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Objective: To prospectively determine the upgrade rate following surgery in benign papilloma initially diagnosed at ultrasound (US)-guided 14-gauge gun biopsy.Methods: A total of 128 benign papillomas were diagnosed in 114 patients after a US-guided biopsy. Surgical excision was recommended where the biopsy indicated benign papilloma, regardless of imaging findings. The upgrade rate to 'atypical' and 'malignancy' was measured on a per-lesion basis. We analysed potential associations between clinical presentation, lesion variables and the results of surgical excision (using logistic regression).Results: Of the 114 patients, 87 eventually underwent surgery: among the 100 supposed benign papillomas, surgical excision revealed fibrocystic change or no residual lesion in nine cases, intraductal papilloma in 74, atypical papilloma in 13, papillary ductal carcinoma in situ (DCIS) in three and one invasive papillary carcinoma. The upgrade rate for an atypical papilloma or papilloma with adjacent foci of atypical ductal hyperplasia (ADH) and malignancy was 13% (95% CI = 7.1-21.2%) and 4% (95% CI = 1.1-9.9%), respectively. The mean lesion size (P = 0.041) was significantly larger when lesions were upgraded to malignancy. Other features were not significantly associated with pathological underestimation (P > 0.05).Conclusion: Surgical excision should be considered for benign intraductal papillomas above 1.5 cm in size. [ABSTRACT FROM AUTHOR]

High-molecular-weight fucoidan (Fucoidan P), sourced from Undaria pinnatifida exhibits several health benefits, including immunomodulation. However, the mechanisms underlying the immune-enhancing effects of Fucoidan P remain unclear. Here, we investigated the immune-enhancing effects and the potential mechanisms of Fucoidan P using RAW 264.7 macrophages and cyclophosphamide (CP)-induced immunosuppression rat model. In macrophages, Fucoidan P showed dose-dependent stimulation by increasing cell proliferation, nitric oxide production, and gene expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines. These effects are mediated through the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Moreover, orally administered Fucoidan P was evaluated in immunosuppressed rats treated with CP. Fucoidan P administration increased hematological values and natural killer cell activity, and positively affected nitrite and prostaglandin E2 levels. The Fucoidan P treatment groups exhibited improved serum cytokine levels as well as splenic and intestinal cytokine mRNA expression compared to the model group. Fucoidan P also mitigated splenic damage and increased the phosphorylation of NF-κB and NF-κB inhibitor alpha (IκBα). Furthermore, Fucoidan P treatment altered the gut microbiota composition, enhancing the alpha diversity, evenness, and abundance of Bacteroidetes, which are associated with immune function. Taken together, our findings suggest that Fucoidan P exerts beneficial effects on immune function by activating NF-κB and modulating gut microbiota. These findings suggested its potential as a therapeutic agent for immune enhancement., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Since the introduction of powered circular staplers in colorectal surgery, there has been growing interest in their impact on reducing complications, particularly anastomotic leakage. This study compared short-term postoperative outcomes between powered and manual circular staplers., Methods: This retrospective study included colorectal cancer patients at the tertiary referral center from April to October 2023 who underwent anterior or low anterior resection (LAR) using a circular stapler. According to energy source, patients were divided into powered and manual groups, which used two powered and four types of manual staplers, respectively. All open, laparoscopic, and robotic approaches were included. Propensity score matching (PSM) analysis was used to reduce selection bias. Postoperative complications within 30 days, especially for anastomosis-related complications, were compared between the groups., Results: Among 511 patients, the powered group was 161 (32%). After PSM, 143 pairs of 286 patients were analyzed. The proportions of LAR were 53.8% and 51.0%, and initial diverting stoma rates were 23.1% and 22.4% for the Powered and Manual groups, respectively. Comprehensive complication rates were similar between the Powered group and the Manual group, without statistical significance (13.3% vs. 21.0%, P = 0.063). Anastomotic leakage was not different between the Powered and Manual groups (4.2% vs. 4.9%, P = 0.782). There was no significant difference in other complications, including anastomotic bleeding, ileus, surgical site infection, and intra-abdominal hematoma., Conclusions: The study implies that powered circular staplers may not significantly reduce postoperative complications, including anastomotic leakages, compared to manual staplers in colorectal surgery of high-volume centers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A boronate-ester structure forming a pH-responsive polymer dot (Plu-PD) coated biosensor between carbonized-sp 2 rich dopamine-alginate [PD(Alg)] and boronic acid-grafted Pluronic (BA-Pluronic) was developed for the electrochemical and fluorescence detection of cancer cells. The reduced fluorescence (FL) resulting from fluorescence resonance energy transfer (FRET) mediated by π-π interactions within Plu-PD was successfully reinvigorated through the specific cleavage of the boronate-ester bond, triggered by the acidic conditions prevailing in the cancer microenvironment. The anomalous variations in extracellular pH levels observed in cancer (pH ∼6.8), as opposed to the normal cellular pH range of approximately 7.4, serve as robust indicators for discerning cancer cells from their healthy counterparts. Moreover, the Plu-PD coated surface demonstrated remarkable adaptability in modulating its surface structure, concurrently exhibiting tunable electroconductivity under reduced pH conditions, thereby imparting selective responsiveness to cancer cells. The pH-modulated conductivity change was validated by a reduction in resistance from 211 ± 9.7 kΩ at pH 7.4 to 73.9 ± 9.4 kΩ and 61.5 ± 11.5 kΩ at pH 6.8 and 6.0, respectively. The controllable electrochemical characteristics were corroborated through in vitro treatment of cancer cells (HeLa, B16F10, and SNU-C2A) via LED experiments and wireless output analysis. In contrast, identical treatments yielded a limited response in normal cell line (CHO-K1). Notably, the Plu-PD coated surface can be seamlessly integrated with a wireless system to facilitate real-time monitoring of the sensing performance in the presence of cancer and normal cells, enabling rapid and accurate cancer diagnosis using a smartphone., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: The prevalence of type 1 diabetes (T1D) is increasing worldwide, with a much higher proportion of adult patients. However, achieving stable glycemic control is difficult in these patients., Objective: After periodic implementation of structured education for patients with T1D through the Home and Self-Care Program, a pilot home health care project promoted by the Korean government, we evaluated the program's effects on glycemic control., Methods: This study was conducted from April 2020 to March 2023. We analyzed 119 participants with T1D aged >15 years. Nursing and nutrition education were provided separately up to 4 times per year, with physician consultation up to 6 times per year. A distinguishing feature of this study compared with previous ones was the provision of remote support using a general-purpose smartphone communication app offered up to 12 times annually on an as-needed basis to enhance the continuity of in-person education effects. Patients were followed up on at average intervals of 3 months for up to 24 months. The primary end point was the mean difference in glycated hemoglobin (HbA 1c ) at each follow-up visit from baseline. For continuous glucose monitoring (CGM) users, CGM metrics were also evaluated., Results: The mean HbA 1c level of study participants was 8.6% at baseline (mean duration of T1D 10.02, SD 16.10 y). The HbA 1c level reduction in participants who received at least 1 structured educational session went from 1.63% (SD 2.03%; P<.001; adjustment model=1.69%, 95% CI 1.24%-2.13% at the first follow-up visit) to 1.23% (SD 1.31%; P=.01; adjustment model=1.28%, 95% CI 0.78%-1.79% at the eighth follow-up visit). In the adjustment model, the actual mean HbA 1c values were maintained between a minimum of 7.33% (95% CI 7.20%-7.46% at the first follow-up visit) and a maximum of 7.62% (95% CI 7.41%-7.82% at the sixth follow-up visit). Among CGM users, after at least 1 session, the mean time in the target range was maintained between 61.59% (adjusted model, 95% CI 58.14%-65.03% at the second follow-up visit) and 54.7% (95% CI 50.92%-58.48% at the eighth follow-up visit), consistently staying above 54.7% (corresponding to an HbA 1c level of <7.6%). The mean time below the target range (TBR) also gradually improved to the recommended range (≤4% for TBR of <70 mg/dL and ≤1% for TBR of <54 mg/dL)., Conclusions: The Home and Self-Care Program protocol for glycemic control in patients with T1D is effective, producing significant improvement immediately and long-term maintenance effects, including on CGM indexes., (©Dae-Jeong Koo, Sun-Joon Moon, Suhyeon Moon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee, Cheol-Young Park. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 11.09.2024.)

