Utilizing Laser-Induced Fluorescence to Evaluate the Efficiency of Carbon Dioxide and Diode Lasers in Dentin Sealing after Tooth Preparation: An in-vitro Study.

Adhesive dentistry has made it feasible to design restorations with high aesthetic qualities and little invasiveness. However, the freshly cut dentin after the tooth preparation needs to be sealed to prevent its contaminations, bacterial leakage, and hypersensitivity. Consequently, the immediate dentin sealing (IDS) method has been advised. This study examines different dentinal tubule sealing methods via CO2 laser, diode laser (980-nm) and a two-step self-etch adhesive system applied directly to the fresh cut dentin preceding the placement of the provisional phase. The sealing efficiency of each laser and bond system was evaluated based on the laser-induced fluorescence (LIF) properties and image analysis by scanning electron microscopy. Moreover, the obtained LIF spectra were evaluated using partial least square progression. A two-step adhesive containing a high concentration of S-PRG fillers produced a thick layer that was not perfectly uniform at all sites due to uneven filler distribution in the bond with totally and partially closed dentinal tubules. However, the peaks of the LIF spectra dropped after applying laser because of its sealing effectiveness. Accordingly, CO2 and diode lasers have strong evidence in dentinal tubule sealing and a definitive treatment modality for dentinal hypersensitivity. Moreover, IDS with an adhesive system is superior in occluding dentinal tubules in a biomimetic manner based on its filler content and bioactive properties.

Prevalence, indications and fetal outcomes of operative vaginal delivery in Sub-Saharan Africa, systematic review, and meta-analysis.

PURPOSE: This systematic review and meta-analysis is intended to assess the prevalence, indications, and fetal outcome of operative vaginal delivery in sub-Saharan Africa. METHOD: In this study, 17 studies with a total population of 190,900 were included in both systematic review and meta-analysis. Search for relevant articles was done by using international online databases (like Google Scholar, PubMed, HINARI, EMBASE, Web of Science, and African journals) and online repositories of Universities in Africa. The JOANNA Briggs Institute standard data extraction format was used to extract and appraise high-quality articles before being included in this study. The Cochran Q and I2 statistical tests were used to test the heterogeneity of the studies. The publication bias was tested by a Funnel plot and Egger's test. The overall pooled prevalence, indications, and fetal outcome of operative vaginal delivery along a 95% CI using forest plots and tables. RESULT: The overall pooled prevalence of operative vaginal delivery in sub-Saharan Africa was 7.98% (95% CI; 5.03-10.65; I2 = 99.9%, P < 0.001). The indications of operative vaginal delivery in sub-Saharan African countries include the prolonged second stage of labor 32.81%, non-reassuring fetal heart rate 37.35%, maternal exhaustion 24.81%, big baby 22.37%, maternal cardiac problems 8.75%, and preeclampsia/eclampsia 2.4%. Regarding the fetal outcome, favourable fetal outcomes were 55% (95% CI: 26.04, 84.44), p = < 0.56, I2: 99.9%). From those births with unfavourable outcomes, the need for the resuscitation of new-born was highest 28.79% followed by poor 5th minute Apgar score, NICU admission, and fresh stillbirth, 19.92, 18.8, and 3.59% respectively. CONCLUSION: The overall prevalence of operative vaginal delivery (OVD) in sub-Saharan Africa was slightly higher compared to other countries. To reduce the increased applications and adverse fetal outcomes of OVD, capacity building for obstetrics care providers and drafting guidelines are required.

Nanostructured Carbons: Towards Soft-Bioelectronics, Biosensing and Theraputic Applications.

