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Bone morphogenetic protein 15 (BMP15) is an X-linked gene encoding an oocyte secreted factor, which plays varied functions in the female fertility between mono-ovulatory and poly-ovulatory mammalian species. We previously found that knockout of BMP15 completely blocked porcine follicular development at preantral stages. However, the specific function of BMP15 on porcine oocytes in vitro maturation remains largely unknown. Here, we injected the pre-assembled crRNA + tracrRNA + Cas9 ribonucleoprotein (ctRNP) complex into the cytoplasm of germinal vesicle stage porcine oocytes to disrupt BMP15. The ctRNP composed of Cas9 nuclease and crRNA-tracrRNA complex at 1.2/1 content ratio. The tested crRNA-tracrRNA complex concentration ranging from 50 to 200 ng/μL, all presented effective editing of BMP15 in porcine oocytes, and the 125 ng/μL crRNA-tracrRNA complex presented the highest editing efficiency (39.23 ± 3.33%). Surprisingly, we found approximately 95% edited oocytes presented monoallelic mutations, and only 5% edited oocytes harbored biallelic mutations. Interestingly, the coinjected two crRNAs guided the ctRNP complex to concurrently cut within a 10 bp window of the PAM (protospacer adjacent motif), resulting in a precise deletion within BMP15 in 85.9% edited oocytes, and additional deletion happened in 14.1% edited oocytes, which resulted in large fragment deletions in BMP15. Most deletions caused frameshift and introduced premature stop codon in BMP15, resulting in the disruption of BMP15 protein expression, which was confirmed by the Western blot analysis showing the reduced BMP15 protein expression in ctRNP injected oocytes. The disruption of BMP15 attenuated the activation of SMAD1/5/8 signaling, and impaired cumulus expansion of porcine cumulus cell-oocyte complexes (COCs). Our study proved that delivering CRISPR ctRNP into porcine oocytes by microinjection was able to edit BMP15 efficiently, providing a new strategy to investigate the functions of oocyte-specific secreted factors in oocyte in vitro maturation.

The past four decades have seen an increase in the incidence of early-onset gastrointestinal cancer. Because early-stage cancer detection is vital to reduce mortality rate, mass screening colonoscopy provides the most effective prevention strategy. However, conventional endoscopy is a painful and technically challenging procedure that requires sedation and experienced endoscopists to be performed. To overcome the current limitations, technological innovation is needed in colonoscopy. In recent years, researchers worldwide have worked to enhance the diagnostic and therapeutic capabilities of endoscopes. The new frontier of endoscopic interventions is represented by robotic flexible endoscopy. Among all options, self-propelling soft endoscopes are particularly promising thanks to their dexterity and adaptability to the curvilinear gastrointestinal anatomy. For these devices to replace the standard endoscopes, integration with embedded sensors and advanced surgical navigation technologies must be investigated. In this review, the progress in robotic endoscopy was divided into the fundamental areas of design, sensing, and imaging. The article offers an overview of the most promising advancements on these three topics since 2018. Continuum endoscopes, capsule endoscopes, and add-on endoscopic devices were included, with a focus on fluid-driven, tendon-driven, and magnetic actuation. Sensing methods employed for the shape and force estimation of flexible endoscopes were classified into model- and sensor-based approaches. Finally, some key contributions in molecular imaging technologies, artificial neural networks, and software algorithms are described. Open challenges are discussed to outline a path toward clinical practice for the next generation of endoscopic devices.

Traditionally, graduates from colleges of pharmacy in Saudi Arabia work mainly in hospital settings, and only a few graduates work in other practice settings. However, several initiatives and national plans have recently been introduced to facilitate employment in community pharmacies and the pharmaceutical industry/companies. Consequently, the objectives of this study were to explore the current state of career placement, type of employment sectors, and practice settings that Doctor of Pharmacy (PharmD) graduates join based on recent developments in the profession.This study is a cross-sectional, descriptive study. The target population was PharmD graduates from Unaizah College of Pharmacy, Qassim University, Saudi Arabia. Consequently, all 162 graduates from three recent cohorts (2018-2020) were contacted to participate in this survey.A total of 157 graduates participated in this study, yielding a response rate of 96.91 %. Of the participants, 92 (58.6 %) were female graduates. The overall rate of employment was 84.7 %. Moreover, a higher proportion of male graduates than female graduates (97.1 % versus 73.7 %, P = 0.006) were employed. In this study, the three main sectors that the graduates joined were the pharmaceutical industry and companies (41.2 %), community pharmacies (29.4 %), and medical cities, hospitals and clinics (23.5 %). In addition, almost the same proportions of male and female graduates joined the pharmaceutical industry and companies (40.3 % versus 42.1 %). However, a higher proportion of male graduates than female graduates joined community pharmacies (32.3 % versus 26.3 %). Conversely, a higher proportion of female graduates joined medical cities, hospitals and clinics compared to male graduates (28.1 % versus 19.4 %).The current employment of PharmD graduates in the job market is generally high, but further improvement could be made, especially for female graduates. Moreover, the study findings showed that jobs are shifting toward community pharmacies and the pharmaceutical industry. Therefore, we believe that decision-makers in pharmacy education and curriculum developers must consider these trends and ensure that there is adequate preparation for careers in community pharmacy practice and other sectors of the profession in the curriculum.

