Mediating effect of cognitive appraisal and coping on anticipatory grief in family caregivers of patients with cancer: a Bayesian structural equation model study.

BACKGROUND: Anticipatory grief is common among family caregivers of cancer patients and may be related to caregiver burden, family resilience, psychological capital, cognitive appraisal, and coping strategies. The purpose of this study was to examine the mediating role of cognitive appraisal and coping strategies in the relationship between caregiver burden, family resilience, psychological capital, and anticipatory grief among caregivers of cancer patients. METHODS: This study surveyed from January to September 2023 among 265 caregivers of lung and breast cancer patients in two public hospitals. They completed measures of caregiver burden, family resilience, psychological capital, cognitive appraisal, coping, and anticipatory grief. AMOS software was used to model the data with Bayesian structural equation modeling. RESULTS: Bayesian structural equation modeling results showed that caregiver burden had a direct effect on anticipatory grief. The chain mediating effects for cognitive appraisal tendency and coping tendency between caregiver burden, family resilience, psychological capital, and anticipatory grief, respectively. Coping tendency acted as a mediator between psychological capital and anticipatory grief. CONCLUSIONS: The relationships between caregiver burden, family resilience, and psychological capital with anticipatory grief are embedded in the mediating effects of cognitive appraisal and coping. Early identification and intervention for caregiver burden, family resilience, psychological capital, cognitive appraisal, and coping methods may prevent anticipatory grief in caregivers of cancer patients.

In-situ nanoplatform with synergistic neutrophil intervention and chemotherapy to prevent postoperative tumor recurrence and metastasis.

In addition to residual tumor cells, surgery-induced inflammation significantly contributes to tumor recurrence and metastasis by recruiting polymorphonuclear neutrophils (PMNs) and promoting their involvement in tumor cell proliferation, invasion and immune evasion. Efficiently eliminating residual tumor cells while concurrently intervening in PMN function represents a promising approach for enhanced postoperative cancer treatment. Here, a chitosan/polyethylene oxide electrospun fibrous scaffold co-delivering celecoxib (CEL) and doxorubicin-loaded tumor cell-derived microparticles (DOX-MPs) is developed for postoperative in-situ treatment in breast cancer. This implant (CEL/DOX-MPs@CP) ensures prolonged drug retention and sustained release within the surgical tumor cavity. The released DOX-MPs effectively eliminate residual tumor cells, while the released CEL inhibits the function of inflammatory PMNs, suppressing their promotion of residual tumor cell proliferation, migration and invasion, as well as remodeling the tumor immune microenvironment. Importantly, the strategy is closely associated with interference in neutrophil extracellular trap (NET) released from inflammatory PMNs, leading to a substantial reduction in postoperative tumor recurrence and metastasis. Our results demonstrate that CEL/DOX-MPs@CP holds great promise as an implant to enhance the prognosis of breast cancer patients following surgery.

Interplay of kernel shape and surface structure for NIR luminescence in atomically precise gold nanorods.

It is challenging to attain strong near-infrared (NIR) emissive gold nanoclusters. Here we show a rod-shaped cluster with the composition of [Au28(p-MBT)14(Hdppa)3](SO3CF3)2 (1 for short, Hdppa is N,N-bis(diphenylphosphino)amine, p-MBT is 4-methylbenzenethiolate) has been synthesized. Single crystal X-ray structural analysis reveals that it has a rod-like face-centered cubic (fcc) Au22 kernel built from two interpenetrating bicapped cuboctahedral Au15 units. 1 features NIR luminescence with an emission maximum at 920 nm, and the photoluminescence quantum yield (PLQY) is 12%, which is 30-fold of [Au21(m-MBT)12(Hdppa)2]SO3CF3 (2, m-MBT is 3-methylbenzenethiolate) with a similar composition and 60-fold of Au30S(S­t­Bu)18 with a similar structure. time-dependent DFT(TDDFT)calculations reveal that the luminescence of 1 is associated with the Au22 kernel. The small Stokes shift of 1 indicates that it has a very small excited state structural distortion, leading to high radiative decay rate (kr) probability. The emission of cluster 1 is a mixture of phosphorescence and thermally activated delayed fluorescence(TADF), and the enhancement of the NIR emission is mainly due to the promotion of kr rather than the inhibition of knr. This work demonstrates that the metal kernel and the surface structure are both very important for cluster-based NIR luminescence materials.

