High-Throughput Roll-to-Roll Processed Large-Area Perovskite Solar Cells Using Rapid Radiation Annealing Technique.

The development of a stable roll-to-roll (R2R) process for flexible large-area perovskite solar cells (PSCs) and modules is a pressing challenge. In this study, we introduced a new R2R PSC manufacturing system that employs a two-step deposition method for coating perovskite and uses intensive pulsed light (IPL) for annealing. This system has successfully fabricated small-sized cells and the first-ever large-sized, R2R-processed flexible modules. A key focus of our work was to accelerate the conversion of PbI2 to perovskite. To this end, we utilized IPL annealing and incorporated additives into the PbI2 layer. With these modifications, the R2R-processed perovskite films achieved a power conversion efficiency (PCE) of 16.87%, representing the highest reported value for R2R two-step processed PSCs. However, these cells exhibited hysteresis in reverse and forward PCE measurements. To address this, we introduced a dual-annealing process consisting of IPL followed by a 2-min thermal heating step. This approach successfully reduced hysteresis, resulting in low-hysteresis, R2R-processed flexible PSCs. Moreover, we fabricated large-scale flexible modules (10 × 10 cm2) with a PCE of 11.25% using the dual-annealing system, marking a significant milestone in this field.

Mechanism Behind the Loss of Fast Charging Capability in Nickel-Rich Cathode Materials.

Fast charging technology for electric vehicles (EVs), offering rapid charging times similar to conventional vehicle refueling, holds promise but faces obstacles owing to kinetic issues within lithium-ion batteries (LIBs). Specifically, the significance of cathode materials in fast charging has grown because Ni-rich cathodes are employed to enhance the energy density of LIBs. Herein, the mechanism behind the loss of fast charging capability of Ni-rich cathodes during extended cycling is investigated through a comparative analysis of Ni-rich cathodes with different microstructures. The results revealed that microcracks and the resultant cathode deterioration significantly compromised the fast charging capability over extended cycling. When thick rocksalt impurity phases form throughout the particles owing to electrolyte infiltration via microcracks, the limited kinetics of Li+ ions create electrochemically unreactive areas under high-current conditions, resulting in the loss of fast charging capability. Hence, preventing microcrack formation by tailoring microstructures is essential to ensure stability in fast charging capability. Understanding the relationship between microcracks and the loss of fast charging capability is essential for developing Ni-rich cathodes that facilitate stable fast charging upon extended cycling, thereby promoting widespread EV adoption.

Lithospermum erythrorhizon Siebold & Zucc. extract reduces the severity of endotoxin-induced uveitis.

BACKGROUND: Uveitis is an inflammatory eye condition that threatens vision, and effective anti-inflammatory treatments with minimal side effects are necessary to treat uveitis. PURPOSE: This study aimed to investigate the effects of Lithospermum erythrorhizon Siebold & Zucc. against endotoxin-induced uveitis in rat and mouse models. METHODS: Endotoxin-induced uveitis models of rats and mice were used to evaluate the effects of l. erythrorhizon treatment. Clinical inflammation scores and retinal thickness were assessed in the extract of l. erythrorhizon-treated rats. Histopathological examination revealed inflammatory cell infiltration into the ciliary body. Protein concentration, cellular infiltration, and prostaglandin-E2 levels were measured in the aqueous humor of the extract of l. erythrorhizon-treated rats. Protective effects of l. erythrorhizon on the anterior segment of the eye were examined in mice with endotoxin-induced uveitis. Additionally, we investigated the effect of l. erythrorhizon on the expression of pro-inflammatory cytokines [tumor necrosis factor alpha, interleukin-6, and interleukin-8] in lipopolysaccharide-stimulated THP1 human macrophages and examined the involvement of nuclear factor kappaB/activator protein 1 and interferon regulatory factor signaling pathways. Furthermore, three components of l. erythrorhizon were identified and assessed for their inhibitory effects on LPS-induced inflammation in RAW264.7 macrophage cells. RESULTS: Treatment of the extract of l. erythrorhizon significantly reduced clinical inflammation scores and retinal thickening in rats with endotoxin-induced uveitis. Histopathological examination revealed decreased inflammatory cell infiltration into the ciliary body. The extract of l. erythrorhizon effectively reduced the protein concentration, cellular infiltration, and PG-E2 levels in the aqueous humor of rats with endotoxin-induced uveitis. In mice with endotoxin-induced uveitis, the extract of l. erythrorhizon demonstrated a protective effect on the anterior segment of the eye by reducing inflammation and retinal thickening. The extract of l. erythrorhizon suppressed the expression of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-6, and interleukin-8) in lipopolysaccharide-induced inflammation in THP1 human macrophages, by modulating nuclear factor kappaB/activator protein 1 and interferon regulatory factor signaling pathways. Moreover, shikonin, acetylshikonin, and ß, ß-dimethylacryloylshikonin showed dose-dependent inhibition of nitric oxide, tumor necrosis factor alpha and interleukin-6 production in RAW264.7 macrophage cells. CONCLUSION: The extract of l. erythrorhizon is a potential therapeutic agent for uveitis management. Administration of the extract of l. erythrorhizon led to reduced inflammation, retinal thickening, and inflammatory cell infiltration in rat and mouse models of uveitis. The compounds (shikonin, acetylshikonin, and ß, ß-dimethylacryloylshikonin) identified in this study played crucial roles in mediating the anti-inflammatory effects of l. erythrorhizon. These findings indicate that the extract of l. erythrorhizon and its constituent compounds are promising candidates for further research and development of novel treatment modalities for uveitis.

