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Background: Breast cancer is the global leading cancer burden in women and the hormone receptor-positive (HR+) subtype is a major part of breast cancer. Though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are highly effective therapy for HR+ subtype, acquired resistance is inevitable in most cases. Herein, we investigated the paternally expressed gene 10 (PEG10)-associated mechanism of acquired resistance to CDK4/6 inhibitors. Methods: Palbociclib-resistant cells were generated by exposing human HR+ breast cancer cell lines to palbociclib for 7–9 months. In vitro mechanistic study and in vivo xenograft assay were performed. For clinical relevance, public mRNA microarray data sets of early breast cancer were analyzed and PEG10 immunohistochemical staining was performed using pre-CDK4/6 inhibitor tumor samples. Results: We observed that PEG10 was significantly upregulated in palbociclib-resistant cells. Ectopic overexpression of PEG10 in parental cells caused CDK4/6 inhibitor resistance and enhanced epithelial–mesenchymal transition (EMT). On the contrary, PEG10-targeting siRNA or antisense oligonucleotides (ASOs) combined with palbociclib synergistically inhibited proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice and suppressed EMT as well. The mechanistic study confirmed that high PEG10 expression suppressed p21, a natural CDK inhibitor, and SIAH1, a post-translational degrader of ZEB1, augmenting CDK4/6 inhibitor resistance. Then PEG10 siRNA combined with palbociclib suppressed cell cycle progression and EMT via activating p21 and SIAH1, respectively. Consequently, combined PEG10 inhibition and palbociclib overcame CDK4/6 inhibitor resistance. Furthermore, high PEG10 expression was significantly associated with a shorter recurrence-free survival (RFS) based on public mRNA expression data. In pre-CDK4/6 inhibitor treatment tissues, PEG10 positivity by IHC also showed a trend toward a shorter progression-free survival (PFS) with CDK4/6 inhibitor. These results support clinical relevance of PEG10 as a therapeutic target. Conclusions: We demonstrated a novel PEG10-associated mechanism of CDK4/6 inhibitor resistance. We propose PEG10 as a promising therapeutic target for overcoming PEG10-associated resistance to CDK4/6 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods: A multicenter randomized phase II trial involving 364 patients with LARC (cT3–4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45–50.4 Gy in 25–28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2–5 weeks from the last cycle of chemotherapy in the experimental arm and 6–8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted total knee arthroplasty (r-TKA) can reportedly achieve more accurate implant positioning than conventional total knee arthroplasty (c-TKA), although its learning curve is controversial. Moreover, few studies have investigated r-TKA in Asians, who have different anatomical characteristics. This study aimed to determine the learning curve for r-TKA and compare implant positions between r-TKA and c-TKA according to the learning curve in Asian patients. Methods: This prospective study included 50 consecutive c-TKAs (group C), followed by 50 consecutive r-TKAs conducted using the MAKO robotic system (Stryker, USA). Cumulative summation analyses were performed to assess the learning curve for operative time in r-TKA. Accordingly, the r-TKA cases were divided into the initial (group I) and proficiency cases (group P). The femoral and tibial component positions in the coronal, sagittal, and axial planes and lower limb alignment were compared among the three groups. Results: r-TKA was associated with a learning curve for operative time in 18 cases. The operative time was significantly shorter in groups C and P than that in group I, with no significant difference between groups C and P. Groups I and P demonstrated fewer outliers with respect to lower limb alignment, femoral component coronal position, axial position, and tibial component sagittal position than those in group C, with no significant difference between groups I and P. Conclusion: The operative time did not differ significantly between r-TKA and c-TKA after the learning curve. Surgeons could expect more accurate and reproducible lower limb alignment and implant positioning with r-TKA in Asian patients, irrespective of the learning curve. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted total knee arthroplasty (r-TKA) can reportedly achieve more accurate implant positioning than conventional total knee arthroplasty (c-TKA), although its learning curve is controversial. Moreover, few studies have investigated r-TKA in Asians, who have different anatomical characteristics. This study aimed to determine the learning curve for r-TKA and compare implant positions between r-TKA and c-TKA according to the learning curve in Asian patients. Methods: This prospective study included 50 consecutive c-TKAs (group C), followed by 50 consecutive r-TKAs conducted using the MAKO robotic system (Stryker, USA). Cumulative summation analyses were performed to assess the learning curve for operative time in r-TKA. Accordingly, the r-TKA cases were divided into the initial (group I) and proficiency cases (group P). The femoral and tibial component positions in the coronal, sagittal, and axial planes and lower limb alignment were compared among the three groups. Results: r-TKA was associated with a learning curve for operative time in 18 cases. The operative time was significantly shorter in groups C and P than that in group I, with no significant difference between groups C and P. Groups I and P demonstrated fewer outliers with respect to lower limb alignment, femoral component coronal position, axial position, and tibial component sagittal position than those in group C, with no significant difference between groups I and P. Conclusion: The operative time did not differ significantly between r-TKA and c-TKA after the learning curve. Surgeons could expect more accurate and reproducible lower limb alignment and implant positioning with r-TKA in Asian patients, irrespective of the learning curve. [ABSTRACT FROM AUTHOR]