Miltefosine is the first and only drug approved for the treatment of leishmaniasis. It is also known as a PI3K/AKT signaling pathway inhibitor utilized in anti-cancer or anti-viral therapies. However, the impact of miltefosine on male fertility has not been fully understood. Therefore, this study was performed to investigate the effects of miltefosine on sperm function during capacitation. Duroc spermatozoa were exposed to 0, 2.5, 5, 10, 20, 40, and 80μM miltefosine and induced for capacitation. Our results showed that miltefosine dramatically increased the expression of PI3K/AKT signaling pathway-associated proteins. Sperm motility, motion kinetics, capacitation, and tyrosine phosphorylation were significantly suppressed by miltefosine. However, intracellular ATP levels and cell viability were not significantly affected. Our findings suggest that miltefosine may disrupt sperm function by abnormally increasing the levels of PI3K/AKT signaling pathway-associated proteins. Therefore, the harmful effects of miltefosine on male reproduction should be considered when using this drug., 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 © 2024 Elsevier B.V. All rights reserved.)

Cerebrospinal fluid (CSF) plays an important role in brain tumors, including medulloblastoma (MBL). Recent advancements in mass spectrometry systems and 'Omics' data analysis methods enable unbiased, high proteome depth research. We conducted proteomic profiling of the total CSF in MBL patients with the purpose of finding a potential diagnostic biomarker for MBL. We quantified 1112 proteins per CSF sample. Feature selection identified four elevated soluble proteins (SPTBN1, HSP90AA1, TKT, and NME1-NME2) in MBL CSF. Validation with ELISA confirmed that TKT was significantly elevated in MBL. Additionally, TKT-positive extracellular vesicles were significantly enriched in MBL CSF and correlated with the burden of leptomeningeal seeding. Our results provide insights into the proteomics data of the total CSF of MBL patients. Furthermore, we identified the significance of TKT within the total CSF and its presence within circulating EVs in the CSF. We suggest that TKT may serve as a biomarker for MBL., (© 2024. The Author(s).)

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Serotonin (5-HT) is a biogenic monoamine that acts as a neurotransmitter in the central nervous system and as a paracrine, exocrine, or endocrine messenger in peripheral tissues. In this study, we hypothesized that inhibition of serotonin signaling using 5-HT receptor 2B (HTR2B) inhibitors could potentially impede the progression of CRC. We treated CT26 and COLO-205 cells with SB204741, an inhibitor of HTR2B, and evaluated CRC cell proliferation and migration. We then evaluated the effects of HTR2B inhibition in a xenograft mouse model of human colorectal cancer. We also evaluated the role of a novel inhibitor, GM-60186, using both in vitro and in vivo models. RNA sequencing analysis was performed to elucidate the underlying mechanism of the anti-tumor effects of pharmacological inhibition of HTR2B on CRC. In both CRC cell lines and xenograft mouse models, we show that pharmacological inhibition of HTR2B with SB204741 and GM-60186 significantly inhibits CRC cell proliferation and migration. HTR2B inhibition leads to the suppression of extracellular signal-regulated kinase (ERK) signaling, a critical pathway in CRC pathogenesis. Notably, transcriptomic analysis reveals distinct gene expression changes associated with HTR2B inhibition, providing insight into its therapeutic potential. In this study, we found that pharmacological inhibition of HTR2B suppressed CRC proliferation via ERK signaling. In addition, we proposed a novel HTR2B inhibitor for the treatment of CRC. This study highlights the potential role of HTR2B signaling in CRC. These inhibitors may contribute to new therapeutics for CRC treatment., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Benzene occurs naturally and is widely applied in the production process of petrochemical products. It is mainly exposed through the respiratory tract and dermal and metabolized in the liver, leading to systemic health effects, and 1,2,4-trihydroxybenzene (THB) is a benzene metabolite used as a hair dye ingredient in some countries. In an effort to identify a toxic mechanism of THB, we first analyzed the hair of consumers who used a shampoo containing THB, and contrary to our expectations, THB was not persistent in the hair. Following, we treated THB to human keratinocytes and HeLa Chang liver cells. Membrane damage was observed in both cell lines, which was more notable in HeLa Chang liver cells than in keratinocytes. Thus, we decided on HeLa Chang liver cells as target cells for further study. Cell viability decreased sharply between 20 μg/ml and 40 μg/mL, inducing G2/M phase arrest and non-apoptotic cell death. The expression of carcinogenesis-, DNA damage-, and transcriptional dysregulation-related genes were notably up-regulated, and the structure and function of mitochondria were disrupted. The volume of the ER and acidic compartments decreased, and intracellular ROS and calcium ion levels increased. More interestingly, we found that THB formed unique structures within the cells, especially around the nuclear membrane, and that those structures seemed to dig into the nucleus over time. A reverse docking analysis also showed that SULT1A1, CYP2E1, and CAT, known to play a significant role in protecting cells from harmful factors, might be potential target proteins for THB. Taken together, we suggest that THB induces non-apoptotic cell death via structural damage of intracellular organelles, especially the nuclear membrane., 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 © 2024. Published by Elsevier Inc.)

