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Spodoptera frugiperda is a long-distance migratory pest with strong dispersal ability, fast reproduction speed and destructive feeding, so it is difficult to prevent and control. Pyrethroid insecticides are commonly used in pest insects control, And since the voltage-gated sodium channel (VGSC) serves as a major target of pyrethroids, it is important to study this gene for pest control. VGSC is an integral transmembrane protein consisting of approximately 2,000 amino acid residues found in neurons, myocytes, endocrine cells, and ovarian cells and involved in the initiation and propagation of excitable cellular action potentials. In this study, the cDNA sequence of the VGSC was identified from S. frugiperda by rapid amplification of cDNA ends (RACE) which contained an open reading frame of 6,261 bp encoding a protein of 2,086 amino acids. The molecular weight of this protein was predicted to be 236 kDa, and the theoretical isoelectric point was 5.21. A phylogenetic tree constructed based on lepidopteran insects showed that the VGSC of S. frugiperda was most closely relative to that of Spodoptera litura. VGSC is a highly conserved protein with Ion channel conserved structural domains of transmembrane proteins. qPCR showed that the VGSC gene was highly expressed in the epidermis of 2nd instar larvae, and its expression level was low in other tissues, such as the foregut and Malpighian tubules. In addition, VGSC was also detected in the prepupal stage, then gradually increased in abundance after entering the adult stage, peaked at the adult males on the 4th day of pupal stage, and decreased afterwards. The recombinant plasmid of pSumo-mut-VGSC was constructed and induced to express a His tag fused VGSC protein. Polyclonal antibodies were prepared from purified recombinant VGSC protein. The antibody was ELISA-titered, and the western blotting results showed that it specifically recognized VGSC, whether it was recombinant or endogenous protein. These results have laid the foundation for future studies on the physiological function of this gene in the growth and development of S. frugiperda., 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 B.V.)

Pyridine derivatives are fundamental in fields such as organic chemistry, materials science, and pharmaceuticals, largely due to their versatile electronic properties. Fluorination of pyridine significantly alters these properties, yet the specific effects of the position and number of fluorine atoms on valence orbitals and cationic structures remain not fully understood. This study examines the impact of fluorine substitution on the valence orbitals and cationic structures of various pyridine derivatives, with a particular emphasis on 2,6-difluoropyridine (2,6-DFP). Using high-resolution vacuum ultraviolet mass-analysed threshold ionisation (VUV-MATI) spectroscopy, the adiabatic ionisation energy of 2,6-DFP was determined to be 78 365 ± 3 cm -1 (9.7160 ± 0.0004 eV). Franck-Condon simulations were conducted to interpret the VUV-MATI spectra, providing detailed insights into the molecular structure and vibrational modes of the cationic form. The analysis indicated a symmetry shift from C 2V to C 1 upon ionisation, highlighted by the presence of out-of-plane ring-bending modes. Natural bond orbital analysis identified the highest occupied molecular orbital (HOMO) and HOMO-1 as π-orbitals, with HOMO-2 being a nonbonding orbital. The introduction of two ortho -fluorine substitutions in 2,6-DFP significantly influenced this electronic configuration, stabilising the nonbonding orbital through interactions with the two fluorine σ-type lone pairs. This stabilisation notably altered the valence orbital ordering compared to that of 2-fluoropyridine, resulting in a substantial difference in the binding energies between the HOMO and HOMO-1. This research provides a deeper understanding of how halogen substitution affects the electronic properties of pyridine derivatives, promoting research in the field of physical chemistry.

The cyclization of heteroatom-functionalized alkynes induced by d 6 -transition-metal centers has traditionally been associated with the vinylidene pathway. However, recent evidence suggests that d 6 -transition-metal centers can also activate alkynes through non-vinylidene pathways. In this study, we conducted a comprehensive experimental and theoretical investigation into the reactions between the Ru(II) complex [Ru([9]aneS3)(bpy)(OH 2 )] 2+ and 2-alkynylanilines. Our study revealed that the selectivity between the vinylidene and non-vinylidene pathways can be tuned by reaction temperature, substrate, and solvent polarity. This strategic control allows for the preferential formation of either C2- or C3-metalated indole zwitterion complexes. Additionally, we identified a rare decyclization mechanism that enables the conversion of C2-metalated indoles to C3-metalated indoles, underscoring the significance of product stability in these pathways. Overall, this work demonstrates practical approaches to control the preference between vinylidene and non-vinylidene pathways, which is crucial for the design of new catalysts and metalated heterocyclic complexes., (© 2024 Wiley-VCH GmbH.)

