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Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Air-water interface (AWI) interactions during cryo-electron microscopy (cryo-EM) sample preparation cause significant sample loss, hindering structural biology research. Organisms like nematodes and tardigrades produce Late Embryogenesis Abundant (LEA) proteins to withstand desiccation stress. Here we show that these LEA proteins, when used as additives during plunge freezing, effectively mitigate AWI damage to fragile multi-subunit molecular samples. The resulting high-resolution cryo-EM maps are comparable to or better than those obtained using existing AWI damage mitigation methods. Cryogenic electron tomography reveals that particles are localized at specific interfaces, suggesting LEA proteins form a barrier at the AWI. This interaction may explain the observed sample-dependent preferred orientation of particles. LEA proteins offer a simple, cost-effective, and adaptable approach for cryo-EM structural biologists to overcome AWI-related sample damage, potentially revitalizing challenging projects and advancing the field of structural biology., (© 2024. The Author(s).)

Metabolic reprogramming sustains malignant head and neck squamous cell carcinoma (HNSCC) to overcome stressful microenvironments, and increased glutamine uptake is a common metabolic hallmark in cancers. Since metabolic reprogramming has been recognized as a new therapeutic target for tumor cells, understanding the regulatory axis of glutamine uptake in HNSCC and its potential downstream effects in its pathogenesis of HNSCC would be incredibly beneficial. Bioinformatic analysis of the Cancer Genome Atlas (TCGA)-HNSCC dataset and RNAseq analysis performed on HNSCC indicated that SLC1A5 was the most dysregulated transporter among the seven homologous glutamate or neutral amino acid transporters in the SLC1A family. To further clarify the role of SLC1A5 in HNSCC, we knocked down SLC1A5 expression. This knockdown decelerated cell growth, induced G0/G1 arrest, diminished tumorigenicity, and increased cleavage caspase3, LC3B, and intracellular Fe 2+ . Inhibitors against apoptosis, autophagy, or ferroptosis rescued the cell viability repressed by SLC1A5 knockdown. SLC1A5 knockdown also suppressed glutamine uptake, enhanced oxidative stress, and increased sensitivity to cisplatin. CRISPR/dCas9-mediated SLC1A5 induction conferred cisplatin resistance and reduced apoptosis, autophagy, and ferroptosis. Reporter assays and western blot data demonstrated that miR-125b-5p targets and attenuates SLC1A5, while the si-NEAT1 increases miR-125b-5p expression. Analysis of the TCGA-HNSCC databases showed concordant upregulation of NEAT1 and downregulation of miR-125b-5p, along with SLC1A5 upregulation in tumors. Analysis of transcriptomic data revealed that tumors harboring higher SLC1A5 expression had significantly lower immune scores in CD8 + , monocytes, and dendritic cells, and higher scores in M0 and M1 macrophages. Disruptions in immune modulation, metabolism, and oxidative stress components were associated with SLC1A5 aberrations in HNSCC. This study concludes that the NEAT1/miR-125b-5p/SLC1A5 cascade modulates diverse activities in oncogenicity, treatment efficacy, and immune cell profiles in head and neck/oral carcinoma., (© 2024. The Author(s).)

Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen., Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT., Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group., Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage., 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 Wang, Wang, Su, Wang, Li, Li, Jing, Xu, Wang, Zheng, Gao, Hu, Gao and Liu.)

Catalpol, a natural iridoid glycoside, has potential therapeutic benefits, including anti-inflammatory and neuroprotective effects. Investigating catalpol's role in angiogenesis is critical for understanding its potential therapeutic applications, particularly in diseases where modulating angiogenesis is beneficial. This study investigates catalpol's influence on angiogenesis and its mechanisms, combining network pharmacology and in vitro experiments. The target genes corresponding to the catalpol were analyzed by SwissTargetPrediction. Then angiogenesis-related targets were acquired from databases like GeneCards. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was employed for Gene Ontology and pathway analysis, while Cytoscape visualized protein interactions. The effect of catalpol on viability and angiogenesis of HUVECs was further examined using Cell Counting Kit-8 and angiogenesis assays. RT-qPCR and western blot were applied to check the expression of angiogenesis-related proteins. Totally, 312 target genes of catalpol and 823 angiogenesis-related targets were obtained with 56 common targets leading to PPI network analysis, highlighting hub genes (AKT1, EGFR, STAT3, MAPK3, and CASP3). These hub genes were mainly enriched in lipid and atherosclerosis pathway and EGFR-related pathway. The in vitro experimental results showed that catalpol achieved a concentration-dependent increase in HUVECs viability. Catalpol also promoted the migration and angiogenesis of HUVECs and up-regulated the expression of EGFR. EGFR knockdown inhibited the effect of catalpol on HUVECs. Catalpol promotes angiogenesis in HUVECs by upregulating EGFR and angiogenesis-related proteins, indicating its potential therapeutic application in vascular-related diseases., (© 2024 John Wiley & Sons Ltd.)

