Effects of a Combination of Polynucleotide and Hyaluronic Acid for Treating Osteoarthritis.

Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNFα levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade.

Efficacy and safety of a submucosal injection solution of sodium alginate for endoscopic resection in a porcine model.

Endoscopic resection techniques require the use of submucosal injection. Normal saline and sodium hyaluronate solutions are mainly used for this purpose, but an ideal solution has not yet been developed. The aim of this study was to assess a new solution, MC-003-a novel submucosal injection solution developed with sodium alginate as the main ingredient. Normal saline, a commercial sodium hyaluronate solution (Endo-Ease), and MC-003 were examined. A total of 18 gastric submucosal cushions were created in the stomachs of six pigs. The height of mucosal elevation was measured sequentially using endoscopic sonography. After euthanizing the animals either 2 h or 5 days after the procedure, pathologic examination was performed for each injection site. Although not statistically significant over the entire study period, MC-003 showed a superior result to normal saline and an equivalent result to Endo-Ease in the submucosal cushion height and its rate of decrease. There were no adverse outcomes after injection of the three solutions and there was no pathologically identified detrimental change in the resected specimens. MC-003 creates a sufficient submucosal fluid cushion without apparent tissue damage. It can be considered as an effective submucosal injection material.

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids.

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.

Application of Titanium-Carbide MXene-Based Transparent Conducting Electrodes in Flexible Smart Windows.

Among various available materials used in transparent and flexible devices, MXenes are attracting attention as a brand-new candidate in this category. Ti3C2Tx MXene as a 2D material has exceptional properties, making it a potential material having numerous applications in different areas. Because of its high conductivity, it can be used in transparent conducting electrodes (TCEs). In this study, the MXenes etched by highly concentrated acid at 50 °C,were spin-coated on polyethylene terephthalate (PET) film and annealed at moderate temperatures up to 170 °C. The adhesion of MXene to PET was found to be remarkably improved by annealing. These TCEs exhibited a sheet resistance of ∼424 Ω/sq. and transmittance of ∼87%. The aging stability of MXene-coated PET films against oxidation under ambient conditions was studied up to 28 days and resistance change was found ∼30% during this period. The flexibility test showed low bending resistance change (∼1.5%) at 1000th cycle and cumulative resistance change of ∼20% at a bending radius of ∼3.9 mm after 1000 cycles. These transparent, flexible, and conducting electrodes were used to fabricate polymer dispersed liquid crystal (PDLC)-based flexible smart windows. The smart windows fabricated by curing PDLC mixture sandwiched between the MXene electrodes were also found flexible in ON/OFF states. The MXene-based flexible smart windows resulted in good opacity in the OFF state and high transparency in the ON state, exhibiting low threshold voltage <10 V and high transmittance ∼80% at 60 V. The flexible smart windows operated normally even at ∼4 mm bending radius.

FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth.

Fas-associated factor 1 (FAF1) has gained a reputation as a member of the FAS death-inducing signalling complex. However, the role of FAF1 in the immunity response is not fully understood. Here, we report that, in the human retinal pigment epithelial (RPE) cell line ARPE-19 cells, FAF1 expression level was downregulated by Toxoplasma gondii infection, and PI3K/AKT inhibitors reversed T. gondii-induced FAF1 downregulation. In silico analysis for the FAF1 promoter sequence showed the presence of a FOXO response element (FRE), which is a conserved binding site for FOXO1 transcription factor. In accordance with the finding, FOXO1 overexpression potentiated, whereas FOXO1 depletion inhibited intracellular FAF1 expression level. We also found that FAF1 downregulation by T. gondii is correlated with enhanced IRF3 transcription activity. Inhibition of PI3K/AKT pathway with specific inhibitors had no effect on the level of T. gondii-induced IRF3 phosphorylation but blocked IRF3 nuclear import and ISGs transcription. These results suggest that T. gondii can downregulate host FAF1 in PI3K/AKT/FOXO1-dependent manner, and the event is essential for IRF3 nuclear translocation to active the transcription of ISGs and thereby T. gondii proliferation.

Diversity of Acupuncture Point Selections According to the Acupuncture Styles and Their Relations to Theoretical Elements in Traditional Asian Medicine: A Data-Mining-Based Literature Study.

