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Several P 1B -type ATPases are important Cd 2+ /Cu 2+ pumps in Aspergillus species, and they are tightly associated with the heavy metal stress tolerance of these ascomycetous fungi. To better understand the roles of the two P 1B -type ATPases, Aspergillus nidulans CrpA Cd 2+ /Cu 2+ pump (orthologue of the Candida albicans Crp1 Cd 2+ /Cu 2+ pump) and Aspergillus fumigatus PcaA Cd 2+ pump (orthologue of the Saccharomyces cerevisiae Pca1 Cd 2+ pump), we have generated individual mutants and characterized their heavy metal susceptibilities. The deletion of CrpA in A. nidulans has led to the increased sensitivity of the fungus to stresses induced by Zn 2+ , Fe 2+ , or the combination of oxidative-stress-inducing menadione sodium bisulfite and Fe 3+ . Heterologous expression of A. fumigatus PcaA in the S. cerevisiae pca1 deletion mutant has resulted in enhanced tolerance of the yeast to stresses elicited by Cd 2+ or Zn 2+ but not by Fe 2+ /Fe 3+ or Cu 2+ . Mammalian host immune defense can attack microbes by secreting Zn 2+ or Cu 2+ , and the oxidative stress induced by host immune systems can also disturb metal (Cu 2+ , Fe 2+ , and Zn 2+ ) homeostasis in microbes. In summary, PcaA and CrpA can protect fungal cells from these complex stresses that contribute to the virulence of the pathogenic Aspergillus species. Moreover, due to their presence on the fungal cell surface, these P 1B -type ATPases may serve as a novel drug target in the future. IMPORTANCE Mammalian host immune defense disrupts heavy metal homeostasis of fungal pathogens. P1B-type ATPase of Aspergillus fumigatus and Aspergillus nidulans may help to cope with this stress and serve as virulence traits. In our experiments, both A. nidulans Cd2+/Cu2+ pump CrpA and A. fumigatus Cd2+ pump PcaA protected fungal cells from toxic Zn2+, and CrpA also decreased Fe2+ susceptibility most likely indirectly. In addition, CrpA protected cells against the combined stress induced by the oxidative stressor menadione and Fe3+. Since P1B-type ATPases are present on the fungal cell surface, these proteins may serve as a novel drug target in the future.

Background/aim: Immunotherapy has been considered a promising approach for brain tumor treatment since the discovery of the brain lymphatic system. Glioblastoma (GBM), the most aggressive type of brain tumor, is associated with poor prognosis and a lack of effective treatment options., Materials and Methods: To test the efficacy of human anti-PD-1, we used a humanized PD-1 knock-in mouse to establish an orthotopic GBM-bearing model., Results: Nivolumab, a human anti-PD-1, effectively inhibited tumor growth, increased the survival rate of mice, enhanced the accumulation and function of cytotoxic T cells, reduced the accumulation and function of immunosuppressive cells and their related factors, and did not induce tissue damage or biochemical changes. The treatment also induced the accumulation and activation of CD8 + cytotoxic T cells, while reducing the accumulation and activation of myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages in the immune microenvironment., Conclusion: Nivolumab has the potential to be a treatment for GBM., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Impactful translational research requires new approaches to computational analysis and bioethics, both of which have been advanced by adoption of community-engagement strategies. Community knowledge and experience will hone data collection, research, and insights and accelerate the impact of derived translational applications to improve individual health, medical decision-making, and public health policy. In the context of translational research with big health data, meaningful community-researcher engagement will require developing and deploying coengagement tools across the research life cycle and developing approaches for novel coproduction., (© 2023 by The Hastings Center. All rights reserved.)

Hepatocellular carcinoma (HCC) has a very poor prognosis with a 5-year survival rate of < 20%; hence, early diagnosis is crucial. Despite regular checkups for high-risk groups of HCC, there are a few cases in which it is discovered as a late-stage HCC. Therefore, this study aimed to investigate the characteristics of patients with delayed HCC detection during regular surveillance. Between January 2010 and December 2020, we analyzed patients with newly diagnosed HCCs who underwent HCC surveillance by ultrasound or computed tomography scan at least twice and were followed up for more than 1 year for hepatitis B, hepatitis C, and chronic liver disease. The mean age of 223 HCC patients was 70 years, of which 152 were male, accounting for 68.1%. Among them, 196 patients (87%) were diagnosed with Barcelona clinic liver cancer stage 0 or A, while 27 (13%) were diagnosed with Barcelona clinic liver cancer stages B and C. When classified according to the TNM criteria, 154 patients (69%) were in stage I, and 69 (31%) were in stage II or higher. Multivariate analysis was performed to identify the risk factors for patients diagnosed with late-stage HCC. The Child-Turcotte-Pugh (CTP) score was identified as a highly significant factor (P = .002, HR 1.547, 95% CI 1.177-2.032), whereas the presence of cirrhosis, body mass index, and sex had no significant effect. We found that in patients with chronic liver disease who were screened regularly, those with higher CTP scores were more likely to be diagnosed with HCC in the late-stages. Therefore, although the presence of cirrhosis is also important for HCC surveillance, careful attention is needed in patients with high CTP scores., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Solid-state batteries (SSBs) have emerged as a promising alternative to conventional liquid electrolyte batteries due to their potential for higher energy density and improved safety. However, achieving high performance in SSBs is difficult because of inadequate contact and interfacial reactions that generate high interfacial resistance, as well as inadequate solid-solid contact between electrodes. These chronic issues are associated with inhomogeneous ion and electron transport networks owing to imperfect solid-solid interfacial contact. This study developed an optimal interfacial engineering strategy to facilitate an ion-electron transport network by designing an active material (NCM622) uniformly filled with a thin layer of a solid electrolyte (garnet-type Li 6.25 Ga 0.25 La 3 Zr 2 O 12 ) and conductive additives. The optimal composite electrode architecture enhanced the high capacity, high rate capability, and long-term cycle stability, even at room temperature, owing to the percolating network for facile ionic conduction that assured a homogeneous reaction. In addition to mitigating the mechanical degradation of the cathode electrode, it also reduced the crosstalk effects on the anode-solid electrolyte interface. Effectively optimizing the selection and use of conductive additives in composite electrodes offers a promising approach to addressing key performance-limiting factors in SSBs, including interfacial resistance and solid-solid contact issues. This study underscores the critical importance of cathode architecture design for achieving high-performance SSBs by ensuring that the interfaces are intact with solid electrolytes at both the cathode and anode interfaces while promoting uniform reactions. This study provides valuable insights into the development of SSBs with improved performance, which could have significant implications for a wide range of applications.

Background and Purpose: Tumor recurrence after liver transplantation (LT) impedes the curative chance for hepatocellular carcinoma (HCC) patients. This study aimed to develop a deep pathomics score (DPS) for predicting tumor recurrence after liver transplantation using deep learning., Patients and Methods: Two datasets of 380 HCC patients who underwent LT were enrolled. Residual convolutional neural networks were used to identify six histological structures of HCC. The individual risk score of each structure and DPS were derived by a modified DeepSurv network. Cox regression analysis and Concordance index were used to evaluate the prognostic significance. The cellular exploration of prognostic immune biomarkers was performed by quantitative and spatial proximity analysis according to three panels of 7-color immunofluorescence., Results: The overall classification accuracy of HCC tissue was 97%. At the structural level, immune cells were the most significant tissue category for predicting post-LT recurrence (HR 1.907, 95% CI 1.490-2.440). The C-indices of DPS achieved 0.827 and 0.794 in the training and validation cohorts, respectively. Multivariate analysis for recurrence-free survival (RFS) showed that DPS (HR 4.795, 95% CI 3.017-7.619) was an independent risk factor. Patients in the high-risk subgroup had a shorter RFS, larger tumor diameter and a lower proportion of clear tumor borders. At the cellular level, a higher infiltration of intratumoral NK cells was negatively correlated with recurrence risk., Conclusions: This study established an effective DPS. Immune cells were the most significant histological structure related to HCC recurrence. DPS performed well in post-LT recurrence prediction and the identification of clinicopathological features., (© 2023. The Author(s).)