T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre + ) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, the lungs of FSF-TIM3/LysM-Cre + mice display excessive inflammation and features of disease-associated pathology. We further revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, both TIM-3 blockade and GB1107, a galectin-3 inhibitor, ameliorated lung inflammation in FSF-TIM3/LysM-Cre +/- mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we demonstrated the association of TIM-3 with both lung inflammation and galectin-3. Collectively, our findings suggest that myeloid TIM-3 is an important regulator in the lungs and that modulation of TIM-3 and galectin-3 could offer therapeutic benefits for inflammation-associated lung diseases., (© 2024. The Author(s).)

6'-Sialyllactose (6'-SL), found in human breast milk, exhibits anti-inflammatory, immune function-enhancing, brain development-promoting, and gut health-improving effects. However, its effects on muscle fatigue remain unknown. Here, we aimed to investigate the effects of 6'-SL on blood lactate level, muscle fiber type, and oxidative phosphorylation protein complexes (OXPHOS) in muscle after exercise using C57BL/6J male mice. C57BL/6J mice were randomly assigned to control or 100 mg/kg 6'-SL. After 12 weeks of 6'-SL administration, the mice were made to perform treadmill exercise; their blood lactate and glucose levels were measured at the basal level (rest) and 0, 5, and 10 min after treadmill exercise. Results showed that 6'-SL treatment in C57BL/6J mice significantly reduced blood lactate level and improved blood glucose level. Moreover, 6'-SL increased the expression of slow-myosin heavy chain (MHC) and OXPHOS in gastrocnemius muscle. In addition, 6'-SL treatment for 12 weeks did not affect food intake, serum biomarkers of tissue injury, and lipid profiles compared with those of the controls. These findings indicate that non-toxic 6'-SL suppressed muscle fatigue during exercise by promoting protein expression of muscle fibers, especially slow-twitch muscle fibers characterized by abundant OXPHOS complexes and decreased blood lactate level. This study suggests that 6'-SL holds promise as a nutritional supplement in exercise and clinical settings, subject to further validation.

Despite its widespread use as a stabilizer across various industries over the past several decades, the health effects of chronic exposure to PFOA are still unclear. We administered PFOA by oral gavage (0, 12.5, 50, and 200 μg/day/mouse, eight groups) to male and female mice for six months. Body weight gain decreased with dose accompanied by increased liver weight, and PFOA altered liver damage-related-blood biochemical indicators and induced pathological lesions, including hepatocellular hypertrophy, cholangiofibrosis, and centrilobular hepatocellular vacuolation. Loss of the Golgi apparatus, formation of lamellar body-like structures, and lipid accumulation were observed in the liver of PFOA-treated mice. We also cohabited five pairs of male and female mice for the last ten days of administration, dosed PFOA to dam up to 28 days after birth, and investigated effects on reproduction and development. The survival rate of pups and the sex ratio of surviving mice decreased significantly at the highest dose. PFOA tissue concentration increased with the dose in the parent mice's liver and the pups' blood and brain. Taken together, we suggest that PFOA primarily affects the liver and reproduction system and that disturbance in lipid metabolism and Golgi's structural stability may be involved in PFOA-induced toxicity., 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 © 2024 Elsevier Ltd. All rights reserved.)

Oridonin, a natural terpenoid isolated from the leaves of Isodon rubescens (Hemsley) H.Hara, is widely used in oriental medicine for its anticancer properties across various cancer types. Despite its prevalent use, the toxic effects of oridonin on male reproduction, particularly its impact on sperm functions and the mechanisms involved, are not well understood. This study aimed to explore the effects and underlying mechanisms of oridonin on sperm functions. We initially treated Duroc boar spermatozoa with varying concentrations of oridonin (0, 5, 50, 75, 100, and 150 µM) and incubated them to induce capacitation. We then assessed cell viability and several sperm functions, including sperm motility and motion kinematics, capacitation status, and ATP levels. We also analyzed the expression levels of proteins associated with the phosphatidylinositol 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (AKT) signaling pathway and phosphotyrosine proteins. Our results indicate that oridonin adversely affects most sperm functions in a dose-dependent manner. We observed significant decreases in AKT, p-AKT (Thr308), phosphatase and tensin homolog (PTEN), p-PDK1, and p-PI3K levels following oridonin treatment, alongside an abnormal increase in phosphotyrosine proteins. These findings suggest that oridonin may disrupt normal levels of tyrosine-phosphorylated proteins by inhibiting the PI3K/PDK1/AKT signaling pathway, which is crucial for cell proliferation, metabolism, and apoptosis, thus potentially harming sperm functions. Consequently, we recommend considering the reproductive toxicity of oridonin when using it as a therapeutic agent., 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 © 2024 Elsevier Inc. All rights reserved.)

Engaging the public and community organizations in local health actions greatly assists disease prevention and control. However, it remains unclear how organization-public relationships (OPR) and communication networks within communities contribute to community health actions. To fill this gap, a survey was conducted among community members in Shanghai, China, who were challenged by the Omicron wave of the COVID-19 pandemic. Results revealed that integrated connectedness to a storytelling network (ICSN) was a significant predictor of residents' community engagement. Trust, control mutuality, commitment, and ICSN were positively associated with community engagement intentions through the sense of community and organizational efficacy. This study is a step toward understanding how organizations and members collectively respond to health crises at the community level.

