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This study retrospectively assessed radiographic outcomes and risk factors associated with non-union in femoral shaft fragmentary segmental fractures (AO/OTA 32C3) treated with reamed antegrade intra-medullary nailing. Radiological outcomes, including union and alignment, were evaluated. The risk factors for non-union were investigated, including demographics and treatment-related characteristics, such as the number of interlocking screws, segmentation length, main third fragment length, distance of the main third fragment, width ratio and exposed nail length in one cortex from immediate post-operative radiographs. Multivariate logistic regression was used for statistical analysis. Among 2295 femoral shaft fracture patients from three level-1 trauma centers, 51 met the inclusion criteria. The radiological union was achieved in 37 patients (73%) with a mean union time of 10.7 ± 4.8 months. The acceptable axial alignment was observed in 30 patients (59%). Multiple logistic regression analysis identified only exposed nail length as a significant risk factor for non-union (odds ratio: 1.599, p = 0.003) and the cut-off value was 19.1 mm (sensitivity, 0.786; specificity, 0.811). The study revealed high rates of non-union (27%) and malalignment (41%). Therefore, patients who underwent intramedullary nailing with an exposed nail length greater than 19.1 mm or about twice the nail diameter should be cautioned of the potential non-union., (© 2024. The Author(s).)

Key Message: Bulked segregant RNA seq of pools of pepper accessions that are susceptible or resistant to Broad bean wilt virus 2 identifies a gene that might confer resistance to this devastating pathogen. The single-stranded positive-sense RNA virus Broad bean wilt virus 2 (BBWV2) causes substantial damage to pepper (Capsicum annuum) cultivation. Here, we describe mapping the BBWV2 resistance locus bwvr using a F 7:8 recombinant inbred line (RIL) population constructed by crossing the BBWV2-resistant pepper accession 'SNU-C' with the susceptible pepper accession 'ECW30R.' All F 1 plants infected with the BBWV2 strain PAP1 were susceptible to the virus, and the RIL population showed a 1:1 ratio of resistance to susceptibility, indicating that this trait is controlled by a single recessive gene. To map bwvr, we performed bulked segregant RNA-seq (BSR-seq). We sequenced pools of resistant and susceptible lines from the RILs and aligned the reads to the high-quality 'Dempsey' reference genome to identify variants between the pools. This analysis identified 519,887 variants and selected the region from 245.9-250.8 Mb of the Dempsey reference genome as the quantitative trait locus region for bwvr. To finely map bwvr, we used newly designed high-resolution melting (HRM) and Kompetitive allele specific PCR (KASP) markers based on variants obtained from the BSR-seq reads and the PepperSNP16K array. Comparative analysis identified 11 SNU-C-specific SNPs within the bwvr locus. Using markers derived from these variants, we mapped the candidate bwvr locus to the region from 246.833-246.949 kb. SNU-C-specific variants clustered near DEM.v1.00035533 within the bwvr locus. DEM.v1.00035533 encodes the nitrate transporter NPF1.2 and contains a SNP within its 5' untranslated region. The bwvr locus, which contains four genes including DEM.v1.00035533, could represent a valuable resource for global pepper breeding programs., (© 2024. The Author(s).)

Study Design: Retrospective observational study., Objective: To determine the proximity between screw and endplate of the upper instrumented vertebra (UIV) using a cortical bone trajectory (CBT) screw as a predictive factor for radiographic adjacent segment degeneration (ASD) in patients surgically treated with transforaminal lumbar interbody fusion (TLIF) with CBT screws (CBT-TLIF) with lumbar spinal stenosis., Summary of Background Data: The risk factors for radiographic ASD after CBT-TLIF remain unknown., Methods: Among patients surgically treated with CBT-TLIF at a single institute, 239 consecutive patients (80 males and 159 females) were enrolled. ASD was defined by the presence of one or more of the following three radiologic criteria on the adjacent segment: >3 mm anteroposterior translation, >10° segmental kyphosis, or >50% loss of disc height comparing immediate postoperative and 1-year follow-up radiographs. Clinical and radiological features associated with the development of ASD were retrospectively measured. Univariate and multivariate analyses were performed to identify risk factors associated with radiographic ASD., Results: Radiographic ASD was observed in 71 (29.7%) cases at 1-year postoperative follow-up. The preoperative Pfirrmann grade of the adjacent segment (>grade 2), multi-level fusion (>2 levels), and proximity between the tip of CBT screws and endplate on the UIV were significantly associated with radiographic ASD (OR = 3.98, 95% CI [1.06-15.05], P=0.042 versus OR = 3.03, 95% CI [1.00-9.14], P=0.049 versus OR = 0.53, 95% CI [0.40-0.72], P<0.001). The cut-off value of the distance between the tip of the screw and endplate on UIV for radiographic ASD was approximately 2.5 mm (right-sided CBT screw; cut-off value 2.48 mm/ left-sided CBT screw; cut-off value 2.465 mm)., Conclusion: Radiographic adjacent segment degeneration progression can occur when the cortical trajectory bone screw is close to the endplate of the upper instrumented vertebrae in patients with lumbar spinal stenosis undergoing fusion surgery., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest in relation to the present study including financial, consultant, institutional, or other relationships., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To develop and validate an artificial intelligence (AI)-based diagnostic system for analysing facial skin images using expert judgements and explore its feasibility for skin ageing research, specifically by evaluating facial skin changes in Korean women of various ages., Methods: Our AI-based facial skin diagnosis system (Dr. AMORE®) uses facial images of Korean women to analyse wrinkles, pigmentation, skin pores, and other skin red spots. The system is trained using clinical expert evaluations and deep learning. We assessed the system's precision and sensitivity by analysing the correlation between the diagnoses by the AI system and those of the experts. We used 120 images of Korean women aged 10-60 years to evaluate the changes in various facial skin characteristics with ageing., Results: The precision and sensitivity of the developed system were excellent (>0.9%), and the diagnosis scores using the detected area and intensity of each item were correlated significantly higher with the visual evaluation results of the clinical experts (>0.8, p < 0.001). We also analysed facial images of Korean women aged 10-60 years to quantify changes in the scores of wrinkles, pigmentation, and skin pores with age. We identified the age group with the most significant changes as 20s to 30s. Analysis of the detailed skin characteristics of each item showed that wrinkles and pigmentation changed significantly in the 20s-30s, and skin pores increased significantly in the 10s-20s. There was no significant correlation with age or change according to the age group for skin red spots., Conclusion: Developed AI-based facial skin diagnosis system can automatically diagnose skin conditions based on clinical expert judgement using only photographic images and analyse various items in detail, quantitatively, and visually. This AI system can provide new and useful approaches in research areas that require a lot of resources and different characterizations, such as the study of facial skin ageing., (© 2023 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Purpose: The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex., Materials and Methods: This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea., Results: A total of 1,170 patients with colorectal, gastric, or non-small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits., Conclusion: Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