The uniaxial warm tensile experiments were carried out in deformation temperatures (50-250 °C) and strain rates (0.005 to 0.0167 s-1) to investigate the material workability and to predict flow stress of AZ31B magnesium alloy. The back-propagation artificial neural network (BP-ANN) model, a hybrid models with a genetic algorithm (GABP-ANN), and a constrained nonlinear function (CFBP-ANN) were investigated. In order to train the exploited machine learning models, the process parameters such as strain, strain rate, and temperature were accounted as inputs and flow stress was considered as output; moreover, the experimental flow stress values were also normalized to constructively run the neural networks and to achieve better generalization and stabilization in the trained network. Additionally, the proposed model's closeness and validness were quantified by coefficient of determination (R2), relative mean square error (RMSE), and average absolute relative error (AARE) metrics. The computed statistical outcomes disclose that the flow stress predicted by both GABP-ANN and CFBP-ANN models exhibited better closeness with the experimental data. Moreover, compared with the GABP-ANN model outcomes, the CFBP-ANN model has a relatively higher predictability. Thus, the outcomes confirm that the proposed CFBP-ANN model can result in the accurate description of AZ31 magnesium alloy deformation behavior, showing potential for the purpose of practicing finite element analysis.

Constitutive equations were recognized for AZ31B magnesium alloy at higher temperatures and strain rates from conventional empirical models like the original Johnson-Cook (JC), modified JC, and modified Zerilli-Armstrong (ZA) models for capturing the material warm deformation behavior. Uniaxial warm tensile tests were performed at temperatures (50 to 250 °C) and strain rates (0.005 to 0.0167 s-1) to probe AZ31 magnesium alloy flow stress values. Depending on the calculated flow stress, constitutive equations were recognized, and these established models were assessed by the coefficient of determination (R2), relative mean square error (RMSE), and average absolute relative error (AARE) metrics. The results demonstrated that the flow stress calculated by the modified JC and ZA models revealed good agreement against the test data. Thus, the outcomes confirmed that the recognized modified JC and modified ZA models could effectively forecast AZ31 magnesium alloy flow behavior by capturing the material deformation behavior accurately.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema., Competing Interests: Ana Bosch: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Lilly, Roche, Novartis; Support for attending meetings and/or travel from Roche; Participation on a Data Safety Monitoring Board or Advisory; Giuseppe Curigliano: Consulting fees from BMS, Roche, Pfizer, Novartis, Lilly, Astra Zeneca, Daichii Sankyo, Merck, Seagen, Ellipsis, Gilead; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Lilly, Pfizer, Relay; Support for attending meetings and/or travel from Daichii Sankyo; Jana De Boniface: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca; Carsten Denkert: Grants from Myriad, Roche, BMBF, European Commission, GBG Foundation; consulting fees from MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Roche, Lilly; Peter Dubsky: Honoraria for presentations and Advisory from Roche and Astra Zeneca to Hirslanden Klinik St. Anna; Michael Knauer: Grants or contracts Agendia BV; Consulting fees from Myriad, Exact Sciences; Thorsten Kühn: Consulting fees from Merit Medical, Endomag, Hologic, Sirius Medical; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GILEAD, MSD, Pfizer, Exact Sciences; Support for attending meetings and/or travel from Gilead, MSD; Sibylle Loibl: Grants or contracts from Abbvie, AZ, BMS/Celgene, DAichi Synkyo, Gilead, Molecular Health, Novartis, Pfizer, Roche; Royalties or licenses for Ki 67 Analyser, VM SCOPE; Consulting fees from AZ, Amgen, Abbvie, BMS, Celgene, Daichi Sankyo Eirgenix, Gilead, Lilly, Merck, MSD, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeutics, Incyte, Roche, Sanofi, Seagen; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AZ, Gilead, Roche, Seagen, MSD, Pierre Fabre, MEDSCAPE; Patents planned, issued or pending EP14153692.0; EP21152186.9; EP15702464.7; EP15702464.7; Participation on a Data; Safety Monitoring Board or Advisory Board from Daichi Sankyo; Receipt of equipment, materials, drugs, medical writing, gifts or other services Daichiy Sankyo, Gilead, Novartis, AstraZeneca, Roche, Seagen; Icro Meattini: Consulting fees from Novartis, Pfizer, Eli Lilly, Seagen, Gilead; Katja Pinker: Consulting fees from Genentech, Inc., Merantix Healthcare, AURA Health Technologies GmbH; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: European Society of Breast Imaging (active), Bayer (active), Siemens Healthineers (ended), DKD 2019 (ended), Olea Medical (ended), Roche (ended); Trine Tramm: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Roche; Support for attending meetings and/or travel from Roche and Novartis; Jong Han Yu: Consulting fees from Gencurix; Walter Paul Weber: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MSD; all other others have no conflicts of interest to declare., (© 2023 The Author(s).)

An exploration for 11β-HSD1 inhibitors from the whole plant of Euphorbia sikkimensis led to the identification of 10 undescribed triterpenoids 1-10, as well as 7 known triterpenoids (11-17). Their structures were determined by a combination of spectrum elucidations, conformational analyses and quantum chemical calculations. (23E)-25-methoxy-eupha-14,23-diene-3β,7α-diol (1) and (23E)-3β-dihydroxy-27-noreupha-7,23-diene-25-one (2) are two rare cases that feature a rearrangement of Me-30 (14 → 8) and a degradation of Me-27, respectively, in the euphane-type triterpenoid family. It is an interesting phenomenon that (23E)-3β-hydroxy-25-methoxy-eupha-8,23-diene-7-one (4) and (23E)-3β-hydroxy-25-methoxy-lanost-8,23-diene-7-one (5) coexist in the same plant, sharing the same planar structure but belonging to different structural types of triterpenoids. Compounds 3-5 and 14 show significant inhibitory activity against 11β-HSD1 with IC 50 values of 6.50 ± 0.22, 1.31 ± 0.34, 9.38 ± 0.64, and 8.27 ± 0.33 μM, respectively. The structure-activity relationship study shows that the euphane-type triterpenoids exhibit the best inhibitory activity, which is in accord with the fact of the euphane-type triterpenoids having the best ability to bind to the active pocket of 11β-HSD1 in the molecular docking experiments., 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 © 2023 Elsevier Ltd. All rights reserved.)