Patients on maintenance hemodialysis exhibit a notably higher risk of cardio-cerebrovascular complications that constitute the major cause of death. Preceding studies have reported conflicting associations between traditional lipid measures and clinical outcome in dialysis patients. In this prospective longitudinal study, we utilized quantitative lipidomics to elucidate, at molecular resolution, changes in lipidome profiles of erythrocyte and plasma samples collected from maintenance hemodialysis patients followed up for 86 months (≈7 years). Primary outcome was defined as cardiovascular-related deaths or new-onset cardio-cerebrovascular events. Cox regression model uncovered plasma/erythrocyte lipids associated with incident cardio-cerebrovascular events in the erythrocyte cohort (n = 117 patients, 37 events) and plasma cohort (n = 45 patients, 11 events), respectively. Both the erythrocyte lipid panel [PA 40:5, PI 34:2, PC 42:6, AUC = 0.83] and plasma lipid panel [PC O-34:1, GM3 18:1; O2/25:0, TG 44:1(16:1_28:0), AUC = 0.94] significantly improved the prediction of cardio-cerebrovascular-related outcome compared to the base model comprising age, sex and dialysis vintage alone. Our findings underscore the pathophysiological significance of anionic phospholipid accretion in erythrocytes in the development of cardio-cerebrovascular complications in dialysis patients. In particular, distorted membrane lipid asymmetry leads to compromised membrane deformability, aberrant cell-cell interactions and altered glutathione metabolism in the erythrocytes of high-risk individuals even at relatively early stage of hemodialysis. Our findings thus underscore the importance of maintaining the RBC pool to lower the risk of cardio-cerebrovascular complications in dialysis patients., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Regulatory T cells (Tregs) establish dominant immune tolerance but obstruct tumor immune surveillance, warranting context-specific mechanistic insights into the functions of tumor-infiltrating Tregs (TIL-Tregs). We show that enhanced posttranslational O-linked N-acetylglucosamine modification (O-GlcNAcylation) of cellular factors is a molecular feature that promotes a tumor-specific gene expression signature and distinguishes TIL-Tregs from their systemic counterparts. We found that altered glucose utilization through the glucose transporter Glut3 is a major facilitator of this process. Treg-specific deletion of Glut3 abrogates tumor immune tolerance, while steady-state immune homeostasis remains largely unaffected in mice. Furthermore, by employing mouse tumor models and human clinical data, we identified the NF-κB subunit c-Rel as one such factor that, through Glut3-dependent O-GlcNAcylation, functionally orchestrates gene expression in Tregs at tumor sites. Together, these results not only identify immunometabolic alterations and molecular events contributing to fundamental aspects of Treg biology, specifically at tumor sites but also reveal tumor-specific cellular properties that can aid in the development of Treg-targeted cancer immunotherapies., Competing Interests: Competing interests: Garima Sharma is an employee of ImmunoBiome Inc, South Korea. SHI is the founder and major shareholder of ImmunoBiome Inc, South Korea. SML is an employee of Lipidall Technologies Company Limited, China. The authors have no conflicting financial interests., (© 2024. The Author(s), under exclusive licence to CSI and USTC.)

Aims: This population-based study aimed to investigate the impact of mental disorders on the risk of mortality and cardiovascular disease (CVD) outcomes in adults with new-onset type 1 diabetes., Materials and Methods: We included 17,429 patients with new-onset type 1 diabetes without CVD from the Korean National Health Insurance Service database. Mental disorders include depression, bipolar, persistent affective and other affective disorders, anxiety, eating disorders, personality and behavioral disorders, and substance abuse. Individuals with or without mental disorders were matched 1:1 by age, sex, and year of the index date. The primary outcomes were all-cause mortality and composite CVD events. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using multivariate Cox proportional hazards regression models., Results: During a median follow-up of 7.99 years, all-cause mortality (composite CVD outcomes) occurred in 1,562 patients (1,993 patients with CVD outcomes) with mental disorders and 1,211 patients (1,611 patients with CVD outcomes) without mental disorders. The adjusted HR for all-cause mortality and composite CVD outcomes in patients with mental disorders was 1.35 and 1.32, respectively, compared to those without mental disorders. The aHR for the all-cause mortality and composite CVD events was 1.27 and 1.28 in the subgroup with one mental disorder and 1.57 and 1.43 in the subgroup with multiple mental disorders, compared to those without mental disorders., Conclusions: Mental disorders are associated with an elevated risk of all-cause mortality and CVD in adults with newly diagnosed type 1 diabetes. Early detection and greater attention to premature death and CVD development are required in patients with new-onset type 1 diabetes and mental disorders., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: Loneliness is a risk factor for mental and physical disorders. Rapid individualization, with increasing associated social burden, is a contributing factor to loneliness among Koreans. This study aimed to investigate the relationship between loneliness and mental disorders, as well as to determine whether long-term loneliness is a factor predicting the occurrence of mental disorders in adults., Methods: The National Mental Health Survey of Korea 2021, a nationally representative survey on mental disorders, was conducted. Responses from 5511 participants were collected using the Korean version of the Composite International Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders fourth edition, Structured Clinical Interview for Internet Gaming Disorder, and the World Health Organization Adult Attention-deficit Hyperactivity Disorder (ADHD) self-report scale. Loneliness and its duration were investigated among these participants., Results: Loneliness was reported by approximately 2.9% of the general population. Loneliness was associated with an increased adulthood prevalence of alcohol use disorders, nicotine use disorders, depressive disorders, anxiety disorders, adult ADHD, and internet gaming disorders. Long-term loneliness was significantly associated with an elevated risk of alcohol use disorders, nicotine use disorders, depressive disorders, and anxiety disorders. Internet gaming disorder was associated with loneliness lasting > 1 year., Conclusion: Various adult psychiatric disorders were associated with loneliness. The significant dose-effect relationship indicated the importance of early detection of and intervention for loneliness to reduce its negative consequences on mental health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The class I phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is a key regulator of cell survival, growth, and proliferation and is among the most frequently mutated pathways in cancer. However, where and how PI3K-AKT signaling is spatially activated and organized in mammalian cells remains poorly understood. Here, we identify focal adhesions (FAs) as subcellular signaling hubs organizing the activation of PI3K-PI(3,4,5)P 3 -AKT signaling in human cancer cells containing p110α mutations under basal conditions. We find that class IA PI3Ks are preferentially recruited to FAs for activation, resulting in localized production of PI(3,4,5)P 3 around FAs. As the effector protein of PI(3,4,5)P 3 , AKT1 molecules are dynamically recruited around FAs for activation. The spatial recruitment/activation of the PI3K-PI(3,4,5)P 3 -AKT cascade is regulated by activated FA kinase (FAK). Furthermore, combined inhibition of p110α and FAK results in a more potent inhibitory effect on cancer cells. Thus, our results unveil a growth-factor independent, compartmentalized organization mechanism for PI3K-PI(3,4,5)P 3 -AKT signaling., Competing Interests: Declaration of interests S.M.L. is an employee of LipidALL Technologies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The aging population highlights the need to maintain both physical and psychological well-being. Frailty, a multidimensional syndrome, increases vulnerability to adverse outcomes. Although physical exercise is effective, adherence among older adults with frailty is often low due to barriers. Motion-based video games (MBVGs) may enhance motivation and engagement., Objective: This study aims to evaluate the effect of individualized exercise programs that combine MBVGs, intergenerational support, and therapeutic frameworks on physical, cognitive, and social frailty outcomes in community-dwelling older adults., Methods: This randomized controlled trial was conducted from March 2022 to October 2023 across 6 community centers in Hong Kong. Participants aged 60 years and above with mild neurocognitive disorder were recruited, screened, and randomly assigned to either an intervention (n=101) or control group (n=101). The intervention included an 18-week program with 12 supervised exercise sessions utilizing motion-based technology, led by occupational therapists and assisted by youth volunteers. Data were collected at baseline (T1) and postintervention (T2), focusing on physical, cognitive, and social frailty outcomes, as well as client-related metrics. Statistical analyses were performed using SPSS, with significance set at P<.05., Results: A total of 202 participants were recruited, with a mean age of 78.8 years (SD 7.8). Both groups showed improvements in balance from T1 to T2, with a significant time effect (β=-0.63, P=.03). The intervention group demonstrated enhancements in hand strength and BMI, but no statistically significant between-group differences were observed. The intervention group also exhibited significant improvements in cognitive function (β=2.43, P<.001), while the control group's scores declined. Short-term memory improved for both groups, with no significant differences noted. Both groups experienced a reduction in depression levels, with a significant within-group effect at T2 (β=-1.16, P=.001). Improvements in social connectedness and eHealth literacy were observed in both groups, with the latter showing a significant within-group effect at T2 (β=3.56, P=.002). No significant effects were found for social isolation, physical activities, or quality of life., Conclusions: The growing aging population necessitates innovative strategies to support aging in place. Results indicated statistically significant improvements only in BMI and cognition, while other outcomes such as loneliness, balance, and eHealth literacy showed positive trends but lacked significance. Despite the limitations observed, particularly regarding the role of volunteer support and the diverse needs of community-dwelling older adults, the findings contribute to the foundation for future research aimed at enhancing biopsychosocial outcomes. Future studies should explore tailored interventions that consider individual preferences and abilities, as well as evaluate specific components of motion-based video games to optimize their effectiveness., (© Arkers Kwan Ching Wong, Melissa Qian Zhang, Jonathan Bayuo, Karen Kit Sum Chow, Siu Man Wong, Bonnie Po Wong, Bob Chung Man Liu, David Chi Ho Lau, Tobias Kowatsch. Originally published in JMIR Serious Games (https://games.jmir.org).)