Signaling pathways activated and regulated by stem cell-derived exosome therapy.

Stem cell-derived exosomes exert comparable therapeutic effects to those of their parental stem cells without causing immunogenic, tumorigenic, and ethical disadvantages. Their therapeutic advantages are manifested in the management of a broad spectrum of diseases, and their dosing versatility are exemplified by systemic administration and local delivery. Furthermore, the activation and regulation of various signaling cascades have provided foundation for the claimed curative effects of exosomal therapy. Unlike other relevant reviews focusing on the upstream aspects (e.g., yield, isolation, modification), and downstream aspects (e.g. phenotypic changes, tissue response, cellular behavior) of stem cell-derived exosome therapy, this unique review endeavors to focus on various affected signaling pathways. After meticulous dissection of relevant literature from the past five years, we present this comprehensive, up-to-date, disease-specific, and pathway-oriented review. Exosomes sourced from various types of stem cells can regulate major signaling pathways (e.g., the PTEN/PI3K/Akt/mTOR, NF-κB, TGF-ß, HIF-1α, Wnt, MAPK, JAK-STAT, Hippo, and Notch signaling cascades) and minor pathways during the treatment of numerous diseases encountered in orthopedic surgery, neurosurgery, cardiothoracic surgery, plastic surgery, general surgery, and other specialties. We provide a novel perspective in future exosome research through bridging the gap between signaling pathways and surgical indications when designing further preclinical studies and clinical trials.

Occurrence, spatial distribution, and ecological risk of benzotriazole UV stabilizers (BUVs) in sediments from Bohai sea of China.

Benzotriazoles are a class of ultraviolet absorbents which absorb UV ranging from 280 to 400 nm and are widely used in personal care products and industrial production. Their residues in environmental matrices have received great concern in recent years, but most studies have focused on pollution in water and few have examined BUVs in marine sediments. In this study, we investigated the occurrence, potential sources, and ecological risk of 15 types of BUVs in the sediments of Bohai Sea in China for the first time. The total concentrations of the 15 BUVs ranged from 0.139 to 4.125 ng/g dw with a median concentration of 0.340 ng/g. UV-327 and UV-360 were predominant among the BUV congeners, accounting for 22.6% and 17.7% of the total concentration of Σ15BUVs, respectively. The detection frequencies of the BUV congeners generally exceeded 95%, reflecting the wide use and persistence of these chemicals. The concentrations of the BUV congeners in this study were one order of magnitude lower than those in other areas. Moreover, the distributions of BUVs presented a decreasing gradient from nearshore to offshore, indicating that coastal input was the main influencing factor. Two potential primary sources, plastic manufacturing and domestic wastewater, were identified via principle component analysis. The ecological risks of BUVs to aquatic organisms in the sediments were evaluated using the risk quotient (RQ) method. Generally, the risk to aquatic organisms from exposure to BUVs in Bohai Sea could be considered low at the measured concentrations. While our study provides important new insight into the ecological risks of BUVs in the estuary, further research on the pollution levels and toxicity risks of BUVs in Bohai Sea should be conducted to better understand the ecological effect of these pollutants.

The addition of Psathyrostachys Huashanica Keng 6Ns large segment chromosomes has positive impact on stripe rust resistance and plant spikelet number of common wheat.

BACKGROUND: Developing novel germplasm by using wheat wild related species is an effective way to rebuild the wheat resource bank. The Psathyrostachys huashanica Keng (P. huashanica, 2n = 2x = 14, NsNs) is regarded as a superior species to improve wheat breeding because of its multi-resistance, early maturation and numerous tiller traits. Introducing genetic components of P. huashanica into the common wheat background is the most important step in achieving the effective use. Therefore, the cytogenetic characterization and influence of the introgressed P. huashanica large segment chromosomes in the wheat background is necessary to be explored. RESULTS: In this study, we characterized a novel derived line, named D88-2a, a progeny of the former characterized wheat-P. huashanica partial amphiploid line H8911 (2n = 7x = 49, AABBDDNs). Cytological identification showed that the chromosomal composition of D88-2a was 2n = 44 = 22II, indicating the addition of exogenous chromosomes. Genomic in situ hybridization demonstrated that the supernumerary chromosomes were a pair of homologues from the P. huashanica and could be stably inherited in the common wheat background. Molecular markers and 15 K SNP array indicated that the additional chromosomes were derived from the sixth homoeologous group (i.e., 6Ns) of P. huashanica. Based on the distribution of the heterozygous single-nucleotide polymorphism sites and fluorescence in situ hybridization karyotype of each chromosome, this pair of additional chromosomes was confirmed as P. huashanica 6Ns large segment chromosomes, which contained the entire short arm and the proximal centromere portion of the long arm. In terms of the agronomic traits, the addition line D88-2a exhibited enhanced stripe rust resistance, improved spike characteristics and increased protein content than its wheat parent line 7182. CONCLUSIONS: The new wheat germplasm D88-2a is a novel cytogenetically stable wheat-P. huashanica 6Ns large segment addition line, and the introgressed large segment alien chromosome has positive impact on plant spikelet number and stripe rust resistance. Thus, this germplasm can be used for genetic improvement of cultivated wheat and the study of functional alien chromosome segment.