Rationale: Angiosarcoma is a mesenchymal soft tissue sarcoma with a tendency for vascular endothelial differentiation. It is highly malignant with a poor prognosis but has a low incidence. Epithelioid angiosarcoma of the gastrointestinal tract is rare, and simultaneous multiple lesions of the stomach and small intestine are even rarer. It is easy to be misdiagnosed clinically. We report on a case of preoperative misdiagnosis of gastric cancer and postoperative diagnosis of epithelioid angiosarcoma with multiple lymph node metastases., Patient Concerns: A 75-year-old patient who was admitted to the hospital because of fatigue, melena and dysuria for >1 month., Diagnosis, Interventions and Outcomes: Gastroscopy revealed gastric fundus ulcer and the biopsy revealed poorly differentiated adenocarcinoma of the fundus. We performed a radical gastrectomy for gastric cancer during which multiple ulcers were found in the jejunum and resected. Postoperative pathology showed multiple epithelioid angiosarcoma in the stomach and small intestine with lymph node metastases. The patient did not receive further treatment and died 2 month after the surgery., Lessons: Gastrointestinal epithelioid angiosarcoma is one of the differential diagnoses of gastrointestinal adenocarcinoma and surgery is the main treatment. The lymph nodes are one of the main sites of metastasis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in treating solid tumors, there are still challenges that need to be addressed. To overcome these limitations, other immune cells, such as natural killer (NK) cells and macrophages (M), have been developed as attractive options for efficient cancer immunotherapy of solid tumors. CAR-NK cells exhibit substantial clinical improvements with "off-the-shelf" availability and low toxicity. CAR-M cells have promising therapeutic potential because macrophages can infiltrate the TME of solid tumors. Here, we review the recent advances and future perspectives associated with engineered immune cell-based cancer immunotherapies for solid tumors. We also summarize ongoing clinical trials investigating the safety and efficacy of engineered immune cells, such as CAR-T, CAR-NK, and CAR-M, for targeting solid tumors.

The genus Aspergillus , one of the most abundant airborne fungi, is classified into hundreds of species that affect humans, animals, and plants. Among these, Aspergillus nidulans , as a key model organism, has been extensively studied to understand the mechanisms governing growth and development, physiology, and gene regulation in fungi. A. nidulans primarily reproduces by forming millions of asexual spores known as conidia. The asexual life cycle of A. nidulans can be simply divided into growth and asexual development (conidiation). After a certain period of vegetative growth, some vegetative cells (hyphae) develop into specialized asexual structures called conidiophores. Each A. nidulans conidiophore is composed of a foot cell, stalk, vesicle, metulae, phialides, and 12,000 conidia. This vegetative-to-developmental transition requires the activity of various regulators including FLB proteins, BrlA, and AbaA. Asymmetric repetitive mitotic cell division of phialides results in the formation of immature conidia. Subsequent conidial maturation requires multiple regulators such as WetA, VosA, and VelB. Matured conidia maintain cellular integrity and long-term viability against various stresses and desiccation. Under appropriate conditions, the resting conidia germinate and form new colonies, and this process is governed by a myriad of regulators, such as CreA and SocA. To date, a plethora of regulators for each asexual developmental stage have been identified and investigated. This review summarizes our current understanding of the regulators of conidial formation, maturation, dormancy, and germination in A. nidulans .

Ligand shells of gold nanoclusters play important roles in regulating their molecular and electronic structures. However, the similar but distinct impacts of the homologous analogues of the protecting ligands remain elusive. The C 2v symmetric monoarsine-protected cluster [Au 13 (AsPh 3 ) 8 Cl 4 ] + (Au 13 As 8 ) was facilely prepared by direct reduction of (Ph 3 As)AuCl with NaBH 4 . This cluster is isostructural with its previously reported stibine analogue [Au 13 (SbPh 3 ) 8 Cl 4 ] + (Au 13 Sb 8 ), enabling a comparative study between them. Au 13 As 8 exhibits a blue-shifted electronic absorption band, and this is probably related to the stronger π-back donation interactions between the Au 13 core and AsPh 3 ligands, which destabilize its superatomic 1P and 1D orbitals. In comparison to the thermodynamically less stable Au 13 Sb 8 , Au 13 As 8 achieves a better trade-off between catalytic stability and activity, as demonstrated by its excellent catalytic performance towards the aldehyde-alkyne-amine (A 3 ) coupling reaction. Moreover, the ligand exchange reactions between Au 13 As 8 with phosphines, as exemplified by PPh 3 and Ph 2 P(CH 2 ) 2 PPh 2 , suggest that Au 13 As 8 may be a good precursor cluster for further cluster preparation through the "cluster-to-cluster" route., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Importance: Work-related musculoskeletal disorders are common among otolaryngologists and can be associated with decreased productivity, missed workdays, and reduced quality of life. Ergonomic risk for surgeons is elevated during common otolaryngology procedures; current ergonomic interventions lack the ability to provide real-time feedback. The ability to quantify and mitigate ergonomic risk during surgery may reduce work-related musculoskeletal disorders., Objective: To quantify the association of vibrotactile biofeedback with intraoperative ergonomic risk to surgeons during tonsillectomy., Design, Setting, and Participants: This cross-sectional study was conducted between June 2021 and October 2021 at a freestanding tertiary care children's hospital and included 11 attending pediatric otolaryngologists. Data analysis was conducted from August to October 2021., Interventions: Real-time quantification of ergonomic risk during tonsillectomy and the use of a vibrotactile biofeedback posture monitor., Main Outcomes and Measures: Association of vibrotactile biofeedback with objective measures of ergonomic risk. Assessment tools included the Rapid Upper Limb Assessment, craniovertebral angle, and time spent in an at-risk posture., Results: Eleven surgeons (mean [SD] age 42 [7] years; 2 women [18%]) performed 126 procedures with continuous posture monitoring in the presence (80 [63%]) and absence (46 [37%]) of vibrotactile biofeedback. No complications or delays associated with the device were reported. Intraoperative vibrotactile biofeedback was associated with improved Rapid Upper Limit Assessment neck, trunk, and leg scores by 0.15 (95% CI, 0.05-0.25), improved craniovertebral angle by 1.9 (95% CI, 0.32-3.40), and decreased overall time spent in an at-risk posture by 30% (95% CI, 22%-39%)., Conclusions and Relevance: The results of this cross-sectional study suggest that use of a vibrotactile biofeedback device to quantify and mitigate ergonomic risk for surgeons is feasible and safe while performing surgery. Vibrotactile biofeedback was associated with reduced ergonomic risk during tonsillectomy and may have a role in improving surgical ergonomics and preventing work-related musculoskeletal disorders.

Background & Aims: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment., Methods: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR., Results: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice., Conclusions: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The effects of alumina particle size and jet pressure on the bond strength of polyetheretherketone (PEEK) were examined to determine the airborne particle abrasion parameters with minimal effects on PEEK and to achieve optimal bond strength, as a reference for future clinical use. An alumina particle with four particle sizes and three jet pressures was used to air-abrade PEEK. Surface roughness ( R a ), morphology, chemical structure, and wettability were analyzed using a stylus profilometer, scanning electron microscope, X-ray diffractometer, and contact angle analyzer, respectively. The shear bond strength (SBS) of PEEK and dental resin cement was analyzed using a universal testing machine ( n = 10). The failure modes and debonded fracture surfaces were observed using optical microscopy. Airborne particle abrasion increased the R a and hydrophobicity of PEEK and deposited alumina residues. The SBS generally decreased after thermal cycling. A large particle size damaged the PEEK surface. The effects of different particle sizes and jet pressures on the SBS were only significant in certain groups. Adhesive failure was the main mode for all groups. Within the limitations of this study, 110 μm grain-sized alumina particles combined with a jet pressure of 2 bar prevented damage to PEEK, providing sufficient SBS and bonding durability between PEEK and dental resin cement.