Aromadendrin (ARO) is an active plant compound that exerts anti-inflammatory effects. However, its ameliorative effects on chronic obstructive pulmonary disease (COPD) remain unclear. Therefore, we investigated the inhibitory effects of ARO on bronchial inflammation using an experimental model of COPD. In vivo analysis confirmed a notable increase in the number of neutrophils/macrophages and the formation of reactive oxygen species (ROS), myeloperoxidase (MPO), interleukin (IL)-6/IL1β, and monocyte chemoattractant protein (MCP)-1 in the bronchoalveolar lavage (BAL) fluid of COPD mice, which was attenuated by oral gavage of ARO. In addition, hematoxylin and eosin staining showed a notable cell influx in the lungs of the COPD group, which was ameliorated by ARO. Western blotting revealed that ARO decreased the upregulation of neutrophil elastase expression in the lungs of the COPD group. Furthermore, periodic acid-Schiff staining showed that increased mucus formation in the lungs of the COPD group was downregulated by ARO. ARO also blocked CREB activation in the lungs of COPD mice. This in vivo, anti-inflammatory effect of ARO was accompanied by its modulatory effect on the activation of the MAPK/NF-κB/NLRP3 inflammasome. In summary, our study demonstrated that ARO has protective effects on bronchial inflammation by attenuating immune cell accumulation, toxic molecule/cytokine/chemokine formation, and MAPK/NF-κB/NLRP3 inflammasome activation, suggesting the potential development of ARO as an adjuvant for the prevention and treatment of COPD.

Background: The wearable monitoring device (WMD) is emerging as a promising tool for community-dwelling older adults to monitor personal health, enhance awareness of their activities, and promote healthy behaviors. However, the sustained use of WMDs among this population remains a significant challenge., Objective: This study aims to implement an interventional program that promotes and motivates the continued use of WMDs among older adults through a peer and professional support approach. This program will facilitate the integration of WMDs into their daily lives., Methods: This feasibility trial examined the following: (1) the usability of the WMD from the users' perspectives; (2) the feasibility of the Live With Wearable Monitoring Device program; and (3) the effectiveness of the Live With Wearable Monitoring Device program among community-dwelling older adults. The intervention, based on Self-Determination Theory, involved using the Live With Wearable Monitoring Device program over a 3-month period, with ongoing professional and peer support provided by community health workers, aided by a nurse and social workers. This support included 1 home visit and biweekly communication via WhatsApp. Data were collected at baseline and at 1, 3, and 6 months., Results: A total of 39 participants were enrolled in the intervention group, while 37 participants were in the control group. The recruitment rate was high (76/89, 85%), and the attrition rate was low (8/76, 11%), indicating that the program is feasible for older adults. Participants in the intervention group exhibited higher self-efficacy, lower anxiety levels, and used the smartwatch more frequently, in terms of both days and hours, compared with the control group. A between-group difference was observed in self-efficacy between the intervention and control groups (β=3.31, 95% CI 0.36-6.25, P=.03), with statistically significant higher mean values recorded at all 4 time points., Conclusions: It is clear that merely providing a WMD to older adults does not guarantee its usage, particularly for those unfamiliar with how to utilize its health-related functions in their daily routines. This study implemented a theory-based program aimed at enhancing the ongoing use of WMDs among older adults, suggesting that continuous professional and peer support may significantly influence WMD usage., Trial Registration: ClinicalTrials.gov NCT05269303; https://clinicaltrials.gov/ct2/show/NCT05269303., (©Arkers Kwan Ching Wong, Jonathan Bayuo, Jing Jing Su, Frances Kam Yuet Wong, Karen Kit Sum Chow, Bonnie Po Wong, Siu Man Wong, Vivian Hui. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.11.2024.)