Background: Immune-modulating antibodies targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated promising antitumor efficacy in various types of cancers, especially highly mutated ones. Genetic alterations in DNA damage response and repair (DDR) genes can lead to genetic instability, often accompanied by a high tumor mutation burden (TMB). However, few studies have validated the aberration of DDR genes as a predictive biomarker for response to immune-modulating antibodies., Methods: The KM-06 open-label, multicenter, single-arm, phase II trial evaluated the safety and efficacy of nivolumab in refractory solid cancers with DDR gene mutations assessed by clinically targeted sequencing. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or for 24 months. The primary endpoint was the objective response rate (ORR) as per RECIST V.1.1 criteria., Results: A total of 48 patients were enrolled in the study (median age 61, 58.3% male). The most common cancer type was colorectal cancer (41.7%), followed by prostate and biliary tract cancer (8.3% each). Eight patients achieved a partial response as their best overall response, resulting in an ORR of 17.8%. The disease control rate was 60.0%. The median progression-free survival was 2.9 months. Treatment-related adverse events of any grade and grade ≥3 occurred in 44 (91.7%) and 4 (8.3%) patients, respectively. Clinically targeted sequencing data inferred both TMB and microsatellite instability (MSI). Using a TMB cut-off of 12 mut/Mb, there were significant differences in overall survival (p=0.00035), progression-free survival (p=0.0061), and the best overall response (p=0.05). In the RNA sequencing analysis, nivolumab responders showed activation of the interleukin signaling pathway. Patients who experienced early progression presented high epithelial-mesenchymal transition signaling pathway activation. The responders exhibited a marked increase in PD-1-/Ki67+CD8 T cells at the early stage of treatment (C3D1) compared with non-responders (p=0.03)., Conclusions: In this phase II trial, nivolumab demonstrated moderate efficacy and manageable toxicity in patients with solid cancer harboring DDR gene mutations. A high TMB (>12 mut/Mb) and MSI score (>2.5) determined through clinically target sequencing presented significant discriminatory power for the nivolumab response., Trial Registration Number: NCT04761744., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to assess the pharmacokinetics and determine the bioequivalence of two orally administered megestrol acetate suspensions (625 mg/5 mL) in healthy Korean male subjects. A randomized, open-label, single-dose crossover study was conducted involving fifty-four healthy male subjects who were randomized into two sequence groups. Each subject received either a test or reference drug formulation of 625 mg/5 mL megestrol acetate with a two-week washout period between treatments. Plasma samples were collected before and up to 120 hours after administration, and their plasma drug concentrations were analyzed using validated liquid chromatography-mass spectrometry/mass spectrometry. The pharmacokinetic parameters were calculated, and bioequivalence was confirmed if the 90% confidence intervals of the geometric mean ratios were within the specified bounds of 80.00% to 125.00%. In total, fifty-two subjects completed the study, contributing to the pharmacokinetic analysis. The 90% confidence intervals for the geometric mean ratios of the test formulation compared to the reference formulation were 93.85% to 108.90% for maximum plasma concentration and 91.60% to 101.78% for area under the concentration-time curve from the point of administration to last time point of blood sampling. Throughout the study, no serious or unexpected adverse events were observed. The pharmacokinetic profiles of both formulations of megestrol acetate (625 mg) were comparable and well tolerated in healthy Korean male adult subjects. The test formulation met regulatory criteria for bioequivalence., Trial Registration: ClinicalTrials.gov Identifier: NCT06147908., Competing Interests: Conflict of Interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2024 Translational and Clinical Pharmacology.)

Conventional 2D or even recently developed 3D in vitro culture models for hypothalamus and pituitary gland cannot successfully recapitulate reciprocal neuroendocrine communications between these two pivotal neuroendocrine tissues known to play an essential role in controlling the body's endocrine system, survival, and reproduction. In addition, most current vitro culture models for neuroendocrine tissues fail to properly reflect their complex multicellular structure. In this context, we developed a novel microscale chip platform, termed the 'hypothalamic-pituitary (HP) axis-on-a-chip,' which integrates various cellular components of the hypothalamus and pituitary gland with biomaterials such as collagen and hyaluronic acid. We used non-toxic blood coagulation factors (fibrinogen and thrombin) as natural cross-linking agents to increase the mechanical strength of biomaterials without showing residual toxicity to overcome drawbacks of conventional chemical cross-linking agents. Furthermore, we identified and verified SERPINB2 as a reliable neuroendocrine toxic marker, with its expression significantly increased in both hypothalamus and pituitary gland cells following exposure to various types of toxins. Next, we introduced SERPINB2-fluorescence reporter system into loaded hypothalamic cells and pituitary gland cells within each chamber of the HP axis on a chip, respectively. By incorporating this SERPINB2 detection system into the loaded hypothalamic and pituitary gland cells within our chip platform, Our HP axis-on-chip platform can better mimic reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland in the brain microenvironments with improved efficiency in evaluating neuroendocrine toxicities of certain drug candidates., (© 2024 IOP Publishing Ltd.)

Antigen-experienced CD8 + T cells form effector and central memory T cells (T EM and T CM cells, respectively); however, the mechanism(s) controlling their lineage plasticity remains incompletely understood. Here we show that the transcription cofactor Tle3 critically regulates T EM and T CM cell fates and lineage stability through dynamic redistribution in antigen-responding CD8 + T cell genome. Genetic ablation of Tle3 promoted CD8 + T CM cell formation at the expense of CD8 + T EM cells. Lineage tracing showed that Tle3-deficient CD8 + T EM cells underwent accelerated conversion into CD8 + T CM cells while retaining robust recall capacity. Tle3 acted as a coactivator for Tbet to increase chromatin opening at CD8 + T EM cell-characteristic sites and to activate CD8 + T EM cell signature gene transcription, while engaging Runx3 and Tcf1 to limit CD8 + T CM cell-characteristic molecular features. Thus, Tle3 integrated functions of multiple transcription factors to guard lineage fidelity of CD8 + T EM cells, and manipulation of Tle3 activity could favor CD8 + T CM cell production., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Mammalian target of rapamycin (mTOR) is known to regulate self-renewal ability and potency of embryonic stem cells (ESCs) and adult stem cells in opposite manners. However, its effects vary even among adult stem cells and are not reported in fetal stem/progenitor cells. This study investigated the role of mTOR in the function of human fetal cartilage-derived progenitor cells (hFCPCs)., Methods: mTOR activity in hFCPCs was first examined via the level of phosphor-mTOR until passage 19, together with doubling time of cells and senescence-associated b-galactosidase (SA-bGal). Then, the effect of 100 nM rapamycin, the inhibitor of mTOR, was investigated on self-renewal ability, proliferation rate and osteogenic/adipogenic potential of hFCPCs in vitro. Expression of stemness genes (Oct-4, Sox2 and Nanog) and cell cycle regulators (CDK4 and Cyclin D1) was measured at mRNA or protein levels., Results: mTOR activity was maintained constantly at high levels in hFCPCs until passage 19, while their proliferation rate was decreasing from 48 h at passage 13 to 70 h at passage 9 and senescent cells were observed at passage 18 (8.3 ± 1.2%) and 19 (15.6 ± 1.9%). Inhibition of mTOR in hFCPCs impaired their colony forming frequency (CFU-F) by 4 folds, while showing no change in their doubling time and expression of CDK4 and Cyclin D1. Upon mTOR inhibition, Oct4 expression decreased by 2 folds and 4 folds at the mRNA and protein levels, respectively, while that of Sox2 and Nanog did not change significantly. Finally, mTOR inhibition reduced osteogenic and adipogenic differentiation of hFCPCs in vitro., Conclusion: This study has shown that mTOR plays an important role in the self-renewal ability of hFCPCS but not in their proliferation, The effect of mTOR appears to be associated with Oct-4 expression and important in the osteogenic and adipogenic differentiation ability of hFCPCs., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

Background: Immune checkpoint inhibitors (ICIs) are one of the main pillars of cancer therapy. Since other studies such as clinical trial and retrospective study have limitations for detecting the immune-related adverse events (irAEs) characterized by unpredictable onset, nonspecific symptoms and wide clinical spectrum, we aimed to identify the incidence of irAEs and to detect and evaluate the signals using real-world data., Methods: Cancer patients treated with anticancer medications were analyzed using the nationwide health insurance claims database of South Korea from 2017 to 2019, and Clinical Data Warehouse (CDW) database of Asan Medical Center (AMC), a tertiary referral hospital, from 2012 to 2019. AEs of ICI users were compared with those of non-ICI anticancer medication users. PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab) were evaluated. We defined an AE as a newly added diagnosis after the ICI prescription using an ICD-10 diagnostic code. A signal was defined as an AE that was detected by any one of the four indices of data mining: hazard ratio (HR), proportional claims ratio (PCR), claims odds ratio (COR), or information component (IC). All detected signals were reviewed and classified into well-known or potential irAEs. Signal verification was performed for targeted AEs using CDW of AMC using diagnostic codes and text mining., Results: We identified 118 significant signals related to ICI use. We detected 31 well-known irAEs, most of which were endocrine diseases and skin diseases. We also detected 33 potential irAEs related to disorders in the nervous system, eye, circulatory system, digestive system, skin and subcutaneous tissues, and bones. Especially, portal vein thrombosis and bone disorders such as osteoporosis with pathological fracture and fracture of shoulder, upper arm, femur, and lower leg showed high HR in ICI users than in non-ICI users. The signals from hospital database were verified using diagnostic codes and text mining., Conclusion: This real-world data analysis demonstrated an efficient approach for signal detection and evaluation of ICI use. An effective real-world pharmacovigilance system of the nationwide claims database and the EMR could complement each other in detecting significant AE signals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Kim, Heo, Kim, Lee, Seo, Myung, Oh and Park.)