Background and Aims: RAS protein activator like 2 (RASAL2) is a newly discovered metabolic regulator involved in energy homeostasis and adipogenesis. However, whether RASAL2 is involved in hepatic lipid metabolism remains undetermined. This study explored the function of RASAL2 and elucidated its potential mechanisms in nonalcoholic fatty liver disease (NAFLD)., Methods: NAFLD models were established either by feeding mice a high-fat diet or by incubation of hepatocytes with 1 mM free fatty acids (oleic acid:palmitic acid=2:1). Pathological changes were observed by hematoxylin and eosin staining. Lipid accumulation was assessed by Oil Red O staining, BODIPY493/503 staining, and triglyceride quantification. The in vivo secretion rate of very low-density lipoprotein was determined by intravenous injection of tyloxapol. Gene regulation was analyzed by chromatin immunoprecipitation assays and hydroxymethylated DNA immunoprecipitation combined with real-time polymerase chain reaction., Results: RASAL2 deficiency ameliorated hepatic steatosis both in vivo and in vitro . Mechanistically, RASAL2 deficiency upregulated hepatic TET1 expression by activating the AKT signaling pathway and thereby promoted MTTP expression by DNA hydroxymethylation, leading to increased production and secretion of very low-density lipoprotein, which is the major carrier of triglycerides exported from the liver to distal tissues., Conclusions: Our study reports the first evidence that RASAL2 deficiency ameliorates hepatic steatosis by regulating lipid metabolism through the AKT/TET1/MTTP axis. These findings will help understand the pathogenesis of NAFLD and highlight the potency of RASAL2 as a new molecular target for NAFLD., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Herein, the in situ N -alkylation between tripyridine molecules and C 2 H 5 OH was employed to obtain four iodometallates (M n + = Pb 2+ , Cu + and Ag + ). Among them, the alkylation degree of the tripyridine molecules is different, and the in situ -generated tripyridine derivatives showed different configurations. This is not only related to the structure of the inorganic anions but also related to the tripyridine molecule itself. The two moieties were actually templates for each other. The Pb 2+ compound 1 was found to effectively catalyze the degradation of Rhodamine B (RhB), with its degradation efficiency reaching 94% in 70 min. In contrast, the degradation efficiency for the Cu + and Ag + compounds 2-4 did not exceed 50%. The free radical trapping test indicated that with the Pb 2+ compound as the photocatalyst, both superoxide ion radicals (˙O 2 - ) and holes (h + ) played a key role. Alternatively, with compound 3 or 4 as the photocatalyst, only ˙O 2 - played a role. The differences should be related to the band gap of the materials, where the Pb 2+ compound has a slightly wider band gap, leading to a higher exciton separation efficiency. Due to the involvement of more free radicals, the usual intermediates did not appear in the catalytic process of 1, while the colored species appeared in the catalytic process of 3 and 4. The cyclic test verified that compound 1 still had high catalytic activity after recycling five times. Also, we investigated the catalytic capacity of 1 for the degradation of 5-times the quantity of RhB. The degradation rate reached 99% in 5.5 hours, indicating that 1 has a good photocatalytic performance for degrading a high concentration of RhB. However, given that the amount of catalyst and dye used in each study was different, it was difficult to compare the results. Thus, herein, we introduced for the first time the method of calculating the TOF value to better evaluate the photodegradation performance of each hybrid material.

Background: Preeclampsia (PE) is known to arise from insufficient trophoblast invasion as uterine spiral arteries lack remodeling. A significant reduction in placental perfusion induces an ischemic placental microenvironment due to reduced oxygen delivery to the placenta and fetus, leading to oxidative stress. Mitochondria are involved in the regulation of cellular metabolism and the production of reactive oxygen species (ROS). NME/NM23 nuceloside diphosphate kinase 4 ( NME4 ) gene is known to have the ability to supply nucleotide triphosphate and deoxynucleotide triphosphate for replication and transcription of mitochondria. Our study aimed to investigate changes in NME4 expression in PE using trophoblast stem-like cells (TSLCs) from induced pluripotent stem cells (iPSCs) as a model of early pregnancy and peripheral blood mononuclear cells (PBMNCs) as a model of late preterm pregnancy., Methods: Transcriptome analysis using TSLCs was performed to identify the candidate gene associated with the possible pathophysiology of PE. Then, the expression of NME4 associated with mitochondrial function, p53 associated with cell death, and thioredoxin (TRX) linked to ROS were investigated through qRT-PCR, western blotting and deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay., Results: In patients with PE, NME4 was significantly downregulated in TSLCs but upregulated in PBMNCs. p53 was shown to be upregulated in TSLCs and PBMNCs of PE. In addition, western blot analysis confirmed that TRX expression had the tendency to increase in TSLCs of PE. Similarly, TUNEL analysis confirmed that the dead cells were higher in PE than in normal pregnancy., Conclusion: Our study showed that the expression of the NME4 differed between models of early and late preterm pregnancy of PE, and suggests that this expression pattern may be a potential biomarker for early diagnosis of PE., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

The prevalence of dry eye in children is increasing with changes in the environment and the widespread use of electronic products. However, due to poor ability to express themselves and hidden symptoms of children, lack of understanding of dry eye in children, children with dry eye are likely to be misdiagnosed. Dry eye can seriously affect the quality of children's learning, life, vision and visual development. Therefore, it is urgent to raise awareness of clinical workers about dry eye in children, prevent the occurrence of related complications of dry eye, and avoid permanent visual damage to children. This review discusses and summarizes the epidemiology and common risk factors of children with dry eye, with the aim of improving doctors' understanding of dry eye in children.

Background: Chinese American family caregivers of persons with dementia experience high rates of psychosocial distress and adverse health outcomes. Due to their immigrant and minority status, they face substantial obstacles to care and support, including stigma and misperception of dementia, limited knowledge and use of welfare and services, and poor social support. Few interventions have been developed or tested for this vulnerable population., Objective: This study aims to pilot-test the Wellness Enhancement for Caregivers (WECARE) intervention, a culturally tailored program delivered via WeChat, a social media app highly popular in the Chinese population. The 7-week WECARE was designed specifically for Chinese American dementia caregivers to improve their caregiving skills, reduce stress, and enhance psychosocial well-being. Feasibility, acceptability, and preliminary efficacy of the WECARE were assessed in this pilot., Methods: A total of 24 Chinese American family caregivers of persons with dementia were recruited for a pre-post 1-arm trial of the WECARE. By subscribing to the WECARE official account, participants received interactive multimedia programs on their WeChat account multiple times a week for 7 weeks. A backend database automatically delivered program components and tracked user activities. Three online group meetings were organized to facilitate social networking. Participants completed a baseline and a follow-up survey. Feasibility was assessed by the follow-up rate and curriculum completion rate; acceptability was assessed by user satisfaction and perceived usefulness of the program; and efficacy was assessed with pre-post differences in 2 primary outcomes of depressive symptoms and caregiving burden., Results: The intervention was completed by 23 participants with a retention rate of 96%. Most of them (n=20, 83%) were older than 50 years and the majority (n=17, 71%) were female. The backend database revealed that the mean curriculum completion rate was 67%. Participants also reported high rates of user satisfaction and perceived usefulness of the intervention and high ratings of weekly programs. The intervention led to significant improvement in participants' psychosocial health outcomes; their depressive symptoms reduced from 5.74 to 3.35 with an effect size of -0.89 and caregiving burden decreased from 25.78 to 21.96 with an effect size of -0.48., Conclusions: This pilot study suggests that WeChat-based WECARE intervention was feasible and acceptable; it also demonstrated initial efficacy in improving psychosocial well-being in Chinese American dementia caregivers. Further research with a control group is needed to assess its efficacy and effectiveness. The study highlights the need for more culturally appropriate mobile health interventions for Chinese American family caregivers of persons with dementia., (©Y Alicia Hong, Kang Shen, Hae-Ra Han, Van Ta Park, Pramita Bagchi, Huixing Kate Lu, Hsiaoyin Chen, Judy Huei-yu Wang. Originally published in JMIR Aging (https://aging.jmir.org), 05.04.2023.)