A systematic exploration of ginsenoside Rg5 reveals anti-inflammatory functions in airway mucosa cells.

Background: Hyperactivated airway mucosa cells overproduce mucin and cause severe breathing complications. Here, we aimed to identify the effects of saponins derived from Panax ginseng on inflammation and mucin overproduction. Methods: NCI-H292 cells were pre-incubated with 16 saponins derived from P. ginseng, and mucin overproduction was induced by treatment with phorbol 12-myristate 13-acetate (PMA). Mucin protein MUC5AC was quantified by enzyme-linked immunosorbent assay, and mRNA levels were analyzed using quantitative polymerase chain reaction (qPCR). Moreover, we performed a transcriptome analysis of PMA-treated NCI-H292 cells in the absence or presence of Rg5, and differential gene expression was confirmed using qPCR. Phosphorylation levels of signaling molecules, and the abundance of lipid droplets, were measured by western blotting, flow cytometry, and confocal microscopy. Results: Ginsenoside Rg5 effectively reduced MUC5AC secretion and decreased MUC5AC mRNA levels. A systematic functional network analysis revealed that Rg5 upregulated cholesterol and glycerolipid metabolism, resulting in the production of lipid droplets to clear reactive oxygen species (ROS), and modulated the mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathways to regulate inflammatory responses. Rg5 induced the accumulation of lipid droplets and decreased cellular ROS levels, and N-acetyl-l-cysteine, a ROS inhibitor, reduced MUC5AC secretion via Rg5. Furthermore, Rg5 hampered the phosphorylation of extracellular signal-regulated kinase and p38 proteins, affecting the NF-κB signaling pathway and pro-inflammatory responses. Conclusion: Rg5 alleviated inflammatory responses by reducing mucin secretion and promoting lipid droplet-mediated ROS clearance. Therefore, Rg5 may have potential as a therapeutic agent to alleviate respiratory disorders caused by hyperactivation of mucosa cells.