Background: Alpha-synuclein (α-syn) is considered the main pathophysiological protein component of Lewy bodies in synucleinopathies. α-Syn is an intrinsically disordered protein (IDP), and several types of structural conformations have been reported, depending on environmental factors. Since IDPs may have distinctive functions depending on their structures, α-syn can play different roles and interact with several proteins, including amyloid-beta (Aβ) and tau, in Alzheimer's disease (AD) and other neurodegenerative disorders. Main body: In previous studies, α-syn aggregates in AD brains suggested a close relationship between AD and α-syn. In addition, α-syn directly interacts with Aβ and tau, promoting mutual aggregation and exacerbating the cognitive decline. The interaction of α-syn with Aβ and tau presented different consequences depending on the structural forms of the proteins. In AD, α-syn and tau levels in CSF were both elevated and revealed a high positive correlation. Especially, the CSF α-syn concentration was significantly elevated in the early stages of AD. Therefore, it could be a diagnostic marker of AD and help distinguish AD from other neurodegenerative disorders by incorporating other biomarkers. Conclusion: The overall physiological and pathophysiological functions, structures, and genetics of α-syn in AD are reviewed and summarized. The numerous associations of α-syn with Aβ and tau suggested the significance of α-syn, as a partner of the pathophysiological roles in AD. Understanding the involvements of α-syn in the pathology of Aβ and tau could help address the unresolved issues of AD. In particular, the current status of the CSF α-syn in AD recommends it as an additional biomarker in the panel for AD diagnosis. [ABSTRACT FROM AUTHOR]

Background: Glycolysis metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options. The ubiquitin–proteasome system facilitates the turnover of most intracellular proteins with E3 ligase conferring the target selection and specificity. Ubiquitin protein ligase E3 component N-recognin 7 (UBR7), among the least studied E3 ligases, recognizes its substrate through a plant homeodomain (PHD) finger. Here, we bring into focus on its suppressive role in glycolysis and HCC tumorigenesis, dependent on its E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine 120 (H2BK120ub). Methods: In this study, we carried out high-throughput RNAi screening to identify epigenetic candidates in regulating lactic acid and investigated its possible roles in HCC progression. Results: UBR7 loss promotes HCC tumorigenesis both in vitro and in vivo. UBR7 inhibits glycolysis by indirectly suppressing HK2 expression, a downstream target of Nrf2/Bach1 axis. Mechanically, UBR7 regulates H2BK120ub to bind to Keap1 promoter through H2BK120ub monoubiquitination, thereby modulating Keap1 expression and downstream Nrf2/Bach1/HK2 signaling. Pharmaceutical and genetic inhibition of glycolytic enzymes attenuate the promoting effect of UBR7 deficiency on tumor growth. In addition, methyltransferase ALKBH5, downregulated in HCC, regulated UBR7 expression in an m6A-dependent manner. Conclusions: These results collectively establish UBR7 as a critical negative regulator of aerobic glycolysis and HCC tumorigenesis through regulation of the Keap1/Nrf2/Bach1/HK2 axis, providing a potential clinical and therapeutic target for the HCC treatment. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of mild cognitive impairment (MCI) is essential for timely treatment planning. With recent advances in the wearable technology, interest has increasingly shifted toward computer-aided self-diagnosis of MCI using wearable electroencephalography (EEG) devices in daily life. However, no study so far has investigated the optimal electrode configurations for the efficient diagnosis of MCI while considering the design factors of wearable EEG devices. In this study, we aimed to determine the optimal channel configurations of wearable EEG devices for the computer-aided diagnosis of MCI. Method: We employed an EEG dataset collected from 21 patients with MCI and 21 healthy control subjects. After evaluating the classification accuracies for all possible electrode configurations for the two-, four-, six-, and eight-electrode conditions using a support vector machine, the optimal electrode configurations that provide the highest diagnostic accuracy were suggested for each electrode condition. Results: The highest classification accuracies of 74.04% ± 4.82, 82.43% ± 6.14, 86.28% ± 2.81, and 86.85% ± 4.97 were achieved for the optimal two-, four-, six-, and eight-electrode configurations, respectively, which demonstrated the possibility of precise machine-learning-based diagnosis of MCI with a limited number of EEG electrodes. Additionally, further simulations with the EEG dataset revealed that the optimal electrode configurations had significantly higher classification accuracies than commercial EEG devices with the same number of electrodes, which suggested the importance of electrode configuration optimization for wearable EEG devices based on clinical EEG datasets. Conclusions: This study highlighted that the optimization of the electrode configuration, assuming the wearable EEG devices can potentially be utilized for daily life monitoring of MCI, is necessary to enhance the performance and portability. [ABSTRACT FROM AUTHOR]