Purpose: This study aimed to screen targeted agents as second-line treatment with a standard-of-care (SOC) controlled umbrella trial design in advanced gastric cancer (AGC)., Patients and Methods: Patients with HER2-negative AGC from eight Korean cancer centers were screened for druggable targets using immunohistochemistry (IHC) and in situ hybridization, and randomly assigned to the biomarker versus control group at a 4:1 ratio. In the biomarker group, patients were treated with specific targeted agent plus paclitaxel: pan-ERBB inhibitor for epidermal growth factor receptor (EGFR) 2+/3+ patients (afatinib; EGFR cohort), PIK3Cβ inhibitor for phosphatase and tensin homolog (PTEN) loss/null patients (GSK2636771; PTEN cohort), and anti-PD-1 inhibitor for PD-L1+, deficient mismatch repair/microsatellite instability-high, or Epstein-Barr virus-related cases (nivolumab; NIVO cohort). NONE cohort in the biomarker group without predefined biomarkers and control group received SOC (paclitaxel with or without ramucirumab). The primary end point was progression-free survival (PFS), and the secondary end points were efficacy and safety., Results: A total of 318 patients were randomly assigned into the control (n = 64) and biomarker (n = 254; EGFR, n = 67; PTEN, n = 37; NIVO, n = 48; NONE, n = 102) groups. Median follow-up was 35 months. Median PFS and overall survival (OS) were 3.7 (95% CI, 3.1 to 4.1) and 8.6 (95% CI, 7.6 to 9.8) months in the biomarker group and 4.0 (95% CI, 3.0 to 4.6) and 8.7 (95% CI, 7.1 to 9.9) months in the control group. Afatinib addition led to marginal survival benefits to patients with EGFR 3+ compared with SOC (PFS, 4.0 v 2.2 months; P = .09), but GSK2636771 did not prolong the survival of patients with PTEN loss. Addition of nivolumab showed a durable survival benefit (median OS, 12.0 v 7.6 months; P = .08)., Conclusion: Although biomarker group did not show better survival than the control group, IHC-based screening and allocation of patients with AGC to the second-line treatment in an umbrella design were feasible for effective early screening of novel agents.

Background: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC)., Methods: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m 2 or dose level 2, 80 mg/m 2 ) on Days 1, 8, 15 every four weeks. In phase II, patients with Epstein-Barr virus-related, deficient mismatch repair or programmed cell death-ligand-1-positive AGC were enrolled. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and progression-free survival (PFS, phase II). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and exploratory biomarker analysis., Results: Dose level 2 was selected as RP2D. In phase II, 48 patients were enrolled. The median PFS and OS were 3.9 and 11.2 months, respectively. The ORR was 23.3%, and the median response duration was 16.7 months. Grade 3 or higher treatment-related adverse events, mainly neutropenia, occurred in 20 patients (41.7%). Targeted sequencing revealed that patients with RTK/RAS pathway alterations or the HLA-A02 supertype had better survival. Patients with elevated baseline interleukin-1 receptor antagonist levels had worse survival., Conclusions: Although the study did not meet its primary end point, nivolumab and paclitaxel for AGC demonstrated a durable response with manageable toxicity profiles. Genomic analysis or plasma cytokine analysis may provide information for the selection of patients who would benefit more from immunotherapy combined with chemotherapy., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Main Conclusion: LSC CO17-1AK and anti-HER2 VHH-FcK can be produced in a single plant and exhibit anti-tumor activities comparable to those of their respective parent antibodies. Recombinant monoclonal antibodies (mAbs) which can be applied to treat various cancers, are primarily produced using mammalian, insect, and bacteria cell culture systems. Plant expression systems have also been developed to produce antibodies. Plant expression systems present several advantages, including a lack of human pathogenic agents, efficient production costs, and easy large-scale production. In this study, we generated a transgenic plant expressing anti-colorectal cancer large single chain (LSC) CO17-1AK and anti-human epidermal growth factor receptor 2 (HER2) VHH-FcK mAbs by cross-pollinating plants expressing LSC CO17-1AK and anti-HER2 VHH-FcK, respectively. F 1 siblings expressing both LSC CO17-1AK and anti-HER2 VHH-FcK were screened using polymerase chain reaction and Western-blot analyses. The cell enzyme-linked immunosorbent assay (Cell ELISA) confirmed the binding of LSC CO17-1AK and anti-HER2 VHH-FcK to target proteins in the SW620 human colorectal cancer and the SKBR-3 human breast cancer cell lines, respectively. The wound healing assay confirmed the inhibitory activity of both antibodies against SW620 and SKBR-3 cell migration, respectively. In conclusion, both LSC CO17-1AK mAb and anti-HER2 VHH-FcK can be produced in a single plant, achieve binding activities to SW620 and SKBR-3 cancer cells, and inhibitory activity against SW620 and SKBR-3 cell migration similar to their parental antibodies, respectively., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Poor outcomes and high complication and reoperation rates have been reported with tension-band wiring (TBW) in the management of patellar fractures and particularly the comminuted ones. The purpose of this study was to investigate the functional outcomes and complication rates of patellar fractures managed with open reduction and internal fixation (ORIF) with a plate., Methods: MEDLINE, EMCare, CINAHL, AMED and HMIC were searched, and the PRISMA guidelines were followed. Two independent reviewers extracted the data from the included studies and assessed them for the risk of bias., Results: Plating of patellar fractures is associated with satisfactory range of movement (ROM) and postoperative function and low pain levels. We found a 10.44% complication rate and a low reoperation rate. Reoperations were mainly performed for metalwork removal., Conclusion: ORIF with plating of patellar fractures is a safe alternative in the management of patellar fractures and may be associated with a lower complication and reoperation rate compared to TBW. Future randomized prospective studies are needed to validated the results of the present systematic review., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Although acetylsalicylic acid has been widely used for decades to treat and prevent various diseases, its potential effects on endometrial receptivity and subsequent pregnancy rates are still controversial due to conflicting data: many reports have shown positive effects of acetylsalicylic acid, whereas others have found that it has no effect. Furthermore, the direct effects of acetylsalicylic acid on various functions of normal endometrial cells, especially endometrial stem cells, and their underlying molecular mechanisms have not yet been proven. Recently, studies have revealed that a reduced number of active stem/progenitor cells within endometrial tissue limits cyclic endometrial regeneration and subsequently decreases pregnancy success rates, suggesting that endometrial stem cells play a critical role in endometrial regeneration and subsequent endometrial receptivity., Methods: We assessed whether aspirin treatment can inhibit various endometrial stem cell functions related to regenerative capacity, such as self-renewal, migration, pluripotency/stemness, and differentiation capacity, in vitro. Next, we evaluated whether SERPINB2 regulates the effects of aspirin on endometrial stem cell functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. To further investigate whether aspirin also inhibits various endometrial stem cell functions in vivo, aspirin was administered daily to mice through intraperitoneal (i.p.) injection for 7 days., Results: In addition to its previously identified roles, to the best of our knowledge, we found for the first time that acetylsalicylic acid directly inhibits various human endometrial stem cell functions related to regenerative capacity (i.e., self-renewal, migration, differentiation, and capacity) through its novel target gene SERPINB2 in vitro. Acetylsalicylic acid exerts its function by suppressing well-known prosurvival pathways, such as Akt and/or ERK1/2 signaling, through a SERPINB2 signaling cascade. Moreover, we also found that acetylsalicylic acid markedly inhibits regenerative capacity-related functions in endometrial stem cells within tissue., Conclusions: We have found that acetylsalicylic acid has diverse effects on various endometrial stem cell functions related to regenerative capacity. Our findings are a critical step toward the development of more effective therapeutic strategies to increase the chances of successful pregnancy. Video Abstract., (© 2023. The Author(s).)

Stimulus-activated signaling pathways orchestrate cellular responses to control plant growth and development and mitigate the effects of adverse environmental conditions. During this process, signaling components are modulated by central regulators of various signal transduction pathways. Protein phosphorylation by kinases is one of the most important events transmitting signals downstream, via the posttranslational modification of signaling components. The plant serine and threonine kinase SNF1-related protein kinase (SnRK) family, which is classified into three subgroups, is highly conserved in plants. SnRKs participate in a wide range of signaling pathways and control cellular processes including plant growth and development and responses to abiotic and biotic stress. Recent notable discoveries have increased our understanding of how SnRKs control these various processes in rice ( Oryza sativa ). In this review, we summarize current knowledge of the roles of OsSnRK signaling pathways in plant growth, development, and stress responses and discuss recent insights. This review lays the foundation for further studies on SnRK signal transduction and for developing strategies to enhance stress tolerance in plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Son and Park.)