Establishment of Korean Pediatric Reference Intervals for Estradiol using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is a reliable and accurate method for measuring steroid hormone levels. There is an increasing need for sensitive and precise methods to measure estradiol in pediatric patients. Here, we established reference intervals for estradiol in healthy children using a UHPLC-MS/MS-based method for the first time in South Korea. METHODS: Serum estradiol was measured using a Sciex Triple QuadTM 6500 + UHPLC-MS/MS (Sciex, Framingham, MA, USA). Reference intervals for estradiol were established according to the CLSI document EP28-A3c:2008. The reference intervals were validated using serum samples from 634 pediatric patients, including neonates, children, and adolescents. Among them, 389 specimens were used in analysis of the specimen acceptance time. Statistical analysis was performed using MedCalc (MedCalc, Ostend, Belgium) and Analyse-it (Analyse-it Software Ltd., Leeds, United Kingdom) software. RESULTS: Reference intervals for boys (n = 297) were <16.6, <7.3, <19.0, <30.5, 7.6-96.5, and 10.6-134.4 pmol/L among those aged <1, 1-5, 6-9, 10-11, 12-14, and 15-17 years, respectively. Reference intervals for girls (n = 337) were <114.7, <24.2, <34.8, 8.0-177.0, 10.4-480.5, and 9.1-486.7 pmol/L among those aged <1, 1-5, 6-9, 10-11, 12-14, and 15-17 years, respectively. Overall, there was no effect of specimen acceptance time on estradiol measurements in boys or girls, except for that in the group aged 10-11 years. CONCLUSIONS: The reference intervals for healthy children were validated using a UHPLC-MS/MS-based method. The highly analytical sensitive UHPLC-MS/MS method may be useful for estradiol determination in pediatric patients.

PD-L1-directed PlGF/VEGF blockade synergizes with chemotherapy by targeting CD141+ cancer-associated fibroblasts in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year overall survival rate. Patients with PDAC display limited benefits after undergoing chemotherapy or immunotherapy modalities. Herein, we reveal that chemotherapy upregulates placental growth factor (PlGF), which directly activates cancer-associated fibroblasts (CAFs) to induce fibrosis-associated collagen deposition in PDAC. Patients with poor prognosis have high PIGF/VEGF expression and an increased number of PIGF/VEGF receptor-expressing CAFs, associated with enhanced collagen deposition. We also develop a multi-paratopic VEGF decoy receptor (Ate-Grab) by fusing the single-chain Fv of atezolizumab (anti-PD-L1) to VEGF-Grab to target PD-L1-expressing CAFs. Ate-Grab exerts anti-tumor and anti-fibrotic effects in PDAC models via the PD-L1-directed PlGF/VEGF blockade. Furthermore, Ate-Grab synergizes with gemcitabine by relieving desmoplasia. Single-cell RNA sequencing identifies that a CD141+ CAF population is reduced upon Ate-Grab and gemcitabine combination treatment. Overall, our results elucidate the mechanism underlying chemotherapy-induced fibrosis in PDAC and highlight a combinatorial therapeutic strategy for desmoplastic cancers.

Preoperative quadriceps muscle strength deficit severity predicts knee function one year after anterior cruciate ligament reconstruction.

Quadriceps strength is critical for patients with anterior cruciate ligament (ACL) reconstruction; however, little is known about the relationship between preoperative quadriceps strength deficit and postoperative subjective knee functions. The study aimed to investigate the relationship between preoperative quadriceps strength and postoperative knee function in patients after ACL reconstruction. Seventy-five male patients with primary ACL reconstruction surgery with hamstring autografts between 2014 and 2017 were included. An isokinetic dynamometer assessed quadriceps strength while self-reported knee functions were measured by the International Knee Documentation Committee (IKDC) and Lysholm scores at baseline and 1 year after surgery. The three identified groups (Q1-Q3) were classified according to the preoperative quadriceps muscle strength deficit. Q1 were patients with < 25% quadriceps muscle strength deficit, Q2 showed a 25-45% deficit, and Q3 included those with a deficit > 45%. We compared knee functions between the three groups and examined the associations between preoperative variables and functional knee outcomes. The preoperative quadriceps muscle strength deficit had a negative association with the knee functional scores at 1 year follow-up including the IKDC score (rs = - 0.397, p = 0.005) and the Lysholm score (rs = - 0.454, p < 0.001), but not other factors. Furthermore, only the Q1 group, with < 25% deficit in preoperative quadriceps muscle strength, showed a significant correlation in postoperative IKDC score (r = - 0.462, p = 0.030), and Lysholm score (r = - 0.446, p = 0.038). Preoperative quadriceps muscle strength deficit had a significant negative relationship with postoperative function at 1 year following ACL reconstruction.

Effects of Cooling Rate during Quenching and Tempering Conditions on Microstructures and Mechanical Properties of Carbon Steel Flange.