Articular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self-healing capacity and damaging bone structures. To tackle this problem, a scaffold-mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε-caprolactone) and strontium (Sr)-doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn-embedded scaffolds (SrBGn-µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation-related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow-derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn-µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background/purpose: T cells require second immune checkpoint molecules for activation and immune memory after antigen presentation. We found that inducible co-stimulator (ICOS) has been a favorable prognostic factor amongst B7 immune checkpoint co-stimulators (ICSs) families in head and neck squamous cell carcinoma (HNSCC) and oral SCC (OSCC)., Materials and Methods: This study analyzed the expression of non-B7 tumor necrosis factor (TNF) superfamily ICSs in the Cancer Genome Atlas (TCGA) HNSCC cohort, our OSCC cohort, and TCGA pan-cancer datasets. The correlation in expression, prognosis, and immune status was assessed., Results: The higher expression of CD27, CD30, CD40L, death domain 3 (DR3), and OX40, presumably on the T cell surface, defined better overall survival of HNSCC patients. Besides, CD27, CD30, CD40L, and OX40 were highly correlated with ICOS expression in tumors. CD27, CD40L, and DR3 expression are higher in HPV+ HNSCC tumors than in HPV- tumors. The combined expression level of CD27/OX40 or CD27/CD40L/OX40 enables the potent survival prediction of small, less nodal involvement, early stage, and HPV + tumor subsets. Tumors expressing high CD27, CD30, CD40L, ICOS, and OX40 exhibited enhanced immune cell infiltration. The high correlation in the expression of these ICSs was also noted in the vast majority of tumor types in TCGA datasets., Conclusion: The findings of this study not only confirm the potential of the concordant stimulation of CD27, CD30, CD40L, ICOS, and OX40 as a crucial strategy in cancer immunotherapy but also inspire further exploration into the field, highlighting the promising future of cancer treatment., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Purpose: This population-based cohort study aimed to examine the association with childhood attention deficit/hyperactivity disorder (ADHD) and bullying experiences during adolescence among Digital Generation individuals, exploring both traditional and cyberbullying., Methods: This study included data from 15,240 participants, collected from the Taiwan Adolescent to Adult Longitudinal Study project. Participants, initially in seventh and 10th grade in 2015, were selected through a multistage stratified sampling approach. Self-report questionnaires assessed traditional and cyberbullying victimization experiences during adolescence, with 5-year longitudinal follow-up. Childhood ADHD diagnoses were identified by linking data to Taiwan's National Health Insurance Research Database from 2000 to 2015. Logistic regression models were employed to examine the relationship between childhood ADHD and bullying victimization while controlling for relevant covariates., Results: Individuals diagnosed with childhood ADHD exhibited a significantly higher likelihood of experiencing bullying during adolescence (adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.28-1.80). This association extended to various forms of bullying, including physical (aOR = 1.42, 95% CI: 1.20-1.68), verbal (aOR = 1.42, 95% CI: 1.20-1.67), relational (aOR = 1.45, 95% CI: 1.22-1.71), and cyber (aOR = 1.35, 95% CI: 1.14-1.61). Additional factors positively associated with bullying victimization included male, binge drinking, and depression, while a positive campus atmosphere was protective against bullying. However, there is no evidence for interactions between these factors and ADHD in their associations with bullying., Discussion: Childhood ADHD increases the risk of both traditional and cyberbullying during adolescence. Recognizing this risk is essential for targeted interventions and further research on underlying mechanisms., (Copyright © 2024. Published by Elsevier Inc.)

Biomimetic stress-relaxing hydrogels with reversible crosslinks attract significant attention for stem cell tissue regeneration compared with elastic hydrogels. However, stress-relaxing hyaluronic acid (HA)-based hydrogels fabricated using conventional technologies lack stability, biocompatibility, and mechanical tunability. Here, it is aimed to address these challenges by incorporating calcium or phosphate components into the HA backbone, which allows reversible crosslinking of HA with alginate to form interpenetrating networks, offering stability and mechanical tunability for mimicking cartilage. Diverse stress-relaxing hydrogels (τ1/2; SR50, 60-2000 s) are successfully prepared at ≈3 kPa stiffness with self-healing and shear-thinning abilities, favoring hydrogel injection. In vitro cell experiments with RNA sequencing analysis demonstrate that hydrogels tune chondrogenesis in a biphasic manner (hyaline or calcified) depending on the stress-relaxation properties and phosphate components. In vivo studies confirm the potential for biphasic chondrogenesis. These results indicate that the proposed stress-relaxing HA-based hydrogel with biphasic chondrogenesis (hyaline or calcified) is a promising material for cartilage regeneration., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Inactivating mutations in the melanocortin 4 receptor ( MC4R ) gene cause monogenic obesity. Interestingly, female patients also display various degrees of reproductive disorders, in line with the subfertile phenotype of MC4RKO female mice. However, the cellular mechanisms by which MC4R regulates reproduction are unknown. Kiss1 neurons directly stimulate gonadotropin-releasing hormone (GnRH) release through two distinct populations; the Kiss1 ARH neurons, controlling GnRH pulses, and the sexually dimorphic Kiss1 AVPV/PeN neurons controlling the preovulatory LH surge. Here, we show that Mc4r expressed in Kiss1 neurons is required for fertility in females. In vivo , deletion of Mc4r from Kiss1 neurons in female mice replicates the reproductive impairments of MC4RKO mice without inducing obesity. Conversely, reinsertion of Mc4r in Kiss1 neurons of MC4R null mice restores estrous cyclicity and LH pulsatility without reducing their obese phenotype. In vitro , we dissect the specific action of MC4R on Kiss1 ARH vs Kiss1 AVPV/PeN neurons and show that MC4R activation excites Kiss1 ARH neurons through direct synaptic actions. In contrast, Kiss1 AVPV/PeN neurons are normally inhibited by MC4R activation except under elevated estradiol levels, thus facilitating the activation of Kiss1 AVPV/PeN neurons to induce the LH surge driving ovulation in females. Our findings demonstrate that POMC ARH neurons acting through MC4R, directly regulate reproductive function in females by stimulating the "pulse generator" activity of Kiss1 ARH neurons and restricting the activation of Kiss1 AVPV/PeN neurons to the time of the estradiol-dependent LH surge, and thus unveil a novel pathway of the metabolic regulation of fertility by the melanocortin system., Competing Interests: Declaration of interests: The authors declare they have no competing interest.

Objective: To investigate the effect of CD8 + CD28 - T cells on acute graft-versus-host disease(aGVHD) after haploidentical hematopoietic stem cell transplantation(haplo-HSCT)., Methods: The relationship between absolute count of CD8 + CD28 - T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT, and the differences in the incidence rate of chronic graft-versus host disease(cGVHD), infection and prognosis between different CD8 + CD28 - T absolute cells count groups were compared., Results: aGVHD occurred in 40 of 60 patients after haplo-HSCT, with an incidence rate of 66.67%. The median occurrence time of aGVHD was 32.5(20-100) days. At 30 days after the transplantation, the absolute count of CD8 + CD28 - T cells of aGVHD group was significantly lower than that of non-aGVHD group ( P =0.03). Thus the absolute count of CD8 + CD28 - T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent. At 30 days after transplantation, the incidence rate of aGVHD in the low cell count group (CD8 + CD28 - T cells absolute count < 0.06/μl) was significantly higher than that in the high cell count group (CD8 + CD28 - T cells absolute count ≥0.06/μl, P =0.011). Multivariate Cox regression analysis further confirmed that the absolute count of CD8 + CD28 - T cells at 30 days after transplantation was an independent risk factor for aGVHD, and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group ( P =0.015). The incidence of cGVHD, fungal infection, EBV infection and CMV infection were not significantly different between the two groups with different CD8 + CD28 - T cells absolute count. The overall survival, non-recurrent mortality and relapse rates were not significantly different between different CD8 + CD28 - T cells absolute count groups., Conclusion: Patients with delayed CD8 + CD28 - T cells reconstitution after haplo-HSCT are more likely to develop aGVHD, and the absolute count of CD8 + CD28 - T cells can be used to predict the incidence of aGVHD to some extent. The absolute count of CD8 + CD28 - T cells after haplo-HSCT was not associated with cGVHD, fungal infection, EBV infection, and CMV infection, and was also not significantly associated with the prognosis after transplantation.