Background: There is insufficient evidence on the clinical effectiveness and safety of infliximab (IFX) treatment of Takayasu arteritis (TA) in infants. Methods: We evaluated the therapeutic effectiveness and safety of IFX in a retrospective case series of 10 infantile TA patients. Observations included assessment of clinical symptoms, laboratory testing, and vascular imaging. Results: Fever was the presenting symptom for 8 of 10 infants with TA. During acute episodes, leucocyte and inflammatory indices were significantly increased. Vascular imaging showed the most commonly involved arteries to be carotid arteries, abdominal aortas, and coronary arteries (9 cases, 90%). Two weeks after initiating IFX treatment, leukocyte and platelet counts decreased and hemoglobin levels increased. There were statistically significant clinical improvements 6 weeks after starting treatment compared with before treatment (p < 0.05). Inflammatory indices decreased 2 weeks after starting IFX treatment compared with before treatment (p < 0.05). Vascular lesions began to recover within 1.5-3 months of initiating IFX therapy, and involved vessels significantly recovered within 13 months. Some arteries remained stenotic, with intimal thickening and uneven lumen wall thicknesses. The only adverse event was a treatment-responsive allergic reaction during IFX infusion in one infant. Conclusions: Fever was the main manifestation of illness and was often accompanied by significantly increased inflammatory indices. IFX treatment was apparently effective and reduced or eliminated need for glucocorticoids. IFX had a reasonably good safety profile. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are nanosized membrane-enclosed compartments that serve as messengers in cell-to-cell communication, both in normal physiology and in pathological conditions. EVs can transfer functional proteins and genetic information to alter the phenotype and function of recipient cells, which undergo different changes that positively affect their structural and functional integrity. Biological fluids are enriched with several subpopulations of EVs, including exosomes, microvesicles (MVs), and apoptotic bodies carrying several cargoes, such as lipids, proteins, and nucleic acids. EVs associated with the reproductive system are actively involved in the regulation of different physiological events, including gamete maturation, fertilization, and embryo and fetal development. EVs can influence follicle development, oocyte maturation, embryo production, and endometrial-conceptus communication. EVs loaded with cargoes are used to diagnose various diseases, including pregnancy disorders; however, these are dependent on the type of cell of origin and pathological characteristics. EV-derived microRNAs (miRNAs) and proteins in the placenta regulate inflammatory responses and trophoblast invasion through intercellular delivery in the placental microenvironment. This review presents evidence regarding the types of extracellular vesicles, and general aspects of isolation, purification, and characterization of EVs, particularly from various types of embryos. Further, we discuss EVs as mediators and messengers in reproductive biology, the effects of EVs on placentation and pregnancy disorders, the role of EVs in animal reproduction, in the male reproductive system, and mother and embryo cross-communication. In addition, we emphasize the role of microRNAs in embryo implantation and the role of EVs in reproductive and therapeutic medicine. Finally, we discuss the future perspectives of EVs in reproductive biology. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are nanosized membrane-enclosed compartments that serve as messengers in cell-to-cell communication, both in normal physiology and in pathological conditions. EVs can transfer functional proteins and genetic information to alter the phenotype and function of recipient cells, which undergo different changes that positively affect their structural and functional integrity. Biological fluids are enriched with several subpopulations of EVs, including exosomes, microvesicles (MVs), and apoptotic bodies carrying several cargoes, such as lipids, proteins, and nucleic acids. EVs associated with the reproductive system are actively involved in the regulation of different physiological events, including gamete maturation, fertilization, and embryo and fetal development. EVs can influence follicle development, oocyte maturation, embryo production, and endometrial-conceptus communication. EVs loaded with cargoes are used to diagnose various diseases, including pregnancy disorders; however, these are dependent on the type of cell of origin and pathological characteristics. EV-derived microRNAs (miRNAs) and proteins in the placenta regulate inflammatory responses and trophoblast invasion through intercellular delivery in the placental microenvironment. This review presents evidence regarding the types of extracellular vesicles, and general aspects of isolation, purification, and characterization of EVs, particularly from various types of embryos. Further, we discuss EVs as mediators and messengers in reproductive biology, the effects of EVs on placentation and pregnancy disorders, the role of EVs in animal reproduction, in the male reproductive system, and mother and embryo cross-communication. In addition, we emphasize the role of microRNAs in embryo implantation and the role of EVs in reproductive and therapeutic medicine. Finally, we discuss the future perspectives of EVs in reproductive biology. [ABSTRACT FROM AUTHOR]