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation.

Plant heat shock factor binding proteins (HSBPs) are well known for their implication in the negative regulation of heat stress response (HSR) pathways. Herein, we report on the hitherto unknown functions of HSBP1 in Brassica rapa (BrHSBP1) . BrHBSP1 was found to be predominant in flower buds and young leaves, while its segmental duplicate, BrHSBP1-like , was abundant in green siliques. Exposure to abiotic stress conditions, such as heat, drought, cold, and H 2 O 2 , and to phytohormones was found to differentially regulate BrHSBP1 . The activity of BrHSBP1-GFP fusion proteins revealed their cellular localization in nuclei and cytosols. Transgenic overexpression of BrHSBP1 (BrHSBP1 OX ) improved pod and seed sizes, while CRISPR-Cas BrHSBP1 knock-out mutants ( Brhsbp1&#95;KO ) were associated with aborted seed and pod development. The transcriptomic signatures of BrHSBP1 OX and Brhsbp1&#95;KO lines revealed that 360 and 2381 genes, respectively, were differentially expressed (Log2FC≥2, p adj <0.05) expressed relative to control lines. In particular, developmental processes, including plant reproductive structure development (RSD)-related genes, were relatively downregulated in Brhsbp1&#95;KO. Furthermore, yeast two-hybrid assays confirmed that BrHSBP1 can physically bind to RSD and other genes. Taking the findings together, it is clear that BrHSBP1 is involved in seed development via the modulation of RSD genes. Our findings represent the addition of a new regulatory player in seed and pod development in B. rapa ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Muthusamy, Son, Park and Lee.)

Purpose: Immune checkpoint inhibitors (ICIs) have been demonstrated to be effective for unresectable or metastatic hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA) in prior prospective trials. However, the clinical outcomes of ICIs in patients with combined HCC-CCA (cHCC-CCA) have not been investigated. Accordingly, we retrospectively evaluated the effectiveness and safety of ICIs in patients with unresectable or metastatic cHCC-CCA., Methods: Among 101 patients with histologically documented cHCC-CCA who received systemic therapy, 25 received ICIs between January 2015 and September 2021 and were included in the current analysis. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were retrospectively evaluated., Results: The median age was 64 years (range 38-83) and 84% (n = 21) of patients were males. Most patients had Child-Pugh A liver function (n = 22, 88%) and hepatitis B virus infection (17, 68%). Nivolumab (n = 17, 68%) was the most frequently used ICI, followed by pembrolizumab (n = 5, 20%), atezolizumab plus bevacizumab (n = 2, 8%), and ipilimumab plus nivolumab (n = 1, 4%). All patients, except one, had previously received systemic therapy; median two lines (1-5 lines) of systemic therapy were administered prior to ICIs. With a median follow-up duration of 20.1 months (95% CI 4.9-35.2 months), the median PFS was 3.5 months (95% CI 2.4-4.8 months), and the median OS was 8.3 months (95% CI 6.8-9.8 months). The ORR was 20.0% (n = 5, nivolumab for 2 patients, pembrolizumab for 1, atezolizumab plus bevacizumab for 1, and ipilimumab plus nivolumab for 1) and the duration of response was 11.6 months (95% CI 11.2-12.0 months)., Conclusions: ICIs displayed clinical anti-cancer effectiveness, aligning with the results of prior prospective studies for HCC or CCA. Further international studies are required to define the optimal strategies for managing unresectable or metastatic cHCC-CCA., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain scarce. We aimed to investigate the differences in scalp parameters between individuals in their 20s and 50s and analyze their sex-specific variations., Materials and Methods: Two hundred participants (160 women and 40 men) were equally divided into 20s and 50s age groups. Biophysical parameters of the scalp, including elasticity, pH, trans-epidermal water loss (TEWL), sebum production, desquamation, firmness, redness, and yellowness, were measured in the vertex, occipital, and temporal regions. Hair density and thickness were measured in the temporal region. The accumulation of advanced glycation end products (AGEs) in the skin was noninvasively measured in a subset of 60 women., Results: Skin firmness and redness increased with age in women, whereas yellowness increased with age in both sexes. Sebum production and pH levels were significantly lower in the 50s age group than in the 20s age group, particularly in women. TEWL was lower in men in their 50s than in those in their 20s, particularly in the occipital region. A significant reduction in hair density was observed in the 50s age group in both sexes. AGE accumulation in the skin increased with age and was correlated with scalp skin yellowness., Conclusion: Age-related changes in scalp parameters have important implications for hair health and scalp condition. These findings emphasize the importance of considering age and sex when developing hair care strategies., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Single-cell RNA sequencing (scRNA-seq) massively profiles transcriptomes of individual cells encapsulated in barcoded droplets in parallel. However, in real-world scRNA-seq data, many barcoded droplets do not contain cells, but instead, they capture a fraction of ambient RNAs released from damaged or lysed cells. A typical first step to analyze scRNA-seq data is to filter out cell-free droplets and isolate cell-containing droplets, but distinguishing them is often challenging; incorrect filtering may mislead the downstream analysis substantially. We propose SiftCell, a suite of software tools to identify and visualize cell-containing and cell-free droplets in manifold space via randomization (SiftCell-Shuffle) to classify between the two types of droplets (SiftCell-Boost) and to quantify the contribution of ambient RNAs for each droplet (SiftCell-Mix). By applying our method to datasets obtained by various single-cell platforms, we show that SiftCell provides a streamlined way to perform upstream quality control of scRNA-seq, which is more comprehensive and accurate than existing methods., Competing Interests: Declaration of interests H.M.K. owns stocks in Regeneron Pharmaceuticals. J.H.L. is an inventor of pending patent applications related to Seq-Scope., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs)., Materials and Methods: Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector-based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer., Results: Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs., Conclusion: CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Epilepsy's impact on cardiovascular function and autonomic regulation, including heart-rate variability, is complex and may contribute to sudden unexpected death in epilepsy (SUDEP). Lateralization of autonomic control in the brain remains the subject of debate; nevertheless, ultra-short-term heart-rate variability (HRV) analysis is a useful tool for understanding the pathophysiology of autonomic dysfunction in epilepsy patients. A retrospective study reviewed medical records of patients with temporal lobe epilepsy who underwent presurgical evaluations. Data from 75 patients were analyzed and HRV indices were extracted from electrocardiogram recordings of preictal, ictal, and postictal intervals. Various HRV indices were calculated, including time domain, frequency domain, and nonlinear indices, to assess autonomic function during different seizure intervals. The study found significant differences in HRV indices based on hemispheric laterality, language dominancy, hippocampal atrophy, amygdala enlargement, sustained theta activity, and seizure frequency. HRV indices such as the root mean square of successive differences between heartbeats, pNN50, normalized low-frequency, normalized high-frequency, and the low-frequency/high-frequency ratio exhibited significant differences during the ictal period. Language dominancy, hippocampal atrophy, amygdala enlargement, and sustained theta activity were also found to affect HRV. Seizure frequency was correlated with HRV indices, suggesting a potential relationship with the risk of SUDEP.

Immune-related adverse events (irAEs) induced by checkpoint inhibitors involve a multitude of different risk factors. Here, to interrogate the multifaceted underlying mechanisms, we compiled germline exomes and blood transcriptomes with clinical data, before and after checkpoint inhibitor treatment, from 672 patients with cancer. Overall, irAE samples showed a substantially lower contribution of neutrophils in terms of baseline and on-therapy cell counts and gene expression markers related to neutrophil function. Allelic variation of HLA-B correlated with overall irAE risk. Analysis of germline coding variants identified a nonsense mutation in an immunoglobulin superfamily protein, TMEM162. In our cohort and the Cancer Genome Atlas (TCGA) data, TMEM162 alteration was associated with higher peripheral and tumor-infiltrating B cell counts and suppression of regulatory T cells in response to therapy. We developed machine learning models for irAE prediction, validated using additional data from 169 patients. Our results provide valuable insights into risk factors of irAE and their clinical utility., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The incidence of Guillain-Barré syndrome (GBS) changed significantly during the coronavirus disease 2019 (COVID-19) pandemic. Emerging reports suggest that viral vector-based vaccines may be associated with an elevated risk of GBS., Methods: In this nationwide time-series correlation study, we examined the age-specific incidence of GBS from January 2011 to August 2022, as well as data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations and infections from February 2021 to August 2022. We compared the forecasted estimates of age-specific GBS incidence, using the pre-SARS-CoV-2 period as a benchmark, with the actual incidence observed during the post-vaccination period of the pandemic. Furthermore, we assessed the temporal association between GBS, SARS-CoV-2 vaccinations, and COVID-19 for different age groups., Results: In the age group of 60 and older, the rate ratio was significantly elevated during June-August and November 2021. A significant, strong positive association was observed between viral vector-based vaccines and GBS incidence trends in this age group (r=0.52, p=0.022). For the 30 to 59 years age group, the rate ratio was notably high in September 2021. A statistically significant, strong positive association was found between mRNA-based vaccines and GBS incidence in this age group (r=0.61, p=0.006)., Conclusion: Viral vector-based SARS-CoV-2 vaccines were found to be temporally associated with an increased risk of GBS, particularly in older adults. To minimize age-specific and biological mechanism-specific adverse events, future vaccination campaigns should adopt a more personalized approach, such as recommending homologous mRNA-based SARS-CoV-2 vaccines for older adults to reduce the heightened risk of GBS.