(1) Background: In recent years, large language models (LLMs) such as ChatGPT have gained significant attention in various fields, including dentistry. This scoping review aims to examine the current applications and explore potential uses of LLMs in the orthodontic domain, shedding light on how they might improve dental healthcare. (2) Methods: We carried out a comprehensive search in five electronic databases, namely PubMed, Scopus, Embase, ProQuest and Web of Science. Two authors independently screened articles and performed data extraction according to the eligibility criteria, following the PRISMA-ScR guideline. The main findings from the included articles were synthesized and analyzed in a narrative way. (3) Results: A total of 706 articles were searched, and 12 papers were eventually included. The applications of LLMs include improving diagnostic and treatment efficiency in orthodontics as well as enhancing communication with patients. (4) Conclusions: There is emerging research in countries worldwide on the use of LLMs in orthodontics, suggesting an upward trend in their acceptance within this field. However, the potential application of LLMs remains in its early stage, with a noticeable lack of extensive studies and tailored products to address specific clinical needs.

Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we examined the effects of a systemic MDR A. baumannii infection and found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-1 and caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. Together, our results suggest that non-canonical inflammasome activation via the (Interferon) IFN pathway plays a critical role in the host response against MDR A. baumannii infection., Competing Interests: Competing interests S.M.M. is an Editorial Board Member for Communications Biology but was not involved in the editorial review of, nor the decision to publish, this article. The other authors declare no competing interests., (© 2024. The Author(s).)

Background: In Korea, substantial disparities exist in physical environments across regions, exacerbating the polarization between metropolitan and provincial areas and urban and rural regions., Objectives: This study examines the differences in the physical activity and self-rated health of local communities in relation to satisfaction with the physical environment. By identifying and addressing these underlying causes of health disparities, the study provides foundational data to inform policy efforts., Methods: The study utilized data from the 2023 Community Health Survey conducted by the Korea Disease Control and Prevention Agency. It included 231,752 individuals aged 19 and older (105,754 men and 125,998 women) selected through a two-stage probability proportional systematic sampling method. One-on-one online interviews were conducted from 16 May to 31 July 2023. The physical environment was assessed based on public satisfaction with safety, natural and living environments, public transportation, and medical services. Study variables included subjective health status and physical activity, with subvariables for physical activity encompassing the duration of vigorous and moderate physical activity, walking, and flexibility exercises. For data analysis, MANOVA and ANOVA were conducted, with Bonferroni correction for multiple comparisons., Results: Considerable variations in physical activity were observed based on satisfaction with the local community environment. Regarding self-rated health, significant differences were found in safety levels, living environment, and medical services. Satisfaction with the physical environment positively influenced physical activity and self-rated health., Conclusion: Therefore, it is imperative to reduce disparities in the physical environment between regions and enhance residents' satisfaction.

An effective orthodontic treatment should not only aim for satisfactory occlusal outcomes but also consider its impact on facial esthetics. The study aims to evaluate and compare the perception of profile esthetics of skeletal Class II patients treated with two orthodontic modalities: (1) Two-phase approach involving functional appliances followed by fixed appliances with premolar extractions, or (2) One-phase approach using fixed appliances with premolar extractions. Additionally, the study aims to evaluate the correlation between the perceived esthetics and the corresponding cephalometric measurements. The study included 40 skeletal Class II adolescents who underwent either two-phase (n = 20, mean age = 12.38 ± 1.18) or one-phase (n = 20, mean age = 12.53 ± 0.79) orthodontic treatments. Eighty profile silhouettes (pre- and post-treatment) were assessed by 64 raters, including 23 orthodontists, 21 general dental practitioners, and 20 laypersons. The raters used a visual analog scale (VAS) to access profiles, upper and lower lips, and chin esthetics. At pre-treatment, all three groups of raters gave significantly lower scores to the profile silhouettes of the two-phase group compared to the one-phase group (P < 0.01); however, after treatment, they rated the two-phase group significantly higher (P ≤ 0.001). The two-phase group exhibited greater improvements in profile and upper and lower lip esthetics as perceived by all raters (P ≤ 0.001). Furthermore, cephalometric results revealed greater reductions in SNA, ANB, Wits appraisal, and G'-Sn-Pog' in the two-phase group compared to the one-phase group (P < 0.05). Five cephalometric parameters (SNB, SNPog, overjet, overbite, and UL-SnPog') demonstrated significant correlations with VAS scores given by orthodontists (P < 0.05). In conclusion, the two-phase group showed greater subjective and objective improvements in facial esthetics than the one-phase group. Additionally, the anteroposterior mandibular position and upper lip protrusion may be the primary cephalometric parameters correlated with subjective facial profile perceptions., (© 2024. The Author(s).)