Aim: To investigate the longitudinal changes in brain volume and cognitive function associated with diabetes at midlife, and to examine whether long-term hyperglycaemia, insulin resistance or secretory function is associated with brain atrophy and cognitive decline., Materials and Methods: We used data from 2377 participants with both baseline and 4-year follow-up brain magnetic resonance images and neuropsychological measures from the Ansan cohort of the Korean Genome Epidemiology Study. Time-weighted mean glycaemic values were calculated using all measurements over an average duration of 10.6 years from cohort initiation to baseline visits., Results: Type 2 diabetes was associated with greater white matter volume reduction (adjusted volume difference = -1.96 ml, 95% CI: -3.73, -0.18) and executive function decline (adjusted Z score difference = -0.14, 95% CI: -0.23, -0.05) during the follow-up period of 4.2 years. Decline of verbal and visual memory or verbal fluency was not associated with diabetes. Greater executive function decline was associated with higher time-weighted mean HbA1c level over the preceding 10.6 years (P < .001), but not with insulin resistance markers in the diabetes group. Participants with diabetes, whose time-weighted average HbA1c level was maintained above 6.5% over the previous decade, showed greater decline in executive function and global cognition than the normal glucose group., Conclusions: Long-term hyperglycaemia was a major independent factor associated with rapid cognitive decline in middle-aged adults with diabetes. Maintaining ideal glucose levels in diabetes at midlife might prevent later rapid cognitive decline., (© 2022 John Wiley & Sons Ltd.)

Objective: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model., Methods: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model., Results: On the 10th day after inoculation, hCD45 + leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3 + leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks., Conclusion: Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Purpose: Cancer antigen 15-3 (CA15-3) is a serum tumor marker for breast cancer (BC) extensively used in clinical practice. CA15-3 is non-invasive, easily available, and a cost-effective tumor marker for immediate diagnosis, monitoring and prediction of BC recurrence. We hypothesized that an elevation of CA15-3 may have prognostic impact in patients with early BC with normal serum CA15-3 level., Methods: This was a retrospective cohort study, which included patients with BC who received curative surgery at a comprehensive single institution between 2000 and 2016. CA15-3 levels from 0 to 30 U/mL were considered normal, and patients who had CA15-3 > 30 U/mL, were excluded from the study., Results: The mean age of study participants (n = 11,452) was 49.3 years. The proportion of participants with elevated CA15-3 ≥ 1 standard deviation (SD) compared with the previous examination during follow-up was 23.3% (n = 2,666). During the follow-up (median follow-up 5.8 years), 790 patients experienced recurrence. The fully-adjusted hazard ratio (HR) for recurrence comparing participants with stable CA15-3 level to subjects with elevated CA15-3 level was 1.76 (95% confidence interval [CI], 1.52-2.03). In addition, if the CA15-3 was elevated ≥ 1 SD, the risk was much higher (HR, 6.87; 95% CI, 5.81-8.11) than in patients without elevated CA15-3 ≥ 1 SD. In sensitivity analysis, the recurrence risk was consistently higher in participants with elevated CA15-3 levels than in participants without elevated CA15-3 levels. The association between elevated CA15-3 levels and incidence of recurrence was observed in all subtypes and the association was stronger in patients with N+ than in patients with N0 stage ( p -value for interaction < 0.01)., Conclusion: The results of the present study demonstrated that elevation of CA15-3 in patients with early BC and initial normal serum CA15-3 levels has a prognostic impact., Competing Interests: The authors declared that have no competing interests., (© 2023 Korean Breast Cancer Society.)

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began spreading rapidly in the community in November 2021, becoming the dominant variant in the Republic of Korea in 2022. Although its pathogenesis in healthy individuals was low, the severity and hospitalization rate was higher in the elderly and immunocompromised patients. We aimed to investigate the immunogenicity in acute and convalescent phases of breakthrough infection by Omicron in elderly individuals. Serological data were assessed by electrochemiluminescence immunoassay, enzyme-linked immunosorbent assay, and plaque-reduction neutralization tests. SARS-CoV-2-specific antibody and immunoglobulin G levels in the acute phase were higher in third dose-vaccinated elderly than in first and second dose-vaccinated patients. The neutralization antibody titer was detected only in third dose-vaccinated patients, and the titer was higher for the Delta than the Omicron variant. In the convalescent phase of Omicron infection, the neutralization antibody titer of vaccinated patients was higher for the Delta than the Omicron variant except in unvaccinated individuals. We demonstrated that the cause of the vulnerability to Omicron variant infection in third dose-vaccinated elderly was due to the low neutralization antibody level against Omicron. A fourth dose of vaccination is required in the elderly to reduce hospitalization and mortality caused by the Omicron variant.

Background and Aims: This study aimed to compare the long-term cumulative recurrence rates of hepatocellular carcinoma (HCC) and prognosis after curative resection for HCC in noncirrhotic patients with nonalcoholic fatty liver disease (NAFLD) versus hepatitis B virus (HBV) infection., Methods: We retrospectively analyzed the data of 791 patients without recurrence within 1 year after curative resection for HCC from January 2005 to December 2015. Of these, 63 and 728 were NAFLD and HBV patients without cirrhosis, respectively., Results: Recurrence of HCC was observed in 6 (9.5%) and 210 (28.8%) patients in the NAFLD and HBV groups, respectively, during median follow-ups of 69.9 and 85.2 months. Cumulative recurrence rates in the NAFLD group at 2, 4, 6, 8 and 10 years (3.6, 9.4, 12.4, 12.4 and 12.4%, respectively) were significantly lower than in the HBV group (1.7, 16.9, 27.2, 37.1 and 44.4%, respectively) ( P  = 0.008). Cumulative overall survival (OS) rates in the NAFLD group at 2, 4, 6, 8 and 10 years (98.2, 96.0, 84.0, 84.0 and 84.0 %, respectively) were significantly lower than in the HBV group (99.3, 98.4, 97.3, 95.7 and 93.6%, respectively) ( P  = 0.003). HBV infection, with or without fatty liver compared to NAFLD, were significant predictors for the recurrence of HCC ( P  < 0.05 for all) and OS ( P  < 0.05 for all), respectively., Conclusions: Noncirrhotic NAFLD patients showed lower recurrence rates of HCC but poorer survival outcomes than noncirrhotic HBV patients with or without fatty liver. The recurrence risk of HCC remains even in noncirrhotic NAFLD patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Evaluation of prostate cancer (PCa) when serum prostate-specific antigen (PSA) level is vaguely elevated is complicated. This is because serum PSA levels only reflect the number of prostate epithelial cells. We aimed to compare PSA and various prostate volume-related factors to determine which one can best predict PCa in patients with a PSA level of 2.5-20 ng/mL., Methods: Patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy at the Inje University Sanggye Paik Hospital between January 2018 and July 2021 and who had a PSA level of 2.5-20 ng/mL were retrospectively identified (n=275). Among them, based on biopsy results, patients were divided into cancer group and non-cancer groups, and age, PSA, total prostate volume (TPV), peripheral zone volume (PZV), peripheral zone PSA density (PZ-PSAD), transitional zone-PSAD (TZ-PSAD), and PSAD were compared and analyzed using receiver operating characteristic (ROC) and univariate analyses., Results: The areas under ROC curves (AUCs) for age, total PSA, TPV, PZV, PZ-PSAD, TZ-PSAD, and PSAD for predicting PCa in patients with a PSA level of 2.5-20.0 ng/mL were 0.678, 0.680, 0.671, 0.639, 0.731, 0.736, and 0.764, respectively. In univariate and multivariate analysis, all categorical variables were divided based on the cut-off value and used to predict PCa. Those with a PSAD of ≥0.218 ng/mL 2 were found to be at an increased risk of PCa than those with a PSAD of <0.218 ng/mL 2 [odds ratio (OR) =3.51; 95% confidence interval (CI): 1.306-9.415], which was the best result, followed by TZ-PSAD with a cut-off value of 0.353. At a PSAD level of 0.218 ng/mL 2 , 85.0% of the PCa group could avoid unnecessary biopsy and 61.4% of the non-PCa group could reduce missed diagnosis when the TRUS findings were inaccurate., Conclusions: PSAD may inform biopsy decisions as the best predictor of PCa when TRUS findings are ambiguous in patients with a PSA level of 2.5-20.0 ng/mL., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-1855/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