Local Delivery of Dual Stem Cell-Derived Exosomes Using an Electrospun Nanofibrous Platform for the Treatment of Traumatic Brain Injury.

Traumatic brain injury poses serious physical, psychosocial, and economic threats. Although systemic administration of stem cell-derived exosomes has recently been proven to be a promising modality for traumatic brain injury treatment, they come with distinct drawbacks. Luckily, various biomaterials have been developed to assist local delivery of exosomes to improve the targeting of organs, minimize nonspecific accumulation in vital organs, and ensure the protection and release of exosomes. In this study, we developed an electrospun nanofibrous scaffold to provide sustained delivery of dual exosomes derived from mesenchymal stem cells and neural stem cells for traumatic brain injury treatment. The electrospun nanofibrous scaffold employed a functionalized layer of polydopamine on electrospun poly(ε-caprolactone) nanofibers, thereby enhancing the efficient incorporation of exosomes through a synergistic interplay of adhesive forces, hydrogen bonding, and electrostatic interactions. First, the mesenchymal stem cell-derived exosomes and the neural stem cell-derived exosomes were found to modulate microglial polarization toward M2 phenotype, play an important role in the modulation of inflammatory responses, and augment axonal outgrowth and neural repair in PC12 cells. Second, the nanofibrous scaffold loaded with dual stem cell-derived exosomes (Duo-Exo@NF) accelerated functional recovery in a murine traumatic brain injury model, as it mitigated the presence of reactive astrocytes and microglia while elevating the levels of growth associated protein-43 and doublecortin. Additionally, multiomics analysis provided mechanistic insights into how dual stem cell-derived exosomes exerted its therapeutic effects. These findings collectively suggest that our novel Duo-Exo@NF system could function as an effective treatment modality for traumatic brain injury using sustained local delivery of dual exosomes from stem cells.

Immunomodulatory effect of PLGA-encapsulated mesenchymal stem cells-derived exosomes for the treatment of allergic rhinitis.

Introduction: Allergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases. Methods: In order to achieve sustained and protected release of MSC-Exos for intranasal administration, we fabricated Poly(lactic-co-glycolic acid) (PLGA) micro and nanoparticles-encapsulated MSC-Exos (PLGA-Exos) using mechanical double emulsion for local treatment of AR. Preclinical in vivo imaging, ELISA, qPCR, flow cytometry, immunohistochemical staining, and multiomics sequencing were used for phenotypic and mechanistic evaluation of the therapeutic effect of PLGA-Exos in vitro and in vivo. Results: The results showed that our PLGA platform could efficiently encapsulate and release the exosomes in a sustained manner. At protein level, PLGA-Exos treatment upregulated IL-2, IL-10 and IFN-γ, and downregulated IL-4, IL-17 and antigen-specific IgE in ovalbumin (OVA)-induced AR mice. At cellular level, exosomes treatment reduced Th2 cells, increased Tregs, and reestablished Th1/Th2 balance. At tissue level, PLGA-Exos significantly attenuated the infiltration of immune cells (e.g., eosinophils and goblet cells) in nasal mucosa. Finally, multiomics analysis discovered several signaling cascades, e.g., peroxisome proliferator-activated receptor (PPAR) pathway and glycolysis pathway, that might mechanistically support the immunomodulatory effect of PLGA-Exos. Discussion: For the first time, we present a biomaterial-facilitated local delivery system for stem cell-derived exosomes as a novel and promising strategy for AR treatment.

Broad Complex-Z2 directly activates BmMBF2 to inhibit the silk protein synthesis in the silkworm, Bombyx mori.