Introduction: Road traffic injuries (RTIs) are the leading cause of mortality among children and adolescents. This study aimed to compare clinical characteristics and identify factors associated with severe RTIs based on types of road users among children and adolescents with RTIs., Methods: A retrospective multicentre observational study was conducted using the Emergency Department-based Injury In-depth Surveillance registry in South Korea. A total of 78 021 participants younger than 19 years who presented with RTIs to the participating emergency departments from 2011 to 2021 were classified into four groups: passengers, pedestrians, motorcyclists and bicyclists. Demographic and injury-related factors were analysed using a multivariate logistic regression model to determine associations with severe RTIs, as indicated by the Excess Mortality Ratio-based Injury Severity Score of ≥16. The prevalence of traumatic brain injury (TBI), hospitalisations, intensive care unit (ICU) admissions and severe RTIs among road users was compared., Results: Head injuries were most prevalent in passengers (55.3%), motorcyclists (46.7%) and bicyclists (50.1%). Motorcyclists exhibited the highest proportion of TBI (8.3%), total admissions (28.8%), ICU admissions (8.2%), severe RTIs (41.0%) and mortality (2.0%). Safety devices significantly reduced severe RTIs in passengers and motorcyclists (adjusted OR (95% CI) 0.77 (0.70 to 0.85) and 0.69 (0.62 to 0.76), respectively., Conclusion: The distinct clinical characteristics and factors associated with severe RTIs among different road user types in children and adolescents highlight the need for targeted interventions. Tailoring strategies to the specific requirements of each group is essential for effectively mitigating the occurrence of severe RTIs in this vulnerable demographic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, the effects of chlorine substitution on the valence orbitals and electronic states of 3-chloropyridine (3-CP) were investigated utilizing high-resolution vacuum ultraviolet mass-analyzed threshold ionization (VUV-MATI) spectroscopy and computational methods. High-quality vibrational spectra were obtained from the VUV-MATI spectra of 3-CP isotopomers (35Cl and 37Cl), revealing high-quality vibrational spectra for the lowest cationic states. The adiabatic ionization energies (AIEs) of these isotopomers were accurately determined, providing detailed information about the electronic structure and ionization dynamics. Intense spectra peaks were linked with the D1 excited state of the 3-CP cation, with vibronic transitions in this state closely matching those predicted by Franck-Condon simulations. This provided insights into the cationic structure and the roles of the highest occupied molecular orbital (HOMO) and the HOMO-1. The HOMO was primarily a π orbital of the pyridine ring, while the HOMO-1 consisted of nonbonding orbitals. The AIEs suggested that meta-chlorine substitution stabilizes nonbonding orbitals less effectively than ortho substitution, indicating closely spaced electronic states in the 3-CP cation. Minor discrepancies in vibrational frequencies and intensities, particularly above 800 cm-1, suggested the presence of vibronic coupling, warranting further investigation. Overall, this study provided a comprehensive understanding of the vibronic and ionization properties of 3-CP, emphasizing the influence of the position of the chlorine substitution on molecular orbitals and the value of advanced theoretical and experimental approaches for analyzing the vibrational spectra of complex molecules., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Macrophages, a critical subset of innate immune cells, play a pivotal role in cytokine production during disease progression, tissue injury, and pathogen invasion. Their intricate involvement in the manifestation of chronic low-grade inflammation associated with the aging process is widely acknowledged. Notably, in aged tissues, macrophages exhibit an altered phenotype characterized by an augmented synthesis of pro-inflammatory cytokines and chemokines, a profile intimately associated with a phenomenon known as inflammaging. Macrophages possess the capacity to undergo cellular senescence, a state of permanent growth arrest, in response to diverse stressors, including aging. Senescent macrophages secrete an array of pro-inflammatory molecules, growth factors, and matrix metalloproteinases, collectively referred to as the Senescence-Associated Secretory Phenotype (SASP). The SASP exacerbates the state of chronic inflammation observed in aging tissues. Thus, disruptions in macrophage function and signaling pathways due to aging result in escalated production of inflammatory mediators, perpetuating inflammaging. Recent research has uncovered novel mechanisms centred around innate immune signaling and mitochondrial dysfunction in macrophages, highlighting their crucial role in the development of inflammaging and associated pathological conditions. This review delves into the latest scientific findings on these emerging mechanisms in macrophage senescence related to aging and explores the prospects of targeting macrophages to address age- associated conditions effectively.

Background: Enhanced angiogenesis following myocardial infarction (MI) is beneficial to preserve cardiac function. The present study aimed to investigate whether acetylated derivatives of cordycepin altered its original antitumor properties and exerted cardioprotective effects by promoting angiogenesis in vitro and in vivo ., Methods: Cordycepin and its derivatives with single (DA), double (DAA), and triple acetyl groups (DAAA) were assessed. The cell viability of leukemia U937 cells, malignant hepatoma Huh-7 cells, and human umbilical vascular endothelial cells (HUVECs) treated with cordycepin, DA, DAA, and DAAA were determined. The expression of β-catenin in U937 cells, as well as the expression of p65, p38 and other related signal regulators in HUVECs elicited by lipopolysaccharides (LPS) were also observed. Angiogenesis was determined by tube formation in HUVECs and Matrigel plug assay in mice. Cardiac function following administration of DAAA was evaluated in mice MI model simulated by coronary artery ligation., Results: The inhibitory effects of cordycepin and its acetylated derivatives on U937 cells, Huh-7 cells, HUVECs, and the expression of β-catenin in U937 cells were mitigated with increasing acetylation. Intriguingly, DAAA preserved the cell viability of HUVECs compared to other acetylated derivatives. Although DAAA had a significantly diminished antitumor effect compared to cordycepin, it promoted angiogenesis in mice and tube formation in HUVECs and attenuated LPS-induced phosphorylation of p65 and p38. Additionally, administration of DAAA improved cardiac function following coronary artery ligation in mice., Conclusion: DAAA could be considered a promising adjunctive therapy to prevent post-MI heart failure through promoting angiogenesis., Competing Interests: 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., (© 2024 The Authors.)

