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Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, which are accompanied by memory loss and cognitive disruption. Rhodiola sachalinensis (RSE) is a medicinal plant that has been used in northeastern Asia for various pharmacological activities. We attempted to carry out the bioconversion of RSE (Bio-RSE) using the mycelium of Bovista plumbe to obtain tyrosol-enriched Bio-RSE. The objective of this study was to investigate the effects of Bio-RSE on the activation of the cholinergic system and the inhibition of oxidative stress in mice with scopolamine (Sco)-induced memory impairment. Sco (1 mg/kg body weight, i.p.) impaired the mice’s performance on the Y-maze test, passive avoidance test, and water maze test. However, the number of abnormal behaviors was reduced in the groups supplemented with Bio-RSE. Bio-RSE treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. Bio-RSE dramatically improved the cholinergic system by decreasing acetylcholinesterase activity and regulated oxidative stress by increasing antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)). The reduction in nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in the brain tissue due to scopolamine was restored by the administration of Bio-RSE. Bio-RSE also significantly decreased amyloid-beta 1–42 (Aβ1–42) and amyloid precursor protein (APP) expression. Moreover, the increased malondialdehyde (MDA) level and low total antioxidant capacity in Sco-treated mouse brains were reversed by Bio-RSE, and an increase in Nrf2 and HO-1 was also observed. In conclusion, Bio-RSE protected against Sco-induced cognitive impairment by activating Nrf2/HO-1 signaling and may be developed as a potential beneficial material for AD.

Pig-human xenotransplantation can trigger cell-mediated immune responses. We explored the role of gangliosides in inflammation related to immune rejection in xenotransplantation. Co-culture of xenogeneic cells (pig-MSCs and RAW264.7) was used to emulate xenotransplantation conditions. MTT assay results indicated that cell viability was significantly decreased in pADMSCs co-cultured with RAW264.7 cells. GM1 and GM3 were highly expressed in pADMSCs co-cultured with RAW264.7 cells. pADMSCs co-cultured with RAW264.7 cells strongly expressed pro-inflammatory proteins such as COX-2, iNOS, p50, p65, pIκBα, and TNF-α. GM1-knockdown pADMSCs co-cultured with RAW 264.7 cells did not show significantly altered cell viability, but pro-inflammatory proteins were markedly inhibited. Co-culture of pADMSCs with RAW264.7 cells induced significant phosphorylation (p) of JNK1/2 and pERK1/2. However, pERK1/2 and pJNK1/2 were decreased and MEK1/2 and Raf1 were suppressed in GM1-knockdown pADMSCs co-cultured with RAW264.7 cells. Thus, the Raf-1/MEK1/2/ERK1/2 and JNK1/2 pathways were significantly upregulated in response to increases of GM1 in co-cultured xenogeneic cells. However, the inflammatory response was suppressed in co-culture of GM1-knockdown pADMSCs with RAW264.7 cells via down-regulation of the Raf-1/MEK1/2/ERK1/2 and JNK1/2 pathways. Therefore, the ganglioside GM1 appears to play a major role in the inflammatory response in xenotransplantation via the Raf-1/MEK1/2/ERK1/2 and JNK1/2 pathways.

Recently, as the anti-aging role of melanin in the skin and the inhibition of melanin production has been identified, the development of materials capable of maintaining skin homeostasis has been attracting attention. In this study, we further investigated the anti-melanogenic effect of Codonopsis pilosula extract (CPE) and, under oxidative stress, the cytoprotective effect in Melan-a melanocytes exposed to H2O2. First, CPE treatment significantly reduced melanin production by inhibiting melanogenesis-associated proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 2 (TRP 2), as a result of the phosphorylation of MAPK/JNK in Melan-a cells. Next, to investigate the protective effects of the CPE on oxidative-stress-induced skin injury and its molecular mechanism, we determined the effect of CPE after inducing oxidative stress by exposing melanocytes to H2O2. CPE protected cells from H2O2-induced cytotoxicity by reducing the expression of the gene encoding the Bax pro-apoptotic protein, whereas it induced the genes encoding the B-cell lymphoma 3 (Bcl2) family and MITF, which is a transcriptional regulator that promotes melanocyte differentiation. Furthermore, our results show that CPE enhanced the production of autophagy-related proteins such as Beclin-1 and light chain 3 (LC3) II; this was substantially reversed by 3-methyladenin (MA, an autophagy inhibitor) pretreatment. Collectively, our findings demonstrate that CPE treatment exhibits not only an anti-melanogenic effect in normal melanocytes, but also a cytoprotective effect in melanocytes subjected to oxidative stress by inducing autophagy and MITF expression. Therefore, we believe that CPE is a potent candidate for cell maintenance in melanocytes.