Recently, nanostructured carbon-based soft bioelectronics and biosensors have received tremendous attention due to their outstanding physical and chemical properties. The ultrahigh specific surface area, high flexibility, lightweight, high electrical conductivity, and biocompatibility of 1D and 2D nanocarbons, such as carbon nanotubes (CNT) and graphene, are advantageous for bioelectronics applications. These materials improve human life by delivering therapeutic advancements in gene, tumor, chemo, photothermal, immune, radio, and precision therapies. They are also utilized in biosensing platforms, including optical and electrochemical biosensors to detect cholesterol, glucose, pathogenic bacteria (e. g., coronavirus), and avian leucosis virus. This review summarizes the most recent advancements in bioelectronics and biosensors by exploiting the outstanding characteristics of nanocarbon materials. The synthesis and biocompatibility of nanocarbon materials are briefly discussed. In the following sections, applications of graphene and CNTs for different therapies and biosensing are elaborated. Finally, the key challenges and future perspectives of nanocarbon materials for biomedical applications are highlighted.

Utilization of gold nanoparticles for the detection of squamous cell carcinoma of the tongue based on laser-induced fluorescence and diffuse reflectance characteristics: an in vitro study.

Squamous cell carcinoma is a very common type of oral cancer that affects the health of people with an unacceptably high mortality rate attributed to the difficulties in detecting the disease at an early stage. Therefore, effective techniques for early diagnosis and effective therapy of oral cancer are necessary. In the present study, we exploit the ability of gold nanoparticles (AuNPs) to undergo coupled surface plasmon resonance when closely spaced to improve diagnosing squamous cell carcinoma of the tongue. The prepared AuNPs are characterized by UV-VIS spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy. The size of the prepared AuNPs is 12 ± 2 nm with narrow size distributions and exhibited high stability with a zeta potential of - 16.5 mV. The light fluorescence of the normal and cancer cells is recorded before and after NP addition using a spectrometer upon excitation by 405-nm laser irradiation. Furthermore, the light reflectance of the examined samples is measured at different laser wavelengths (red to NIR region). The obtained results show that the cancer cells mixed with AuNPs produce a higher fluorescence peak at 489.2 nm than the cancer cells without AuNPs. Moreover, the optical diffuse reflectance analyses reveal that the addition of AuNPs enhances cancer detection especially at the 635-nm irradiation with sensitivity (94%), specificity (87%), and overall accuracy (91%).

Energy Efficient UAV Flight Path Model for Cluster Head Selection in Next-Generation Wireless Sensor Networks.

Wireless sensor networks (WSNs) are one of the fundamental infrastructures for Internet of Things (IoTs) technology. Efficient energy consumption is one of the greatest challenges in WSNs because of its resource-constrained sensor nodes (SNs). Clustering techniques can significantly help resolve this issue and extend the network's lifespan. In clustering, WSN is divided into various clusters, and a cluster head (CH) is selected in each cluster. The selection of appropriate CHs highly influences the clustering technique, and poor cluster structures lead toward the early death of WSNs. In this paper, we propose an energy-efficient clustering and cluster head selection technique for next-generation wireless sensor networks (NG-WSNs). The proposed clustering approach is based on the midpoint technique, considering residual energy and distance among nodes. It distributes the sensors uniformly creating balanced clusters, and uses multihop communication for distant CHs to the base station (BS). We consider a four-layer hierarchical network composed of SNs, CHs, unmanned aerial vehicle (UAV), and BS. The UAV brings the advantage of flexibility and mobility; it shortens the communication range of sensors, which leads to an extended lifetime. Finally, a simulated annealing algorithm is applied for the optimal trajectory of the UAV according to the ground sensor network. The experimental results show that the proposed approach outperforms with respect to energy efficiency and network lifetime when compared with state-of-the-art techniques from recent literature.

A radiographic and histological study to compare red (650 nm) versus near infrared (810 nm) diode lasers photobiomodulation for alveolar socket preservation.