This study investigated the mechanical properties of steel in flanges, with the goal of obtaining high strength and high toughness. Quenching was applied alone or in combination with tempering at one of nine combinations of three temperatures TTEM and durations tTEM. Cooling rates at various flange locations during quenching were first estimated using finite element method simulation, and the three locations were selected for mechanical testing in terms of cooling rate. Microstructures of specimens were observed at each condition. Tensile test and hardness test were performed at room temperature, and a Charpy impact test was performed at -46 °C. All specimens had a multiphase microstructure composed of matrix and secondary phases, which decomposed under the various tempering conditions. Decrease in cooling rate (CR) during quenching caused reduction in hardness and strength but did not affect low-temperature toughness significantly. After tempering, hardness and strength were reduced and low-temperature toughness was increased. Microstructures and mechanical properties under the various tempering conditions and CRs during quenching were discussed. This work was based on the properties directly obtained from flanges under industrial processes and is thus expected to be useful for practical applications.

Patients older than 50 years had similar results of knee strength and anteroposterior stability after ACL reconstruction compared to younger patients.

PURPOSE: To evaluate knee strength, ligament stability, and functional outcomes in patients older than 50 years who underwent anterior cruciate ligament (ACL) reconstruction, and to compare these results with those obtained from a younger patient group (< 40 years). METHODS: Forty patients older than 50 years and 50 patients younger than 40 years who underwent ACL reconstruction were retrospectively studied. Isokinetic extensor and flexor muscle strength were evaluated. The peak torque was determined at speeds of 60°/s and 180°/s. The highest peak torque at each velocity was compared with that on the uninjured side. Patients were also evaluated for knee anteroposterior (AP) laxity and functional outcomes, which were measured by the Lysholm and International Knee Documentation Committee (IKDC) scores. All tests were evaluated at baseline and 1 year postoperatively. RESULTS: The groups were comparable at the baseline. Both groups had significant improvements in all parameters, including isokinetic muscle strength, AP laxity, and functional scores, at 1 year postoperatively (all p < 0.05). Compared with younger patients, older patients had similar results for extensor and flexor strength, AP laxity, and Lysholm score (n.s.). However, younger patients had better IKDC scores than did older patients [median 81.1; 95% confidence interval (CI) 95% CI 78.9-88.7 vs. median 75.6; 95% CI 70.1-79.3, p = 0.007]. CONCLUSIONS: Though with lower IKDC scores, older patients with ACL reconstruction had comparable results of knee strength and ligament laxity to younger patients. ACL reconstruction is recommended for treating patients older than 50 years with ACL insufficiency, especially for those with high functional demand. LEVEL OF EVIDENCE: Retrospective cohort study, III.

The growth of K562 human leukemia cells was inhibited by therapeutic neural stem cells in cellular and xenograft mouse models.

To confirm the anti-tumor effect of engineered neural stem cells (NSCs) expressing cytosine deaminase (CD) and interferon-ß (IFN-ß) with prodrug 5-fluorocytosine (FC), K562 chronic myeloid leukemia (CML) cells were co-cultured with the neural stem cell lines HB1.F3.CD and HB1.F3.CD.IFN-ß in 5-FC containing media. A significant decrease in the viability of K562 cells was observed by the treatment of the NSC lines, HB1.F3.CD and HB1.F3.CD.IFN-ß, compared with the control. A modified trans-well assay showed that engineered human NSCs significantly migrated toward K562 CML cells more than human normal lung cells. In addition, the important chemoattractant factors involved in the specific migration ability of stem cells were found to be expressed in K562 CML cells. In a xenograft mouse model, NSC treatments via subcutaneous and intravenous injections resulted in significant inhibitions of tumor mass growth and extended survival dates of the mice. Taken together, these results suggest that gene therapy using genetically engineered stem cells expressing CD and IFN-ß may be effective for treating CML in these mouse models.

Correction: Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting.

[This corrects the article DOI: 10.18632/oncotarget.8719.].

Comparison of Knee Stability, Strength Deficits, and Functional Score in Primary and Revision Anterior Cruciate Ligament Reconstructed Knees.