3 [Retracted B, Li Y, Yuan S, Tomlinson S, He S. Upregulation of the opioid receptor in liver cancer promotes liver cancer progression both in vitro and in vivo retraction in /10.3892/ijo.2023.5504. 5833540 2 [Retracted B, Liang W, Liao Y, Li Z, Wang Y, Yan C. PEA15 promotes liver metastasis of colorectal cancer by upregulating the ERK/MAPK signaling pathway retraction in /10.3892/or.2023.8574. [Extracted from the article]

This document is a correction notice for an article titled "Learning curve of robot-assisted total knee arthroplasty and its effects on implant position in Asian patients: a prospective study." The authors of the original article identified minor typographical errors in Tables 1 and 3, but these errors do not affect the results. The corrected version of the article is available online. The publisher, Springer Nature, remains neutral and does not take a position on jurisdictional claims or institutional affiliations. The authors of the original article are Ho Jung Jung, Min Wook Kang, Jong Hwa Lee, and Joong Il Kim. [Extracted from the article]

6017264 4 Dong H, Wang W, Mo S. RETRACTED ARTICLE: SP1-induced lncRNA AGAP2-AS1 expression promotes chemoresistance of breast cancer by epigenetic regulation of MyD88. Retrieved from https://www.oncotarget.com/article/22058/text/ 3 Zhang W, Cai X, Yu J, Lu X, Qian Q, Qian W. Exosome-mediated transfer of lncRNA RP11-838N2.4 promotes erlotinib resistance in non-small cell lung cancer retraction in /10.3892/ijo.2022.5458. [Extracted from the article]

*c-TKA, conventional total knee arthroplasty; r-TKA, robot-assisted total knee arthroplasty; group C, conventional total knee arthroplasty group; group I, initial phase group; group P, proficiency phase group The original article [[1]] has been corrected. Learning curve of robot-assisted total knee arthroplasty and its effects on implant position in asian patients: a prospective study. [Extracted from the article]

Background: This study aimed to analyze the structural brain network in patients with occipital lobe epilepsy (OLE) and investigate the differences in structural brain networks between patients with OLE and healthy controls. Methods: Patients with OLE and healthy controls with normal brain MRI findings were enrolled. They underwent diffusion tensor imaging using a 3.0T MRI scanner, and we computed the network measures of global and local structural networks in patients with OLE and healthy controls using the DSI studio program. We compared network measures between the groups. Results: We enrolled 23 patients with OLE and 42 healthy controls. There were significant differences in the global structural network between patients with OLE and healthy controls. The assortativity coefficient (-0.0864 vs. -0.0814, p = 0.0214), mean clustering coefficient (0.0061 vs. 0.0064, p = 0.0203), global efficiency (0.0315 vs. 0.0353, p = 0.0086), and small-worldness index (0.0001 vs. 0.0001, p = 0.0175) were lower, whereas the characteristic path length (59.2724 vs. 53.4684, p = 0.0120) was higher in patients with OLE than those in the healthy controls. There were several nodes beyond the occipital lobe that showed significant differences in the local structural network between the groups. In addition, the assortativity coefficient was negatively correlated with the duration of epilepsy (r=-0.676, p = 0.001). Significance: We first evaluated alterations in the structural brain network of patients with OLE. There were significant differences in the global structural network between patients with OLE and healthy controls. We also found several regions of nodes that showed significantly altered local structural networks in patients with OLE. This study could suggest that epilepsy is a network disease, and this also may apply to OLE. [ABSTRACT FROM AUTHOR]

Background: Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor–node–metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck–lymph node radiotherapy in patients with NPC. Methods: Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression. Results: DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73–0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively. Conclusion: Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool. [ABSTRACT FROM AUTHOR]

Background: Nematodes are parasitic animals that cause over 100 billion US dollars loss in agricultural business. The whole-genomes of two Streptomyces strains, Streptomyces spectabilis KCTC9218T and Streptomyces sp. AN091965, were sequenced. Both strains produce spectinabilin, an antinematode drug. Its secondary metabolism was examined to aid the development of an efficient nematicidal drug-producing host strain. Results: The whole-genome sequences of S. spectabilis KCTC9218T and Streptomyces sp. AN091965 were analyzed using PacBio and Illumina sequencing platforms, and assembled using hybrid methodology. The total contig lengths for KCTC9218T and AN091965 were 9.97 Mb and 9.84 Mb, respectively. A total of 8,374 and 8,054 protein-coding genes, as well as 39 and 45 secondary metabolite biosynthetic gene clusters were identified in KCTC9218T and AN091965, respectively. 18.4 ± 6.45 mg/L and 213.89 ± 21.30 mg/L of spectinabilin were produced by S. spectabilis KCTC9218T and Streptomyces sp. AN091965, respectively. Pine wilt disease caused by nematode was successfully prevented by lower concentration of spectinabilin injection than that of abamectin recommended by its manufacturer. Production of multiple antinematode drugs, including spectinabilin, streptorubin B, and undecylprodigiosin was observed in both strains using high-resolution liquid chromatography mass spectrometry (LC–MS) analysis. Conclusions: Whole-genome sequencing of spectinabilin-producing strains, coupled with bioinformatics and mass spectrometry analyses, revealed the production of multiple nematicidal drugs in the KCTC9218T and AN091965 strains. Especially, Streptomyces sp. AN091965 showed high production level of spectinabilin, and this study provides crucial information for the development of potential nematicidal drug producers. [ABSTRACT FROM AUTHOR]