Previous findings indicated that the laser photobiomodulation is more effective than the control or placebo in preserving the alveolar socket. This study aimed to compare two different lasers regarding their effectiveness in aiding alveolar socket preservation. Twenty extraction sockets were selected then divided into two equal groups. Group A was exposed to 650 nm Diode laser, and Group B to 810 nm Diode laser following the same protocol and parameters after a standard alveolar socket preservation procedure with collagen plug. Radiographic analysis with cone beam computed tomography was done to compare the alveolar bone surface area immediately after extraction and three months post-operatively, while bone samples collected before implant drilling were histologically examined for newly formed bone evaluation and histomorphometric analysis in terms of percentage of new bone surface area, percentage of unmineralized bone and finally, immunohistochemical analysis of Osteocalcin reaction surface area as well as optical density. Radiographically, infrared (810 nm) Diode effect on alveolar bone surface area has significantly exceeded the red laser, while histologically, red (650 nm) Diode has demonstrated statistical significance regarding all parameters; newly formed bone surface area percentage, unmineralized bone area percentage and finally Osteocalcin bone marker reaction surface area percentage and optical density. Under the specified conditions and laser parameters, photobiomodulation using the 810 nm Diode got the upper hand radiographically, yet histologically, the red 650 nm Diode managed to dominate all histological parameters when both employed as an adjunct to alveolar socket preservation procedures.

Is It Possible to Eliminate Postoperative Shunt Infections?: Results of a Modified Hydrocephalus Clinical Research Network Protocol.

BACKGROUND: Postoperative shunt infection is a nightmare in neurosurgical practice with additional morbidity and mortality. A lot of protocols have contributed to the reduction of ventriculoperitoneal shunt (VPS) infections but not eradication. The aim of the study was to evaluate the rigid application of a modified Hydrocephalus Clinical Research Network (HCRN) protocol in the prevention of postoperative shunt infection. METHODS: We retrospectively evaluated children with congenital hydrocephalus who underwent VPS insertion, and in whom the protocol was applied from June 2019 to January 2020. Follow-up ranged from 11 to 24 months. RESULTS: Thirty-seven procedures were performed including 35 primary shunt insertions and two revision surgeries. The median age was 5 months (range, 1-30 months), and 25 patients were males. The most common cause for VPS placement was congenital hydrocephalus without identifiable cause in 28 cases (80%). The endoscope-assisted technique was used in the insertion of the proximal end in six cases (17%). The mean follow-up was 19.4 months (11-24 months). The rate of shunt infection was 0% till the last follow-up. CONCLUSION: The preliminary results showed an effective method for the prevention of postoperative shunt infections using the modified protocol. These initial findings need to be validated in a large prospective study before widespread application can be recommended.

Evaluating Postoperative Prognosis: A Single Surgeon's Experience With Total Mesorectal Excision in Middle and Lower Rectal Cancer Cases in Iraq.

INTRODUCTION: Surgical intervention for rectal cancer is widely recognized for its potential to significantly impact quality of life, chiefly due to the high probability of permanent colostomy and the associated postoperative complications. OBJECTIVE: This study aimed to evaluate the short-term outcomes and morbidity associated with total mesorectal excision for middle and lower rectal cancer within an Iraqi cohort, in a prospective setting. METHODS: This study prospectively collected and analyzed data from 89 patients who underwent a standardized radical rectal resection, with a follow-up period extending to one month post-surgery. RESULTS: The mean age of patients was 54.4 ± 12.9 years, with a gender distribution of 46 males and 43 females. A total of 33 patients presented with preoperative comorbidities, which heightened the risk of adverse short-term outcomes by a factor of 7.51. The most prevalent comorbidities were hypertension and diabetes mellitus, affecting 22 and 20 patients, respectively. Patients aged 60 years and above were at a 3.97 times greater risk of developing complications. The overall complication rate was 21.35%, with wound infections (9.0%) and cardiovascular events (3.4%) being the most common. Mortality during the follow-up was 1.1%. CONCLUSION: The findings indicate that increased age and the presence of comorbidities are significant risk factors for morbidity and mortality post-surgery. Neoadjuvant chemoradiotherapy or radiotherapy was shown to reduce morbidity and mortality rates while improving survival. The morbidity and mortality rates observed in this study concur with existing literature.