The surface topological features of bioimplants are among the key indicators for bone tissue replacement because they directly affect cell morphology, adhesion, proliferation, and differentiation. In this study, we investigated the physical, electrochemical, and biological responses of sandblasted titanium (SB-Ti) surfaces with pore geometries fabricated using a plasma electrolytic oxidation (PEO) process. The PEO treatment was conducted at an applied voltage of 280 V in a solution bath consisting of 0.15 mol L -1 calcium acetate monohydrate and 0.02 mol L -1 calcium glycerophosphate for 3 min. The surface chemistry, wettability, mechanical properties and corrosion behavior of PEO-treated sandblasted Ti implants using hydroxyapatite particles (PEO-SB-Ti) were improved with the distribution of calcium phosphorous porous oxide layers, and showed a homogeneous and hierarchically porous surface with clusters of nanopores in a bath containing calcium acetate monohydrate and calcium glycerophosphate. To demonstrate the efficacy of PEO-SB-Ti, we investigated whether the implant affects biological responses. The proposed PEO-SB-Ti were evaluated with the aim of obtaining a multifunctional bone replacement model that could efficiently induce osteogenic differentiation as well as antibacterial activities. These physical and biological responses suggest that the PEO-SB-Ti may have a great potential for use an artificial bone replacement compared to that of the controls., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Periodontal ligament (PDL) cells play a crucial role in maintaining periodontal integrity and function by providing cell sources for ligament regeneration. While biophysical stimulation is known to regulate cell behaviors and functions, its impact on epigenetics of PDL cells has not yet been elucidated. Here, we aimed to investigate the cytoskeletal changes, epigenetic modifications, and lineage commitment of PDL cells following the application of stretch stimuli to PDL. PDL cells were subjected to stretching (0.1 Hz, 10 %). Subsequently, changes in focal adhesion, tubulin, and histone modification were observed. The survival ability in inflammatory conditions was also evaluated. Furthermore, using a rat hypo-occlusion model, we verified whether these phenomena are observed in vivo . Stretched PDL cells showed maximal histone 3 acetylation (H3Ace) at 2 h, aligning perpendicularly to the stretch direction. RNA sequencing revealed stretching altered gene sets related to mechanotransduction, histone modification, reactive oxygen species (ROS) metabolism, and differentiation. We further found that anchorage, cell elongation, and actin/microtubule acetylation were highly upregulated with mechanosensitive chromatin remodelers such as H3Ace and histone H3 trimethyl lysine 9 (H3K9me3) adopting euchromatin status. Inhibitor studies showed mechanotransduction-mediated chromatin modification alters PDL cells behaviors. Stretched PDL cells displayed enhanced survival against bacterial toxin (C12-HSL) or ROS (H 2 O 2 ) attack. Furthermore, cyclic stretch priming enhanced the osteoclast and osteoblast differentiation potential of PDL cells, as evidenced by upregulation of lineage-specific genes. In vivo , PDL cells from normally loaded teeth displayed an elongated morphology and higher levels of H3Ace compared to PDL cells with hypo-occlusion, where mechanical stimulus is removed. Overall, these data strongly link external physical forces to subsequent mechanotransduction and epigenetic changes, impacting gene expression and multiple cellular behaviors, providing important implications in cell biology and tissue regeneration., 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.)

Objectives: The fibroblast growth factor receptor (FGFR) members including FGFR1-4 have been identified as promising novel therapeutic targets and prognostic markers in multiple solid tumors. However, the predictive role of the expression of FGFR proteins in oral squamous cell carcinoma (OSCC) requires further exploration., Materials and Methods: Immunohistochemical evaluation of FGFR1-4 was performed on 161 paired OSCC samples. The associations of FGFRs with clinicopathologic and prognostic parameters were analyzed. To further assess the contribution of FGFRs to OSCC proliferation, cell lines, and one PDX model was utilized to examine the anti-tumor effect of the pan-FGFR inhibitor AZD4547., Results: All FGFR members were found to be overexpressed in OSCC tumors when compared to normal tissues, and their expression was significantly associated with poor overall survival and disease-free survival. Multivariate Cox regression analysis revealed high expression of FGFR1 (p = 0.014) and FGFR4 (p = 0.009) were independent prognostic factors and co-overexpression of FGFR1 and FGFR4 with lymph node metastasis increased HR for death (p = 0.02). The pan-FGFR inhibitor AZD4547 showed anti-tumor activity in cell lines and in a patient-derived xenograft of OSCC., Conclusions: This study highlights the co-overexpression of FGFR1 and FGFR4 as a significantly poor prognosis indicator in OSCC when combined with lymph node metastasis., (© 2023 Wiley Periodicals LLC.)