Background: The options for first-line treatment of advanced oesophageal squamous cell carcinoma are scarce, and the outcomes remain poor. The anti-PD-1 antibody, tislelizumab, has shown antitumour activity in previously treated patients with advanced oesophageal squamous cell carcinoma. We report interim analysis results from the RATIONALE-306 study, which aimed to assess tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma., Methods: This global, randomised, double-blind, parallel-arm, placebo-controlled, phase 3 study was conducted at 162 medical centres across Asia, Europe, Oceania, and North America. Patients (aged ≥18 years) with unresectable, locally advanced, recurrent or metastatic oesophageal squamous cell carcinoma (regardless of PD-L1 expression), Eastern Cooperative Oncology Group performance status of 0-1, and measurable or evaluable disease per Response Evaluation Criteria in Solid Tumours (version 1.1) were recruited. Patients were randomly assigned (1:1), using permuted block randomisation (block size of four) and stratified by investigator-chosen chemotherapy, region, and previous definitive therapy, to tislelizumab 200 mg or placebo intravenously every 3 weeks on day 1, together with an investigator-chosen chemotherapy doublet, comprising a platinum agent (cisplatin 60-80 mg/m 2 intravenously on day 1 or oxaliplatin 130 mg/m 2 intravenously on day 1) plus a fluoropyrimidine (fluorouracil [750-800 mg/m 2 intravenously on days 1-5] or capecitabine [1000 mg/m 2 orally twice daily on days 1-14]) or paclitaxel (175 mg/m 2 intravenously on day 1). Treatment was continued until disease progression or unacceptable toxicity. Investigators, patients, and sponsor staff or designees were masked to treatment. The primary endpoint was overall survival. The efficacy analysis was done in the intention-to-treat population (ie, all randomly assigned patients) and safety was assessed in all patients who received at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03783442., Findings: Between Dec 12, 2018, and Nov 24, 2020, 869 patients were screened, of whom 649 were randomly assigned to tislelizumab plus chemotherapy (n=326) or placebo plus chemotherapy (n=323). Median age was 64·0 years (IQR 59·0-69·0), 563 (87%) of 649 participants were male, 86 (13%) were female, 486 (75%) were Asian, and 155 (24%) were White. 324 (99%) of 326 patients in the tislelizumab group and 321 (99%) of 323 in the placebo group received at least one dose of the study drug. As of data cutoff (Feb 28, 2022), median follow-up was 16·3 months (IQR 8·6-21·8) in the tislelizumab group and 9·8 months (IQR 5·8-19·0) in the placebo group, and 196 (60%) of 326 patients in the tislelizumab group versus 226 (70%) of 323 in the placebo group had died. Median overall survival in the tislelizumab group was 17·2 months (95% CI 15·8-20·1) and in the placebo group was 10·6 months (9·3-12·1; stratified hazard ratio 0·66 [95% CI 0·54-0·80]; one-sided p<0·0001). 313 (97%) of 324 patients in the tislelizumab group and 309 (96%) of 321 in the placebo group had treatment-related treatment-emergent adverse events. The most common grade 3 or 4 treatment-related treatment-emergent adverse events were decreased neutrophil count (99 [31%] in the tislelizumab group vs 105 [33%] in the placebo group), decreased white blood cell count (35 [11%] vs 50 [16%]), and anaemia (47 [15%] vs 41 [13%]). Six deaths in the tislelizumab group (gastrointestinal and upper gastrointestinal haemorrhage [n=2], myocarditis [n=1], pulmonary tuberculosis [n=1], electrolyte imbalance [n=1], and respiratory failure [n=1]) and four deaths in the placebo group (pneumonia [n=1], septic shock [n=1], and unspecified death [n=2]) were determined to be treatment-related., Interpretation: Tislelizumab plus chemotherapy as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy. Given that the interim analysis met its superiority boundary for the primary endpoint, as confirmed by the independent data monitoring committee, this Article represents the primary study analysis., Funding: BeiGene., Competing Interests: Declaration of interests KK has served in consulting roles for AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, MSD, and Ono Pharmaceutical and has received honoraria from Bristol Myers Squibb, MSD, and Ono Pharmaceutical. ER has participated on a data safety monitoring board or advisory board for BeiGene. RAH has served in consulting roles for Ipsen. SRP has received research grants from ImmuneOncia Therapeutics and Incyte and has received honoraria from MSD Korea. YY has received travel grants from BeiGene. LS has received grants from Baiji Shenzhou (Beijing) Biotechnology, Beijing Xiantong Biomedical Technology, Beihai Kangcheng (Beijing) Medical Technology, Jacobio Pharmaceuticals, Qilu Pharmaceutical, Yaojie Ankang (Nanjing) Technology, and Zai Lab Pharmaceutical (Shanghai); consulting fees from Haichuang Pharmaceutical, Harbour Biomed, and Mingji Biopharmaceutical; honoraria from CStone Pharmaceuticals, Hengrui, Hutchison Whampoa, and Zai Lab; and participated on an advisory board for Boehringer Ingelheim, Bristol Myers Squibb, Merck, MSD, Roche, Sanofi, and Servier. TK has received grants from Amgen, BeiGene, Bristol Myers Squibb, Chugai Pharmaceutical, EPS Corporation, Merck Biopharma, MSD, Ono Pharmaceutical, Parexel International, Shionogi & Co, and Taiho Pharmaceutical; honoraria from Bristol Myers Squibb, Covidien Japan, MSD, Oncolys BioPharma, Ono Pharmaceutical, and Taiho Pharmaceutical; and participated on a data safety monitoring board or advisory board for Astellas Pharma, Bristol Myers Squibb, Merck Biopharma, MSD, and Oncolys BioPharma. EVC has received grants from Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Ipsen, Lilly, MSD, Merck KGaA, Novartis, Roche, and Servier and honoraria from AbbVie, Array, Astellas, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, MSD, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seattle Genetics, Servier, Sirtex, Terumo, Taiho Pharmaceutical, TRIGR, and Zymeworks. PJ-F has received honoraria from Bristol Myers Squibb, HRA Pharmaceutical, LEO Pharma, Lilly, MSD, Novartis, Rovi, and Sanofi and participated on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, HRA Pharmaceutical, Lilly, MSD, Mylan, and Novartis. LW and JS are employees of BeiGene and have no additional competing interests. LL is an employee of BeiGene with stock or stock options. HHY has received grants from BeiGene, Bristol Myers Squibb, CARsgen Therapeutics, MacroGenics, and Merck; honoraria from BeiGene; travel grants from BeiGene; and has participated on a data safety monitoring board or advisory board for ALX Oncology, Amgen, AstraZeneca, Astellas, BeiGene, Bristol Myers Squibb, MacroGenics, Merck, OncXerna, Zymeworks, and Novartis. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The endometrium, the inner lining of the uterine cavity, plays essential roles in embryo implantation and its subsequent development. Although some positive results were preliminarily archived, the regeneration of damaged endometrial tissues by administrating stem cells only is very challenging due to the lack of specific microenvironments and their low attachment rates at the sites of injury. In this context, various biomaterial-based scaffolds have been used to overcome these limitations by providing simple structural support for cell attachment. However, these scaffold-based strategies also cannot properly reflect patient tissue-specific structural complexity and thus show only limited therapeutic effects., Method: Therefore, in the present study, we developed a customizable Lego-like multimodular endometrial tissue architecture by assembling individually fabricated tissue blocks., Results: Each tissue block was fabricated by incorporating biodegradable biomaterials and certain endometrial constituent cells. Each small tissue block was effectively fabricated by integrating conventional mold casting and 3D printing techniques. The fabricated individual tissue blocks were properly assembled into a larger customized tissue architecture. This structure not only properly mimics the patient-specific multicellular microenvironment of the endometrial tissue but also properly responds to key reproductive hormones in a manner similar to the physiological functions., Conclusion: This customizable modular tissue assembly allows easy and scalable configuration of a complex patient-specific tissue microenvironment, thus accelerating various tissue regeneration procedures., (© 2023. The Author(s).)

Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation. Accuracy for cancer detection and tissue-of-origin localization is achieved using our algorithm, which incorporates cancer type-specific profiles of mutation distribution and chromatin organization in tumor tissues as model references. Our integrative model detects early-stage cancers, including those of pancreatic origin, with high sensitivity that is comparable to that of late-stage detection. Model interpretation reveals the contribution of cancer type-specific genomic and epigenomic features. Our methodologies may lay the groundwork for accurate cfDNA-based cancer diagnosis, especially at early stages., (© 2023. The Author(s).)

Repetitive sequence-based PCR (rep-PCR) is a potential epidemiological technique that can provide high-throughput genotype fingerprints of heterogeneous Mycobacterium strains rapidly. Previously published rep-PCR primers, which are based on nucleotide sequences of Gram-negative bacteria may have low specificity for mycobacteria. Moreover, it was difficult to ensure the continuity of the study after the commercial rep-PCR kit was discontinued. Here, we designed a novel rep-PCR for Mycobacterium intracellulare , a major cause of nontuberculous mycobacterial pulmonary disease with frequent recurrence. We screened the 7,645 repeat sequences for 200 fragments from the genome of M. intracellulare ATCC 13950 in silico , finally generating five primers with more than 90% identity for a total of 226 loci in the genome. The five primers could make different band patterns depending on the genome of three different M. intracellulare strains using an in silico test. The novel rep-PCR with the five primers was conducted using 34 bacterial samples of 7 species containing 25  M. intracellulare clinical isolates, compared with previous published rep-PCRs. This shows distinguished patterns depending on species and blotting assay for 6 species implied the sequence specificity of the five primers. The Designed rep-PCR had a 95-98% of similarity value in the reproducibility test and showed 7 groups of fingerprints in M. intracellulare strains. Designed rep-PCR had a correlation value of 0.814 with VNTR, reference epidemiological method. This study provides a promising genotype fingerprinting method for tracing the recurrence of heterogeneous M. intracellulare ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shin, Ha, Kim, Choi, Park, Park, Park, Byun, Jung, Baik, Lee, Kang, Yoo and Shin.)

Background: Telework has benefits for many people with disabilities. The pandemic may create new employment opportunities for people with disabilities by increasing employer acceptance of telework, but this crucially depends on the occupational structure., Objective: We compare people with and without disabilities in the expansion of telework as the pandemic began, and the evolution of telework during the pandemic., Methods: We use U.S. data from the American Community Survey from 2008 to 2020 and the Current Population Survey over May 2020 to April 2022 period. Prevalence and trends are analyzed using linear probability and multinomial logit regressions., Results: While workers with disabilities were more likely than those without disabilities to telework before the pandemic, they were less likely to telework during the pandemic. The occupational distribution accounts for most of this difference. Tight labor markets, as measured by state unemployment rates, particularly favor people with disabilities obtaining telework jobs. While people with cognitive/mental health and mobility impairments were the most likely to telework during the pandemic, tight labor markets especially favored the expansion of telework for people with vision impairments and difficulty with daily activities inside the home., Conclusions: Many people with disabilities benefit from working at home, and the pandemic has increased employer acceptance of telework, but the current occupational distribution limits this potential. Tighter labor markets during the recovery offer hope that employers will increasingly hire people with disabilities in both telework and non-telework jobs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Every year, invasive pathogens cause significant damage to crops. Thus, identifying genes conferring broad-spectrum resistance to invading pathogens is critical for plant breeding. We previously demonstrated that OsWRKY114 contributes to rice ( Oryza sativa L.) immunity against the bacterial pathovar Xanthomonas oryzae pv. oryzae ( Xoo ). However, it is not known whether OsWRKY114 is involved in defense responses to other pathogens. In this study, we revealed that OsWRKY114 enhances innate immunity in rice against the fungal pathogen Fusarium fujikuroi , which is the causal agent of bakanae disease. Transcript levels of various gibberellin-related genes that are required for plant susceptibility to F. fujikuroi were reduced in rice plants overexpressing OsWRKY114 . Analysis of disease symptoms revealed increased innate immunity against F. fujikuroi in OsWRKY114 -overexpressing rice plants. Moreover, the expression levels of OsJAZ genes, which encode negative regulators of jasmonic acid signaling that confer immunity against F. fujikuroi , were reduced in OsWRKY114 -overexpressing rice plants. These results indicate that OsWRKY114 confers broad-spectrum resistance not only to Xoo but also to F. fujikuroi . Our findings provide a basis for developing strategies to mitigate pathogen attack and improve crop resilience to biotic stress.

Organisms regulate gene expression to produce essential proteins for numerous biological processes, from growth and development to stress responses. Transcription and translation are the major processes of gene expression. Plants evolved various transcription factors and transcriptome reprogramming mechanisms to dramatically modulate transcription in response to environmental cues. However, even the genome-wide modulation of a gene's transcripts will not have a meaningful effect if the transcripts are not properly biosynthesized into proteins. Therefore, protein translation must also be carefully controlled. Biotic and abiotic stresses threaten global crop production, and these stresses are seriously deteriorating due to climate change. Several studies have demonstrated improved plant resistance to various stresses through modulation of protein translation regulation, which requires a deep understanding of translational control in response to environmental stresses. Here, we highlight the translation mechanisms modulated by biotic, hypoxia, heat, and drought stresses, which are becoming more serious due to climate change. This review provides a strategy to improve stress tolerance in crops by modulating translational regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Son and Park.)

The expression of GPR50 in CSLC and several breast cancer cell lines was assessed by RT-PCR and online platform (UALCAN, GEPIA, and R2 gene analysis). The role of GPR50 in driving CSLC, sphere formation, cell proliferation, and migration was performed using shGPR50 gene knockdown, and the role of GPR50-regulated signaling pathways was examined by Western blotting and Luciferase Assay. Herein, we confirmed that the expression of G protein-coupled receptor 50 (GPR50) in cancer stem-like cells (CSLC) is higher than that in other cancer cells. We examined that the knockdown of GPR50 in CSLC led to decreased cancer properties, such as sphere formation, cell proliferation, migration, and stemness. GPR50 silencing downregulates NF-kB signaling, which is involved in sphere formation and aggressiveness of CSLC. In addition, we demonstrated that GPR50 also regulates ADAM-17 activity by activating NOTCH signaling pathways through the AKT/SP1 axis in CSLC. Overall, we demonstrated a novel GPR50-mediated regulation of the NF-κB-Notch signaling pathway, which can provide insights into CSLC progression and prognosis, and NF-κB-NOTCH-based CSLC treatment strategies.