Comparing to primary surgery, revision ACL reconstruction is more technically demanding and has a higher failure rate. Theoretically, rehabilitation can improve knee function after ACL reconstruction surgery. This study aimed to compare knee stability, strength, and function between primary and revision ACL reconstructed knees. 40 primary and 40 revision ACL reconstruction surgeries were included between April 2013 and May 2016. Patients with revision surgery had a higher anteroposterior translation comparing those with primary reconstruction (median laxity, 2.0 mm vs. 3.0 mm, p = 0.0022). No differences were noted in knee extensor at 60°/sec or 180°/sec (p = 0.308, p = 0.931, respectively) or in flexor muscle strength at 60°/sec or 180°/sec between primary and revision ACL reconstruction knees (p = 0.091, p = 0.343, respectively). There were also no significant differences between functional scores including IKDC score and Lysholm score in primary versus revision surgeries at 12th months after index operation (p = 0.154, p = 0.324, respectively). In conclusion, despite having higher anteroposterior instability, patients with revision ACL reconstruction can have non-inferior outcomes in isokinetic knee strength and function compared to those with primary ACL reconstruction after proper rehabilitation.

Clinical Etiology of Hypermetabolic Pelvic Lesions in Postoperative Positron Emission Tomography/Computed Tomography for Patients With Rectal and Sigmoid Cancer.

PURPOSE: The purpose of this study was to present various clinical etiologies of hypermetabolic pelvic lesions on postoperative positron emission tomography/computed tomography (PET/CT) images for patients with rectal and sigmoid cancer. METHODS: Postoperative PET/CT images for patients with rectal and sigmoid cancer were retrospectively reviewed to identify hypermetabolic pelvic lesions. Positive findings were detected in 70 PET/CT images from 45 patients; 2 patients who were lost to follow-up were excluded. All PET findings were analyzed in comparison with contrast-enhanced CT. RESULTS: A total of 43 patients were classified into 2 groups: patients with a malignancy including local recurrence (n = 30) and patients with other benign lesions (n = 13). Malignant lesions such as a local recurrent tumor, peritoneal carcinomatosis, and incidental uterine malignancy, as well as various benign lesions such as an anastomotic sinus, fistula, abscess, reactive lymph node, and normal ovary, were observed. CONCLUSION: PET/CT performed during postoperative surveillance of rectal and sigmoid colon cancer showed increased fluorodeoxyglucose uptake not only in local recurrence, but also in benign pelvic etiologies. Therefore, physicians need to be cautious about the broad clinical spectrum of hypermetabolic pelvic lesions when interpreting images.

Potential Anti-proliferative and Immunomodulatory Effects of Marine Microalgal Exopolysaccharide on Various Human Cancer Cells and Lymphocytes In Vitro.

Marine microalgal exopolysaccharides (EPSs) have drawn great attention due to their biotechnological potentials such as anti-viral, anti-oxidant, anti-lipidemic, anti-proliferative, and immunomodulatory activities, etc. In the present study, the EPS derived from microalgae Thraustochytriidae sp.-derived mutant GA was investigated for its anti-proliferation and immunomodulation. Anti-cancer efficacy of the microalgal EPS was examined for the alterations in cell proliferation and cell cycle-related gene expression that occur in three types of human cancer cell lines, BG-1 ovarian, MCF-7 breast, and SW-620 colon cancer cell lines, by its treatment. Alterations in immunoreactivity by the microalgal EPS were examined by measuring its influence on the growth of T and B lymphocytes and cytokine production of T cells. In cell viability assay, the microalgal EPS inhibited cancer cell growth at the lowest concentration of 10-11 dilution and in a dose-responsive manner within the range of dilution of 10-11~10-3. In addition, the protein expression of cell cycle progression genes such as cyclin D1 and E in these cancer cell lines was significantly reduced by the microalgal EPS in a dose- and a time-dependant manner. In cell proliferation assay using T and B cells, the microalgal EPS induced B cell proliferation even at the lowest dilution of 10-11, but not T cells. In cytokine assay, the microalgal EPS decreased the formation of IL-6 and INF-γ at 10-3 dilution compared to the control and had no significant effects on TNF-α. Collectively, these findings suggest that the EPS derived from microalgae Thraustochytriidae sp. GA has an anti-proliferative activity against cancer cells and an immunomodulatory effect by having an influence on B cell proliferation and cytokine secretion of T cells.