Pathological dermal scars such as keloids present significant clinical challenges lacking effective treatment options. Given the distinctive feature of highly stiffened scar tissues, deciphering how matrix mechanics regulate pathological progression can inform new therapeutic strategies. Here, it is shown that pathological dermal scar keloid fibroblasts display unique metamorphoses to stiffened matrix. Compared to normal fibroblasts, keloid fibroblasts show high sensitivity to stiffness rather than biochemical stimulation, activating cytoskeletal-to-nuclear mechanosensing molecules. Notably, keloid fibroblasts on stiff matrices exhibit nuclear softening, concomitant with reduced lamin A/C expression, and disrupted anchoring of lamina-associated chromatin. This nuclear softening, combined with weak adhesion and high contractility, facilitates the invasive migration of keloid fibroblasts through confining matrices. Inhibiting lamin A/C-driven nuclear softening, via lamin A/C overexpression or actin disruption, mitigates such invasiveness of keloid fibroblasts. These findings highlight the significance of the nuclear mechanics of keloid fibroblasts in scar pathogenesis and propose lamin A/C as a potential therapeutic target for managing pathological scars., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Breast cancer (BC) is the most prevalent cancer type and is the principal cause of cancer-related death in women. Anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) immunotherapy has shown promising effects in metastatic triple-negative breast cancer (TNBC), but the potential factors affecting its efficacy have not been elucidated. Immune-related long noncoding RNAs (irlncRNAs) have been reported to be involved in immune escape to influence the carcinogenic process through the PD-1/PD-L1 signaling pathway. Therefore, exploring the potential regulatory mechanism of irlncRNAs in PD-1/PD-L1 immunotherapy in TNBC is of great importance., Methods: We retrieved transcriptome profiling data from The Cancer Genome Atlas (TCGA) and identified differentially expressed irlncRNA (DEirlncRNA) pairs. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct a risk assessment model., Results: Receiver operating characteristic (ROC) curve analysis indicated that the risk model may serve as a potential prediction tool in TNBC patients. Clinical stage and risk score were proved to be independent prognostic predictors by univariate and multivariate Cox regression analyses. Subsequently, we investigated the correlation between the risk model and tumor-infiltrating immune cells and immune checkpoints. Finally, we identified USP30-AS1 through the StarBase and Multi Experiment Matrix (MEM) databases, predicted the potential target genes of USP30-AS1, and then discovered that these target genes were closely associated with immune responses., Conclusions: Our study constructed a risk assessment model by irlncRNA pairs regardless of expression levels, which contributed to predicting the efficacy of immunotherapy in TNBC. Furthermore, the lncRNA USP30-AS1 in the model was positively correlated with the expression of PD-L1 and provided a potential therapeutic target for TNBC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1975/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Integral imaging is a kind of true three-dimensional (3D) display technology that uses a lens array to reconstruct vivid 3D images with full parallax and true color. In order to present a high-quality 3D image, it's vital to correct the axial position error caused by the misalignment and deformation of the lens array which makes the reconstructed lights deviate from the correct directions, resulting in severe voxel drifting and image blurring. We proposed a sub-pixel marking method to measure the axial position error of the lenses with great accuracy by addressing the sub-pixels under each lens and forming a homologous sub-pixel pair. The proposed measurement method relies on the geometric center alignment of image points, which is specifically expressed as the overlap between the test 3D voxel and the reference 3D voxel. Hence, measurement accuracy could be higher. Additionally, a depth-based sub-pixel correction method was proposed to eliminate the voxel drifting. The proposed correction method takes the voxel depth into consideration in the correction coefficient, and achieves accurate error correction for 3D images with different depths. The experimental results well confirmed that the proposed measuring and correction methods can greatly suppress the voxel drifting caused by the axial position error of the lenses, and greatly improve the 3D image quality.

Background: Oral squamous cell carcinoma (OSCC) is a prevalent neoplasm worldwide, necessitating a deeper understanding of its pathogenesis. VGF nerve growth factor inducible (VGF), a neuropeptide, plays critical roles in nerve and endocrine cell regulation., Methods: In this study, the TCGA datasets were initially screened, identifying the upregulation of VGF in various malignancies. We focused on OSCC cell lines, identifying the suppressor mRNA miR-432-5p as a negative regulator of VGF. Additionally, we examined the prognostic value of VGF expression in OSCC tumors and its impact on cellular functions., Results: VGF expression was found to be an independent prognostic predictor in OSCC tumors. Cells expressing VGF exhibited increased oncogenicity, influencing the proliferation and migration of oral mucosal fibroblast. Transcriptome analysis revealed associations between VGF and various pathological processes, including malignancies, exosome release, fibrosis, cell cycle disruption, and tumor immune suppression. Moreover, IL23R expression, a favorable OSCC prognostic factor, was inversely correlated with VGF expression. Exogenous IL23R expression was found to suppress VGF-associated mobility phenotypes., Conclusions: This study highlights the multifaceted role of VGF in OSCC pathogenesis and introduces the miR-432-5p-VGF-IL23R regulatory axis as a critical mediator. The combined expression of VGF and IL23R emerges as a potent predictor of survival in oral carcinoma cases, suggesting potential implications for future therapeutic strategies., (© 2024. The Author(s).)

China has adopted a national carbon emissions trading market to promote emission reductions, but until now, overallocation of allowances suffer low carbon prices and thus to unfulfilled emission reduction goals. We report a general equilibrium modeling that indicates the flexible compliance and price adjustment mechanism of the carbon market, along with explores the solution to the oversupply of allowances in the China's national carbon market. We find that, under the current policy, the initial loose allowance allocation decreases the overall carbon price, and simultaneously the total amount of banked carbon allowances reaches 4.880 billion tons in 2030, resulting in the level of carbon price cannot achieve NDC (Nationally Determined Contribution) targets. However, by introducing carbon market price adjustment schemes, we observe that the cumulative amount of allowances can effectively reduce, enabling the carbon price rising. Importantly, the amount of the supply of allowances decreases most under the benchmark decrease scenario, which increases the emission reduction pressure of the enterprises from the beginning, leading to the largest economic losses, the price-based adjustment mechanism raises the carbon price to expected level at the minimize economic losses, and the quantity-based adjustment mechanism is more sensitive to policy parameters compared to the price -based adjustment mechanism. These findings offer a promising avenue for selecting cost-effective price adjustment mechanism to improve price mechanism design for national carbon markets., 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. The policy scenario refers to the flexible mechanism design of the existing China's national ETS, as well as potential adjustment polices to overcome oversupply in the mainstream ETSs. First, the national ETS policy scenario (Current Policy, CP) follows the existing national carbon market policies and only includes the flexible compliance. Second, benchmark value decline scenario (Benchmark Decline, BD) reflects both cap adjustment and flexible compliance. Third quantity-based supply-side adjustment scenario (Quantity-based adjustment, QA) reflects both flexible compliance and price adjustment mechanism, where adjusts carbon prices via flexibly adjusting allowances supply based on the allowance quantity. Fourth, the price-based supply-side adjustment scenario (Price-based adjustment, PA) reflects both flexible compliance and price adjustment mechanism, where adjusts carbon prices via flexibly adjusting allowances supply based on carbon price. The main parameters in the model are shown in Table 2., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN)., Methods: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed., Results: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment., Conclusion: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Although depression has been linked to the habit of consuming sugar-sweetened beverages (SSBs), little is known about their long-term relationships and the mediating role of sleep problems. This study examines the associations between childhood depressive symptoms trajectories and adolescent SSB-habit trajectories and whether these associations were mediated by sleep problems. Data came from 1560 adolescents participating in a longitudinal study across grades 1 through 12 in northern Taiwan. Group-based trajectory modeling was used to identify development of childhood depressive symptoms and an SSB habit in adolescence. Multinomial logistic regression was conducted to examine the influence of childhood depressive symptoms and adolescent SSB habit. Mediation analysis was conducted to test whether sleep problems mediated the associations examined. Four distinct trajectories of childhood depressive symptoms were identified: low-stable (30.79%), moderate-stable (42.32%), increasing (12.29%), and high-stable (11.60%). Three distinct trajectories of SSB habit in adolescence were identified: low-stable (44.32%), increasing (15.02%), and high-stable (40.65%). Children who had moderate-stable (aOR = 1.35; CI: 1.04-1.77), high-stable (aOR = 2.01; CI: 1.28-3.15), or increasing (aOR = 1.97; CI: 1.26-3.06) trajectories of depressive symptoms relative to those in the low-stable group were significantly more likely to belong to the high-stable trajectory of SSBs than to the low-stable SSBs group. The Z-mediation test showed that sleep problems significantly mediated the associations between trajectories of childhood depressive symptoms and trajectories of SSBs during adolescence (all p < 0.05). Childhood depressive symptoms conferred risks for adolescent SSB habits; and the effects were seen, in part, through increasing sleep problems., Competing Interests: Declaration of competing interest none, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To analyze the clinical characteristics, treatment, and prognosis of adult patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL)., Methods: Clinical data of 113 T lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients from January 2006 to January 2019 were collected from three hematology research centers, including Peking University Third Hospital, the First Medical Center of Chinese PLA General Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Medical University. The clinical characteristics and prognosis of ETP-ALL/LBL patients were analyzed compared with non-ETP-ALL/LBL patients., Results: In 113 T-ALL/LBL patients, 13 cases (11.5%) were diagnosed as ETP-ALL/LBL, including 11 males, with a median age of 28(18-53) years. Compared with non-ETP-ALL/LBL patients, there were no significant differences in age, sex, incidence of large mediastinal mass, clinical stage, international prognostic index (IPI) score, white blood cell (WBC) count and lactate dehydrogenase (LDH) level among ETP-ALL/LBL patients. Among 13 ETP-ALL/LBL patients, 9 cases (69.2%) achieved complete remission (CR), and there was no statistically significant difference in response rate induced by chemotherapy between ETP-ALL/LBL patients and non-ETP-ALL/LBL patients. Among patients who received chemotherapy without allogeneic hematopoietic stem cell transplantation (allo-HSCT), ETP-ALL/LBL group had a worse 5-year overall survival (OS) rate compared with non-ETP-ALL/LBL group (0 vs 7.1%, P =0.008), while in patients with allo-HSCT, there was no significant difference for 5-year OS rate between the two group (37.5% vs 40.2%, P >0.05). Multivariate Cox regression analysis showed that CR after induction therapy, allo-HSCT, and LDH level were independent prognostic factors affecting T-ALL/LBL patients., Conclusion: No significant difference in response rate induced by chemotherapy is observed between ETP-ALL/LBL and non-ETP-ALL/LBL patients. Allo-HSCT consolidation after induction of remission therapy may have significant favorable influence on OS for patients with ETP-ALL/LBL.