Objective: Intra-atrial reentrant tachycardia is an important late-onset complication in patients undergoing the Fontan procedure. However, the protective effects of prophylactic cryoablation against late-onset intra-atrial reentrant tachycardia are unclear. This study investigated the late development of intra-atrial reentrant tachycardia in patients undergoing the lateral tunnel Fontan procedure and the role of prophylactic cryoablation., Methods: This was a single-center retrospective cohort study of patients who underwent the lateral tunnel Fontan procedure between 1988 and 2003. Univariate and multivariable competing risks regression models were used to determine the associations of prophylactic cryoablation and covariates with the outcomes of interest: late-onset intra-atrial reentrant tachycardia, all-cause mortality, and cardiovascular mortality., Results: In total, 130 patients who underwent the lateral tunnel Fontan procedure, 30 of whom had undergone prophylactic cryoablation, were included in this study and followed up for a median of 23.6 years (interquartile range, 17.7-26.5). Intra-atrial reentrant tachycardia was identified in 14 patients (10.8%), none of whom underwent prophylactic cryoablation. The median Fontan-to-intra-atrial reentrant tachycardia time was 17.2 years (interquartile range, 11.1-23.1). Prophylactic cryoablation was protective against late-onset intra-atrial reentrant tachycardia (P < .0001) and cardiovascular mortality (P < .0001) in the type 3 test., Conclusions: None of the patients who underwent prophylactic cryoablation developed late-onset intra-atrial reentrant tachycardia during a median follow-up time of 22.9 years. Our study demonstrated that prophylactic cryoablation was effective in preventing late-onset intra-atrial reentrant tachycardia and cardiovascular mortality in patients undergoing the lateral tunnel Fontan., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background/aim: Silibinin, has been investigated for its potential benefits and mechanisms in addressing vanadium pentoxide (V2O5)-induced pulmonary inflammation. This study explored the anti-inflammatory activity of silibinin and elucidate the mechanisms by which it operates in a mouse model of vanadium-induced lung injury., Materials and Methods: Eight-week-old male BALB/c mice were exposed to V2O5 to induce lung injury. Mice were pretreated with silibinin at doses of 50 mg/kg and 100 mg/kg. Histological analyses were performed to assess cell viability and infiltration of inflammatory cells. The expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and activation of the MAPK and NF-[Formula: see text]B signaling pathways, as well as the NLRP3 inflammasome, were evaluated using real-time PCR, western blot analysis, and immunohistochemistry. Whole blood analysis was conducted to measure white blood cell counts., Results: Silibinin treatment significantly improved cell viability, reduced inflammatory cell infiltration, and decreased the expression of pro-inflammatory cytokines in V2O5-induced lung injury. It also notably suppressed the activation of the MAPK and NF-[Formula: see text]B signaling pathways, along with a marked reduction in NLRP3 inflammasome expression levels in lung tissues. Additionally, silibinin-treated groups exhibited a significant decrease in white blood cell counts, including neutrophils, lymphocytes, and eosinophils., Conclusion: These findings underscore the potent anti-inflammatory effects of silibinin in mice with V2O5-induced lung inflammation, highlighting its therapeutic potential. The study not only confirms the efficacy of silibinin in mitigating inflammatory responses but also provides a foundational understanding of its role in modulating key inflammatory pathways, paving the way for future therapeutic strategies against pulmonary inflammation induced by environmental pollutants., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The Jr a antigen is a high-prevalence red blood cell (RBC) antigen. Reports on cases of fatal hemolytic disease of the fetus and newborn and acute hemolytic transfusion reactions suggest that antibodies against Jr a (anti-Jr a ) have potential clinical significance. Identifying anti-Jr a is challenging owing to a lack of commercially available antisera. We developed an alternative approach to rapidly predict the presence of anti-Jr a using the TaqMan single-nucleotide polymorphism (SNP)-genotyping method., Methods: Residual peripheral blood samples from 10 patients suspected of having the anti-Jr a were collected. Two samples with confirmed Jr(a-) RBCs and anti-Jr a were used to validate the TaqMan genotyping assay by comparing the genotyping results with direct sequencing. The accuracy of the assay in predicting the presence of anti-Jr a was verified through crossmatching with in-house Jr(a-) O+ RBCs., Results: The TaqMan-genotyping method was validated with two Jr(a-) RBC- and anti-Jr a -confirmed samples that showed concordant Jr a genotyping and direct sequencing results. Jr a genotyping for the remaining samples and crossmatching the serum samples with inhouse Jr(a-) O+ RBCs showed consistent results., Conclusions: We validated a rapid, simple, accurate, and cost-effective method for predicting the presence of anti-Jr a using a TaqMan-based SNP-genotyping assay. Implementing this method in routine practice in clinical laboratories will assist in solving difficult problems regarding alloantibodies to high-prevalence RBC antigens and ultimately aid in providing safe and timely transfusions and proper patient care.

Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study aims to illuminate regional disparities and identify vulnerable areas in stroke care across Gyeonggi Province's hospital service areas., Methods: Using data from the Korea National Cardio-cerebrovascular Disease Management Commission, we included 4,427 acute stroke patients admitted in 2018 to hospitals within Gyeonggi Province. Our evaluation focused on: 1) stroke care quality indicators, including rates of defect-free care, intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), and acute reperfusion therapy (either IVT or EVT); 2) intra-regional treatment rates; and 3) one-year mortality across the province and its 12 hospital service areas. These were compared both with national averages and inter-regionally. Vulnerable areas were pinpointed by evaluating the number of quality indicators falling below the national average and through visual distribution mapping, categorizing each indicator into higher (ranks 1-4), middle (ranks 5-8), and lower (ranks 9-12) tiers., Results: Despite fewer qualified stroke centers and specialists, Gyeonggi Province exhibited higher defect-free care rates (84.6 % vs. 80.7 %), intra-regional treatment rates (57.8 % vs. 51.0 %), and marginally lower one-year mortality (16.2 % vs. 17.3 %) compared to national averages. Notable regional disparities were observed; the highest-performing areas for defect-free care and acute reperfusion therapy exceeded the lowest by 1.4 and 3.3 times, respectively. Nine out of twelve areas fell below the national average for EVT rates, seven for IVT and reperfusion therapy rates, and five for intra-regional treatment rates. Pyeongtaek, with all stroke care quality indicators below the national average coupled with the highest one-year mortality, emerges as a critical area needing improvement in acute stroke care., Conclusion: This study not only exposes the regional disparities in stroke care within Gyeonggi Province's hospital service areas but also identifies areas most vulnerable. Consequently, a customized support strategy for these areas is imperative., 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 © 2024. Published by Elsevier Inc.)