Bio-hydrogen production is of significant interest as it is capable of consuming waste material and synthesizing hydrogen which is a green gas. In this study, we examined the dose-dependent effect of iron shaving on bio-hydrogen production from an integrated dark and photo fermentation system from an artificial food waste. Overall, introduction of iron shaving enhanced the bio-gas production. Statistical analysis was performed on the extracted parameters obtained from fitting the experimental data to Gompertz function, revealing that the bio-gas production can be significantly enhanced by addition of iron shaving at concentrations up to 500 mg/L, with a maximum enhancement at 200 mg/mL. GC analysis showed that introduction of iron shaving at 200 mg/L also maximized the hydrogen percentage in the produced bio-gas. Based on the HPLC results, it was postulated that the dark-fermentation step was probably the step that was more affected by the introduction of iron shaving. Investigation of the pH showed that the acidification of the solution approximately coincided with the termination of the process. Our finding suggests that a more efficient buffer-assisted setup can significantly enhance the bio-hydrogen efficiency.

A new method is presented for the analysis of electromagnetic scattering from arbitrarily shaped PEC object coated by homogeneous spherical dielectric material. The analysis of the internal PEC objects is performed using the equivalence principle algorithm (EPA). First, the scattering operator of EPA is evaluated for the PEC object in terms of RWG basis functions where the background is filled by coating material. Then a translation procedure is introduced to translate scattering operator evaluated in terms of RWG basis functions to a new scattering operator in terms of spherical wave harmonics (SWHs). This new scattering operator relates SWH coefficients of the scattered wave by internal PEC to those of the incident wave. By invoking the boundary conditions on the surface of spherical coating using the mode-matching technique, the coefficients of the scattered wave outside the coating material are evaluated. Since the scattering operator is independent from the coating radius, the problem may be solved by only analysis of boundary conditions on the surface of spherical coating for various values of coating radii without needing to repeat the analysis of internal PEC object. Several numerical examples are investigated to evaluate validity and efficiency of the proposed method.

The Joint Workshop on Induced Special Regions convened scientists and planetary protection experts to assess the potential of inducing special regions through lander or rover activity. An Induced Special Region is defined as a place where the presence of the spacecraft could induce water activity and temperature to be sufficiently high and persist for long enough to plausibly harbor life. The questions the workshop participants addressed were: (1) What is a safe stand-off distance, or formula to derive a safe distance, to a purported special region? (2) Questions about RTGs (Radioisotope Thermoelectric Generator), other heat sources, and their ability to induce special regions. (3) Is it possible to have an infected area on Mars that does not contaminate the rest of Mars? The workshop participants reached a general consensus addressing the posed questions, in summary: (1) While a spacecraft on the surface of Mars may not be able to explore a special region during the prime mission, the safe stand-off distance would decrease with time because the sterilizing environment, that is the martian surface would progressively clean the exposed surfaces. However, the analysis supporting such an exploration should ensure that the risk to exposing interior portions of the spacecraft (i.e., essentially unsterilized) to the martian surface is minimized. (2) An RTG at the surface of Mars would not create a Special Region but the short-term result depends on kinetics of melting, freezing, deliquescence, and desiccation. While a buried RTG could induce a Special Region, it would not pose a long-term contamination threat to Mars, with the possible exception of a migrating RTG in an icy deposit. (3) Induced Special Regions can allow microbial replication to occur (by definition), but such replication at the surface is unlikely to globally contaminate Mars. An induced subsurface Special Region would be isolated and microbial transport away from subsurface site is highly improbable.