Telomeres at the end of eukaryotic chromosomes are extended by a specialized set of enzymes and telomere-associated proteins, collectively termed here the telomere "replisome." The telomere replisome acts on a unique replicon at each chromosomal end of the telomeres, the 3' DNA overhang. This telomere replication process is distinct from the replisome mechanism deployed to duplicate the human genome. The G-rich overhang is first extended before the complementary C-strand is filled in. This overhang is extended by telomerase, a specialized ribonucleoprotein and reverse transcriptase. The overhang extension process is terminated when telomerase is displaced by CTC1-STN1-TEN1 (CST), a single-stranded DNA-binding protein complex. CST then recruits DNA polymerase α-primase to complete the telomere replication process by filling in the complementary C-strand. In this chapter, the recent structure-function insights into the human telomere C-strand fill-in machinery (DNA polymerase α-primase and CST) will be discussed., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

MALT (mucosa-associated lymphoid tissue) lymphomas are low-grade extra-nodal B-cell lymphomas that may involve various sites in the head and neck including the thyroid, salivary, and lacrimal glands. Development of MALT lymphoma in the head and neck is often associated with auto-immune diseases such as Sjögren syndrome or Hashimoto thyroiditis. Here, we report a case of a MALT lymphoma of the left buucal mucosa that likely arose in the parotid gland. The patient was successfully treated with surgical excision with chemotherapy and remained disease-free at the 10-year follow-up. Since it was rare in the head and neck region, we present this case., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Background: Drug-resistant infections kill hundreds of thousands of people globally every year. In previous work, we found that tri-methoxy- and pyridine-substituted imidazoles show strong antibacterial activities., Objective: The aim of this work was to investigate the antibacterial activities and bacterial resistances of imidazoles bearing an aromatic heterocyclic, alkoxy, or polycyclic moiety on the central ring., Methods: Three series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4- yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (13a-e, 14a-d, and 15a-f) were synthesized and their antibacterial activity was evaluated. The structures were confirmed by their 1 H NMR, 13 C NMR, and HRMS spectra. All the synthesized compounds were screened against Gram-positive, Gramnegative, and multidrug-resistant bacterial strains., Results: More than half of the compounds showed moderate or strong antibacterial activity. Among them, compound 13e (MICs = 1-4 μg/mL) showed the strongest activity against Gram-positive and drug-resistant bacteria as well as high selectivity against Gram-negative bacteria. Furthermore, it showed no cytotoxicity against HepG2 cells, even at 100 μM, and no hemolysis at 20 μM., Conclusion: These results indicate that compound 13e is excellent candicate for further study as a potential antibacterial agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This study aimed to introduce a novel radially pedicled in-situ split-thickness skin graft (STSG). The morbidity, esthetic, and functional outcomes of the radially pedicled in-situ STSG were in comparison with those of the distal STSG., Study Design: Retrospective analysis., Setting: A single-institution review., Methods: Seventy patients with oral cancer who underwent radical surgical resection and simultaneous radial forearm free flap (RFFF) reconstruction from July 2021 to March 2022 were included. De-epithelialized RFFFs and traditional RFFFs were used to repair oral defects of 35 patients in Group A and Group B, respectively, while radially pedicled in-situ STSGs and distal STSGs taken from abdomens were used to repair donor site defects in the above groups, respectively. Patient demographics, wound healing complications, and esthetic and functional outcomes of the forearms were compared between the 2 groups., Results: No significant difference between Group A and Group B was observed in terms of donor site and recipient site complications. The esthetic outcome was superior in Group A compared to Group B (P = .011). The extension range, sensation, and pinch strength of operated forearms were significantly reduced in both groups after surgery (P < .05), however, intergroup differences were not observed., Conclusion: Taken together, our results suggest that radially pedicled in-situ STSG is an applicable technique for direct closure and better esthetic outcomes in the forearm donor site., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) ensures favorable outcomes and reduces the risk of cardiac events in patients on dialysis. However, the effect of PPSV23 vaccination on renal function remains unknown, particularly in patients with chronic kidney disease (CKD). Therefore, we investigated the association between PPSV23 efficacy and renal progression in older patients (age ≥ 75 years) with CKD., Methods: This multicenter, longitudinal cohort study was conducted using data (2008-2016) from the Epidemiology and Risk Factors Surveillance of CKD database. This database was associated with Taiwan's National Health Insurance Research Database (for period: 2008-2019). A total of 1195 older patients with CKD were recruited from 14 hospitals and communities across Taiwan. Renal progression was defined as a > 25% reduction in estimated glomerular filtration rate from the baseline value., Results: A significant reduction in the risk of renal progression was observed in patients who had received PPSV23 (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.35-0.91). However, when stratified by CKD stage, this significant reduction was observed in patients with early-stage CKD but not in those with late-stage CKD. Furthermore, a significant reduction in the risk of renal progression was noted in male patients and those with hypertension., Conclusion: Our findings support the protective effect of PPSV23 against renal deterioration in older patients with CKD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