Purpose: This study compared the anti-pseudomonal effects between nephrite-impregnated contact lenses (CLs) and conventional and cosmetic CLs., Methods: After inoculation with Pseudomonas aeruginosa (P.aeruginosa) , we counted the number of bacteria on the CL surface and observed each surface using atomic force microscopy (AFM) and scanning electron microscopy (SEM). To estimate potential harm of nephrite-impregnated CLs, we conducted a safety test using a rabbit model, treated with all CL types., Results: Both conventional and cosmetic CLs ( n  = 258 ± 2.9 × 10 4 , 368 ± 2.2 × 10 4 ) showed significantly decreased number of attached bacteria when compared with those without nephrite impregnation ( n  = 134 ± 0.8 × 10 4 , 238 ± 2.5 × 10 4 , p  < 0.0001, respectively). AFM and SEM revealed that P. aeruginosa was less attached to the nephrite-impregnated CLs than to the conventional and cosmetic CLs, although those with nephrite impregnation had rougher surface. In the safety test, there were no significant differences in the findings between four groups, and the clarity and stability of all corneas were preserved., Conclusions: Nephrite may be used as a next-generation substance to reduce infectious keratitis caused by P. aeruginosa when added to CLs.

Rheumatoid arthritis (RA) is an autoimmune disease primarily affecting the joints and requires various treatments, including medication, injection, and physiotherapy. Wu tou decoction (WTD) is a traditional Chinese medicine prescribed for RA, with several articles documenting its effectiveness in RA treatment. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of WTD for RA. We searched for randomized controlled trials (RCTs) comparing WTD with conventional treatments (including medication, injection, and physiotherapy) from its inception to May 2024. Primary outcomes were disease activity scores, including effective rate, tender joint count, and morning stiffness. Secondary outcomes comprised blood test results (erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor) and adverse events. Nineteen RCTs involving 1794 patients were included. Statistically, WTD demonstrated better improvement than conventional treatments (18 medications and 1 injection) across the effective rate, joint scale, and blood tests, regardless of the treatment type (monotherapy or combination therapy). Adverse events were reported in 11 studies, with no statistical differences observed between them. The numerical results showed that WTD may offer potential benefits for managing RA. However, the significant discrepancy between clinical practice and the low quality of the RCTs remains a limitation. Therefore, further well-designed studies with larger patient cohorts are needed to draw definitive conclusions.

Sodium-dependent glucose cotransporter-2 (SGLT2) inhibitors, antidiabetic drugs that reduce blood sugar levels by inhibiting glucose reabsorption in the renal proximal tubules, also ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the effects of SGLT2 inhibition on hepatic steatosis and nonalcoholic steatohepatitis (NASH) using an in vitro model of NAFLD progression. HepG2 cells and a coculture of Hepa1c1c7 and Raw 264.7 cells were treated with 400 μM palmitic acid (PA), followed by treatment with or without 10 μM empagliflozin and dapagliflozin. In HepG2 cells, PA increased hepatic lipid accumulation, the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), exocytosis mediators (VAMP3 and SNAP23), and ER stress markers (GRP78, PERK, IRE1α, ATF6, ATF4, and CHOP), and the gene and protein expression of CD36. SGLT2 inhibitors reversed the effects of PA. SGLT2 inhibition via siRNA reduced proinflammatory-cytokine gene expression in thapsigargin-treated HepG2 cells. Transfection with CD36 siRNA reversed the elevated ATF4 and CHOP expression in PA-treated HepG2 cells. SGLT2 inhibition via an SGTL2 inhibitor and SGLT2 siRNA reduced CD36, Tnf-α, Il-6, Il-1β, Vamp2, Snap23, Atf4, and Chop expression in the PA-treated Hepa1c1c7-Raw 264.7 cell coculture and suppressed Tnf-α release in the Hepa1c1c7-Raw 264.7 cell coculture treated with lipopolysaccharide and PA. These findings indicate that SGLT2 inhibitors inhibited NAFLD progression by reducing hepatic lipid accumulation and inflammation., 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 © 2024. Published by Elsevier Inc.)

Galectin-9 is a multifaceted regulator of various pathophysiological processes that exerts positive or negative effects in a context-dependent manner. Here, we elucidated the distinctive functional properties of galectin-9 on myeloid cells within the brain tumor microenvironment. Galectin-9-expressing cells were abundant at the hypoxic tumor edge in the tumor-bearing ipsilateral hemisphere compared to the contralateral hemisphere in an intracranial mouse brain tumor model. Galectin-9 was highly expressed in microglia and macrophages in tumor-infiltrating cells. In primary glia, both the expression and secretion of galectin-9 were influenced by tumors. Analysis of a human glioblastoma bulk RNA-sequencing dataset and a single-cell RNA-sequencing dataset from a murine glioma model revealed a correlation between galectin-9 expression and glial cell activation. Notably, the galectin-9high microglial subset was functionally distinct from the galectin-9neg/low subset in the brain tumor microenvironment. Galectin-9high microglia exhibited properties of inflammatory activation and higher rates of cell death, whereas galectin-9neg/low microglia displayed a superior phagocytic ability against brain tumor cells. Blockade of galectin-9 suppressed tumor growth and altered the activity of glial and T cells in a mouse glioma model. Additionally, glial galectin-9 expression was regulated by Hif-2α in the hypoxic brain tumor microenvironment. Myeloid-specific Hif-2α deficiency led to attenuated tumor progression. Together, these findings reveal that galectin-9 on myeloid cells is an immunoregulator and putative therapeutic target in brain tumors.

Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.