Acupuncture point (AP) selections can vary depending on clinicians' acupuncture style, and therefore, acupuncture style is an important factor in determining the efficacy of acupuncture treatment. However, few studies have examined the differences in AP selections according to the acupuncture styles and theoretical backgrounds causing the differences. We compared the AP prescriptions used for 14 diseases in three classical medical textbooks, Dongeuibogam (DEBG), Saamdoinchimgooyogyeol (SADI), and Chimgoogyeongheombang (CGGHB), which represent unique acupuncture styles and have affected clinicians during this time. AP prescriptions showed more diversity between textbooks than between types of diseases. Among the three textbooks, AP prescriptions of SADI were most different compared to those of DEBG and CGGHB. Importantly, we found each style can be more clearly explained by AP attributes than by the APs per se. Specifically, SADI, DEBG, and CGGHB preferred five transport points located on the limbs, APs of the extra meridians, and source points, respectively. This suggests the possibility that the theoretical diversity of acupuncture styles results in the heterogeneity of AP selections.

Optoelectronics of Multijunction Heterostructures of Transition Metal Dichalcogenides.

Among p-n junction devices with multilayered heterostructures with WSe2 and MoSe2, a device with the MoSe2-WSe2-MoSe2 (NPN) structure showed a remarkably high photoresponse, which was 1000 times higher than the MoSe2-WSe2 (NP) structure. The ideality factor of the NPN structure was estimated to be ∼1, lower than that of the NP structure. It is claimed that the NPN structure formed a thinner depletion region than that of the NP structure because of the difference of carrier concentrations of MoSe2 and WSe2. Hence, the built-in electric field was weaker, and the motion of the photocarriers was facilitated. These behaviors were confirmed experimentally from a photocurrent mapping analysis and Kelvin probe force microscopy. The work function depended on the wavelength of the illuminator, and quasi-Fermi level was estimated. The surface photovoltage on the MoSe2 region was higher than that on WSe2 because the lower bandgap of MoSe2 induces more electron-hole pair generation.

Inside-Out Repair of the Meniscus in Concomitant Anterior Cruciate Ligament Reconstruction: Absorbable Versus Nonabsorbable Sutures.

PURPOSE: To compare the clinical and magnetic resonance imaging (MRI) outcomes of meniscal repair using absorbable versus nonabsorbable sutures in patients undergoing concomitant anterior cruciate ligament reconstruction. METHODS: Data of 142 patients who underwent meniscal repair with concomitant anterior cruciate ligament reconstruction using either absorbable or nonabsorbable sutures for longitudinal meniscal tear were retrospectively reviewed. Inside-out suture technique was used for all meniscal repairs. Weight bearing and flexion (>90°) were allowed after 6 weeks postoperatively. Clinical evaluations were assessed by the International Knee Documentation Committee subjective score, Lysholm score, and Tegner activity score preoperatively and at 2-year follow-up. MRI outcomes at 1-year follow-up were compared to identify the successful healing (complete or partial healing) rate and incidence of additional meniscal tears. Subgroup analysis was performed to evaluate the results of medial or lateral meniscus. RESULTS: Eighty patients underwent meniscal repair using absorbable sutures (mean age, 26.3 ± 11.9 years) and 62 patients with nonabsorbable sutures (mean age, 27.2 ± 10.0 years). There were no differences in zone and length of meniscal tears and stability tests between the groups. At a 2-year follow-up, all clinical scores had improved in both groups but did not differ significantly between the groups. Successful healing rate based on 1-year postoperative MRI was not significantly different between the absorbable and nonabsorbable sutures (93.7% vs 96.8%, P = .469). However, the absorbable sutures showed a lower additional tear incidence than the nonabsorbable sutures (2.5% vs 9.6%, P = .031). Subgroup analysis showed that the successful healing rate was not significantly different between the suture materials in both the medial and lateral menisci. CONCLUSIONS: The use of absorbable sutures leads to comparable healing rates to and lower incidence of additional tears than nonabsorbable sutures in patients undergoing meniscal repair with anterior cruciate ligament reconstruction. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic trial.

Effect of Ti3C2T x MXenes etched at elevated temperatures using concentrated acid on binder-free supercapacitors.

