell applications based on nontoxic and earth-abundant materials.

Metallic Dental Implants Wear Mechanisms, Materials, and Manufacturing Processes: A Literature Review.

OBJECTIVES: From the treatment of damaged teeth to replacing missing teeth, dental biomaterials cover the scientific interest of many fields. Dental biomaterials are one of the implants whose effective life depends vastly on their material and manufacturing techniques. The purpose of this review is to summarize the important aspects for metallic dental implants from biomedical, mechanical and materials science perspectives. The review article will focus on five major aspects as mentioned below. Tooth anatomy: Maximizing the implant performance depends on proper understanding of human tooth anatomy and the failure behavior of the implants. Major parts from tooth anatomy including saliva characteristics are explored in this section. Wear mechanisms: The prominent wear mechanisms having a high impact on dental wear are abrasive, adhesive, fatigue and corrosion wear. To imitate the physiological working condition of dental implants, reports on the broad range of mastication force and various composition of artificial saliva have been included in this section, which can affect the tribo-corrosion behavior of dental implants. Dental implants classifications: The review paper includes a dedicated discussion on major dental implants types and their details for better understanding their applicability and characteristics. Implant materials: As of today, the most established dental implant materials are SS316L, cobalt chrome alloy and titanium. Detailed discussion on their material properties, microstructures, phase transformations and chemical compositions have been discussed here. Manufacturing techniques: In terms of different production methods, the lost wax casting method as traditional manufacturing is considered. Selective Laser Melting (SLM) and Directed Energy Deposition (DED) as additive manufacturing techniques (AM) have been discussed. For AM, the relationships between process-property-performance details have been explored briefly. The effectiveness of different manufacturing techniques was compared based on porosity distribution, mechanical and biomechanical properties. SUMMARY: Despite having substantial research available on dental implants, there is a lack of systematic reviews to present a holistic viewpoint combining state-of-the-art from biomedical, mechanical, materials science and manufacturing perspectives. This review article attempts to combine a wide variety of analyzing approaches from those interdisciplinary fields to deliver deeper insights to researchers both in academia and industry to develop next-generation dental implants.

Vaccine-induced thrombosis and thrombocytopenia (VITT); Exploring the unknown.

Vaccination is supposed to be the most reliable means to end the COVID 19 pandemic, but recently there have been reports of thrombosis and thrombocytopenia in patients receiving the vaccine especially ChAdOx1 nCoV-19 (AstraZeneca University of Oxford and Serum Institute of India). This has been termed as vaccine-induced immune thrombotic thrombocytopenia (VITT), thrombosis with thrombocytopenia syndrome (TTS) and vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). This is a challenging situation and patients are treated with Fondaparinaux and Rivaroxaban after thrombocytopenia is corrected. Herewith, we report a case of VITT who presented to our hospital and was successfully treated over a weeks' time.

Late onset crohns ileitis-A diagnostic dilemma.

Crohn's disease may affect individuals across all age groups. Usually, it tends to start at a young age, hence late onset Crohn's disease may be difficult to diagnose. The incidence of late-onset inflammatory bowel disease in the United States is 4 to 8 per 100,000 per year. The incidence of Crohn's disease is more in the United States and Europe and less in Asia and Africa. This makes it more challenging to suspect Crohn's disease in an elderly individual of Indian origin. It may be confused with Irritable bowel syndrome or Intestinal tuberculosis.

Picking up an insulinoma - The challenges ahead.

Insulinoma is a rare pancreatic neuroendocrine tumour (PNET) with an incidence rate of 4 per million population, and the most common cause of hypoglycaemia due to endogenous hyperinsulinism. We present the story of a 61-year-old male, who was extensively evaluated at many hospitals for his symptoms of giddiness, uneasiness and recurrent black outs for the last 3 months, his symptoms disappearing with a carbohydrate rich meal or sweets. Random sugar and fasting sugar values noted were low, with elevated insulin and C-peptide levels. Diagnosis of insulinoma was confirmed by a DOTA PET scan involving the tail of the pancreas and then surgically removed. Early detection is crucial for early surgery to allay symptoms. We describe our diagnostic and treatment plan with reference to previously published reports.