Characteristics of 18F-fluorodeoxyglucose uptake in anastomotic sinus and fistula following rectal cancer surgery.

PURPOSE: To assess the characteristics of 18F-fluorodeoxyglucose (FDG) uptake in persisting anastomotic sinus and fistula following rectal cancer surgery. METHODS: Eight patients with anastomotic sinus and fistula were retrospectively studied. RESULTS: A total of 13 anastomotic sinuses (n=11) and fistulas (n=2) were observed. Sixteen FDG-positron emission tomography/computed tomography studies for 13 lesions performed and 26 uptake patterns were evaluated. Twenty-one lesions were found to have diffuse increased uptake, whereas four lesions had focal uptake. There was only one lesion without FDG uptake. CONCLUSIONS: Increased FDG uptake is frequently observed in anastomotic sinus and fistula, which should be known to avoid making wrong diagnosis.

Anti-proliferative Effect of Engineered Neural Stem Cells Expressing Cytosine Deaminase and Interferon-ß against Lymph Node-Derived Metastatic Colorectal Adenocarcinoma in Cellular and Xenograft Mouse Models.

PURPOSE: Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, genetically engineered human neural stem cells (HB1.F3) expressing Escherichia coli cytosine deaminase (CD) (HB1.F3.CD) and human interferon-ß (IFN-ß) (HB1.F3.CD.IFN-ß) were employed against lymph node-derived metastatic colorectal adenocarcinoma. MATERIALS AND METHODS: CD can convert a prodrug, 5-fluorocytosine (5-FC), to active 5-fluorouracil, which inhibits tumor growth through the inhibition of DNA synthesis,while IFN-ß also strongly inhibits tumor growth by inducing the apoptotic process. In reverse transcription polymerase chain reaction analysis, we confirmed that HB1.F3.CD cells expressed the CD gene and HB1.F3.CD.IFN-ß cells expressed both CD and IFN-ß genes. RESULTS: In results of a modified trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-ß cells selectively migrated toward SW-620, human lymph node-derived metastatic colorectal adenocarcinoma cells. The viability of SW-620 cells was significantly reduced when co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-ß cells in the presence of 5-FC. In addition, it was found that the tumor-tropic properties of these engineered human neural stem cells (hNSCs) were attributed to chemoattractant molecules including stromal cell-derived factor 1, c-Kit, urokinase receptor, urokinase-type plasminogen activator, and C-C chemokine receptor type 2 secreted by SW-620 cells. In a xenograft mouse model, treatment with hNSC resulted in significantly inhibited growth of the tumor mass without virulent effects on the animals. CONCLUSION: The current results indicate that engineered hNSCs and a prodrug treatment inhibited the growth of SW-620 cells. Therefore, hNSC therapy may be a clinically effective tool for the treatment of lymph node metastatic colorectal cancer.

A Novel FLCN c.1489_1490delTG Mutation that Escapes the Nonsense-Mediated Decay System.

A novel FLCN c.1489_1490delTG (p.Val497Glyfs*22) mutation at the genomic DNA and mRNA levels was identified in a 43-year-old woman with complaining of recurrent primary spontaneous pneumothorax. The aberrant FLCN mRNA escaped the nonsense-mediated decay system (NMD) because of a premature termination code located in an NMD-incompetent region. To the best of our knowledge, this is the first case report of an FLCN mutation escaping the NMD.

Cowden Syndrome Detected by FDG PET/CT in an Endometrial Cancer Patient.

Cowden syndrome (CS) is a rare autosomal dominant disorder characterized by multiple hamartomas in various tissues and cancers (breast, thyroid, and endometrium). We report CS of the esophagus and gastrointestinal tract that was incidentally detected by positron emission tomography/computed tomography (PET/CT) at postoperative surveillance in an endometrial cancer patient. PET/CT showed mildly increased FDG uptake along the entire esophagus and stomach. Upper GI endoscopy and histologic examination revealed glycogenic acanthosis of the esophagus and several hundred gastric polyps. In our case, increased FDG uptake of the esophageal wall contributed to the diagnosis of CS.