Serratia marcescens Endocarditis in Prosthetic Valves.

Serratia marcescens endocarditis is a rare occurrence. We describe a case of Serratia endocarditis in a patient with a prosthetic valve. The clinical course was complicated by widespread embolic phenomena causing stroke, gangrene of extremities, and septic emboli to the lungs, spleen, and eyes. She was not considered suitable for surgery due to severe consumptive coagulopathy and thrombocytopenia in the setting of widespread emboli. The patient was transitioned to do not resuscitate status and discharged to a long-term care facility with a grave prognosis explained to the family.

Population Pharmacokinetic and Exposure-Response Analyses for Efficacy and Safety of Risankizumab in Patients With Active Crohn's Disease.

The population pharmacokinetics (PK) of risankizumab and exposure-response relationships for efficacy and safety in patients with Crohn's disease (CD) were characterized using data from phase II and III studies to support dosing regimen selection. A two-compartment model with first-order absorption and first-order elimination adequately described risankizumab PK. Covariates including sex, baseline fecal calprotectin, corticosteroid use, baseline creatinine clearance, body weight, and baseline albumin were statistically correlated with risankizumab clearance, but their impact on exposure was not clinically relevant for efficacy or safety. Exposure-response analyses showed that exposures associated with the 600 mg intravenous (i.v.) induction dose at Weeks 0, 4, and 8 achieved a near maximal response for all efficacy end points evaluated, with negligible added benefit from the 1,200 mg i.v. regimen. By Week 52 of the maintenance treatment, trends of higher responses were observed for the exposure range associated with the 360 mg subcutaneous (s.c.) every-8-weeks (Q8W) regimen for most of the evaluated efficacy end points, particularly for the more stringent end points, such as endoscopic remission and ulcer-free endoscopy. Exposure-response analyses for safety did not identify any apparent relationship between exposure and safety. These results supported the final dose recommendation of 600 mg i.v. at Weeks 0, 4, and 8, followed by 360 mg s.c. at Week 12 and Q8W thereafter in patients with CD.

In vitro controlled elemental analysis to evaluate the combined effect of acidulated phosphate fluoride with Er:YAG and diode lasers.

Background: Acidulated phosphate fluoride (APF) application is used for dental caries prevention. Combining APF with different laser wavelengths increases acid resistance in enamel. Aim: To assess the effects of Er:YAG (2940 nm) laser and diode (940 nm) laser after the application of APF on morphology and mineral content of enamel surfaces of human teeth in vitro. Materials and Methods: Twenty (20) freshly extracted third molar crowns were collected and split longitudinally into halves. Ten (10) halves were given to each of the following groups: group 1 (control), group 2 (application of 1.23% APF gel only), group 3 (diode laser; 1 W for 60 sec, contact mode after APF gel), and group 4 (Er:YAG; 80 mJ, 0.8 W, 10 Hz; in pulsed mode for 10 sec after APF gel). Specimens were morphologically examined by scanning electron microscope (SEM), and mineral content was analysed by energy dispersive X-ray (EDX). Collected data were statistically analysed by ANOVA. Results: Morphologic results were superior in group 3 followed by group 2 and group 1 with the least change in group 4. EDX of calcium (Ca), phosphorous (P), and Ca/P ratio weight % showed the highest value with no statistical significance between groups 2 and 1, and higher with statistical significance in groups 3 and 4 in descending order. Carbon weight % showed highest results in group 4 then 3, 2, and 1. Fluoride weight % showed highest statistical results in group 4 then 2, 3, and 1. Conclusion: The diode laser showed superior morphological results after APF application compared to the Er:YAG laser. The Er:YAG increased fluoride absorption on outer enamel surfaces.