Background: The superposition of COVID-19 and climate change has brought great challenges to global food security. As a major economic crop in the world, studying its phenotype to cultivate high-quality wheat varieties is an important way to increase grain yield. However, most of the existing phenotyping platforms have the disadvantages of high construction and maintenance costs, immobile and limited in use by climatic factors, while the traditional climate chambers lack phenotypic data acquisition, which makes crop phenotyping research and development difficult. Crop breeding progress is slow. At present, there is an urgent need to develop a low-cost, easy-to-promote, climate- and site-independent facility that combines the functions of crop cultivation and phenotype acquisition. We propose a movable cabin-type intelligent artificial climate chamber, and build an environmental control system, a crop phenotype monitoring system, and a crop phenotype acquisition system. Result: We selected two wheat varieties with different early vigor to carry out the cultivation experiments and phenotype acquisition of wheat under different nitrogen fertilizer application rates in an intelligent artificial climate chamber. With the help of the crop phenotype acquisition system, images of wheat at the trefoil stage, pre-tillering stage, late tillering stage and jointing stage were collected, and then the phenotypic information including wheat leaf area, plant height, and canopy temperature were extracted by the crop type acquisition system. We compared systematic and manual measurements of crop phenotypes for wheat phenotypes. The results of the analysis showed that the systematic measurements of leaf area, plant height and canopy temperature of wheat in four growth periods were highly correlated with the artificial measurements. The correlation coefficient (r) is positive, and the determination coefficient (R2) is greater than 0.7156. The root mean square error (RSME) is less than 2.42. Among them, the crop phenotype-based collection system has the smallest measurement error for the phenotypic characteristics of wheat trefoil stage. The canopy temperature RSME is only 0.261. The systematic measurement values of wheat phenotypic characteristics were significantly positively correlated with the artificial measurement values, the fitting degree was good, and the errors were all within the acceptable range. The experiment showed that the phenotypic data obtained with the intelligent artificial climate chamber has high accuracy. We verified the feasibility of wheat cultivation and phenotype acquisition based on intelligent artificial climate chamber. Conclusion: It is feasible to study wheat cultivation and canopy phenotype with the help of intelligent artificial climate chamber. Based on a variety of environmental monitoring sensors and environmental regulation equipment, the growth environment factors of crops can be adjusted. Based on high-precision mechanical transmission and multi-dimensional imaging sensors, crop images can be collected to extract crop phenotype information. Its use is not limited by environmental and climatic factors. Therefore, the intelligent artificial climate chamber is expected to be a powerful tool for breeders to develop excellent germplasm varieties. [ABSTRACT FROM AUTHOR]

Background: Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells. Results: A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells. Conclusions: These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells. [ABSTRACT FROM AUTHOR]

Background: The South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer's disease (AD) between July 2011 and June 2017 which spanned the 2014 revision. Methods: This multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017). Results: Subjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were ≥98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001). Conclusions: Comparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care. [ABSTRACT FROM AUTHOR]

Background: Renal cancer therapies are challenging owing to the extensive spreading of this cancer to other organs and its ability to pose resistance to current medications. Therefore, drugs targeting novel targets are urgently required to overcome these challenges. The cholesterol side-chain cleavage enzyme (CYP11A1) is closely associated with steroidogenesis, and its downregulation is linked to adrenal dysfunction and several types of carcinoma. We previously found that overexpression of CYP11A1 inhibited epithelial-mesenchymal transition and induced G2/M arrest in the kidney cancer Caki-1 cell line. In this context, natural compounds that exhibit potent CYP11A1 stimulation activity can be promising therpaeutic agents for kidney cancer. Methods: We screened a panel of 1374 natural compounds in a wound-healing assay using CYP11A1-transfected Caki-1 cells. Of these, 167 promising biologically active compounds that inhibited cancer cell migration by more than 75% were selected, and their half-maximal inhibitory concentrations (IC50) were determined. The IC50 of 159 compounds was determined and 38 compounds with IC50 values less than 50 µM were selected for further analysis. Steroid hormones (cholesterol and pregnenolone) levels in cells treated with the selected compounds were quantitated using LC–MS/MS to determine their effect on CYP11A1 activity. Western blotting for CYP11A1, autophagy signaling proteins, and ferroptosis regulators were performed to ivestigate the mechanisms underlying the action of the selected compounds. Results: We screened five promising natural lead compounds that inhibited cancer cell proliferation after three screening steps. The IC50 of these compounds was determined to be between 5.9 and 14.6 μM. These candidate compounds increased the expression of CYP11A1 and suppressed cholesterol levels while increasing pregnenolone levels, which is consistent with the activation of CYP11A1. Our results showed that CYP11A1 activation inhibited the migration of cancer cells, promoted ferroptosis, and triggered autophagy signaling. Conclusions: This study indicates that the CYP11A1-overexpressing Caki-1 cell line is useful for screening drugs against kidney cancer. The two selected compounds could be utilized as lead compounds for anticancer drug discovery, and specifically for the development of antirenal cancer medication. [ABSTRACT FROM AUTHOR]