Introduction: Lenvatinib is approved for the treatment of patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, clinical outcomes of lenvatinib therapy in patients with post-liver transplantation (LT) HCC recurrence remain unclear. We investigated the efficacy and safety of lenvatinib in patients with post-LT HCC recurrence., Methods: This multinational, multicenter, retrospective study included 45 patients with recurrent HCC after LT who received lenvatinib at six institutions in three countries (Korea, Italy, and Hong Kong) from June 2017 to October 2021., Results: At the time of lenvatinib initiation, 95.6% (n = 43) of patients had Child-Pugh A status, and 35 (77.8%) and 10 (22.2%) participants were classified as having albumin-bilirubin (ALBI) grades 1 and 2, respectively. The objective response rate was 20.0%. With a median follow-up duration of 12.9 months (95% confidence interval [CI]: 11.2-14.7), the median progression-free survival and overall survival (OS) were 7.6 (95% CI: 5.3-9.8) months, and 14.5 (95% CI: 0.8-28.2) months, respectively. Patients with ALBI grade 1 showed significantly better OS (52.3 months, [95% CI: not assessable]) than patients with ALBI grade 2 (11.1 months [95% CI: 0.0-30.4 months], p = 0.003). The most common adverse events were hypertension (n = 25, 55.6%), fatigue (n = 17, 37.8%), and anorexia (n = 14, 31.1%)., Conclusion: Lenvatinib showed consistent efficacy and toxicity profiles in patients with post-LT HCC recurrence that were comparable to those reported from previous studies among non-LT HCC patients. The baseline ALBI grade correlated with better OS in post-LT lenvatinib-treated patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The clinical and radiological results before and after surgery were compared and analyzed for patients with multilevel lumbar stenosis who underwent bi-portal endoscopic spine surgery (BESS) and microscopic unilateral laminotomy for bilateral decompression (ULBD). We retrospectively identified 47 and 49 patients who underwent BESS and microscopic ULBD, respectively, who were diagnosed with multi-level lumbar stenosis. Clinical outcomes were evaluated using the visual analog scale score for both back and leg pain, and medication (pregabalin) use and Oswestry Disability Index (ODI) scores for overall treatment outcomes were used pre-operatively and at the final follow-up. Radiological outcomes were evaluated as the percentage of dura expansion volume, and percentage preservation of both facets and both lateral recess angles. The follow-up period of patients was about 17.04 months in the BESS group and about 16.90 months in the microscopic ULBD group. The back and leg visual analog scale (VAS) scores and average pregabalin use decreased more significantly in the BESS group than in the microscopic ULBD group (each p -value 0.0443, <0.001, 0.0378). All radiological outcomes were significantly higher in the BESS group than in the ULBD group. The change in ODI in two-level spinal stenosis showed a significantly higher value in the BESS group compared to the microscopic ULBD group ( p -value 0.0335). Multilevel decompression with the BESS technique in multiple spinal stenosis is an adequate technique as it shows better clinical and radiological results than microscopic ULBD during a short-term follow-up period.

To determine the driving mechanisms between submarine groundwater discharge (SGD) and massive blooms of the green alga Ulva, we examined the magnitude of SGD and SGD-derived nutrient fluxes from November 2019 to July 2020 in Ihotewoo (north) and Bangdu (east) bays, Jeju Island, Korea. The variability of SGD flux at both the sites, where the hydraulic gradient is low, closely followed the daily variability of the tidal range, indicating that SGD flux is primarily driven by tidal pumping. Although the average annual SGD-driven nutrient fluxes were 24-37 % lower in Bangdu Bay than in Ihotewoo Bay, massive Ulva blooms only occurred in Bangdu Bay. A longer residence time (poor water exchange) and continuous SGD input with high dissolved inorganic nitrogen play a significant role in the growth and extentsion of Ulva blooms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We recently reported that lactoferrin (LF) induces Foxp3 + Treg differentiation through binding to TGFβ receptor III (TβRIII), and this activity was further enhanced by TGFβ1. Generally, a low T-cell receptor (TCR) signal strength is favourable for Foxp3 + Treg differentiation. In the present study, we explored the effect of lactoferrin chimera (LFch, containing lactoferricin [aa 17-30] and lactoferrampin [aa 265-284]), along with TGFβ1 on Foxp3 + Treg differentiation. LFch alone did not induce Foxp3 expression, yet LFch dramatically enhanced TGFβ1-induced Foxp3 expression. LFch had little effect on the phosphorylation of Smad3, a canonical transcriptional factor of TGFβ1. Instead, LFch attenuated the phosphorylation of S6 (a target of mTOR), IκB and PI3K. These activities of LFch were completely abrogated by pretreatment of LFch with soluble TGFβ1 receptor III (sTβRIII). Consistent with this, the activity of LFch on TGFβ1-induced Foxp3 expression was also abrogated by treatment with sTβRIII. Finally, the TGFβ1/LFch-induced T cell population substantially suppressed the proliferation of responder CD4 + T cells. These results indicate that LFch robustly enhances TGFβ1-induced Foxp3 + Treg differentiation by diminishing TCR/CD28 signal intensity., (© 2022 John Wiley & Sons Ltd.)

Little is known about alternative treatment options for rhinosinusitis (RS). We aimed to evaluate the efficacy of low-level laser therapy (LLLT) for RS in experimentally induced rabbit models of RS. A total of 18 rabbits were divided into four groups: a negative control group (n = 3), an RS group without treatment (n = 5, positive control group), an RS group with natural recovery (n = 5, natural recovery group), and an RS group with laser irradiation (n = 5, laser-treated group). Computed tomography and histopathological staining were performed for each group. mRNA and protein expression levels of local cytokines (IFN-γ, IL-17, and IL-5) were also measured. Tissue inflammation revealed a significant improvement in the laser-treated group compared with the RS and natural recovery groups (p < 0.01). In addition, sinus opacification in the CT scans and cytokine expression was reduced in the laser-treated group, though without statistical significance. LLLT could be an effective option for the management of RS concerning radiological, histological, and molecular parameters.

Background: In this study, we have investigated whether human fetal cartilage progenitor cells (hFCPCs) have anti-inflammatory activity and can alleviate osteoarthritis (OA) phenotypes in vitro., Methods: hFCPCs were stimulated with various cytokines and their combinations and expression of paracrine factors was examined to find an optimal priming factor. Human chondrocytes or SW982 synoviocytes were treated with interleukin-1β (IL-1β) to produce OA phenotype, and co-cultured with polyinosinic-polycytidylic acid (poly(I-C))-primed hFCPCs to address their anti-inflammatory effect by measuring the expression of OA-related genes. The effect of poly(I-C) on the surface marker expression and differentiation of hFCPCs into 3 mesodermal lineages was also examined., Results: Among the priming factors tested, poly(I-C) (1 µg/mL) most significantly induced the expression of paracrine factors such as indoleamine 2,3-dioxygenase, histocompatibility antigen, class I, G, tumor necrosis factor- stimulated gene-6, leukemia inhibitory factor, transforming growth factor-β1 and hepatocyte growth factor from hFCPCs. In the OA model in vitro, co-treatment of poly(I-C)-primed hFCPCs significantly alleviated IL-1β-induced expression of inflammatory factors such as IL-6, monocyte chemoattractant protein-1 and IL-1β, and matrix metalloproteinases in SW982, while it increased the expression of cartilage extracellular matrix such as aggrecan and collagen type II in human chondrocytes. We also found that treatment of poly(I-C) did not cause significant changes in the surface marker profile of hFCPCs, while showed some changes in the 3 lineages differentiation., Conclusion: These results suggest that poly(I-C)-primed hFCPCs have an ability to modulate inflammatory response and OA phenotypes in vitro and encourage further studies to apply them in animal models of OA in the future., (© 2022. Korean Tissue Engineering and Regenerative Medicine Society.)

This study evaluated the perceived vibration, noise and discomfort levels associated with two nickel-titanium file systems with different kinetics; reciprocating motion (REC) using WaveOne Gold and continuous rotation motion (CON) using ProTaper NEXT. Forty roots with two canals from maxillary premolar and molar of 40 patients were included. Root canals were instrumented using each system for each canal. Patients were surveyed about the vibration, noise and discomfort experienced using visual analogue scale, and their preference. The responses were statistically analysed using Wilcoxon Signed-Rank test, Mann-Whitney U test and Spearman's rank correlation test at the 95% of significance level. The vibration, noise and discomfort experienced were significantly greater in REC than CON (P < 0.05). In REC, male subjects reported significantly higher vibration than female (P < 0.05). Majority respondents (72.5%) preferred the CON method. The perceived vibration, noise and discomfort were less apparent from the CON than the REC., (© 2021 Australian Society of Endodontology Inc.)

Rapid climate change caused by human activity is threatening global crop production and food security worldwide. In particular, the emergence of new infectious plant pathogens and the geographical expansion of plant disease incidence result in serious yield losses of major crops annually. Since climate change has accelerated recently and is expected to worsen in the future, we have reached an inflection point where comprehensive preparations to cope with the upcoming crisis can no longer be delayed. Development of new plant breeding technologies including site-directed nucleases offers the opportunity to mitigate the effects of the changing climate. Therefore, understanding the effects of climate change on plant innate immunity and identification of elite genes conferring disease resistance are crucial for the engineering of new crop cultivars and plant improvement strategies. Here, we summarize and discuss the effects of major environmental factors such as temperature, humidity, and carbon dioxide concentration on plant immunity systems. This review provides a strategy for securing crop-based nutrition against severe pathogen attacks in the era of climate change., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Son and Park.)