Contexte: L'application de fluorure de phosphate acidulé (FPA) est utilisée pour la prévention des caries dentaires. La combinaison de FPA avec différentes longueurs d'onde de laser augmente la résistance de l'émail aux acides. Objectif: Évaluer les effets du laser erbium YAG (2940 nm) et du laser à diode (940 nm) après l'application de FPA sur la morphologie et le contenu minéral des surfaces de l'émail des dents humaines in vitro. Matériaux et méthodologies: Vingt (20) couronnes de troisième molaire fraîchement extraites ont été recueillies et divisées longitudinalement en moitiés. Dix (10) moitiés ont été données à chacun des groupes suivants : groupe 1 (contrôle), groupe 2 (application de gel de FPA à 1,23 % seulement), groupe 3 (laser à diode; 1 W pendant 60 secondes, mode contact après le gel de FPA), et groupe 4 (erbium YAG; 80 mJ, 0,8 W, 10 Hz kl ; en mode pulsé pendant 10 secondes après le gel de FPA). Les spécimens ont été examinés morphologiquement au microscope électronique à balayage (MEB), et le contenu minéral a été analysé par rayons X à dispersion d'énergie (EDX). Les données recueillies ont été analysées statistiquement par ANOVA. Résultats: Les résultats morphologiques étaient supérieurs dans le groupe 3, suivi par le groupe 2 et le groupe 1, avec le changement le moins important dans le groupe 4. Le pourcentage de l'EDX du calcium (Ca), du phosphore (P) et du rapport Ca/P en poids a montré la valeur la plus élevée sans signification statistique entre les groupes 2 et 1, et la plus élevée avec signification statistique dans les groupes 3 et 4 par ordre décroissant. Le pourcentage en poids de carbone a montré les résultats les plus élevés dans le groupe 4, ensuite 3, 2 et 1. Le pourcentage en poids de fluorure a montré les résultats statistiques les plus élevés dans le groupe 4 puis 2, 3 et 1. Conclusion: Le laser à diode a montré des résultats morphologiques supérieurs après l'application de FPA par rapport au laser erbium YAG. L'erbium YAG a augmenté l'absorption du fluorure sur les surfaces externes de l'émail.

Lipid-Polymer Hybrid Nanocarriers for Oral Delivery of Felodipine: Formulation, Characterization and Ex Vivo Evaluation.

Purpose: Felodipine, is a calcium-channel antagonist used for hypertension and angina pectoris. It is practically insoluble in aqueous media and shows low oral bioavailability (15%-20%). This investigation aims to prepare and characterize oral felodipine lipid-polymer hybrid nanocarriers (LPHNs) to increase solubility and control delivery for increasing bioavailability and enhance patient compliance. Methods: The newly microwave-based method was prepared with felodipine LPHNs (H1-H35) successfully. The (H1-H35) were subjected to thermodynamic stability experiments. After that, select nine felodipine LPHNs (F1-F9) that have smart physical stability for further optimization of different characterization processes. Results: The felodipine LPHNs (F4) are considered the most optimized formula. It was characterized by lower particle size (33.3 nm), lower PDI (0.314), high zeta potential (13.6 mV), entrapment efficiency is (81.645% w/w), drug loading is (16.329% w/w), the pH value is 4, excellent percent of light transmittance (95.5%), pseudoplastic rheogram, significantly high (P < 0.05) dissolution rate with sustained drug delivery and success ex-vivo intestinal permeation attributes. The (F4) subject for further investigations of Fourier transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), and transmission electron microscopy (TEM). The results of FTIR, AFM, and TEM indicate there is no interaction between the felodipine and excipients and that the particulate system in the nanoscale dispersion system confirms the high stability. Conclusion: The optimized felodipine LPHNs (F1-F9) formulations were smart formulations for sustained oral delivery of felodipine and that F4 was the most optimized formula according to its characterization processes.