During glycolysis, the muscle isoform of pyruvate kinase PKM2 produces ATP in exchange for dephosphorylation of phosphoenolpyruvate (PEP) into pyruvate. PKM2 has been considered as a tumor-promoting factor in most cancers, whereas the regulatory role of PKM2 during head and neck carcinogenesis remained to be delineated. PKM2 mRNA and protein expression was examined in head and neck tumorous specimens. The role of PKM2 in controlling cellular malignancy was determined in shRNA-mediated PKM2-deficient head and neck squamous cell carcinoma (HNSC) cells. In agreement with the results in other cancers, PKM2 expression is enriched in both mouse and human HNSC tissues. Nevertheless, PKM2 mRNA expression reversely correlated with tumor stage, and greater recurrence-free survival rates are evident in the PKM2 high HNSC population, arguing that PKM2 may be tumor-suppressive. Multifaceted analyses showed a greater in vivo xenografic tumor growth and an enhanced cisplatin resistance in response to PKM2 loss, whereas PKM2 silencing led to reduced cell motility. At the molecular level, metabolic shifts towards mitochondrial metabolism and activation of oncogenic Protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK) signals were detected in PKM2-silencing HNSC cells. In sum, our findings demonstrated that PKM2 differentially modulated head and neck tumorigenicity via metabolic reprogramming.

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation sequencing followed by motif analysis showed that HDAC2 can bind to c-Myc in rs13213007 A/A 293T cells. Cell Counting Kit-8, colony formation, wound-healing, and Transwell assays revealed that HDAC2 upregulates c-Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co-immunoprecipitation, quantitative reverse transcription-polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC., (© 2023 Wiley Periodicals LLC.)

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C-resistant cancers. This study enhances the understanding of ACP52C-induced cancer-specific apoptosis induction and supports the use of ACP52C in anticancer drug development., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Insects and pathogens release effectors into plant cells to weaken the host defense or immune response. While the imports of some bacterial and fungal effectors into plants have been previously characterized, the mechanisms of how caterpillar effectors enter plant cells remain a mystery. Using live cell imaging and real-time protein tracking, we show that HARP1, an effector from the oral secretions of cotton bollworm (Helicoverpa armigera), enters plant cells via protein-mediated endocytosis. The entry of HARP1 into a plant cell depends on its interaction with vesicle trafficking components including CTL1, PATL2, and TET8. The plant defense hormone jasmonate (JA) restricts HARP1 import by inhibiting endocytosis and HARP1 loading into endosomes. Combined with the previous report that HARP1 inhibits JA signaling output in host plants, it unveils that the effector and JA establish a defense and counter-defense loop reflecting the robust arms race between plants and insects., (© 2023. Springer Nature Limited.)