Silk proteins, as natural macromolecules, have extensive applications in biomaterials and biomedicine. In the silkworm, the expression of silk protein genes is negatively associated with ecdysone during the molt stage, while it is positively correlated with juvenile hormone during the intermolt stage. In our previous study, overexpression of an isoform Z2 of Broad Complex (BmBrC-Z2), an ecdysone early response factor, significantly reduced the expression of silk protein genes. However, the underlying regulatory mechanism remains unclear. In this study, we conducted transcriptomic analysis and found that overexpressing BmBrC-Z2 significantly upregulated the expression level of multiprotein bridging factor 2 (BmMBF2), an inhibitor of fibroin heavy chain (FibH). Further investigations revealed that BmBrC-Z2 directly regulated BmMBF2 by binding to cis-regulatory elements, as demonstrated using Dual-Luciferase Reporter Gene Assay, EMSA, and ChIP-PCR assay. Additionally, when using the CRISPR/Cas9 system to knock out BmMBF2, silk protein genes were significantly upregulated during the molt stage of mutant larvae. These findings uncover the negative regulation of silk protein synthesis by the ecdysone signaling cascade, specifically through the manipulation of BmMBF2 expression during the molt stage. This study enhances to our understanding of the temporal regulatory mechanism governing silk protein synthesis and offers a potential strategy for improving silk yield.

ETS1 and RBPJ transcriptionally regulate METTL14 to suppress TGF-ß1-induced epithelial-mesenchymal transition in human bronchial epithelial cells.

Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling. Epithelial-mesenchymal transition (EMT) of bronchial epithelial cells is considered to be a crucial player in asthma. Methyltransferase-like 14 (METTL14), an RNA methyltransferase, is implicated in multiple pathological processes, including EMT, cell proliferation and migration. However, the role of METTL14 in asthma remains uncertain. This research aimed to explore the biological functions of METTL14 in asthma and its underlying upstream mechanisms. METTL14 expression was down-regulated in asthmatic from three GEO datasets (GSE104468, GSE165934, and GSE74986). Consistent with this trend, METTL14 was decreased in the lung tissues of OVA-induced asthmatic mice and transforming growth factor-ß1 (TGF-ß1)-stimulated human bronchial epithelial cells (Beas-2B) in this study. Overexpression of METTL14 caused reduction in mesenchymal markers (FN1, N-cad, Col-1 and α-SMA) in TGF-ß1-treated cells, but caused increase in epithelial markers (E-cad), thus inhibiting EMT. Also, METTL14 suppressed the proliferation and migration ability of TGF-ß1-treated Beas-2B cells. Two transcription factors, ETS1 and RBPJ, could both bind to the promoter region of METTL14 and drive its expression. Elevating METTL14 expression could reversed EMT, cell proliferation and migration promoted by ETS1 or RBPJ deficiency. These results indicate that the ETS1/METTL14 and RBPJ/METTL14 transcription axes exhibit anti-EMT, anti-proliferation and anti-migration functions in TGF-ß1-induced bronchial epithelial cells, implying that METTL14 may be considered an alternative candidate target for the treatment of asthma.

Exudates of Microcystis aeruginosa on oxidative stress and inflammatory responses in gills of Sinocyclocheilus grahami.

Early cyanobacterial blooms studies observed that exposure to blue-green algae led to fish gills impairment. The objective of this work was to evaluate the toxic mechanisms of exudates of Microcystis aeruginosa (MaE) on fish gills. In this study, the toxic mechanism of MaE (2×106 cells/mL) and one of its main components phytosphingosine (PHS) with two concentrations 2.9 ng/mL and 145 ng/mL were conducted by integrating histopathology, biochemical biomarkers, and transcriptomics techniques in Sinocyclocheilus grahami (S. grahami) for 96 h exposure. Damaged gill tissue with epithelial hyperplasia and hypertrophy, remarkable Na+/K+-ATPase (NKA) enzyme activity, disrupted the redox homeostats including lipid peroxidation and inflammatory responses were observed in the fish of MaE exposure group. Compare to MaE exposure, two concentrations of PHS exposure appeared to be a trend of lower degree of tissue damage, NKA activity and oxidative stress, but induced obviously lipid metabolism disorder with higher triglycerides, total cholesterol and total bile acid, which might be responsible for inflammation responses in fish gill. By transcriptome analysis, MaE exposure were primarily enriched in pathways related to gill function and immune response. PHS exposure, with higher number of differentially expressed genes (DEGs), were enriched in Toll-like receptor (TLR), Mitogen-Activated Protein Kinase (MAPK) and NOD-like receptor protein 3 (NLRP3) pathways. We concluded that MaE and PHS were induced the inflammatory responses, with oxidative stress-induced inflammation for MaE exposure but lipid metabolism disorder-induced inflammation for PHS exposure. The present study provided two toxin-induced gill inflammation response pathways under cyanobacterial blooms, which could be a scientific basis for the ecological and health risk assessment in the aquatic environment.