A non-neoplastic mass posterior to the dens is termed a retro-odontoid mass (R-OM). This retrospective study evaluated radiographic and clinical outcomes and R-OM changes after upper cervical spine surgery. This study included 69 patients who underwent upper cervical spine surgery, including atlantoaxial fusion, occipitocervical fusion, or decompression. All patients underwent preoperative magnetic resonance imaging (MRI). Six-month follow-up MRI examinations were performed in 30 patients who had preoperative R-OMs. Radiographic outcomes of the anterior and posterior atlantodental intervals were measured using X-rays and computed tomography. The R-OM and space available for the cord (SAC) were measured using MRI. Clinical outcomes were evaluated using neck and arm pain visual analog scales, the Japanese Orthopedic Association score, the neck disability index, and the patient-reported subjective improvement rate. The anterior atlantodental interval decreased, while the posterior atlantodental interval and SAC increased postoperatively. Among the clinical outcomes, the neck and arm pain and the neck disability index decreased postoperatively, while the Japanese Orthopedic Association score increased. All clinical and radiographic outcomes improved postoperatively. The R-OM either decreased in size or disappeared after fusion surgery in all cases, except in one patient who underwent decompression surgery. In conclusion, stabilization through fusion surgery is essential for treating R-OM., (© 2022. The Author(s).)

Coastal benthic communities in temperate regions have been influenced by climate change, including increasing sea-surface temperature. Nevertheless, scleractinian coral Alveopora japonica Eguchi, 1968, is thriving in shallow subtidal hard bottoms around Jeju Island, off the southern coast of Korea. The presence of this corals has negatively impacted subtidal kelp populations in Jeju Island. However, there is no study to document how the presence or absence of this coral relates to other benthic communities. This study investigated the benthos in three shallow subtidal sites (Shinheung (SH), Bukchon (BC), and Seongsan (SS)) in northern Jeju using underwater photography. Macro-benthic organisms appearing on a 1 × 20 m line transect installed at depths of 5, 10, and 15 m at each site were analyzed. Results showed that of the three sites investigated, A. japonica colonies were most abundant at BC, accounting for 45.9% and 72.8% of the total transect area at 10 m and 15 m, respectively. At SS, A. japonica occupied 15.3% of the total area at 15 m and less than 1% at 5 m and 10 m. The same at SH accounted for 10% of the total area at 5 m, and less than 1% at 10 m and 15 m. Dead and bleached colonies accounted for 1.2-11.5% and 1.8-5.7%, respectively, at 5, 10, and 15 m at three sites. At SS, canopy-forming brown algae Ecklonia cava and Sargassum spp. accounted for 20.2 and 24.3% of the total transect area, respectively, at 5 m depth. In contrast, the percent cover of E. cava and Sargassum spp. at SH and BC ranged from 0.1 to 1.8%, respectively. Moreover, non-geniculate coralline algae dominated the subtidal substrate at SH, ranging between 60.2 and 69% at 15 and 10 m. The low cover of A. japonica in SS (at 5 m) coincided with a high percent cover of canopy-forming brown algae. However, canopy-forming brown algae were rare at all depths at SH and BC and were dominated instead by coralline algae and the scleractinian corals. This study, by utilizing a non-destructive method, provides a baseline qualitative and quantitative information for understanding the site and depth-dependent distribution of A. japonica and algal populations, which is important to understand climate change related changes in benthic communities in Jeju and elsewhere., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: The authors have no potential conflicts of interest to disclose.

Decidualization of the endometrial stromal cells (ESCs) is essential for successful embryo implantation. It involves the transformation of fibroblastic cells into epithelial-like cells that secrete cytokines, growth factors, and proteins necessary for implantation. Previous studies have revealed altered expression of miR-375 in the endometrium of patients with recurrent implantation failure and the ectopic stromal cells of patients with endometriosis. However, the exact molecular mechanisms, particularly the role of microRNAs (miRNAs) in the regulation of decidualization, remain elusive. In this study, we investigated whether decidualization is affected by miR-375 and its potential target(s). The findings demonstrated the downregulation of the expression of miR-375 in the secretory phase compared to its expression in the proliferative phase of the endometrium in normal donors. In contrast, it was upregulated in the secretory phase of the endometrium in infertility patients. Furthermore, during decidualization of ESCs in vitro, overexpression of miR-375 significantly reduced the transcript-level expression of forkhead box protein O1 (FOXO1), prolactin (PRL), and insulin-like growth factor binding protein-1 (IGFBP1), the well-known decidual cell markers. Overexpression of miR-375 also resulted in reduced decidualization-derived intracellular and mitochondrial reactive oxygen species (ROS) levels. Using the luciferase assay, we confirmed that NADPH oxidase 4 (NOX4) is a direct target of miR-375. Collectively, the study showed that the miR-375-mediated NOX4 downregulation reduced ROS production and attenuated the decidualization of ESCs. It provides evidence that miR-375 is a negative regulator of decidualization and could serve as a potential target for combating infertility., (© 2022. The Author(s).)

Many ubiquitin E3 ligases function in plant immunity. Here, we show that Oryza sativa (rice) DDB1 binding WD (OsDWD1) suppresses immune responses by targeting O. sativa non-expresser of pathogenesis-related gene 1 (OsNPR1) for degradation. Knock-down and overexpression experiments in rice plants showed that OsDWD1 is a negative regulator of the immune response and that OsNPR1 is a substrate of OsDWD1 and a substrate receptor of OsCRL4. After constructing the loss-of-function mutant OsDWD1 R239A , we showed that the downregulation of OsNPR1 seen in rice lines overexpressing wild-type (WT) OsDWD1 (OsDWD1 WT -ox) was compromised in OsDWD1 R239A -ox lines, and that OsNPR1 upregulation enhanced resistance to pathogen infection, confirming that OsCRL4 OsDWD1 regulates OsNPR1 protein levels. The enhanced disease resistance seen in OsDWD1 knock-down (OsDWD1-kd) lines contrasted with the reduced disease resistance in double knock-down (OsDWD1/OsNPR1-kd) lines, indicating that the enhanced disease resistance of OsDWD1-kd resulted from the accumulation of OsNPR1. Moreover, an in vivo heterologous protein degradation assay in Arabidopsis thaliana ddb1 mutants confirmed that the CUL4-based E3 ligase system can also influence OsNPR1 protein levels in Arabidopsis. Although OsNPR1 was degraded by the OsCRL4 OsDWD1 -mediated ubiquitination system, the phosphodegron-motif-mutated NPR1 was partially degraded in the DWD1-ox protoplasts. This suggests that there might be another degradation process for OsNPR1. Taken together, these results indicate that OsDWD1 regulates OsNPR1 protein levels in rice to suppress the untimely activation of immune responses., (© 2022 Society for Experimental Biology and John Wiley & Sons Ltd.)

Endometrial receptivity is essential for successful pregnancy, and its impairment is a major cause of embryo-implantation failure. MicroRNAs (miRNAs) that regulate epigenetic modifications have been associated with endometrial receptivity. However, the molecular mechanisms whereby miRNAs regulate endometrial receptivity remain unclear. Therefore, we investigated whether miR-182 and its potential targets influence trophoblast cell attachment. miR-182 was expressed at lower levels in the secretory phase than in the proliferative phase of endometrium tissues from fertile donors. However, miR-182 expression was upregulated during the secretory phase in infertile women. Transfecting a synthetic miR-182-5p mimic decreased spheroid attachment of human JAr choriocarcinoma cells and E-cadherin expression (which is important for endometrial receptivity). miR-182-5p also downregulated N-Myc downstream regulated 1 (NDRG1), which was studied further. NDRG1 was upregulated in the secretory phase of the endometrium tissues and induced E-cadherin expression through the nuclear factor-κΒ (NF-κΒ)/zinc finger E-box binding homeobox 1 (ZEB1) signaling pathway. NDRG1-overexpressing or -depleted cells showed altered attachment rates of JAr spheroids. Collectively, our findings indicate that miR-182-5p-mediated NDRG1 downregulation impaired embryo implantation by upregulating the NF-κΒ/ZEB1/E-cadherin pathway. Hence, miR-182-5p is a potential biomarker for negative selection in endometrial receptivity and a therapeutic target for successful embryo implantation.