Background: Developmental trajectories of clinical skills in training physicians vary among tasks and show interindividual differences. This study examined the predictors of medical internship performance and residency entrance and found subtypes of performance trajectory in training physicians., Methods: This retrospective cohort study involved 888 training physicians who completed a medical internship between 2015 and 2019. After the internship, 627 physicians applied for residency training between 2016 and 2020. Finally, 160 of them completed their first-year residency in internal medicine, surgery, pediatrics, and psychiatry departments between 2016 and 2020. Pearson's correlation coefficients of internship performance and first year-residency performance (n = 160) were calculated. Latent profile analysis identified performance trajectory subtypes according to medical school grade point average (GPA), internship performance, English proficiency, and residency selection procedures. Multivariate logistic regression models of residency acceptance (n = 627) and performance in the top 30%/lower 10% in the first year of residency were also constructed., Results: Medical internship performance showed a significant positive correlation with the medical school GPA ( r = 0.194) and the written score for the medical licensing examination ( r = 0.125). Higher scores in the interview (adjusted odds ratio [aOR], 2.57) and written examination (aOR, 1.45) of residency selection procedures and higher medical internship performance (aOR, 1.19) were associated with a higher chance of residency acceptance. The latent profile analyses identified three training physician subgroups: average performance, consistently high performance (top 30%), and adaptation to changes (lowest 10%). Higher scores in the interview for residency selection (aOR, 1.35) and lower scores for medical internship performance (aOR, 0.79) were associated with a higher chance of performing in the top 30% or lowest 10% in the first year of residency, respectively., Conclusion: Performance in the interview and medical internship predicted being among the top 30% and lowest 10% of performers in the first year of residency training, respectively. Individualized educational programs to enhance the prospect of trainees becoming high-functioning physicians are needed., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

The clinical consequences of perioperative albumin extravasation accompanying major abdominal surgery remain underexplored. We retrospectively reviewed the data of patients who underwent cytoreductive surgery (CRS) and hyperthermic intraoperative peritoneal chemotherapy (HIPEC). Parameters of albumin kinetics, including serum albumin concentration decrease (∆Alb) and extravasated albumin level (Alb shift ), were assessed from surgery until postoperative day (POD) 3. Logistic regression analysis identified factors associated with major complications. The association of albumin kinetics with major complications was evaluated using receiver operating characteristic (ROC) curve analysis. Serum albumin levels decreased during surgery and subsequently increased. Of the 121 analyzed patients, 25 (21%) developed major complications. The ∆Alb and Alb shift during surgery and on POD 3 were greater in patients who developed major complications than in those who did not (12 ± 12 vs. 6 ± 14, p = 0.032, and 127.5 (71.9) vs. 48.5 (44.9), p < 0.001, respectively). Perioperative ∆Alb and Alb shift were associated with major complications. The areas under the ROC curve of Alb shift during the 3 days post-surgery and Alb shift on POD 3 were 0.843 and 0.910, respectively. Alb shift during the 3 days post-surgery and Alb shift on POD 3 were correlated with complications ( p < 0.05). In conclusion, perioperative albumin loss was associated with major complications in patients undergoing CRS and HIPEC. Alb shift was associated with serious complications.

Exposure to particulate matter (PM), especially PM 2.5 , is known to exacerbate asthma, posing a significant public health risk. This study investigated the asthma-reducing effects of photobiomodulation (PBM) in a mice model mimicking allergic airway inflammation exacerbated by PM 2.5 exposure. The mice received sensitization with ovalbumin (OVA) and were subsequently treated with PM 2.5 at a dose of 0.1 mg/kg every 3 days, for 9 times over 3 weeks during the challenge. PBM, using a 610 nm wavelength LED, was applied at 1.7 mW/cm 2 to the respiratory tract via direct skin contact for 20 min daily for 19 days. Results showed that PBM significantly reduced airway hyperresponsiveness, plasma immunoglobulin E (IgE) and OVA-specific IgE, airway inflammation, T-helper type 2 cytokine, histamine and tryptase in bronchoalveolar lavage fluid (BALF), and goblet cell hyperplasia in PM 2.5 -exposed asthmatic mice. Moreover, PBM alleviated subepithelial fibrosis by reducing collagen deposition, airway smooth muscle mass, and expression of fibrosis-related genes. It mitigated reactive oxygen species generation, oxidative stress, endoplasmic reticulum stress, apoptotic cell death, ferroptosis, and modulated autophagic signals in the asthmatic mice exposed to PM 2.5 . These findings suggest that PBM could be a promising intervention for PM 2.5 -induced respiratory complications in patients with allergic asthma.

Background: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs)., Methods: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS., Results: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10-23 years). The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07-65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26-7.64; P = 0.014) were significant risk factors for hemorrhage event., Conclusion: GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Throughout history, various cultures have recognized the significance of insects and have integrated them into traditional medicinal practices. In addition to medicines, insects are garnering attention as a sustainable and nutritious dietary alternative. Although edible insects have long been recognized as food sources in many Asian cultures, recent scientific studies have highlighted their potential therapeutic benefits, particularly in the field of neuroprotection. This review explores insect-derived extracts and peptides, elucidating their neuroprotective potential. This review highlights the potential use of insects as a source of neuroprotective agents. Advancements in neuroprotection may find a key ally in insects as our understanding of the symbiotic relationship between insects and human health becomes more profound.

Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4 + T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001's safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety., (© 2024. The Author(s).)

Lactiplantibacillus ( Lb. ) plantarum is known as a benign bacterium found in various habitats, including the intestines of animals and fermented foods. Since animal intestines lack oxygen, while fermented foods provide a limited or more oxygen environment, this study aimed to investigate whether there were genetic differences in the growth of Lb. plantarum under aerobic vs. anaerobic conditions. Genomic analysis of Lb. plantarum obtained from five sources-animals, dairy products, fermented meat, fermented vegetables, and humans-was conducted. The analysis included not only an examination of oxygen-utilizing genes but also a comparative pan-genomic analysis to investigate evolutionary relationships between genomes. The ancestral gene analysis of the evolutionary pathway classified Lb. plantarum into groups A and B, with group A further subdivided into A1 and A2. It was confirmed that group A1 does not possess the narGHIJ operon, which is necessary for energy production under limited oxygen conditions. Additionally, it was found that group A1 has experienced more gene acquisition and loss compared to groups A2 and B. Despite an initial assumption that there would be genetic distinctions based on the origin (aerobic or anaerobic conditions), it was observed that such differentiation could not be attributed to the origin. However, the evolutionary process indicated that the loss of genes related to nitrate metabolism was essential in anaerobic or limited oxygen conditions, contrary to the initial hypothesis.