Synthesis of PEDOT:PSS Solution-Processed Electronic Textiles for Enhanced Joule Heating.

Textile-based flexible and wearable electronic devices provide an excellent solution to thermal management systems, thermal therapy, and deicing applications through the Joule heating approach. However, challenges persist in designing such cost-effective electronic devices for efficient heating performance. Herein, this study adopted a facile solution-processed strategy, "dip-coating", to develop a high-performance Joule heating device by unformly coating the intrinsically conducting polymer (CP) poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) onto the surface of cotton textiles. The structural and morphological attributes of the cotton/CP mixture were evaluated using various characterization techniques. The electrothermal characteristics of the cotton/CP sample included rapid thermal response, uniform surface temperature distribution up to 94 °C, excellent stability, and endurance in heating performance under various mechanical deformations. The real-time illustration of the fabric heater affixed on a human finger has demonstrated its outstanding potential for thermal therapy applications. The fabricated heater may further expand it purposes toward deicing, defogging, and defrosting applications.

Multi-epitope chimeric vaccine design against emerging Monkeypox virus via reverse vaccinology techniques- a bioinformatics and immunoinformatics approach.

The emerging monkeypox virus (MPXV) is a zoonotic orthopoxvirus that causes infections in humans similar to smallpox. Since May 2022, cases of monkeypox (MPX) have been increasingly reported by the World Health Organization (WHO) worldwide. Currently, there are no clinically validated treatments for MPX infections. In this study, an immunoinformatics approach was used to identify potential vaccine targets against MPXV. A total of 190 MPXV-2022 proteins were retrieved from the ViPR database and subjected to various analyses including antigenicity, allergenicity, toxicity, solubility, IFN-γ, and virulence. Three outer membrane and extracellular proteins were selected based on their respective parameters to predict B-cell and T-cell epitopes. The epitopes are conserved among different strains of MPXV and the population coverage is 100% worldwide, which will provide broader protection against various strains of the virus globally. Nine overlapping MHC-I, MHC-II, and B-cell epitopes were selected to design multi-epitope vaccine constructs linked with suitable linkers in combination with different adjuvants to enhance the immune responses of the vaccine constructs. Molecular modeling and structural validation ensured high-quality 3D structures of vaccine constructs. Based on various immunological and physiochemical properties and docking scores, MPXV-V2 was selected for further investigation. In silico cloning revealed a high level of gene expression for the MPXV-V2 vaccine within the bacterial expression system. Immune and MD simulations confirmed the molecular stability of the MPXV-V2 construct, with high immune responses within the host cell. These results may aid in the development of experimental vaccines against MPXV with increased potency and improved safety.

Microbial Transformations of (+)-Isomenthol by Fusarium lini and Rhizopus stolonifer.

Microbial transformation of (+)-isomenthol (1) by various strains of fungi was investigated. Fusarium lini has successfully converted compound 1 into a new metabolite, 5α-hydroxyisomenthol (2), and a known metabolite, 1α-hydroxyisomenthol (3), whereas incubation with Rhizopus stolonifer only yielded metabolite 3. The transformed metabolites were structurally characterized on the basis of their spectral data.

A Population Pharmacokinetic Model of (R)- and (S-) Oxybutynin and Its Active Metabolites After Oral and Intravesical Administration to Healthy Volunteers.