Rivaroxaban (RXB), a novel oral anticoagulant that directly inhibits factor Xa, is a poorly soluble drug belonging to Biopharmaceutics Classification System (BCS) class II. In this study, a hot-melt extruded amorphous solid dispersion (HME-ASD) containing RXB is prepared by changing the drug:polymer ratio (Polyvinylpyrrolidione-vinyl acetate 64, 1:1–1:4) and barrel temperature (200–240 °C), fixed at 20% of Cremophor® RH 40 and 15 rpm of the screw speed, using the hot-melt extruding technique. This study evaluates the solubility, dissolution behavior, and bioavailability for application to oral drug delivery and optimizes the formulation of rivaroxaban amorphous solid dispersion (RXB-ASD). Based on a central composite design, optimized RXB-ASD (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C, Cremophor® RH 40 20%, screw speed 15 rpm) showed satisfactory results for dependent variables. An in vitro drug dissolution study exhibited relatively high dissolution in four media and achieved around an 80% cumulative drug release in 120 min. Optimized RXB-ASD was stable under the accelerated condition for three months without a change in crystallinity and the dissolution rate. A pharmacokinetic study of RXB-ASD in rats showed that the absorption was markedly increased in terms of rate and amount, i.e., the systemic exposure values, compared to raw RXB powder. These results showed the application of quality by design (QbD) in the formulation development of hot-melt extruded RXB-ASD, which can be used as an oral drug delivery system by increasing the dissolution rate and bioavailability.

The effect of Rhodiola sachalinensis Boriss extract irradiated with 50 kGy gamma rays (HKC) on benign prostatic hyperplasia (BPH) was investigated. Seven-week-old male SD rats received a subcutaneous injection of 20 mg/kg of testosterone propionate (TP) to induce BPH. Then, the testosterone only group received testosterone, the testosterone + finasteride group received testosterone and finasteride (5 mg/kg), the testosterone + HKC group received testosterone and HKC extract (500 mg/kg). Prostate weight and the dihydrotestosterone (DHT) levels in serum or prostate tissue were determined. The mRNA expressions of 5-alpha reductase (AR) in prostate tissue were also measured. Compared to the control group, prostate weight was significantly improved in the TP group and decreased in the HKC and finasteride-treated groups. Furthermore, the mRNA expression of 5-AR in the prostate was significantly reduced in the HKC and finasteride-treated groups. Similarly, the expression levels of α-smooth muscle actin (α-SMA) and cytokeratin, which are associated with prostatic enlargement in the HKC and finasteride groups, were much lower than in the TP group. HKC treatment showed similar efficacy to finasteride treatment on rats with testosterone-induced BPH. HKC may be explored as a potential new drug for BPH treatment.

Raloxifene hydrochloride (RLH) was formulated into a pH-modified supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) to increase drug solubility and dissolution rate. Optimal formulations of pH-modified S-SMEDDSs were developed by incorporating hydroxypropyl-cellulose-L as a precipitation inhibitor and phosphoric acid as a pH modifier (an acidifier). RLH was dissolved to greater extents by all pH-modified S-SMEDDSs compared with non-pH-modified S-SMEDDSs. In particular, phosphoric acid afforded greater drug dissolution than did the other acidifiers tested, perhaps because phosphoric acid better controlled the pH. More than 50% of the RLH was released from the pH-modified S-SMEDDS at pH 2.5 compared with only ~5% of the drug into aqueous buffer (pH 1.2 or 6.8) after dissolution of a conventional tablet. pH-modified S-SMEDDSs with a hydrophilic polymer and phosphoric acid improved the dissolution behavior of a drug exhibiting poor aqueous solubility.

Differential interference contrast microscopy is designed to image unstained and transparent specimens by enhancing the contrast resulting from the Nomarski prism-effected optical path difference. Retinitis pigmentosa, one of the most common inherited retinal diseases, is characterized by progressive loss of photoreceptors. In this study, Differential interference contrast microscopy was evaluated as a new and simple application for observation of the retinal photoreceptor layer and retinitis pigmentosa diagnostics and monitoring. Retinal tissues of Royal College of Surgeons rats and retinal-degeneration mice, both well-established animal models for the disease, were prepared as flatmounts and histological sections representing different elapsed times since the occurrence of the disease. Under the microscopy, the retinal flatmounts showed that the mosaic pattern of the photoreceptor layer was irregular and partly collapsed at the early stage of retinitis pigmentosa, and, by the advanced stage, amorphous. The histological sections, similarly, showed thinning of the photoreceptor layer at the early stage and loss of the outer nuclear layer by the advanced stage. To count and compare the number of photoreceptors in the normal and early-retinitis pigmentosa-stage tissues, an automated cell-counting program designed with MATLAB, a numerical computing language, using a morphological reconstruction method, was applied to the differential interference contrast microscopic images. The number of cells significantly decreased, on average, from 282 to 143 cells for the Royal College of Surgeons rats and from 255 to 170 for the retinal-degeneration mouse. We successfully demonstrated the potential of the differential interference contrast microscopy technique's application to the diagnosis and monitoring of RP.