Benzotriazole ultraviolet absorbents in surface waters and sediments of the Bohai Sea and North Yellow Sea: Spatial trends and influencing factors.

Benzotriazole ultraviolet absorbents (BUAs) of emerging concern were recently monitored in seawater and sediments from the Bohai Sea (BS) and North Yellow Sea (NYS), which are impacted by human activities, to elucidate their regional occurrence patterns, phase distributions, and contamination profiles. Although environmental variables such as sedimentary organic carbon, particle size, and salinity, as well as hydrological conditions, affected the environmental occurrence of BUAs in the BS and NYS, the source dependence of BUA distributions associated with urban impacts and riverine inputs was highlighted. Substantial spatial variability in the composition patterns and contamination profiles of BUAs identified through correlation and principal component analyses were likely caused by region-specific sources and characteristics. The distribution of target BUAs between the sediment and seawater phases showed no dependence on the octanol-water partition coefficient (KOW) but exhibited marked spatial variations. The diversity of BUA sorption behaviors was further explained by the total organic carbon (TOC)-normalized distribution coefficient (KTOC). Classic logKTOC-logKOW linear relationships accurately predicted the phase distributions of UV-326, UV-328, and UV-234, but deviations were found for lighter and heavier BUAs, possibly due to the influences of physical disturbance and microparticle binding.

Region-Specific CD16+ Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16+ neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro-tumor activity by disturbing natural killer (NK) cells are identified. It is found that these CD16+ neutrophils possess abnormal cholesterol accumulation due to activation of the CD16/TAK1/NF-κB axis, which upregulates scavenger receptors for cholesterol intake including CD36 and LRP1. Consequently, these region-specific CD16+ neutrophils not only competitively inhibit cholesterol intake of NK cells, which interrupts NK lipid raft formation and blocks their antitumor signaling but also release neutrophil extracellular traps (NETs) to induce the death of NK cells. Furthermore, CD16-knockout reverses the pro-tumor activity of neutrophils and restored NK cell cytotoxicity. Collectively, the findings suggest that CRC region-specific CD16+ neutrophils can be a diagnostic marker and potential therapeutic target for CRC.

Predictive models for delay in medical decision-making among older patients with acute ischemic stroke: a comparative study using logistic regression analysis and lightGBM algorithm.

OBJECTIVE: To explore the factors affecting delayed medical decision-making in older patients with acute ischemic stroke (AIS) using logistic regression analysis and the Light Gradient Boosting Machine (LightGBM) algorithm, and compare the two predictive models. METHODS: A cross-sectional study was conducted among 309 older patients aged ≥ 60 who underwent AIS. Demographic characteristics, stroke onset characteristics, previous stroke knowledge level, health literacy, and social network were recorded. These data were separately inputted into logistic regression analysis and the LightGBM algorithm to build the predictive models for delay in medical decision-making among older patients with AIS. Five parameters of Accuracy, Recall, F1 Score, AUC and Precision were compared between the two models. RESULTS: The medical decision-making delay rate in older patients with AIS was 74.76%. The factors affecting medical decision-making delay, identified through logistic regression and LightGBM algorithm, were as follows: stroke severity, stroke recognition, previous stroke knowledge, health literacy, social network (common factors), mode of onset (logistic regression model only), and reaction from others (LightGBM algorithm only). The LightGBM model demonstrated the more superior performance, achieving the higher AUC of 0.909. CONCLUSIONS: This study used advanced LightGBM algorithm to enable early identification of delay in medical decision-making groups in the older patients with AIS. The identified influencing factors can provide critical insights for the development of early prevention and intervention strategies to reduce delay in medical decisions-making among older patients with AIS and promote patients' health. The LightGBM algorithm is the optimal model for predicting the delay in medical decision-making among older patients with AIS.