Oxybutynin is a racemic anticholinergic drug used for the symptomatic treatment of detrusor overactivity. The formation of active metabolites related to tolerability problems depends on the route of administration. The objective of this evaluation was to develop a pharmacokinetic model for oral/intravesical administration as the basis for simulations with different dosages. Data from a published changeover clinical study with 18 healthy adults receiving a single oral dose of 5 mg immediate-release oxybutynin and single and multiple intravesical doses of 10 mg oxybutynin solution was evaluated. Enantioselective plasma concentrations of oxybutynin and N-desethyloxybutynin (NDO) were used to establish a population pharmacokinetic model using nonlinear mixed-effects modeling with NONMEM 7.4.1. For both enantiomers, the data were described well by a 2-compartment model for oxybutynin with an additional compartment for NDO. Oxybutynin absorption was modeled by transit compartments for oral and first-order absorption for intravesical application. Bioavailability of the more active (R)-enantiomer was 7% for oral and 10%-22% for intravesical administration. In simulations, intravesical doses of 5 to 15 mg (R)-oxybutynin administered 2 to 3 times daily decreased peak-trough fluctuations of NDO to 8% compared with 24% after oral administration. The NDO/oxybutynin ratio was reduced from 17 after oral administration to unity. Chronic intravesical versus oral administration of (R)-oxybutynin generates distinctly lower and less variable concentrations of (R)-NDO. Pharmacokinetic simulations suggest that exposure for 12.5 mg (R)-oxybutynin administered twice daily might not compromise efficacy and tolerability compared with exposure for standard thrice-daily administrations. This assumption needs to be assessed in clinical studies.

Identification and characterization of potential NBS-encoding resistance genes and induction kinetics of a putative candidate gene associated with downy mildew resistance in Cucumis.

BACKGROUND: Due to the variation and mutation of the races of Pseudoperonospora cubensis, downy mildew has in recent years become the most devastating leaf disease of cucumber worldwide. Novel resistance to downy mildew has been identified in the wild Cucumis species, C. hystrix Chakr. After the successful hybridization between C. hystrix and cultivated cucumber (C. sativus L.), an introgression line (IL5211S) was identified as highly resistant to downy mildew. Nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes are the largest class of disease resistance genes cloned from plant with highly conserved domains, which can be used to facilitate the isolation of candidate genes associated with downy mildew resistance in IL5211S. RESULTS: Degenerate primers that were designed based on the conserved motifs in the NBS domain of resistance (R) proteins were used to isolate NBS-type sequences from IL5211S. A total of 28 sequences were identified and named as cucumber (C. sativus = CS) resistance gene analogs as CSRGAs. Polygenetic analyses separated these sequences into four different classes. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that these CSRGAs expressed at different levels in leaves, roots, and stems. In addition, introgression from C. hystrix induced expression of the partial CSRGAs in cultivated cucumber, especially CSRGA23, increased four-fold when compared to the backcross parent CC3. Furthermore, the expression of CSRGA23 under P. cubensis infection and abiotic stresses was also analyzed at different time points. Results showed that the P. cubensis treatment and four tested abiotic stimuli, MeJA, SA, ABA, and H2O2, triggered a significant induction of CSRGA23 within 72 h of inoculation. The results indicate that CSRGA23 may play a critical role in protecting cucumber against P. cubensis through a signaling the pathway triggered by these molecules. CONCLUSIONS: Four classes of NBS-type RGAs were successfully isolated from IL5211S, and the possible involvement of CSRGA23 in the active defense response to P. cubensis was demonstrated. These results will contribute to develop analog-based markers related to downy mildew resistance gene and elucidate the molecular mechanisms causing resistance in IL5211S in the future.

Selection of appropriate reference genes for gene expression studies by quantitative real-time polymerase chain reaction in cucumber.

Quantitative real-time polymerase chain reaction (QRT-PCR) has become one of the most widely used methods for gene expression analysis. However, the expression profile of a target gene may be misinterpreted due to unstable expression of the reference genes under different experimental conditions. Thus, a systematic evaluation of these reference genes is necessary before experiments are performed. In this study, 10 putative reference genes were chosen for identifying expression stability using geNorm, NormFinder, and BestKeeper statistical algorithms in 12 different cucumber sample pools, including those from different plant tissues and from plants treated with hormones and abiotic stresses. EF1alpha and UBI-ep exhibited the most stable expression across all of the tested cucumber samples. In different tissues, in addition to expression of EF1alpha and UBI-ep, the expression of TUA was also stable and was considered as an appropriate reference gene. Evaluation of samples treated with different hormones revealed that TUA and UBI-ep were the most stably expressed genes. However, for abiotic stress treatments, only EF1alpha showed a relatively stable expression level. In conclusion, TUA, UBI-ep, and EF1alpha will be particularly helpful for reliable QRT-PCR data normalization in these types of samples. This study also provides guidelines for selecting different reference genes under different conditions.