Background: N-methyl-D-aspartate receptors (NMDARs) are considered to be involved in several physiological and pathophysiological processes in addition to the progression of neurological disorders. However, how NMDARs are involved in the glycolytic phenotype of M1 macrophage polarization and the possibility of using them as a bio-imaging probe for macrophage-mediated inflammation remain unclear., Methods: We analyzed cellular responses to NMDAR antagonism and small interfering RNAs using mouse bone marrow-derived macrophages (BMDMs) treated with lipopolysaccharide (LPS). An NMDAR targeting imaging probe, N-TIP, was produced via the introduction of NMDAR antibody and the infrared fluorescent dye FSD Fluor™ 647. N-TIP binding efficiency was tested in intact and LPS-stimulated BMDMs. N-TIP was intravenously administered to mice with carrageenan (CG)- and LPS-induced paw edema, and in vivo fluorescence imaging was conducted. The anti-inflammatory effects of dexamethasone were evaluated using the N-TIP-mediated macrophage imaging technique., Results: NMDARs were overexpressed in LPS-treated macrophages, subsequently inducing M1 macrophage polarization. Mechanistically, NMDAR-mediated Ca 2+ accumulation resulted in LPS-stimulated glycolysis via upregulation of PI3K/AKT/mTORC1 signaling. In vivo fluorescence imaging with N-TIP showed LPS- and CG-induced inflamed lesions at 5 h post-inflammation, and the inflamed lesions could be detected until 24 h. Furthermore, our N-TIP-mediated macrophage imaging technique helped successfully visualize the anti-inflammatory effects of dexamethasone in mice with inflammation., Conclusion: This study demonstrates that NMDAR-mediated glycolysis plays a critical role in M1 macrophage-related inflammation. Moreover, our results suggest that NMDAR targeting imaging probe may be useful in research on inflammatory response in vivo., (© 2023. The Author(s).)

The subtle feature geometry also called a feature line, is considered an important geometric characteristic of automotive outer panels. The influences of material properties and thickness on the radius of curvature of subtle features were investigated in this study. First, the stamping process was simplified to a combined forming process between tensile and bending deformation. Subsequently, test materials, namely, 180B2, 210B2, CR2, CR3, and CR4, with various thickness values were adopted in the finite element analysis and experiments. In addition, the radius of curvature with respect to the material, thickness, punch radius, and punch angle was studied. The simulation results were compared with the experimental results for verification. From this comparison, it was found that the simulation results were in good agreement with the experimental data. Finally, the forming characteristics of the subtle feature-forming process were investigated to determine the effects of the material properties and thickness on the radius of curvature. The reason for the minimum formable radius when the radius of the punch was zero was studied. The results showed that, as the material thickness increased, more concentrated deformation occurred in the central region. In contrast, the radius of curvature of the subtle features increased as the thickness of the central region decreased. Similarly, decreased n-value results were identified for the same reason as the increased radius of curvature., Competing Interests: This author declares that there are no conflicts of interest., (© 2023 The Authors.)

Magnesium (Mg) has many unique properties suitable for applications in the fields of energy conversion and storage. These fields presently rely on noble metals for efficient performance. However, among other challenges, noble metals have low natural abundance, which undermines their sustainability. Mg has a high negative standard reduction potential and a unique crystal structure, and its low melting point at 650 °C makes it a good candidate to replace or supplement numerous other metals in various energy applications. These attractive features are particularly helpful for improving the properties and limits of materials in energy systems. However, knowledge of Mg and its practical uses is still limited, despite recent studies which have reported Mg's key roles in synthesizing new structures and modifying the chemical properties of materials. At present, information about Mg chemistry has been rather scattered without any organized report. The present review highlights the chemistry of Mg and its uses in energy applications such as electrocatalysis, photocatalysis, and secondary batteries, among others. Future perspectives on the development of Mg-based materials are further discussed to identify the challenges that need to be addressed.

In the filamentous fungus Aspergillus nidulans, the velvet family protein VeA and the global regulator of secondary metabolism LaeA govern development and secondary metabolism mostly by acting as the VelB/VeA/LaeA heterotrimeric complex. While functions of these highly conserved controllers have been well studied, the genome-wide regulatory networks governing cellular and chemical development remain to be uncovered. Here, by integrating transcriptomic analyses, protein-DNA interactions, and the known A. nidulans gene/protein interaction data, we have unraveled the gene regulatory networks governed by VeA and LaeA. Within the networks, VeA and LaeA directly control the expression of numerous genes involved in asexual/sexual development and primary/secondary metabolism in A. nidulans. Totals of 3,190 and 1,834 potential direct target genes of VeA and LaeA were identified, respectively, including several important developmental and metabolic regulators such as flbA · B · C , velB · C , areA , mpkB , and hogA . Moreover, by analyzing over 8,800 ChIP-seq peaks, we have revealed the predicted common consensus sequences 5'-TGATTGGCTG-3' and 5'-TCACGTGAC-3' that VeA and LaeA might bind to interchangeably. These findings further expand the biochemical and genomic studies of the VelB/VeA/LaeA complex functionality in the gene regulation. In summary, this study unveils genes that are under the regulation of VeA and LaeA, proposes the VeA- and LaeA-mediated gene regulatory networks, and demonstrates their genome-wide developmental and metabolic regulations in A. nidulans. IMPORTANCE Fungal development and metabolism are genetically programmed events involving specialized cellular differentiation, cellular communication, and temporal and spatial regulation of gene expression. In genus Aspergillus, the global regulators VeA and LaeA govern developmental and metabolic processes by affecting the expression of downstream genes, including multiple transcription factors and signaling elements. Due to their vital roles in overall biology, functions of VeA and LaeA have been extensively studied, but there still has been a lack of knowledge about their genome-wide regulatory networks. In this study, employing the model fungus A. nidulans, we have identified direct targets of VeA and LaeA and their gene regulatory networks by integrating transcriptome, protein-DNA interaction, and protein-protein interaction analyses. Our results demonstrate the genome-wide regulatory mechanisms of these global regulators, thereby advancing the knowledge of fungal biology and genetics.