A Simple and Low-Cost CRISPR/Cas9 Knockout System Widely Applicable to Insects.

The CRISPR/Cas9 gene-editing system is a standard technique in functional genomics, with widespread applications. However, the establishment of a CRISPR/Cas9 system is challenging. Previous studies have presented numerous methodologies for establishing a CRISPR/Cas9 system, yet detailed descriptions are limited. Additionally, the difficulties in obtaining the necessary plasmids have hindered the replication of CRISPR/Cas9 techniques in other laboratories. In this study, we share a detailed and simple CRISPR/Cas9 knockout system with optimized steps. The results of gene knockout experiments in vitro and in vivo show that this system successfully knocked out the target gene. By sharing detailed information on plasmid sequences, reagent codes, and methods, this study can assist researchers in establishing gene knockout systems.

A lava-inspired proteolytic enzyme therapy on cancer with a PEG-based hydrogel enhances tumor distribution and penetration of liposomes.

The enhanced permeability and retention (EPR) effect has become the guiding principle for nanomedicine against cancer for a long time. However, several biological barriers severely resist therapeutic agents' penetration and retention into the deep tumor tissues, resulting in poor EPR effect and high tumor mortality. Inspired by lava, we proposed a proteolytic enzyme therapy to improve the tumor distribution and penetration of nanomedicine. A trypsin-crosslinked hydrogel (Trypsin@PSA Gel) was developed to maintain trypsin's activity. The hydrogel postponed trypsin's self-degradation and sustained the release. Trypsin promoted the cellular uptake of nanoformulations in breast cancer cells, enhanced the penetration through endothelial cells, and degraded total and membrane proteins. Proteomic analysis reveals that trypsin affected ECM components and down-regulated multiple pathways associated with cancer progression. Intratumoral injection of Trypsin@PSA Gel significantly increased the distribution of liposomes in tumors and reduced tumor vasculature. Combination treatment with intravenous injection of gambogic acid-loaded liposomes and intratumoral injection of Trypsin@PSA Gel inhibited tumor growth. The current study provides one of the first investigations into the enhanced tumor distribution of liposomes induced by a novel proteolytic enzyme therapy.

A new therapeutic perspective: Erastin inhibits tumor progression by driving ferroptosis in myelodysplastic syndromes.

Ferroptosis is a recently identified and evolutionarily conserved form of programmed cell death. This process is initiated by an imbalance in iron metabolism, leading to an overload of ferrous ions. These ions promote lipid peroxidation in the cell membrane through the Fenton reaction. As the cell's antioxidant defenses become overwhelmed, a fatal buildup of reactive oxygen species (ROS) occurs, resulting in the rupture of the plasma membrane. Ferroptosis is implicated in conditions such as ischemia-reperfusion injuries and a range of cancers. In our research, we explored ferroptosis in myelodysplastic syndromes (MDS) by measuring iron levels, transferrin receptor expression, and glutathione peroxidase 4 (GPX4) mRNA. Our findings revealed that MDS patients had significantly higher Fe2+ levels in CD33+ cells and increased transferrin receptor mRNA compared to healthy individuals. GPX4 expression was also higher in MDS but not statistically significant. To investigate potential treatments for myeloid hematological diseases through ferroptosis induction, we treated the myelodysplastic syndrome cell line (SKM-1) and two myeloid leukemia cell lines (KG-1 and K562) with erastin, an iron transfer inducer. We observed that erastin treatment led to glutathione depletion, reduced GPX4 activity, and increased ROS, culminating in cell death by ferroptosis. Furthermore, combining erastin with azacitidine demonstrated a synergistic effect on MDS and leukemia cell lines, suggesting a promising approach for treating these hematological conditions with this drug combination. Our experiments confirm erastin's ability to induce ferroptosis in MDS and highlight its potential synergistic use with azacitidine for treatment.

The coordination of bimaxillary alveolar arch widths in subjects with normal occlusion or posterior crossbite: A CBCT retrospective study.