Backgroud: To summarize the clinical characteristics and identify the risk factors for pediatric Takayasu arteritis (TAK) with coronary artery lesions (CALs). Methods: Clinical data of pediatric TAK patients in our center were retrospectively assessed. Independent risk factors for CALs were identified using multivariate logistic regression analysis. Survival analysis was used to compare differences in survival rates between the groups. Results: Among the 66 pediatric TAK cases, the incidence of accompanying CALs was 39.4%. In the CAL group, 19 (73.1%) cases started within 36 months. None of the patients had symptoms of angina or ischemia on electrocardiogram (ECG), the CALs were detected using coronary ultrasound. The CALs most commonly were the left main and right coronary arteries. The lesions were mostly small or middle coronary artery aneurysms; some children may have giant coronary aneurysmal dilations, thrombosis and heart failure. The age of onset and symptom onset to diagnosis in TAK patients with CAL were lower than those in TAK patients without CAL(P < 0.005). TAK patients with CAL had significantly higher CRP,WBC, PLT,TNF-α and IL-2R levels (P < 0.05), lower HGB (P = 0.01), lower rate of renal artery stenosis (RAS) (P = 0.009). In multivariate logistic regression, the risk factors for pediatric TAK combined with CAL included the age of TAK onset (OR = 0.9835, 95% CI: 0.9710–0.9946, P = 0.006) and RAS (OR = 0.1901, 95% CI: 0.0386–0.7503, P = 0.03). In addition, there was no significant difference in survival rates between the two groups after regular treatment. Conclusion: This study showed that the occurrence of CAL in pediatric TAK patients has a relatively more rapid clinical course, and a stronger inflammatory state at the time of diagnosis. The earlier the age of TAK onset and without RAS are more likely to cause CAL. [ABSTRACT FROM AUTHOR]

Background: Obese patients have a higher risk of complications during spinal surgery than non-obese patients. To the best of our knowledge, no studies have examined the differences in clinical and radiological outcomes after biportal endoscopic lumbar discectomy (BELD) between obese and non-obese patients. The study evaluated the association between obesity and outcomes after BELD in patients with lumbar disc herniation. Methods: This was a retrospective case-control study conducted from March 2017 to March 2021 at two hospitals with 360 patients who underwent BELD after showing no improvement with conservative treatment. Clinical and radiologic outcomes were retrospectively analyzed after BELD in the non-obese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30 kg/m2) groups. Demographic data and surgery-related factors were compared between the two groups. Clinical outcomes were followed up for 12 months after surgery and analyzed for differences. Results: A total of 211 patients were enrolled in this study, and through case-control matching, the data of 115 patients (29, obese group; 86, non-obese group) were analyzed. The two groups showed no significant differences in Oswestry Disability Index, European Quality of Life-5 Dimensions (EQ-5D), and visual analog scale scores measured immediately after BELD and 12 months after surgery. After surgery, back pain, radiating leg pain, and EQ-5D scores improved. However, there was no significant difference in improvement, residual herniated disc, hematoma, or recurrence between the groups. Conclusions: Obese patients who underwent BELD for lumbar disc herniation showed no significant difference in clinical and radiologic outcomes compared with non-obese patients. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based concurrent chemoradiotherapy has been identified as the primary and standard treatment for locally advanced nasopharyngeal carcinoma (NPC). However, the side effects of cisplatin affect the compliance to therapy. Thus, the search for a platinum-based substitute for NPC has always been a research focus. However, there is a variability in the efficacy of different platinum-based chemotherapies in the treatment of NPC. We performed a meta-analysis to compare the efficacy and safety of cisplatin-based regimens and other platinum-based derivatives (carboplatin, nedaplatin, and lobaplatin) for locally advanced NPC.Methods: PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov were systematically searched for all potentially eligible clinical trials as of February 15, 2022. The pooled hazard ratios, risk ratio, and 95% confidence interval were calculated using Review Manager Software version 5.4.Results: A total of 1,907 patients with locally advanced NPC were eligible from the 1,265 retrieved records. This systematic review included eight articles, six of which were randomized controlled clinical trials. There was no significant difference in the 3- and 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival between cisplatin-based chemotherapy and other platinum-based chemotherapy. Severe acute hematological side effects (≥ grade 3) during treatment, such as neutropenia, leukopenia, and thrombocytopenia, were equivalent in both groups. However, the incidence of anemia was higher in patients receiving other platinum-based chemotherapies. The risk of nausea, vomiting and weight loss was higher in the cisplatin group; however, there was no significant difference in the other non-hematological and late side effects between the two groups.Conclusions: Other types of platinum-based chemotherapies are as effective as cisplatin-based chemotherapy in the treatment of locally advanced NPC, thus acting as potential alternatives to cisplatin. Further studies providing high-level evidence are needed. [ABSTRACT FROM AUTHOR]