Background and Aims: The association between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is unclear. This study aimed to investigate the impact of spectrum of SLD on the risk of heart failure and cardiovascular (CV) mortality in patients with T2DM., Methods: In a nationwide cohort study, 2,745,689 adults with T2DM were followed from 2009 to 2012 until 2018. Participants were categorized into no steatotic liver disease (no SLD) and SLD groups. The SLD group was stratified based on metabolic risk factors, alcohol consumption and viral hepatitis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for heart failure (HF) and CV mortality risk., Results: The prevalence of MASLD, metabolic alcohol-associated liver disease (MetALD), alcohol-associated liver disease with metabolic dysfunction (ALD with MD) and MASLD with viral hepatitis (VH) was 49.6%, 7.2%, 2.3%, and 2.0%. Individuals with MASLD (adjusted HR [aHR], 1.11), MetALD (aHR, 1.14), ALD with MD (aHR, 1.32) and MASLD with VH (aHR, 1.12) had a higher risk of developing HF compared with the no SLD group. The risk of CV mortality was also increased in those with SLD groups compared to those with no SLD. The risk of new-onset HF and CV mortality showed a J-shaped association with alcohol consumption regardless of SLD status., Conclusion: SLD is independent risk factor of new-onset HF and CV mortality in persons with T2DM, and alcohol consumption has a J-shaped association with risk of HF and CV mortality, regardless of SLD status., (© 2024. The Author(s).)

Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.

Inflammasome sensors activate cellular signaling machineries to drive inflammation and cell death processes. Inflammasomes also control the development of certain diseases independently of canonical functions. Here, we show that the inflammasome protein NLR family CARD domain-containing protein 4 (NLRC4) attenuated the development of tumors in the Apc min/+ mouse model. This response was independent of inflammasome signaling by NLRP3, NLRP6, NLR family apoptosis inhibitory proteins, absent in melanoma 2, apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1 and caspase-11. NLRC4 interacted with the DNA-damage-sensing ataxia telangiectasia and Rad3-related (ATR)-ATR-interacting protein (ATRIP)-Ewing tumor-associated antigen 1 (ETAA1) complex to promote the recruitment of the checkpoint adapter protein claspin, licensing the activation of the kinase checkpoint kinase-1 (CHK1). Genotoxicity-induced activation of the NLRC4-ATR-ATRIP-ETAA1 complex drove the tumor-suppressing DNA damage response and CHK1 activation, and further attenuated the accumulation of DNA damage. These findings demonstrate a noninflammatory function of an inflammasome protein in promoting the DNA damage response and mediating protection against cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m 6 A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m 6 A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: This study aims to organize an intergenerational program to provide unemployed young people with operational skills related to gerontechnology and the experience required to deliver digital outreach rehabilitation services to community-dwelling older people., Methods: A quasi-experimental research design was adopted. The young participants received a 12-session training program on the management of common chronic diseases, communication with older people, the functions and use of interactive games, and techniques to teach and match interactive games with older people. The perception of elderly outcomes (i.e., knowledge and attitude toward elderly care, willingness to care for the elderly), personal outcomes (i.e., life satisfaction, self-efficacy), and desired vocational outcomes (i.e., hours worked in the nongovernmental organization's center, hours spent with older people) were evaluated preprogram and postprogram., Results: Fifty-one young people joined the program. A statistically significant improvement was seen from preprogram to postprogram in their willingness to care for the elderly (p = .016) and life satisfaction (p = .005), as well as in the number of hours that they spent in the community center volunteering or engaged in social services for older people., Discussion: The findings proved that the program could improve the willingness of young people to care for older people, as well as improve their own life satisfaction. Using gerontechnology can serve to bridge the intergenerational gap and bring benefits to both young adults and older people. It may provide policy makers with a way to address the manpower shortage in elderly care services and help frail older people to age in place., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The activation of various homopropargylic pyridines by cis-[Ru II /Os II (dppm) 2 Cl 2 ] (dppm=1,1-bis(diphenylphosphino)methane) has previously been shown to generate a diverse array of metallacycles and metalated heterocyclic complexes. However, a minor structural modification of introducing a halide onto the pyridyl group of the alkyne substrate resulted in the formation of unprecedented Ru(II)/Os(II)-haloquinolizine complexes. These complexes display (1) κ 2 (X,C)-haloquinolizine chelates arising from the cycloisomerization of HC≡CC(OH)(CH 2 (6-X-2-py))(Ph) on [Ru II /Os II (dppm) 2 ] 2+ moieties via a vinylidene pathway, (2) five-membered Ru/Os-X-C-N-C rings (X=F, Cl, Br) ortho- and peri-fused to quinolizinium skeletons, and (3) uncommon M-X-R bonding interactions that are atypical in coordination complexes. Despite being divalent and integrated into a five-membered Ru-X-C-N-C ring system, the X atoms in the Ru(II) complexes are susceptible to substitution by O in the presence of - OH, resulting in the formation of quinolizinium-fused ruthenaoxazole complexes. Overall, this work highlights the importance of considering metal-halocarbon bonding interactions in catalytic or coordination designs., (© 2024 Wiley-VCH GmbH.)

There exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n = 324) from non-fibrosis (F0, n = 195), with an area under receiver operating characteristic curve (AUROC) at 0.775 (95% confidence interval [CI]: 0.735-0.816). Circulating sulfatides (SLs) emerged as central lipids distinctly associated with fibrosis pathogenesis in MASLD. Lipidomics analysis of lipoprotein fractions revealed a redistribution of circulating SLs from high-density lipoproteins (HDLs) onto low-density lipoproteins (LDLs) in MASLD fibrosis. We further verified that patient LDLs with reduced SL content triggered a smaller activation of type II natural killer T lymphocytes, compared with control LDLs. Our results suggest that hepatic crosstalk with systemic immunity mediated by lipoprotein metabolism underlies fibrosis progression at early-stage MASLD., Competing Interests: Declaration of interests S.M.L., G.H.C., and Y.Z. are employees of LipidALL Technologies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Given the crucial role of abnormal homeostasis in tumor cells for maintaining their growth, it may be more efficient with less effort to develop anti-tumor strategies that target multiple combined mechanisms by disrupting intracellular homeostasis. Here, a copper-based nanoinducer (CGBH NNs) with multiple enzyme-like activities is designed and constructed to induce disulfidptosis-enhanced pyroptosis through disrupting multiple intracellular homeostasis for effective tumor immunotherapy. Within the tumor microenvironment (TME), CGBH NNs can disrupt intracellular glucose homeostasis and inhibit NADPH production, leading to accumulation of cystine, which further blocked the substrate and key enzyme for synthesizing glutathione. Subsequently, through cascade catalytic reactions involving enzyme activities (glutathione peroxidase-like, glucose oxidase and peroxidase-like activities), CGBH NNs can produce massive reactive oxygen species (ROS) and further disrupt intracellular redox homeostasis, resulting in the disulfidptosis-enhanced pyroptosis. The tumor cells undergoing immunogenic pyroptosis can release various cytosolic contents and inflammatory factors, eliciting robust immune responses by facilitating immune cell infiltration, and reprogramming the immunosuppressive TME. After the combination with immune checkpoint blockade therapy, CGBH NNs can effectively suppress the tumor growth and prolong the survival time of tumor-bearing mice. This work presents a novel paradigm to trigger disulfidptosis-enhanced pyroptosis by destroying intracellular homeostasis for anti-tumor immunotherapy., (© 2024 Wiley‐VCH GmbH.)

We studied a candidate TPS (thermal protection system) material for reusable re-entry space vehicle applications. The material was based on a high-temperature-resistant material called Cerakwool. A total of six specimens were fabricated with substrate densities of 0.45 g/cm 3 , 0.40 g/cm 3 , and 0.35 g/cm 3 , with two specimens for each density. All specimens were coated with high-emissivity TUFI (toughened unpiece fibrous insulation), with coating thicknesses ranging from 445 to 1606 µm. The specimens were tested using an HVOF (high-velocity oxygen fuel) material ablation test facility. For each density specimen pair, one specimen was tested at 1 MW/m 2 and the remaining one was tested at 0.65 MW/m 2 . The average stagnation point temperature for specimens tested at 1 MW/m 2 was ~893 °C, approximately 200 °C higher than those tested at 0.65 MW/m 2 . This suggests a ~200 °C increase in stagnation point temperature for a 0.35 MW/m 2 rise in incident heat flux. During the tests, internal temperatures were measured at three locations. For all tested specimens, regardless of heat flux test conditions and density, the temperature at ~40 mm from each specimen's stagnation point remained around or below 50 °C, well within the 180 °C design limit set for the TPS back face temperature. Post-test visual inspections revealed no signs of ablation or internal damage, confirming the material's reusability.

Nitrogen (N) is the most essential element for growth, development, and grain yield determination in crops. However, excessive nitrogen application can result in environmental pollution and greenhouse gas emissions that contribute to climate change. In this study, we used 158 rice genetic resources to evaluate the relationships between the soil and plant analysis development (SPAD) value and grain yield (GY) and its components. The SPAD value ranged between 30.5 and 55.8, with a mean of 41.7 ± 5.3, under normal nitrogen conditions (NN, 9 kg/10a), and between 27.5 and 52.3, with a mean of 38.6 ± 4.8, under low nitrogen conditions (LN, 4.5 kg/10a). Under NN conditions, the SPAD values were in the following order: japonica (43.5 ± 5.8), Tongil -type (41.7 ± 2.5), others (41.7 ± 5.2), and indica (38.3 ± 3.8). By contrast, under LN conditions, the SPAD values were in the following order: Tongil -type (40.4 ± 2.1), others (40.1 ± 4.5), japonica (39.6 ± 5.2), and indica (35.6 ± 3.9). The 158 genetic resources showed no correlation between SPAD and yield. Therefore, the low-decrease rate (LDR) and high-decrease rate (HDR) SPAD groups were selected to reanalyze the relationships between the surveyed traits. The SPAD values were positively correlated with 1000-grain weight (TGW) for both LDR and HDR groups (NN: 0.63, LN: 0.53), However, SPAD and GY were positively correlated only in the LDR group. For TGW, the coefficient of determination ( R 2 ) was 20% and 13% under NN and LN conditions, respectively. For GY, R 2 values of 32% and 52% were observed under NN and LN conditions, respectively. Genetic resources with higher SPAD values in the LDR group exhibited the highest yield (NN: 1.19 kg/m 2 , LN: 1.04 kg/m 2 ) under both NN and LN conditions. In conclusion, we selected 10 genetic resources that exhibited higher GY under both NN and LN conditions with minimal yield reductions. These genetic resources represent valuable breeding materials for nitrogen deficiency adaptation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim and Kim.)