Purpose: The use of absorbable skin staplers (ASS) for skin closure has been increasing due to their convenience and time-saving effect. In this study, we evaluated the effectiveness of ASS in reducing skin closure time and its safety regarding surgical site infection (SSI), comparing it to conventional hand sewing (HS) in patients who underwent mastectomy., Methods: A single-center, retrospective study was conducted. The electronic medical records of patients who underwent mastectomy between July 2015 and June 2020 in Samsung Medical Center were reviewed. The data included previously known risk factors for SSI. We compared the time expended on skin closure and the occurrence rate of SSI between the ASS group and the HS group., Results: We included 4,311 patients in the analysis. Among them, 520 patients were treated with ASS and 3,791 patients with HS. The average time for skin closure was 16.2 ± 10.1 minutes in the ASS group and 36.5 ± 29.0 minutes in the HS group (P < 0.001). The SSI rate was 0.38% (2 of 520) in the ASS group and 0.36% (14 of 3,791) in the HS group (P > 0.999)., Conclusion: The use of ASS in mastectomy reduced the time for skin closure significantly but did not increase the SSI. Therefore, it can be an effective and safe choice to use ASS instead of HS for skin closure in mastectomy., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2023, the Korean Surgical Society.)

The intestinal epithelium is a single-cell layer on the mucosal surface that absorbs food-derived nutrients and functions as a barrier that protects mucosal integrity. Hesperidin (hesperetin-7-rhamnoglucoside) is a flavanone glycoside composed of the flavanone hesperetin and the disaccharide rutinose, which has various physiological benefits, including antioxidative, anti-inflammatory, and antiallergic effects. Here, we used human intestinal Caco-2 cell monolayers to examine the effect of hesperidin on intestinal barrier function. Hesperidin-treated Caco-2 cell monolayers displayed enhanced intestinal barrier integrity, as indicated by an increase in transepithelial electrical resistance (TEER) and a decreased apparent permeability (P app ) for fluorescein. Hesperidin elevated the mRNA and protein levels of occludin, MarvelD3, JAM-1, claudin-1, and claudin-4, which are encoded by tight junction (TJ)-related genes. Moreover, hesperidin significantly increased the phosphorylation of AMP-activated protein kinase (AMPK), indicating improved intestinal barrier function. Thus, our results suggest that hesperidin enhances intestinal barrier function by increasing the expression of TJ-related occludin, MarvelD3, JAM-1, and claudin-1 via AMPK activation in human intestinal Caco-2 cells., (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Introduction: Quality of life (QoL) of endocrine surgery patients is an important patient outcome but the role of social determinants of health (SDH) on preoperative QoL is understudied., Methods: This study used preoperative data of 233 endocrine surgery patients participating in a longitudinal QoL study to examine the influence of SDH (patient-level and environmental) on preoperative QoL. Patient-level SDH was assessed with structured survey questions and environmental SDH with the Social Vulnerability Index. Multiple domains of QoL were assessed with the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29)., Results: The average age of the sample was 52.9 y and 76.8% were female, 10% were Hispanic, 55.8% were White, 32.6% were Black, 6.9% were Other, and 4.7% were Asian. Patients with patient-level SDH were more likely to have worse preoperative QoL in multiple PROMIS domains. Patients who lived in the most socially vulnerable areas had the same or better QoL scores in the PROMIS-29 domains than those living in less vulnerable areas. Minority race patients were more likely to have patient-level SDH and to live in the most vulnerable areas., Conclusions: This study is the first to our knowledge to examine the role of patient-level and environmental SDH on preoperative QoL among endocrine surgery patients. The results identified specific patient-level factors that could be used as the basis for interventions aimed to improve patients' QoL. Future studies that evaluate the role of preoperative SDH on long-term QoL and clinical outcomes would further enhance our understanding of the impact of SDH on patient wellbeing., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The increasing global emergence of zoonoses warrants improved awareness of activities that predispose vulnerable communities to greater risk of disease. Zoonotic disease outbreaks regularly occur within Myanmar and at its borders partly due to insufficient knowledge of behavioral risks, hindering participatory surveillance and reporting. This study employed a behavioral surveillance strategy among high-risk populations to understand the behavioral risks for zoonotic disease transmission in an effort to identify risk factors for pathogen spillover. To explore behavioral mechanisms of spillover in Myanmar, we aimed to: (1) evaluate the details around animal contact and types of interaction, (2) assess the association between self-reported unusual symptoms (i.e., any illness or sickness that is not known or recognized in the community or diagnosed by medical providers) and animal contact activities and (3) identify the potential risk factors including behavioral practices of self-reported illness. Participants were enrolled at two community sites: Hpa-An and Hmawbi in Southern Myanmar. A behavioral questionnaire was administered to understand participants' animal exposures, behaviors and self-reported illnesses. From these responses, associations between (1) animal contact activities and self-reported unusual illnesses, and (2) potential risk factors and self-reported unusual illness were tested. Contact with poultry seemed to be very frequent (91.1%) and many participants reported raising, handling and having poultry in their houses as well as slaughtering or being scratched/bitten by them, followed by contact with rodents (57.8%) and swine (17.9%). Compared to participants who did not have any unusual symptoms, participants who had unusual symptoms in the past year were more likely to have sold dead animals (OR = 13.6, 95% CI 6.8-27.2), slaughtered (OR = 2.4, 95% CI 1.7-3.3), raised (OR = 3.4, 95% CI 2.3-5.0) or handled animals (OR = 2.1, 95% CI 1.2-3.6), and had eaten sick (OR = 4.4, 95% CI 3.0-6.4) and/or dead animals (OR = 6.0, 95% CI 4.1-8.8) in the same year. Odds of having reported unusual symptoms was higher among those involved in animal production business (OR = 3.4, 95% CI 1.9-6.2) and animal-involved livelihoods (OR = 3.3, 95% CI 1.5-7.2) compared to other livelihoods. The results suggest that there is a high level of interaction between humans, livestock and wild animals in communities we investigated in Myanmar. The study highlights the specific high-risk behaviors as they relate to animal contact and demographic risk factors for zoonotic spillover. Our findings contribute to human behavioral data needed to develop targeted interventions to prevent zoonotic disease transmission at human-animal interfaces., (© 2023. EcoHealth Alliance.)

Geopolymer concrete is a useful alternative construction material for bridge deck systems, as it is characterized by a low carbon footprint, rapid setting, quick strength development, low cost, freeze-thaw resistance, low shrinkage, and sulphate and corrosion resistance. Heat curing enhances the mechanical properties of geopolymer materials (GPM), but it is not suitable for large structures, as it affects construction activities and increases energy consumption. Therefore, this study investigated the effect of preheated sand at varying temperatures on GPM compressive strength (Cs), the influence of Na 2 SiO 3 (sodium silicate)-to-NaOH (sodium hydroxide-10 molar concentration), and fly ash-to-granulated blast furnace slag (GGBS) ratios on the workability, setting time, and mechanical strength properties of high-performance GPM. The results indicate that a mix design with preheated sand improved the Cs of the GPM compared to sand at room temperature (25 ± 2 °C). This was caused by the heat energy increasing the kinetics of the polymerization reaction under similar curing conditions and with a similar curing period and fly ash-to-GGBS quantity. Additionally, 110 °C was shown to be the optimal preheated sand temperature in terms of enhancing the Cs of the GPM. A Cs of 52.56 MPa was achieved after three hours of hot oven curing at a constant temperature of 50 °C. GGBS in the geopolymer paste increased the mechanical and microstructure properties of the GPM as a result of different formations of crystalline calcium silicate (C-S-H) gel. The synthesis of C-S-H and amorphous gel in the Na 2 SiO 3 (SS) and NaOH (SH) solution increased the Cs of the GPM. We conclude that a Na 2 SiO 3 -to-NaOH ratio (SS-to-SH) of 5% was optimal in terms of enhancing the Cs of the GPM for sand preheated at 110 °C. Additionally, as the quantity of ground GGBS in the geopolymer paste increased, the thermal resistance of the GPM was significantly reduced.