The effect of Ti3C2T x MXene etched at different temperatures (25 °C, 50 °C, and 80 °C) on the capacitance of supercapacitors without the use of conducting carbon-black or a binder was studied. The MXene etched using concentrated HCl acid (12 M)/LiF was used as an active electrode and Ni-foil as a current collector. It was observed that the elevated etching temperature facilitates the etching of the MAX phase and the exfoliation of MXene layers. However, this led to the formation of additional functional groups at the MXene surface as the temperature was increased to 80 °C. The specific capacitance of Ti3C2T x -based supercapacitors increased from 581 F g-1 for MXene etched at 25 °C to 657 F g-1 for those etched at 50 °C at the scan rate of 2 mV s-1. However, the specific capacitance reduced to 421 F g-1 as the etching temperature was increased to 80 °C at the same scan rate. The supercapacitors based on MXenes etched at the intermediate temperature (50 °C) exhibited higher specific capacitance in a wide range of scan rate, symmetry in charge/discharge curves, high cyclic stability at a scan rate of 1000 mV s-1 for up to 3000 cycles. The electrochemical impedance spectroscopy studies indicated low series resistance, reduced charge-transfer resistance, and decreased Warburg impedance for the supercapacitor based on the MXene etched at the intermediate temperature.

Is Lateral Posterior Tibial Slope Correlated With Clinical Outcomes of Lateral Meniscus Allograft Transplantation?

PURPOSE: To investigate (1) the correlation between lateral posterior tibial slope (PTS) and clinical outcomes of lateral meniscus allograft transplantation (MAT) and (2) the difference of lateral PTS between the extrusion and nonextrusion groups or between the failure and nonfailure groups in lateral MAT. METHODS: Between January 2001 and February 2016, we retrospectively evaluated 61 patients (mean age, 29.1 ± 12.2 years) who underwent postoperative magnetic resonance imaging (MRI) and were followed for a minimum of 2 years after primary lateral MAT. The lateral PTS and graft extrusion in the coronal and sagittal planes were assessed by using MRI performed at 1 year postoperatively. Clinical scores and graft failure were evaluated at the last follow-up visit. The correlation between lateral PTS and clinical outcomes (clinical scores, graft extrusion) was analyzed. Lateral PTS was compared between the extrusion and nonextrusion groups and between the failure and nonfailure groups. RESULTS: Mean lateral PTS on MRI was 6.6° ± 3.1° (range, 0.8° to 15.7°). A significant correlation was not identified between lateral PTS and clinical outcomes (clinical scores, graft extrusion in the coronal and sagittal planes). A significant difference in lateral PTS was not identified between the extrusion and nonextrusion groups in the coronal (6.2° ± 2.5° vs 7.0° ± 3.4°, P = .400) and sagittal (anterior horn, 6.5° ± 2.3° vs 6.7° ± 3.7°, P = .988; posterior horn, 6.8° ± 3.5° vs 6.5° ± 2.7°, P = .771) planes. Moreover, a significant difference was not identified between the failure and nonfailure groups (7.5° ± 3.3° vs 6.4° ± 3.0°, P = .388). CONCLUSIONS: A significant correlation between lateral PTS and clinical or radiologic outcomes of lateral MAT was not identified. LEVEL OF EVIDENCE: Level IV, therapeutic case series with subgroup analysis.

Cystic Degeneration of Hepatocellular Carcinoma Mimicking Mucinous Cystic Neoplasm.

Spontaneous regression of tumors is an extremely rare event in hepatocellular carcinoma (HCC) with only a few reports available. With the accumulation of clinical information and tumor immunogenetics, several mechanisms for the cystic changes of HCC have been suggested, including arterial thrombosis, inflammation, and rapid tumor growth. This paper reports an uncommon case of the partial regression of HCC, which was initially misdiagnosed as a mucinous cystic neoplasm of the liver due to the unusual radiologic findings. A 78-year-old female with the hepatitis B virus and liver cirrhosis presented with an approximately 5 cm-sized cystic mass of the liver. From the radiologic evidence of a papillary-like projection from the cyst wall toward the inner side, the initial impression was a mucinous cystic neoplasm of the liver. The patient underwent a surgical resection and finally, cystic degeneration of HCC, in which approximately 80% necrosis was noted. This case suggests that if a cystic neoplasm of liver appears in a patient with a high risk of HCC on a hepatobiliary imaging study, it is prudent to consider the cystic degeneration of HCC in a differential diagnosis.