Telomere maintenance is essential for the genome integrity of eukaryotes, and this function is underpinned by the two-step telomeric DNA synthesis process: telomere G-overhang extension by telomerase and complementary strand fill-in by DNA polymerase alpha-primase (polα-primase). Compared to the telomerase step, the telomere C-strand fill-in mechanism is less understood. Recent studies have provided new insights into how telomeric single-stranded DNA-binding protein CTC1-STN1-TEN1 (CST) and polα-primase coordinate to synthesize the telomeric C-strand for telomere overhang fill-in. Cryogenic electron microscopy (cryo-EM) structures of CST-polα-primase complexes have provided additional insights into how they assemble at telomeric templates and de novo synthesize the telomere C-strand. In this review, we discuss how these latest findings coalesce with existing understanding to develop a human telomere C-strand fill-in mechanism model., Competing Interests: Declaration of interests None declared by the authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Impairments in spatial navigation in humans can be preclinical signs of Alzheimer's disease. Therefore, cognitive tests that monitor deficits in spatial memory play a crucial role in evaluating animal models with early stage Alzheimer's disease. While Chinese tree shrews (Tupaia belangeri) possess many features suitable for Alzheimer's disease modeling, behavioral tests for assessing spatial cognition in this species are lacking. Here, we established reward-based paradigms using the radial-arm maze and cheeseboard maze for tree shrews, and tested spatial memory in a group of 12 adult males in both tasks, along with a control water maze test, before and after bilateral lesions to the hippocampus, the brain region essential for spatial navigation. Tree shrews memorized target positions during training, and task performance improved gradually until reaching a plateau in all 3 mazes. However, spatial learning was compromised post-lesion in the 2 newly developed tasks, whereas memory retrieval was impaired in the water maze task. These results indicate that the cheeseboard task effectively detects impairments in spatial memory and holds potential for monitoring progressive cognitive decline in aged or genetically modified tree shrews that develop Alzheimer's disease-like symptoms. This study may facilitate the utilization of tree shrew models in Alzheimer's disease research., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this paper, sphingomyelin (SM) is detected by a polyaniline hydrogel and Au nanoparticles with enzyme modified electrode (GCE/PAniH/AuNPs@enzyme). After a battery of enzymic degradation, SM can generate H 2 O 2 and enhance the electrochemiluminescence (ECL) response of luminol, which endows the sensor with good sensitivity, specifiity and repeatability. Additionally, the proposed ECL biosensor displays good analytical performances with a wide range from 10.0 μg·mL -1 to 250.0 μg·mL -1 as well as a low detection limit of 3.50 μg·mL -1  (S/N = 3). When the ECL biosensor is used in the detection of SM in milk samples, satisfactory results are obtained, indicating that PAniH/AuNPs@enzyme will serve as a promising ECL material in the applications of H 2 O 2 -related bioassay in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although vaccination has been shown to be one of the most important interventions, COVID-19 vaccine hesitancy remains one of the top 10 global public health challenges worldwide., Objective: The objective of this study is to investigate (1) major determinants of vaccine hesitancy, (2) changes in the determinants of vaccine hesitancy at different time periods, and (3) the potential factors affecting vaccine acceptance., Methods: This study applied a mixed methods approach to explore the potential determinants contributing to vaccine hesitancy among the Taiwanese population. The quantitative design of this study involved using Google Trends search query data. We chose the search term "" (vaccine), selected "" (Taiwan) as the location, and selected the period between December 18, 2020, and July 31, 2021. The rising keywords related to vaccine acceptance and hesitancy were collected. Based on the responses obtained from the qualitative study and the rising keywords obtained in Google Trends, the 3 most popular keywords related to vaccine hesitancy were identified and used as search queries in Google Trends between December 18, 2020, and July 31, 2021, to generate relative search volumes (RSVs). Lastly, autoregressive integrated moving average modeling was used to forecast the RSVs for the 3 keywords between May 29 and July 31, 2021. The estimated RSVs were compared to the observed RSVs in Google Trends within the same time frame., Results: The 4 prevailing factors responsible for COVID-19 vaccine acceptance and hesitancy were doubts about the government and manufacturers, side effects, deaths associated with vaccination, and efficacy of vaccination. During the vaccine observation period, "political role" was the overarching consideration leading to vaccine hesitancy. During the peak of the pandemic, side effects, death, and vaccine protection were the main factors contributing to vaccine hesitancy. The popularity of the 3 frequently searched keywords "side effects," "vaccine associated deaths," and "vaccine protection" continued to rise throughout the pandemic outbreak. Lastly, the highest Google search queries related to COVID-19 vaccines emerged as "side effects" prior to vaccination, deaths associated with vaccines during the period when single vaccines were available, and "side effects" and "vaccine protection" during the period when multiple vaccines were available., Conclusions: Investigating the key factors influencing COVID-19 vaccine hesitancy appears to be a fundamental task that needs to be undertaken to ensure effective implementation of COVID-19 vaccination. Google Trends may be used as a complementary infoveillance tool by government agencies for future vaccine policy implementation and communication., (©Li-Yin Lin, Chun-Ji Lin, Chen-I Kuan, Hung-Yi Chiou. Originally published in JMIR Formative Research (https://formative.jmir.org), 12.09.2023.)

Introduction: Dysphagia is a common complication after heart transplantation (HTPL), but few studies exist on dysphagia after HTPL, and the prevalence is unknown. The objective of our current study was to establish the prevalence and risk factors for dysphagia after HTPL and to classify its characteristics through Videofluoroscopic Swallowing Studies (VFSS)., Methods: The recipients of HTPL carried out at a single center from January 2011 to November 2019 were assessed retrospectively. Dysphagia was evaluated by a bedside swallowing exam and VFSS to evaluate for evidence of aspiration. The duration of ventilator and preoperative extracorporeal membrane oxygenation (ECMO) support, intensive care unit, hospital stay, the progress of oral feeding after surgery, the presence of a tracheostomy, and vocal cord palsy were analyzed. On the third and seventh days following surgery, we looked at the relationship between risk factors and oral feeding progress, respectively. Additionally, we contrasted these risk variables with the no penetration/aspiration (PA) group and the PA group on VFSS., Results: Among the study cohort of 421 patients, 222 (52.7%) patients had access to oral feeding on the third day of surgery. The number of patients who underwent VFSS due to clinically suspected dysphagia was 96 (22.8%). Of these, 54 (56.2%) had aspiration or penetration (PA group), while 42 (43.8%) had no abnormal findings (No-PA group). In the multivariable regression model, preoperative ECMO support, vocal cord abnormalities, tracheostomy, and emergent need for HTPL were identified as independent risk variables for oral feeding progress on postoperative days (PODs) 3 and 7. Among these factors, preoperative ECMO support had the highest odds ratio (OR) at PODs 3 (OR: 4.73, CI: 1.997, 11.203, p < .001) and 7 (OR: 5.143, CI: 2.294, 11.53, p < .001)., Conclusion: We identified the prevalence and potential risk factors for postoperative dysphagia in this retrospective analysis of 421 heart transplant recipients. The pathophysiology of postoperative dysphagia was multifactorial, and it was more common than the incidence after general cardiothoracic surgery., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Compared with conventional scattered backlight systems, integral imaging (InIm) display system with collimated backlight can reduce the voxel size, but apparent voxel separation and severe graininess still exist in reconstructed 3D images. In this paper, an InIm 3D display system with anisotropic backlight control of sub-pixels was proposed to resolve both voxel aliasing and voxel separation simultaneously. It consists of an anisotropic backlight unit (ABU), a transmissive liquid crystal panel (LCP), and a lens array. The ABU with specific horizontal and vertical divergence angles was proposed and designed. Within the depth of field, the light rays emitted from sub-pixels are controlled precisely by the ABU to minimize the voxel size as well as stitch adjacent voxels seamlessly, thus improving the 3D image quality effectively. In the experiment, the prototype of our proposed ABU-type InIm system was developed, and the spatial frequency was nearly two times of conventional scattered backlight InIm system. Additionally, the proposed system eliminated the voxel separation which usually occurs in collimated backlight InIm system. As a result, voxels reconstructed by our proposed system were stitched in space without aliasing and separation, thereby greatly enhancing the 3D resolution and image quality.