In this work, we report the syntheses of three Pt(II) emitters, namely, Pt4N1, Pt4N2, and Pt4N3, to which their tetradentate chelates were assembled by linking two pyrazolate chelates with a single xylenylamino entity. Functionalization of Pt4N1 was achieved upon the addition of electronegative CF 3 substituent on pyridinyl groups and switching to more electron-deficient pyrazinyl groups in giving Pt4N2 and Pt4N3, respectively. The vertically arranged xylenylamino entity has effectively suppressed the inter-molecular π-π stacking and Pt⋅⋅⋅Pt interaction, as shown by the single crystal X-ray structural analyses. Upon fabrication of OLED devices, Pt4N2 and Pt4N3 based devices delivered efficient cyan and green emission, with an EQE max of 15.2 % and 11.2 %, respectively, affirming the successfulness of the tetradentate chelating strategy., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The pleiotropic and protective effects of melatonin have been demonstrated in a variety of animal models of renal injury. While coding RNAs regulated by melatonin in renal tissues are well identified, the functional involvement of long noncoding RNAs (lncRNAs) in melatonin signaling remains undefined. This study identified nuclear enriched abundant transcript 1 ( NEAT 1), a clock-controlled lncRNA that was upregulated by melatonin through the BMAL1/CLOCK heterodimer in renal tubular epithelial cells (TECs). Mechanistic studies showed that melatonin enhanced NEAT 1 expression via increasing BMAL1 stability and thereby the enrichment of BMAL 1 on NEAT 1's promoter. Further studies have revealed that NEAT 1 promotes the proliferation of TECs by increasing levels of H3K27ac and H3K4me1 at the promoter regions of the proliferation gene MKI 67. Treatment of albumin-injured TECs with melatonin promoted proliferation by transactivating NEAT 1 and restoring the expression levels of core clock genes and MKI 67. Moreover, melatonin treatment ameliorated proteinuria, hypoalbuminemia, and fibrotic lesions, which was correlated with increased levels of core clock genes, H3K27ac, Mki 67, and Neat 1 in experimental MN kidneys. Melatonin mediates a novel regulatory axis, BMAL1- NEAT 1- MKI 67, in TEC proliferation, establishing potential therapeutic targets for MN and other renal diseases., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Background/Objectives: The limited translatability of preclinical experimental findings to patients remains an obstacle for successful treatment of brain diseases. Relevant models to elucidate mechanisms behind brain pathogenesis, including cell-specific contributions and cell-cell interactions, and support successful targeting and prediction of drug responses in humans are urgently needed, given the species differences in brain and blood-brain barrier (BBB) functions. Human microphysiological systems (MPS), such as Organ-Chips, are emerging as a promising approach to address these challenges. Here, we examined and advanced a Brain-Chip that recapitulates aspects of the human cortical parenchyma and the BBB in one model. Methods: We utilized human primary astrocytes and pericytes, human induced pluripotent stem cell (hiPSC)-derived cortical neurons, and hiPSC-derived brain microvascular endothelial-like cells and included for the first time on-chip hiPSC-derived microglia. Results: Using Tumor necrosis factor alpha (TNFα) to emulate neuroinflammation, we demonstrate that our model recapitulates in vivo-relevant responses. Importantly, we show microglia-derived responses, highlighting the Brain-Chip's sensitivity to capture cell-specific contributions in human disease-associated pathology. We then tested BBB crossing of human transferrin receptor antibodies and conjugated adeno-associated viruses. We demonstrate successful in vitro/in vivo correlation in identifying crossing differences, underscoring the model's capacity as a screening platform for BBB crossing therapeutic strategies and ability to predict in vivo responses. Conclusions: These findings highlight the potential of the Brain-Chip as a reliable and time-efficient model to support therapeutic development and provide mechanistic insights into brain diseases, adding to the growing evidence supporting the value of MPS in translational research and drug discovery.

In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals., (© 2024. The Author(s).)

Background: Although cyberbullying has emerged as a serious problem even among adults, most researches have been conducted on the adolescents. We aimed to verify the independent effects of cyber victimization, internet use, and the perception of cyberbullying-on-cyberbullying perpetration in South Korea adults., Methods: The data of 1500, 20s to 50s Korea adults from the 2019 Survey on the Cyberbullying conducted by the National Information Society Agency were used., Results: A hierarchical multiple regression analysis indicated that cyber victimization and internet use were positively related to cyberbullying perpetration. In particular, the perception of cyberbullying was negatively associated with cyberbullying perpetration., Conclusion: This study is an early effort to verify the influence of the perception of cyberbullying-on-cyberbullying perpetration. Educating that cyberbullying is an illegal and dangerous behavior is important to prevent cyberbullying perpetration., (Copyright© 2024 Park et al. Published by Tehran University of Medical Sciences.)

The study was carried out in the Phewa Lake of Pokhara Metropolitan City, Gandaki Province, Nepal, for geochemical assessment and characterization of the lake water quality. A total of 28 water samples were collected in each season from the different zones of the lake in March 2022 (pre-monsoon) and November 2022 (post-monsoon). The lake exhibited elevated levels of PO 4 3- , NO 3 - , and NH 3 , indicating that anthropogenic activities are interfering the lake water. The significant differences in many monitored physicochemical parameters between the pre- and post-monsoon visualize dilution effect in the lake during post-monsoon. Piper diagram illustrates that the majority of water samples in the lake are of Ca-HCO 3 type. Additionally, Piper diagram, Gibbs diagram, and Mixing plot illustrate that carbonate weathering is dominant in both seasons. Principal component analysis (PCA) reveals significant correlations among NO 3 - , SO 4 2- , Na + , and Cl - , demonstrating that pollution in the lake water is attributed to agricultural activities and domestic effluents. In the majority of samples, water quality index (WQI) depicts that the lake water quality is very poor to poor in the pre-monsoon and poor to good in the post-monsoon. Sodium absorption ratio (SAR), % Na (percent sodium), electrical conductivity (EC), cation ratio of soil structural stability (CROSS), and United States Salinity Laboratory (USSL) diagram illustrate that the lake water is suitable for irrigation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Inflammasomes are multi-protein complexes that assemble within the cytoplasm of mammalian cells in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), driving the secretion of the pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis. The best-characterized inflammasome complexes are the NLRP3, NAIP-NLRC4, NLRP1, AIM2, and Pyrin canonical caspase-1-containing inflammasomes, and the caspase-11 non-canonical inflammasome. Newer inflammasome sensor proteins have been identified, including NLRP6, NLRP7, NLRP9, NLRP10, NLRP11, NLRP12, CARD8, and MxA. These inflammasome sensors can sense PAMPs from bacteria, viruses and protozoa, or DAMPs in the form of mitochondrial damage, ROS, stress and heme. The mechanisms of action, physiological relevance, consequences in human diseases, and avenues for therapeutic intervention for these novel inflammasomes are beginning to be realized. Here, we discuss these emerging inflammasome complexes and their putative activation mechanisms, molecular and signaling pathways, and physiological roles in health and disease., (© 2024 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.)