OBJECTIVES: To propose a method for evaluating the coordination of maxillomandibular alveolar arch in transverse dimension with cone-beam computed tomography (CBCT) and to apply this method to subjects with normal occlusion at different dentition stages or transverse discrepancy. MATERIALS AND METHODS: Digital data of 130 patients with normal occlusion at different dentition stages or transverse discrepancy were collected for three-dimensional reconstruction. The patients with normal occlusion were divided into Group 1 (>16 years) and Group 2 (≤16 years) based on their age. Adult patients with posterior crossbite were divided into the Group 3. According to the proposed method, the average alveolar arch coordination angle (AACA) and other parameters were analysed in each group. Group 1 was considered as the control group and compared with Group 2 and Group 3. RESULTS: Significant differences were observed in the maxillary posterior segment width among patients with normal occlusion. Group 3 demonstrated increased AACA and mandibular alveolar arch width compared with the normal occlusion group. Pearson correlation analysis indicated a positive relationship between maxillomandibular alveolar arch widths in the normal occlusion groups, with a strong correlation between AACA and the disparity in maxillomandibular widths. CONCLUSION: Adults with normal occlusion exhibit significantly wider maxillary posterior alveolar arches than adolescents, with no marked difference in mandibular widths. The posterior crossbite group showed broader mandibular alveolar arches. There was a strong correlation between AACA and the difference in maxillomandibular widths. This study's method shows potential value for orthodontic transverse diagnosis.

Comparison of the osteogenic potential of fibroblasts from different sources.

OBJECTIVE: With the growing interest in the role of fibroblasts in osteogenesis, this study presents a comparative evaluation of the osteogenic potential of fibroblasts derived from three distinct sources: human gingival fibroblasts (HGFs), mouse embryonic fibroblasts (NIH3T3 cells), and mouse subcutaneous fibroblasts (L929 cells). MC3T3-E1 pre-osteoblast cells were employed as a positive control for osteogenic behavior. DESIGN: Our assessment involved multiple approaches, including vimentin staining for cell origin verification, as well as ALP and ARS staining in conjunction with RT-PCR for osteogenic characterization. RESULTS: Our findings revealed the superior osteogenic differentiation capacity of HGFs compared to MC3T3-E1 and NIH3T3 cells. Analysis of ALP staining confirmed that early osteogenic differentiation was most prominent in MC3T3-E1 cells at 7 days, followed by NIH3T3 and HGFs. However, ARS staining at 21 days demonstrated that HGFs produced the highest number of calcified nodules, indicating their robust potential for late-stage mineralization. This late-stage osteogenic potential of HGFs was further validated through RT-PCR analysis. In contrast, L929 cells displayed no significant osteogenic differentiation potential. CONCLUSIONS: In light of these findings, HGFs emerge as the preferred choice for seed cells in bone tissue engineering applications. This study provides valuable insights into the potential utility of HGFs in the fields of bone tissue engineering and regenerative medicine.

Quantifying the Impact of Environment Loads on Displacements in a Suspension Bridge with a Data-Driven Approach.

Long-span bridges are susceptible to damage, aging, and deformation in harsh environments for a long time. Therefore, structural health monitoring (SHM) systems need to be used for reasonable monitoring and maintenance. Among various indicators, bridge displacement is a crucial parameter reflecting the bridge's health condition. Due to the simultaneous bearing of multiple environmental loads on suspension bridges, determining the impact of different loads on displacement is beneficial for the better understanding of the health conditions of the bridges. Considering the fact that extreme gradient boosting (XGBoost) has higher prediction performance and robustness, the authors of this paper have developed a data-driven approach based on the XGBoost model to quantify the impact between different environmental loads and the displacement of a suspension bridge. Simultaneously, this study combined wavelet threshold (WT) denoising and the variational mode decomposition (VMD) method to conduct a modal decomposition of three-dimensional (3D) displacement, further investigating the interrelationships between different loads and bridge displacements. This model links wind speed, temperature, air pressure, and humidity with the 3D displacement response of the span using the bridge monitoring data provided by the GNSS and Earth Observation for Structural Health Monitoring (GeoSHM) system of the Forth Road Bridge (FRB) in the United Kingdom (UK), thus eliminating the temperature time-lag effect on displacement data. The effects of the different loads on the displacement are quantified individually with partial dependence plots (PDPs). Employing testing, it was found that the XGBoost model has a high predictive effect on the target variable of displacement. The analysis of quantification and correlation reveals that lateral displacement is primarily affected by same-direction wind, showing a clear positive correlation, and vertical displacement is mainly influenced by temperature and exhibits a negative correlation. Longitudinal displacement is jointly influenced by various environmental loads, showing a positive correlation with atmospheric pressure, temperature, and vertical wind and a negative correlation with longitudinal wind, lateral wind, and humidity. The results can guide bridge structural health monitoring in extreme weather to avoid accidents.