Climate warming can increase soil temperature and lead to soil carbon release, but it can also increase soil organic carbon by increasing primary productivity. Cropland soils are considered to have a huge potential to sequester carbon; however, direct observations for the responses of cropland soil organic carbon to climate warming over broad geographic scales are rarely documented. Paddy soil is one of the important cultivated soils in China. Based on the data of 2217 sampling points obtained during the second national soil survey and the data of 2382 sampling points collected during 2017-2019, this study analyzed the change characteristics of soil organic carbon content of paddy surface soil in Sichuan Basin of China and explored the relationships between the soil organic carbon change of paddy soil and temperature, precipitation, cropland use type, fertilization intensity, and grain yield. The results showed that the content of soil organic carbon of paddy soil changed from 13.33 g·kg -1 to 15.96 g·kg -1 , with an increase of 2.63 g·kg -1 , suggesting that soils in the Sichuan Basin have acted as a carbon sink over past 40 years. The soil organic carbon increment of paddy soil varied with different geomorphic regions and different secondary basins. The increase in SOC content in paddy soil was positively correlated with annual average temperature; negatively correlated with annual average precipitation; and initially increased and then decreased with annual average fertilizer application, annual average increase rate of fertilizer application, annual average grain yield, and annual average grain yield growth rate. The relationship between the increase in SOC content and the annual average temperature growth rate was different under different farmland utilizations, and the increase in the annual average temperature growth rate had significant effects with the increase in SOC content only on paddy-dryland rotation. These results indicate that the paddy soil organic carbon change in Sichuan Basin was co-affected by various factors, but climate warming was an important factor leading to the paddy soil organic carbon change, and its influence was controlled by the water conditions determined by farmland use.

Radiotherapy and chemotherapy can impair salivary gland (SG) function, which causes xerostomia and exacerbate other side effects of chemotherapy and oral infection, reducing patients' quality of life. This animal study aimed to assess the efficacy of electroacupuncture (EA) as a means of preventing xerostomia induced by 5-fluorouracil (5-FU). A xerostomia mouse model was induced via four tail vein injections of 5-FU (80 mg/kg/dose). EA was performed at LI4 and LI11 for 7 days. The pilocarpine-stimulated salivary flow rate (SFR) and salivary glands weight (SGW) were recorded. Salivary immunoglobulin A (SIgA) and lysozyme were determined via enzyme-linked immunosorbent assay (ELISA). SG was collected for hematoxylin and eosin staining to measure acini number and acinar cell size. Tumor necrosis factor - α (TNF - α) , interleukin - 1β (IL - 1β) , and aquaporin 5 (AQP5) mRNA expressions in SG were quantified via RT-qPCR. 5-FU caused significant decreases in SFR, SGW, SIgA, lysozyme, AQP5 expression, and acini number, while TNF-α and IL-1β expressions and acinar cell size were significantly increased. EA treatment can prevent 5-FU damage to the salivary gland, while pilocarpine treatment can only elevate SFR and AQP5 expression. These findings provide significant evidence to support the use of EA as an alternative treatment for chemotherapy-induced salivary gland hypofunction and xerostomia.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation., Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management., Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients., Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131 I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99m Tc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors., Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

The accurate diagnosis and treatment of oral squamous cell carcinoma (OSCC) requires an understanding of its genomic alterations. Liquid biopsies, especially cell-free DNA (cfDNA) analysis, are a minimally invasive technique used for genomic profiling. We conducted comprehensive whole-exome sequencing (WES) of 50 paired OSCC cell-free plasma with whole blood samples using multiple mutation calling pipelines and filtering criteria. Integrative Genomics Viewer (IGV) was used to validate somatic mutations. Mutation burden and mutant genes were correlated to clinico-pathological parameters. The plasma mutation burden of cfDNA was significantly associated with clinical staging and distant metastasis status. The genes TTN , PLEC , SYNE1 , and USH2A were most frequently mutated in OSCC, and known driver genes, including KMT2D , LRP1B , TRRAP, and FLNA , were also significantly and frequently mutated. Additionally, the novel mutated genes CCDC168 , HMCN2, STARD9 , and CRAMP1 were significantly and frequently present in patients with OSCC. The mutated genes most frequently found in patients with metastatic OSCC were RORC , SLC49A3 , and NUMBL. Further analysis revealed that branched-chain amino acid (BCAA) catabolism, extracellular matrix-receptor interaction, and the hypoxia-related pathway were associated with OSCC prognosis. Choline metabolism in cancer, O-glycan biosynthesis, and protein processing in the endoplasmic reticulum pathway were associated with distant metastatic status. About 20% of tumors carried at least one aberrant event in BCAA catabolism signaling that could possibly be targeted by an approved therapeutic agent. We identified molecular-level OSCC that were correlated with etiology and prognosis while defining the landscape of major altered events of the OSCC plasma genome. These findings will be useful in the design of clinical trials for targeted therapies and the stratification of patients with OSCC according to therapeutic efficacy.

Gallbladder carcinoma (GC) is a rare type of cancer of the digestive system, with an incidence that varies by region. Surgery plays a primary role in the comprehensive treatment of GC and is the only known cure. Compared with traditional open surgery, laparoscopic surgery has the advantages of convenient operation and magnified field of view. Laparoscopic surgery has been successful in many fields, including gastrointestinal medicine and gynecology. The gallbladder was one of the first organs to be treated by laparoscopic surgery, and laparoscopic cholecystectomy has become the gold standard surgical treatment for benign gallbladder diseases. However, the safety and feasibility of laparoscopic surgery for patients with GC remain controversial. Over the past several decades, research has focused on laparoscopic surgery for GC. The disadvantages of laparoscopic surgery include a high incidence of gallbladder perforation, possible port site metastasis, and potential tumor seeding. The advantages of laparoscopic surgery include less intraoperative blood loss, shorter postoperative hospital stay, and fewer complications. Nevertheless, studies have provided contrasting conclusions over time. In general, recent research has tended to support laparoscopic surgery. However, the application of laparoscopic surgery in GC is still in the exploratory stage. Here, we provide an overview of previous studies, with the aim of introducing the application of laparoscopy in GC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The synthesis of RNA-DNA primer by primosome requires coordination between primase and DNA polymerase α subunits, which is accompanied by unknown architectural rearrangements of multiple domains. Using cryogenic electron microscopy, we solved a 3.6 Å human primosome structure caught at an early stage of RNA primer elongation with deoxynucleotides. The structure confirms a long-standing role of primase large subunit and reveals new insights into how primosome is limited to synthesizing short RNA-DNA primers., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). Many ccRCCs are diagnosed at an advanced stage due to the lack of early symptoms, with a high mortality rate and a poor prognosis. The occurrence and development of ccRCC are closely related to metabolic disorders. This study aims to explore the relationship between metabolic genes and prognosis, immune microenvironment, and tumor development of ccRCC. Using data from TCGA, GEO, and ArrayExpress, we successfully established a risk model ( riskScore ) based on 4 metabolic genes (MGs) that can accurately predict the prognosis and immune microenvironment of ccRCCs. In addition, we determined the role of PAFAH2 in suppressing tumor cell proliferation and migration in ccRCC in vitro. Our research may shed new light on ccRCC patients' prognosis and treatment management., Competing Interests: None., (AJCR Copyright © 2023.)