Background: Clear cell renal carcinoma is commonly known for its metastasis propensity to outspread to other organs and is asymptomatic in the early stage. Recent studies have shown that deficiencies in CYP11A1 expression can lead to fatal adrenal failure if left untreated and are associated with downstream regulation in various cancer types. However, the molecular mechanisms of CYP11A1 and kidney cancer proliferation remain unclear. Methods: Normal and renal carcinoma cell lines (HEK293 and Caki-1) were transfected with plasmid encoding CYP11A1 to overexpress the P450scc protein. Cell cycle distribution was investigated using flow cytometry. The expression of proteins related to C-Raf/ERK/JNK/p38 signaling pathways was examined using western blot. Results: We observed that CYP11A1 overexpression suppressed the cyclin B1 and cell-division cycle 2 expression while cyclin-dependent kinases 2 and 4 were unaffected. Cancer cell migration and invasion were suppressed along with epithelial-intermediate metastatic markers Snail and Vimentin. In addition, in CYP11A1-overexpressing Caki-1 cells, cdc2/cyclinB1 was downregulated while the phosphorylation of cdc25c, a G2/M arrest-related upstream signal, was increased. The intrinsic-mitochondrial apoptosis markers were not significantly altered. We also identified that the C-Raf/ERK/JNK/p38 pathway is an important pro-apoptotic mechanism in CYP11A1-overexpressing cell-based models. Our results suggest that CYP11A1 overexpression recovered the disturbed cell cycle arrest distribution in renal carcinoma cell line Caki-1 through G2/M arrest and C-Raf/ERK/JNK pathway. Conclusions: Our findings may suggest promising new therapeutic targets to suppress kidney cancer proliferation without affecting normal cells, eventually improving the survival of patients with cancer. [ABSTRACT FROM AUTHOR]

Background: Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics.Methods: Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed.Results: In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified.Conclusions: Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: To retrospectively analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) plus recombinant human endostatin (Endostar, CCRT + E) versus CCRT alone in locally advanced nasopharyngeal carcinoma (LANPC).Methods: A retrospective analysis of patients initially treated for LANPC from November 2016 to March 2019 was performed: trial group received CCRT + E and control group received CCRT. Prognoses and adverse effects were evaluated.Results: Eighty-eight patients were included: 43 received CCRT + E and 45 received CCRT. The median follow-up time was 54.0 (range: 8.0-64.0) months. The survival data of the CCRT + E and CCRT groups were as follows: 3-year progression-free survival (PFS) rates, 81.4% and 63.6% (hazard ratio [HR] 0.418, 95%CI 0.181-0.963, P = 0.034); 3-year distant metastasis-free survival (DMFS) rates, 88.3% and 77.3% (HR 0.370, 95%CI 0.132-1.039, P = 0.049); 3-year overall survival rates, 88.2% and 81.9% (HR 0.437, 95%CI 0.151-1.260, P = 0.114); and 3-year locoregional failure-free survival rates, 87.8% and 86.9% (HR 0.795, 95%CI 0.242-2.616, P = 0.705). Three months after radiotherapy, the complete response (CR) rates of cervical lymph node regression were 97.7% and 82.2% for the CCRT + E and CCRT groups (P = 0.041). The corresponding CR rates were 100% and 80.0% for lymph node necrosis (P = 0.001) and 100% and 85.2% for extranodal extension (P = 0.041). The CCRT + E group had higher incidence of grade 3/4 leukopenia (32.6% vs. 13.3%, P = 0.031), with similar results for late toxicity.Conclusions: CCRT + E significantly prolonged 3-year PFS and DMFS in LANPC, and patients had better lymph node regression. [ABSTRACT FROM AUTHOR]