Introduction: Erectile dysfunction (ED) is a common issue that affects older men and is often associated with various health conditions. Phosphodiesterase 5 inhibitors are commonly used to treat ED; however, their effectiveness may be limited, or the medication may be contraindicated. Therefore, topical gels are being developed as an alternative option for the pharmacologic treatment of ED., Objectives: This review aimed to provide an overview of the efficacy and safety of topical agents for the treatment of ED., Methods: The PubMed, Cochrane, Embase, and Web of Science databases were searched. Articles were included that investigated ED and topical agents operating through the skin of the penis, evaluated the effectiveness of the treatment, and involved patients randomized into groups., Results: Topical alprostadil, glyceryl trinitrate (MED2005), and an over-the-counter formulation (MED3000) were used as alternative treatments for ED in 7 articles, which included 3475 patients. Topical alprostadil induced an erection in 67% to 75% of patients. Adequate erections for vaginal penetration were reported in 38.7% of the alprostadil-treated patients vs 6.9% of the placebo-treated patients. Topical alprostadil significantly and dose dependently improved the total score change on the International Index of Erectile Function as compared with the placebo. MED2005 exhibited a rapid onset of action, with nearly 70% effectiveness within 10 minutes. MED3000 met the minimal clinically important difference threshold of a 4-point increase on the erectile function domain of the International Index of Erectile Function, with an improvement of 5.73 points in 24 weeks. Topical therapy for ED also had acceptable safety profiles., Conclusion: Topical agents via various mechanisms are effective and well-tolerated treatments for ED. A fast-acting drug that significantly reduces side effects as compared with other options has been discovered. However, its efficacy relative to current first-line therapies remains unclear. Topical agents present a viable therapeutic alternative for individuals who are unable or unwilling to take oral phosphodiesterase 5 inhibitors., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This systematic review and meta-analysis revealed the effectiveness of meditation in addressing fatigue, given its widespread use as a remedy for sleep disturbances and fatigue., Method: We analyzed 29 randomized controlled trials from MEDLINE and the Cochrane Library, spanning from December 31, 2022. We conducted two metaanalyses using mean difference (MD) with normalized data and standardized mean difference (SMD) with original data., Results: These trials included various populations, with baseline fatigue severity observed at 52.2 ± 16.0 points among 4104 participants. After an average meditation duration of 9.6 ± 4.7 weeks, fatigue scores decreased significantly by 6.4 points of MD [95% CI, 4.3-8.5] compared to controls. The most significant reduction occurred in the sub-healthy group (MD 8.2 [95% CI, 2.7 to 13.8]), followed by the general group (MD 6.9 [95% CI, 0.4 to 13.4]), and the disease group (MD 5.7 [95% CI, 3.4 to 8.0]). Notably, meditation-based anti-fatigue effects were particularly pronounced for mental fatigue (MD 10.0 [95% CI, 4.3 to 15.6]), especially with expert guidance and supplementary homework., Conclusion: These findings align with meta-analysis results using standardized mean difference (SMD), providing evidence for meditation as an effective nonpharmacological intervention for fatigue management, while also informing effective meditation approaches., Registration Number: CRD42023395551 in PROSPERO., 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 © 2024 Elsevier Inc. All rights reserved.)

Recent studies have highlighted the therapeutic potential of stem cells for various diseases. However, unlike other tissues, brain tissue has a specific structure, consisting of synapses. These synapses not only transmit but also process and refine information. Therefore, synaptic regeneration plays a key role in therapy of neurodegenerative disorders. Neurexins (NRXNs) and neuroligins (NLGNs) are synaptic cell adhesion molecules that connect pre- and postsynaptic neurons at synapses, mediate trans-synaptic signaling, and shape neural network properties by specifying synaptic functions. In this study, we investigated the synaptic regeneration effect of human neural stem cells (NSCs) overexpressing NRXNs (F3.NRXN) and NLGNs (F3.NLGN) in a spinal cord injury model. Overexpression of NRXNs and NLGNs in the neural stem cells upregulated the expression of synaptophysin, PSD95, VAMP2, and synapsin, which are synaptic markers. The BMS scores indicated that the transplantation of F3.NRXN and F3.NLGN enhanced the recovery of locomotor function in adult rodents following spinal cord injury. Transplanted F3.NRXN and F3.NLGN differentiated into neurons and formed a synapse with the host cells in the spinal cord injury mouse model. In addition, F3.NRXN and F3.NLGN cells restored growth factors (GFs) and neurotrophic factors (NFs) and induced the proliferation of host cells. This study suggested that NSCs overexpressing NRXNs and NLGNs could be candidates for cell therapy in spinal cord injuries by facilitating synaptic regeneration.

Sialyllactose (SL) is a functional human milk oligosaccharide essential for immune support, brain development, intestinal maturation, and antiviral defense. However, despite its established health benefits, the effect of SL on exercise performance and muscle mass in mice remains unknown. Here, we aimed to investigate, for the first time, the effects of 6'-SL on muscle functions. Seven-week-old male C57BL/6J mice were administered 100 mg/kg 6'-SL for 12 weeks, after which exhaustive treadmill performance was conducted. Moreover, muscle strength was examined by grip strength, and muscle phenotype characteristics such as muscle mass, muscle fiber size, and muscle protein expression were also examined. The administration of 6'-SL significantly improved exhaustive treadmill performance metrics, including distance and exhaustion time. Grip strength was also increased by 6'-SL administration. Additionally, 6'-SL increased muscle mass in both the gastrocnemius (GAS) and soleus. 6'-SL administration led to an increase in the minimum Feret's diameter and the protein expression of total myosin heavy chain in the GAS muscle. In conclusion, 6'-SL administration in vivo led to increased running distance and time by increasing muscle mass and strength. These findings collectively indicate that 6'-SL is a potential agent for improving muscle health and exercise performance.