Breast cancer is the most commonly diagnosed cancer among Chinese American women. Knowing the BRCA1 and BRCA2 (BRCA1/2) gene mutation status can improve breast cancer patients' health outcomes by guiding targeted treatment towards preventing breast cancer recurrence and other BRCA-related cancers. Nevertheless, it is unclear if there is a disparity in knowledge and use of BRCA testing among Chinese American breast cancer patients. This cross-sectional study investigated the possible presence of differences in the knowledge and the use of BRCA testing between Chinese American and Non-Hispanic White (NHW) breast cancer patients. We surveyed 45 Chinese American and 48 NHW adult breast cancer patients who had been diagnosed with breast cancer within the previous two years through telephone interviews. The results showed that race was not statistically related to the use of BRCA testing. BRCA testing utilization was associated with family history ( p < 0.05) and age ( p < 0.05). However, Chinese American participants' understanding of BRCA testing was significantly lower than that of NHW participants ( p = 0.030). Our findings suggest that a disparity exists in BRCA testing knowledge between Chinese American and NHW breast cancer patients. Genetic education and counseling are needed to improve BRCA testing knowledge and uptake among Chinese American breast cancer patients.

Raman spectroscopy provides excellent specificity for in vivo preclinical imaging through a readout of fingerprint-like spectra. To achieve sufficient sensitivity for in vivo Raman imaging, metallic gold nanoparticles larger than 10 nm were employed to amplify Raman signals via surface-enhanced Raman scattering (SERS). However, the inability to excrete such large gold nanoparticles has restricted the translation of Raman imaging. Here we present Raman-active metallic gold supraclusters that are biodegradable and excretable as nanoclusters. Although the small size of the gold nanocluster building blocks compromises the electromagnetic field enhancement effect, the supraclusters exhibit bright and prominent Raman scattering comparable to that of large gold nanoparticle-based SERS nanotags due to high loading of NIR-resonant Raman dyes and much suppressed fluorescence background by metallic supraclusters. The bright Raman scattering of the supraclusters was pH-responsive, and we successfully performed in vivo Raman imaging of acidic tumors in mice. Furthermore, in contrast to large gold nanoparticles that remain in the liver and spleen over 4 months, the supraclusters dissociated into small nanoclusters, and 73% of the administered dose to mice was excreted during the same period. The highly excretable Raman supraclusters demonstrated here offer great potential for clinical applications of in vivo Raman imaging.

Background: At present, about half of the world's population is at risk of being infected with dengue virus (DENV). However, there are no specific drugs to prevent or treat DENV infection. Glycyrrhizae Radix et Rhizome, a well-known traditional Chinese medicine, performs multiple pharmacological activities, including exerting antiviral effects. The aim of this study was to investigate the anti-DENV effects of n -butanol extract from Glycyrrhizae Radix et Rhizome (GRE)., Methods: Compounds analysis of GRE was conducted via ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The antiviral activities of GRE were determined by the CCK-8 assay, plaque assay, qRT-PCR, Western blotting, and the immunofluorescence assay. The DENV-infected suckling mice model was constructed to explore the antiviral effects of GRE in vivo., Results: Four components in GRE were analyzed by UHPLC-MS/MS, including glycyrrhizic acid, glycyrrhetnic acid, liquiritigenin, and isoliquiritigenin. GRE inhibited the attachment process of the virus replication cycle and reduced the expression of the E protein in cell models. In the in vivo study, GRE significantly relieved clinical symptoms and prolong survival duration. GRE also significantly decreased viremia, reduced the viral load in multiple organs, and inhibited the release of pro-inflammatory cytokines in DENV-infected suckling mice., Conclusions: GRE exhibited significant inhibitory activities in the adsorption stage of the DENV-2 replication cycle by targeting the envelope protein. Thus, GRE might be a promising candidate for the treatment of DENV infection.

The purpose of this study was to explore the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. We searched PubMed, Web of Science, Embase, and the Cochrane library from database inception to 30 April 2022. This meta-analysis included eight trials with 387 participants. We found that supplementation of n-3 PUFAs has no significant reduction in TC level (SMD = -0.02; 95% CI: -0.22 ~ 0.18, I 2 = 23.7%) and LDL-c level in serum (SMD = 0.18; 95% CI: -0.18 ~ 0.53, I 2 = 54.9%) of patients with metabolic syndrome. Moreover, we found no significant increase in serum high-density lipoprotein cholesterol level (SMD = 0.02; 95% CI: -0.21 ~ 0.25, I 2 = 0%) in patients with metabolic syndrome after consuming n-3 PUFAs. In addition, we found that n-3 PUFAs can significantly decrease serum triglyceride levels (SMD= -0.39; 95% CI: -0.59 ~ -0.18, I 2 = 17.2%), systolic blood pressure (SMD = -0.54; 95% CI: -0.86 ~ -0.22, I 2 = 48.6%), and diastolic blood pressure (SMD = -0.56; 95% CI: -0.79 ~ 0.33, I 2 = 14.0%) in patients with metabolic syndrome. The results from the sensitivity analysis confirmed that our results were robust. These findings suggest that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in metabolic syndrome. Given the quality of the included studies, further studies are still needed to verify our findings.

Recombinant human growth hormone (rhGH) is a peptide comprising 191 amino acids, that is mainly used to promote the growth of children and plays an important antiaging role. In the present study, a simple and sensitive quantitation method for rhGH in rat plasma was established by LCMS/MS. After simple and rapid enzymatic digestion of the plasma sample, two suitable surrogate peptides (LFDNAMLR and FPTIPLSR) were selected for quantitative analysis. The results showed good linearity over calibration range 10-2000 ng/mL. The quality control (QC) accuracy ranged from -13.8 to 14.3%, and the accuracy of the lower limit of quantification (LLOQ) ranged from -12.9 to 19.0%. The intra-day and inter-day precision ranges for all QCs were 1.7-13.6% and 4.0-7.0%, respectively. The method was successfully applied to intravenous and subcutaneous pharmacokinetic studies in rats. In comparison with previously published methods, our method features simple sample preparation combined with a short sample processing time (3.5 h), wide linear range (10-2000 ng/mL), small plasma volume (35 μL), and LLOQ (10 ng/mL)., Competing Interests: Declaration of Competing Interest The authors declare no competing interests. The authors alone are responsible for the content and writing of this manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Backgruound: We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians., Methods: We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hours/night, >5 to 7 hours/night (reference), and >7 hours/night. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex., Results: During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 h/night had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hours/night group in non-obese individuals, men, and those aged <60 years, and in the >7 hours/night group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively)., Conclusion: This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide and becoming a major cause of liver disease-related morbidity and mortality. The presence of liver fibrosis in patients with NAFLD is closely related to prognosis, including the development of hepatocellular carcinoma and other complications of cirrhosis. Therefore, assessment of the presence of significant or advanced liver fibrosis is crucial. Although liver biopsy has been considered the "gold standard" method for evaluating the degree of liver fibrosis, it is not suitable for extensive use in all patients with NAFLD owing to its invasiveness and high cost. Therefore, noninvasive biochemical and imaging biomarkers have been developed to overcome the limitations of liver biopsy. Imaging biomarkers for the stratification of liver fibrosis have been evaluated in patients with NAFLD using different imaging techniques, such as transient elastography, shear wave elastography, and magnetic resonance elastography. Furthermore, artificial intelligence and deep learning methods are increasingly being applied to improve the diagnostic accuracy of imaging techniques and overcome the pitfalls of existing imaging biomarkers. In this review, we describe the usefulness and future prospects of noninvasive imaging biomarkers that have been studied and used to evaluate the degree of liver fibrosis in patients with NAFLD.