Background: Biportal endoscopic surgery has recently been performed in lumbar discectomy, with advantages over conventional surgery, such as less skin scarring and muscle damage. However, the clinical results have not been established. Although previous studies reported no difference between the biportal endoscopic and microscopic discectomy clinical results, the evidence was weak. Therefore, this study aims to evaluate the efficacy and safety of the biportal endoscopic discectomy versus the microscopic discectomy.Methods: This prospective multicenter randomized controlled equivalence trial is designed to compare the efficacy and safety outcomes of patients who underwent lumbar discectomy using biportal endoscopy or microscopy. We will include 100 participants (50 per group) with a lumbar herniated disc. The primary outcome will be the Oswestry Disability Index (ODI) score 12 months after surgery based on a modified intention-to-treat strategy. The secondary outcomes will include the visual analog scale score for low back and lower extremity radiating pain, the ODI score, the Euro-Qol-5-Dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scar, and surgery-related variables, such as postoperative drainage, operation time, admission duration, postoperative creatine kinase, and implementation status of conversion to open surgery. Radiographic outcomes will also be analyzed using magnetic resonance imaging (MRI) or computed tomography (CT) and simple radiographs. Safety will be assessed by evaluating all adverse and severe adverse events and surgery-related effects. The participants will be assessed by a blinded assessor before surgery (baseline) and 2 weeks and 3, 6, and 12 months after surgery.Discussion: This trial will be the first prospective, multicenter, randomized controlled trial to analyze the efficacy and safety of biportal endoscopic discectomy in lumbar herniated disc. This trial is designed for evaluating the equivalence of the results between biportal endoscopic and microscopic discectomy including adequate sample size, blinded analyses, and prospective registration to reduce bias. This trial will provide enough data on the effectiveness and safety of biportal endoscopic surgery and will be an important study that allows clear conclusions.Trial Registration: Clinical Research Information Service (cris.nih.go.kr.) ( KCT0006191 ). Registered on 27 March 2021. [ABSTRACT FROM AUTHOR]

Background: Recent studies on biportal endoscopic spine surgery in patients with lumbar spinal stenosis have reported good clinical results. However, these studies have been limited by the small sample sizes and use of a retrospective study design. Therefore, we aim to compare the efficacy and safety of biportal endoscopic decompressive laminectomy with those of conventional decompressive laminectomy in a multicenter, prospective, randomized controlled trial.Methods: This study will include 120 patients (60 per group, aged 20-80 years) with 1- or 2-level lumbar spinal stenosis, who will be recruited from six hospitals. The study will be conducted from July 2021 to December 2024. The primary outcome (Oswestry Disability Index at 12 months after surgery) will be evaluated through a modified intention-to-treat method. The secondary outcomes will include the following: visual analog scale score for low back and lower extremity radiating pain, EuroQol 5-dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scars, and some surgery-related variables. Radiographic outcomes will be analyzed using magnetic resonance imaging or computed tomography. All outcomes will be evaluated before the surgery and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for reporting of clinical trial protocols.Discussion: It is hypothesized that the efficacy and safety of biportal endoscopic and conventional decompressive laminectomy will be comparable in patients with lumbar spinal stenosis. The results of this trial will provide a high level of evidence for the efficacy and safety of the biportal endoscopic technique in patients with lumbar spinal stenosis and facilitate the development of clinical practice guidelines. Furthermore, the results of this study may indicate the feasibility of the biportal endoscopic technique for other types of spinal surgery.Trial Registration: The ENDO-B trial is registered at Clinical Research Information Service (CRIS, cris.nih.go.kr ) (KCT0006057; April 52,021). [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate alterations in structural connectivity and structural co-variance network in patients with focal cortical dysplasia (FCD).Methods: We enrolled 37 patients with FCD and 35 healthy controls. All subjects underwent brain MRI with the same scanner and with the same protocol, which included diffusion tensor imaging (DTI) and T1-weighted imaging. We analyzed the structural connectivity based on DTI, and structural co-variance network based on the structural volume with T1-weighted imaging. We created a connectivity matrix and obtained network measures from the matrix using the graph theory. We tested the difference in network measure between patients with FCD and healthy controls.Results: In the structural connectivity analysis, we found that the local efficiency in patients with FCD was significantly lower than in healthy controls (2.390 vs. 2.578, p = 0.031). Structural co-variance network analysis revealed that the mean clustering coefficient, global efficiency, local efficiency, and transitivity were significantly decreased in patients with FCD compared to those in healthy controls (0.527 vs. 0.635, p = 0.036; 0.545 vs. 0.648, p = 0.026; 2.699 vs. 3.801, p = 0.019; 0.791 vs. 0.954, p = 0.026, respectively).Conclusions: We demonstrate that there are significant alterations in structural connectivity, based on DTI, and structural co-variance network, based on the structural volume, in patients with FCD compared to healthy controls. These findings suggest that focal lesions with FCD could affect the whole-brain network and that FCD is a network disease. [ABSTRACT FROM AUTHOR]