Emergent many-body composite excitations of interacting spin-1/2 trimers.

Understanding exotic forms of magnetism in quantum spin systems is an emergent topic of modern condensed matter physics. Quantum dynamics can be described by particle-like carriers of information, known-as quasiparticles that appear from the collective behaviour of the underlying system. Spinon excitations, governing the excitations of quantum spin-systems, have been accurately calculated and precisely verified experimentally for the antiferromagnetic chain model. However, identification and characterization of novel quasiparticles emerging from the topological excitations of the spin system having periodic exchange interactions are yet to be obtained. Here, we report the identification of emergent composite excitations of the novel quasiparticles doublons and quartons in spin-1/2 trimer-chain antiferromagnet Na2Cu3Ge4O12 (having periodic intrachain exchange interactions J1-J1-J2) and its topologically protected quantum 1/3 magnetization-plateau state. The characteristic energies, dispersion relations, and dynamical structure factor of neutron scattering as well as macroscopic quantum 1/3 magnetization-plateau state are in good agreement with the state-of-the-art dynamical density matrix renormalization group calculations.

Haldane and dimer phases in a frustrated spin chain: an exact groundstate and associated topological phase transition.

A Heisenberg spin-s chain with alternating ferromagnetic (FM) ([Formula: see text]) and antiferromagnetic ([Formula: see text]) nearest-neighbor (NN) interactions, exhibits the dimer and spin-2s Haldane phases in the limits [Formula: see text] and [Formula: see text] respectively. These two phases are understood to be topologically equivalent. Induction of the frustration through the next NN FM interaction ([Formula: see text]) produces a very rich quantum phase diagram. With frustration, the whole phase diagram is divided into a FM and a nonmagnetic (NM) phase. For s = 1/2, the full NM phase is seen to be of Haldane-dimer type, but for s > 1/2, a spiral phase comes between the FM and the Haldane-dimer phases. The study of a suitably defined string-order parameter and spin-gap at the phase boundary indicates that the Haldane-dimer and spiral phases have different topological characters. We also find that, along the [Formula: see text] line in the NM phase, an NN dimer state is the exact groundstate, provided [Formula: see text] where κ ⩽ s + h for applied magnetic field h. Without magnetic field, the position of J C is on the FM-NM phase boundary when s = 1/2, but for s > 1/2, the location of J C is on the phase separation line between the Haldane-dimer and spiral phases.

Differential Photoelectrochemical Biosensing Using DNA Nanospacers to Modulate Electron Transfer between Metal and Semiconductor Nanoparticles.

As dynamic biorecognition agents such as functional nucleic acids become widely used in biosensing, there is a need for ultrasensitive signal transduction strategies, beyond fluorescence, that are robust and stable for operation in heterogeneous biological samples. Photoelectrochemical readout offers a pathway toward this goal as it offers the simplicity and scalability of electrochemical readout, in addition to compatibility with a broad range of nanomaterials used as labels for signal transduction. Here, a differential photoelectrochemical biosensing approach is reported, in which DNA nanospacers are used to program the response of two sensing channels. The differences in the motional dynamics of DNA probes immobilized on different channels are used to control the interaction between Au and TiO2 nanoparticles positioned at the two ends of the DNA nanospacer to achieve differential signal generation. Depending on the composition of the DNA constructs (fraction of the DNA sequence i.e., double-stranded), the channels can be programmed to produce a signal-on or a signal-off response. Incident photon-to-current conversion efficiency, UV-vis spectroscopy, and flat-band potential measurement indicate that direct transfer of electrons between metallic and semiconductive nanoparticles is responsible for the signal-on response, and incident light absorption and steric hindrance are responsible for the signal-off response. The differential photoelectrochemical signal readout developed here increases the device sensitivity by up to three times compared to a single channel design and demonstrates a limit of detection of 800 aM.