Comparison of gadoxetic acid-enhanced MR imaging versus four-phase multi-detector row computed tomography in assessing tumor regression after radiofrequency ablation in subjects with hepatocellular carcinomas.

PURPOSE: To assess the diagnostic value of gadoxetic acid-enhanced magnetic resonance (MR) imaging in follow-up of patients with hepatocellular carcinomas (HCCs) who were treated with radiofrequency (RF) ablation and to compare it with that of four-phase multi-detector row computed tomography (CT). MATERIALS AND METHODS: From July 2007 to May 2008, 36 patients (43 HCCs) were enrolled who were treated with RF ablation (tumor size, 20-47 mm; mean, 24.5 mm) and underwent gadoxetic acid-enhanced MR imaging and four-phase (precontrast, arterial, portal venous, and equilibrium) multidetector CT for follow-up. Two radiologists independently reviewed these images, and conspicuity of tumor margins and detection of residual or recurrent tumor were assessed on a five-point scale with receiver operating characteristic (ROC) curve analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated. RESULTS: The mean conspicuity value of tumor margins was significantly higher on MR imaging than on multidetector CT (P < .001). The degree of differentiation between residual/recurrent tumor and hyperemia was significantly greater on MR imaging (P < .001). The mean area under the ROC curve was significantly higher with MR imaging (P = .015), as were sensitivity, specificity, PPV, NPV, and accuracy of detection rate (mean, 100%, 96.2%, 82.4%, 100%, and 96.7%, respectively, vs 41.7%, 56.8%, 13.5%, 85.7%, and 54.7% for multidetector CT). The interobserver agreement rate for MR imaging was higher (0.919) than for multidetector CT (0.672; P < .05). CONCLUSIONS: Diagnostic accuracy, conspicuity of tumor margins, and detection rate of residual or recurrent tumor were found to be better with gadoxetic acid-enhanced MR imaging than with four-phase multidetector CT.

[A case of secondary amyloidosis presenting as massive gastrointestinal bleeding].

Amyloidosis is a disorder characterized by extracellular deposition of amyloid in various tissues and organs. Gastrointestinal manifestations including gastroparesis, constipation, malabsorption, intestinal pseudo-obstruction, and bleeding are common. GI bleeding is a rare initial symptom which can be fatal in some cases. Absence of systemic symptoms and nonspecific endoscopic findings in amyloidosis may make diagnosis difficult. Therefore, amyloidosis-induced GI bleeding should be considered in patients with an obscure hemorrhage. Recently, we experienced a 65-year-old woman who presented with massive hematochezia as a manifestations of amyloidosis. Colonoscopy and SMA angiography showed massive bleeding in the small and large intestine. Colonoscopic biopsy established amyloidosis. We report this case with a review of the relevant literatures.

Hepatitis B virus-neutralizing anti-pre-S1 human antibody fragments from large naïve antibody phage library.

We report the construction of a large nonimmunized human phage antibody library in single-chain variable region fragment (scFv) format, which allowed the selection of antibodies that neutralize hepatitis B virus (HBV) in vitro. We generated 1.1 x 10(10) independent scFv clones using the cDNA of functional variable (V) gene segments of heavy and light chains purified from the peripheral blood mononuclear cells of 50 nonimmunized human donors. Using BIAcore, we selected two clones that recognized pre-S1 and neutralized pre-S1 and HBV binding to Chang liver cells. Clone G10 had the highest affinity (K(D)=1.69 x 10(-7)M), which was higher than that of clone 1E4 that was generated previously from a heavy chain-shuffled immune library. The off-rates of clones were within 10(-3)s(-1) as determined by BIAcore and were comparable to those of antibodies derived from a normal secondary immune response. In the inhibition assays of pre-S1 and virus binding to Chang liver cells using flow cytometry and the polymerase chain reaction, G10 had better neutralizing activity than 1E4. The new phage library may be a valuable source of antibodies with reasonable affinities to different targets, and the anti-pre-S1 G10 may be a good candidate for immunoprophylaxis against HBV infection.