Korea Pathfinder Lunar Orbiter (KPLO) is South Korea’s first space exploration mission, developed by the Korea Aerospace Research Institute. It aims to develop technologies for lunar exploration, explore lunar science, and test new technologies. KPLO was launched on August 5, 2022, by a Falcon-9 launch vehicle from cape canaveral space force station (CCSFS) in the United States and placed on a ballistic lunar transfer (BLT) trajectory. A total of four trajectory correction maneuvers were performed during the approximately 4.5-month trans-lunar cruise phase to reach the Moon. Starting with the first lunar orbit insertion (LOI) maneuver on December 16, the spacecraft performed a total of three maneuvers before arriving at the lunar mission orbit, at an altitude of 100 kilometers, on December 27, 2022. After entering lunar orbit, the commissioning phase validated the operation of the mission mode, in which the payload is oriented toward the center of the Moon. After completing about one month of commissioning, normal mission operations began, and each payload successfully performed its planned mission. All of the spacecraft operations that KPLO performs from launch to normal operations were designed through the system operations design process. This includes operations that are automatically initiated post-separation from the launch vehicle, as well as those in lunar transfer orbit and lunar mission orbit. Key operational procedures such as the spacecraft’s initial checkout, trajectory correction maneuvers, LOI, and commissioning were developed during the early operation preparation phase. These procedures were executed effectively during both the early and normal operation phases. The successful execution of these operations confirms the robust verification of the system operation.

Abstract Backgrounds This study aimed to analyze the clinical outcomes of femoral neck fractures (FNF) in patients treated with a femoral neck system (FNS, DePuy Synthes), which is a recently introduced device. Methods This retrospective cohort study of 43 patients who underwent osteosynthesis using FNS for FNF between July 2019 and June 2021 with a minimum follow-up of 6 months. The researchers examined the patients’ demographic factors and radiologically evaluated the fracture type and fixation status, bone union, and postoperative complications. Results Of 43 patients, 25 were female, and the patients’ mean age and body mass index were 62.1 years and 22.5 kg/m2, respectively. According to the Association of Osteosynthesis/Orthopaedic Trauma Association (AO/OTA) classification, the most common fracture types were 31B1.1 and B1.2 (13 cases each), followed by B2.3, B2.1, and B2.2 (seven, five, and four cases, respectively). Radiological bone union was confirmed in 39 patients (90.7%), and the mean time to union was 3.6 months. Two cases of nonunion, one case of lag screw cut-out, and one case of osteonecrosis were confirmed; all four cases later underwent arthroplasty. The mean time to reoperation was 4.5 months. Meanwhile, five patients underwent implant removal after the bone union, and distal locking screw stripping was noted in three patients. All three patients required metal plate cutting to remove the implants. Conclusions Osteosynthesis of FNF using the newly introduced FNS showed favorable clinical outcomes and no specific hardware-related complications were reported during the follow-up. However, attention must be paid to the issue regarding distal locking screw failure during hardware removal.

This paper presents tunable absorptive dual-notch filters using a stub-loaded coupled line with an inductor. The two-pole Butterworth filter function is modified to attain absorptive responses at a notch frequency. In addition, a stub-loaded coupled line with an inductor is employed to obtain dual-band bandstop responses, the required coupling coefficients, and quality factors based on the modified Butterworth function at two notch frequencies. In the proposed filter, tunable absorptive dual-notch responses are accomplished without using auxiliary circuits, such as an impedance matching network. The two resonant frequencies and the quality factors of the resonators are independently controlled by adjusting the three loading capacitances of the resonator. Three types of filters are designed and then built on a substrate with r = 3.42 and h = 30 mils. The first filter (Filter A) attained a return loss of 11.2-17.1 dB/10.5-24.4 dB at 0.76-0.98 GHz/1.05-1.28 GHz. The measured return loss of the second filter (Filter B) was 12.5-14.8 dB/10.2-12.3 dB at 0.84-1.08 GHz/1.35-1.59 GHz. For Filter C, equipped with a 4-pole response achieved through the cascade connection of two 2-pole filters (Filter B), a return loss of 11.2-15.1 dB/14.2-27.3 dB was obtained at 0.9-1.1 GHz/1.38-1.63 GHz. The application areas of the proposed filters include cognitive radios and carrier aggregation systems requiring two transmit frequencies. [ABSTRACT FROM AUTHOR]