We report laboratory experimental results that support a brine-related hypothesis for the recurring slope lineae (RSL) on Mars in which the subsurface Cl-salts, i.e., hydrous chlorides and oxychlorine salts (HyCOS) are the potential source materials. Our experiments revealed that within the observed RSL temperature window TRSL (250–300 K), the deliquescence of HyCOS could occur in relative humidity ranges (RH ≥ 22%–46%) much lower than those for hydrous (Mg, Fe)-sulfates (RH ≥ 75%–96%). In addition, we demonstrated that the RH values kept by common HyCOS and hydrous sulfates in enclosures have a general trend as RHsulfates > RHperchlorates > RHchlorides (with same type of cation) in wide T range. It means that the required RH range for a Cl-bearing salt to deliquescence can be satisfied by a co-existing salt of different type, e.g., in the subsurface layers of mixed salts on Mars. Furthermore, we found a strong temperature dependence of the deliquescence rates for all tested HyCOS, e.g., a duration of 1–5 sols for all HyCOS at the high end (300 K) of TRSL, and of 20–70 sols for all tested HyCOS (except NaClO4·H2O) at the low end (250 K) of TRSL, which is consistent with the observed seasonal behavior of RSL on Mars. From a mass-balance point of view, the currently observed evidences on Mars do not support a fully-brine-wetted track model, thus we suggest a brine-triggered granular-flow model for the most RSL. Considering the recurrence of RSL in consecutive martian years, our experimental results support the rehydration of remnant HyCOS layers during a martian cold season through H2O vapor-to-salt direct interaction. We found that the evidences of HyCOS rehydration under Mars relevant P-T-RH conditions are detectable in a few minutes by in situ Raman spectroscopy. This rehydration would facilitate the recharge of H2O back into subsurface HyCOS, which could serve as the source material to trigger RSL in a subsequent warm season. The major limiting factor for this rehydration is the H2O supply, i.e., the H2O vapor density carried by current Mars atmospheric circulation and the diffusion rate of H2O vapor into the salt-rich subsurface in a cold season. In a worst-case scenario, these H2O supplies can support a maximum increase of hydration degrees of two for totally dehydrated HyCOS, whereas the full rehydration of subsurface HyCOS layers can be easily reached during a >30° obliquity period that has H2O vapor density 10× to 20× times the value of current obliquity. Overall, our results imply the existence of a large amount of Cl-bearing salts in the subsurface at RSL sites.

Adsorbed and structurally incorporated carbonate in bioapatite, the primary mineral phase of bone, is observed across vertebrates, typically at 2–8 wt%, and supports critical physiological and biochemical functions. Several turtle species contain elevated bone-associated carbonate, a property linked to pH buffering and overwintering survival. Prior studies of turtle bone utilized bulk analyses, which do not provide spatial resolution of carbonate. Using Raman spectroscopy, the goals of this study were to: (1) quantify and spatially resolve carbonate heterogeneity within the turtle shell; (2) determine if cortical and trabecular bone contain distinct carbonate concentrations; and (3) assess if simulated overwintering conditions result in decreased bioapatite carbonation. Here, we demonstrate the potential for Raman spectroscopic analysis to spatially resolve bioapatite carbonation, using the western painted turtle as a model species. Carbonate concentration was highly variable within cortical and trabecular bone, based on calibrated Raman spot analyses and mapping, suggesting heterogeneous carbonate distribution among crystallites. Mean carbonate concentration did not significantly differ between cortical and trabecular bone, which indicates random distribution of crystallites with elevated and depleted carbonate. Carbonate concentrations (range: 5–22 wt%) were not significantly different in overwintering and control animals, deviating from previous bulk analyses. In reconciling bulk and Raman analyses, two hypotheses explain how overwintering turtles potentially access carbonate: (1) mobilization of mineral-associated, surface components of bone crystallites; and (2) selective, dispersed crystallite dissolution. Elevated bioapatite carbonate in the western painted turtle, averaging 11.8 wt%, represents the highest carbonation observed in vertebrates, and is one physiological trait that facilitates overwintering survival.

Health monitoring of rotating machinery is commonly based on vibration signals. Instead, this pioneering research provides bearing diagnostics using strain measurements, obtained from Fiber Bragg Grating (FBG) fiber-optic sensors. Besides detection of the damage via spectral data, these optical sensors also allow the estimation of damage severity through the direct and accurate measurement of the damage size of small spalls in the bearing races, an essential capability for the prognosis of remaining useful life. FBG sensors are small and can be easily placed in the immediate proximity of the bearing or even embedded inside it, thereby ensuring much enhanced signal-to-noise ratio through the minimizing transmission path effects from remote disturbances. These ball-bearing related diagnostic capabilities of FBG sensors are demonstrated via seeded tests, as well as by means of extended monitoring of bearings during fatigue endurance tests. Sensitivity to FBG sensor location is studied, showing acceptable values at all housing measuring points around the bearing. Fiber-optic sensors appear to have promising diagnostic potential for spall-like faults in both the outer and inner races of ball bearings with a very good discrimination power.