Recent studies have shown that autophagy is activated in response to nerve damage and occurs simultaneously with the initial stages of Schwann cell-mediated demyelination. Although several studies have reported that macroautophagy is involved in the peripheral nerve, the role of chaperone-mediated autophagy (CMA) has not yet been investigated in peripheral nerve injury. The present study investigates the role of CMA in the sciatic nerve. Using a mouse model of sciatic nerve injury, the authors employed immunofluorescence analysis to observe the expression of LAMP2A, a critical marker for CMA. RNA sequencing was performed to observe the transcriptional profile of Lamp2a in Schwann cells. Bioinformatics analysis was carried out to observe the hub genes associated with Lamp2a . Expression of Lamp2a , a key gene in CMA, increased following sciatic nerve injury, based on an immunofluorescence assay. To identify differentially expressed genes using Lamp2a , RNA sequence analysis was conducted using rat Schwann cells overexpressing Lamp2a . The nine hub genes ( Snrpf, Polr1d, Snip1, Aqr, Polr2h, Ssbp1, Mterf3, Adcy6 , and Sbds ) were identified using the CytoHubba plugin of Cytoscape. Functional analysis revealed that Lamp2a overexpression affected the transcription levels of genes associated with mitotic spindle organization and mRNA splicing via the spliceosome. In addition, Polr1d and Snrpf1 were downregulated throughout postnatal development but elevated following sciatic nerve injury, according to a bioinformatics study. CMA may be an integral pathway in sciatic nerve injury via mRNA splicing., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We examined the mediating role of depression and anxiety on the relationship between fear of disease progression (FoP) and antiretroviral therapy (ART) adherence and the moderating role of social support in the FoP-depression/anxiety-ART adherence relationship in persons with HIV/AIDS (PWHA). 202 PWHA completed self-report measures. Simple mediation and moderated mediation analyses were performed. FoP was directly and negatively associated with ART adherence, and the mediating role of depression in this relationship was significant. Indirect effect of FoP mediated by anxiety on ART adherence was not significant. The moderating effect of social support was significant in the FoP-depression pathway, while the indirect effect of FoP on ART adherence mediated by depression was greatest at a higher level of social support and lower level of FoP. The results suggest the relevance of high FoP and depression-mediated FoP in ART adherence and social support may attenuate the negative impact of FoP., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Long-term (minimum 19-year) outcome data on clinical results and patient satisfaction after posterior-stabilized total knee arthroplasties (TKAs) are missing in the literature. The purpose of the study was to evaluate the clinical and radiographic results as well as patient satisfaction at a mean of 21.2 years after posterior-stabilized TKAs., Methods: This study included 756 patients (1,350 knees) who had undergone TKAs. There were 96 men and 660 women (mean age, 58 years; range, 40 to 84). The mean follow-up was 21.2 years (range, 19 to 23). At each follow-up visit, the patients were assessed radiographically and clinically. Furthermore, patient satisfaction was determined., Results: The Knee Society total, pain, function, and deformity scores were 42, 18, 33, and 5 points, respectively, at the final follow-up. The mean Western Ontario and McMaster Universities Arthritis Index score was 25 points at the final follow-up. With revision or aseptic loosening as the end point, the 23-year intimated survival for the implant was 96% (95% confidence interval, 91 to 100%). The overall patient satisfaction score at the final follow-up was 83.3 points (range, 81 to 86). Patient satisfaction scores with regard to pain, housework, recreation, and surgery were 84, 81, 82, and 86 points, respectively., Conclusions: The findings of the present, mean 21-year follow-up clinical study suggest excellent results with regard to the revision rates and survivorship of the posterior-stabilized total knee implants. However, consistent with the literature, we found that about 80% of patients expressed overall satisfaction with their primary TKAs. About 8% of patients were either somewhat or very dissatisfied with the procedure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The growing number of companion dogs has contributed to a rapidly growing market for pet products, including dog toys. However, little is known about the hazardous substances released from dog toys. This study aims to examine the potential presence of obesogens, a subset of endocrine-disrupting chemicals (EDCs) that are widely utilized as raw materials in the manufacture of dog toy components, and their effects on dog health. To achieve this, we adapted and employed a migration method typically used for children's products to simulate obesogen exposure in dogs through sucking or chewing toys. We demonstrated that out of various obesogens, bisphenol A (BPA) was released from dog toys into synthetic saliva, whereas phthalates and azo dyes were not detected in any of the leachates. Additionally, we found that BPA induced adipogenic differentiation in canine adipose-derived stem cells (cADSCs). Our RNA sequencing experiments revealed that BPA alters the adipogenesis-related gene signature in cADSCs by elevating the expression levels of ADIPOQ, PLIN1, PCK1, CIDEC, and FABP4. The associated transcriptional changes are involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which may contribute to the promotion of adipogenesis by BPA. Our findings suggest that companion dogs are at risk of BPA exposure, which may contribute to obesity in dogs. Therefore, the implementation of precautionary measures is crucial., 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 © 2024. Published by Elsevier Ltd.)

Cetylpyridinium chloride (CPC) is a quaternary ammonium compound used widely in health and personal care products. Meanwhile, due to its increasing use, its potential adverse health effects are emerging as a topic of public concern. In this study, we first administered CPC by pharyngeal aspiration to determine the survival level (the maximum concentration at which no death is observed) and then administered CPC to mice repeatedly for 28 days using the survival level as the highest concentration. CPC increased the total number of pulmonary cells secreting pro- and anti-inflammatory cytokines and chemokines. Infiltration of inflammatory cells, production of foamy alveolar macrophages, and chronic inflammatory lesions were found in the lung tissue of male and female mice exposed to the highest dose of CPC. We also investigated the toxicity mechanism using BEAS-2B cells isolated from normal human bronchial epithelium. At 6 h after exposure to CPC, the cells underwent non-apoptotic cell death, especially at concentrations greater than 2 μg/mL. The expression of the transferrin receptor was remarkably enhanced, and the expression of proteins that contribute to intracellular iron storage was inhibited. The expression of both mitochondrial SOD and catalase increased with CPC concentration, and PARP protein was cleaved, suggesting possible DNA damage. In addition, the internal structure of mitochondria was disrupted, and fusion between damaged organelles was observed in the cytoplasm. Most importantly, lamellar body-like structures and autophagosome-like vacuoles were found in CPC-treated cells, with enhanced expression of ABCA3 protein, a marker for lamellar body, and a docking score between ABCA3 protein and CPC was considered to be approximately -6.8969 kcal/mol. From these results, we propose that mitochondrial damage and iron depletion may contribute to CPC-induced non-apoptotic cell death and that pulmonary accumulation of cell debris may be closely associated with the inflammatory response. Furthermore, we hypothesize that the formation of lamellar body-like structures may be a trigger for CPC-induced cell death., 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 © 2024 Elsevier B.V. All rights reserved.)