Green Solvent Processed Cellulose/Graphene Oxide Nanocomposite Films with Superior Mechanical, Thermal, and Ultraviolet Shielding Properties.

This study reports for the first time a green process to fabricate Lyocell fiber and graphene oxide (GO) based novel cellulose/graphene oxide nanocomposite (CGN) flexible films for ultraviolet (UV) shielding applications. A polyethelene glycol (PEG) mediated solvent system was utilized to make CGN films via solution casting route. To improve the dispersion of GO sheets in a cellulosic matrix, a reactive interface was formed in between cellulose and oxygenic functionalized groups of GO sheets via cross-linking them with epichlorohydrin (ECH). The addition of GO sheets in cellulose matrix leads to the synergistic changes, which were observed in the structure and surface morphology of CGN nanocomposite films. Enhanced dispersion of GO sheets in CGN films was observed in morphological investigations which is attributed to the adequate cellulose-GO interaction by hydrogen bonding and led to significant enhancement in the mechanical and thermal properties. The tensile strength and Young's modulus of CGN films with 2 wt % GO loading (CGN2) increased to 89 MPa and 4.3 GPa from 55.6 MPa and 2.1 GPa, respectively, as compared to the neat cellulosic film. Additionally, the CGN films exhibited remarkable UV shielding capability which increased with GO loading in a cellulose matrix. The CGN2 film (2 wt % GO loading) possessed outstanding absorbance in the wavelength range of 280 to 400 nm and showed almost complete shielding (∼99%) of UV rays in both the UV-B and the UV-A regions. Moreover, the ultraviolet protection factor of the CGN2 film demonstrated more than 80-fold increase compared to that of the neat cellulose film. The obtained CGN nanocomposite film has a high potential for applications in the field of UV protection.

Population Pharmacokinetics of Glecaprevir/Pibrentasvir in HCV-infected Japanese Subjects in Phase 3 CERTAIN-1 and CERTAIN-2 Trials.

Glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg once daily (Mavyret/Maviret) is an all-oral, pangenotypic, interferon- and ribavirin-free combination regimen approved for the treatment of chronic hepatitis C virus (HCV) infection. The objective of the current analyses was to characterize the pharmacokinetics (PK) of GLE/PIB in HCV-infected Japanese patients. Data from 332 subjects enrolled in 2 Japan phase 3 trials, CERTAIN-1 and CERTAIN-2, were used in the analyses. Pharmacokinetics of GLE/PIB were characterized using a nonlinear mixed-effects modeling. The analyses evaluated the impact of covariates (concomitant medications and demographic and clinical covariates such as renal impairment, effect of cirrhotic status) on GLE/PIB PK. GLE and PIB PK were described by 1- and 2-compartment models, respectively. Presence of cirrhosis, age, and body weight were identified as significant covariates on GLE/PIB PK. A trend toward higher GLE and PIB exposures in older patients and higher PIB exposures in heavier patients was observed; however, these increases were not considered clinically meaningful. GLE and PIB exposures were higher in HCV-infected subjects with cirrhosis (Child-Pugh A; GLE area under the plasma concentration-time curve was 160% higher, and PIB area under the plasma concentration-time curve was 21% higher) compared to subjects without cirrhosis. Renal function (including subjects with end-stage renal disease with dialysis) had no impact on GLE or PIB exposures. The GLE/PIB dose was well tolerated in the Japanese population, and no dose adjustment is needed for the evaluated intrinsic and extrinsic factors.