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1.
Article in English | MEDLINE | ID: mdl-38722961

ABSTRACT

Aerogel fibers are good thermal insulators, suitable for weaving, and show potential as the next generation of intelligent textiles that can effectively reduce heat consumption for personal thermal management. However, the production of continuous aerogel fibers from biomass with sufficient strength and radial elasticity remains a significant challenge. Herein, continuous gel fibers were produced via wet spinning using agarose (AG) as the matrix, 2,2,2,6,6-tetramethylpiperidine-1-oxyl radical-oxidized cellulose nanofibers (TOCNs) as the reinforcing agent, and no other chemical additives by utilizing the gelling properties of AG. Supercritical drying and chemical vapor deposition (CVD) were then used to produce hydrophobic AG-TOCN aerogel fibers (HATAFs). During CVD, the HATAF gel skeleton was covered with an isostructural silica coating. Consequently, the HATAFs can recover from radial compression under 60% strain. Moreover, the HATAFs have low densities (≤0.14 g cm-3), high porosities (≥91.8%), high specific surface areas (≥188 m2 g-1), moderate tensile strengths (≤1.75 MPa), excellent hydrophobicity (water contact angles of >130°), and good thermal insulating properties at different temperatures. Thus, HATAFs are expected to become a new generation of materials for efficient personal thermal management.

2.
Chem Biodivers ; : e202401089, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740553

ABSTRACT

Croton sublyratus (Euphorbiaceae) is a traditional medicinal plant used by the Thai populace to treat helminthic infections and dermatologic conditions. In present study, eight new labdane-type diterpenoids, crotonoids A-H (1-8) and one known analogue (9) were isolated from the aerial parts of C. sublyratus. Compounds 6 and 7 belong to the rare class of 14,15-dinor-labdane diterpenoids. Compound 8 exhibited a rare 14,15,17-trinor-labdane skeleton. The structures of all these diterpenoids were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Compound 9 exhibited moderate anti-inflammatory activity via the inhibition of NO production in lipopolysaccharide-induced RAW 264.7 cells.

3.
Zool Res ; 45(3): 551-566, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38757223

ABSTRACT

Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Proto-Oncogene Proteins p21(ras) , Animals , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/genetics , Carcinoma, Hepatocellular/pathology , Mice , Liver Neoplasms/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Disease Models, Animal , Mice, Transgenic , Mice, Inbred C57BL , Humans
4.
Reprod Toxicol ; : 108604, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38703919

ABSTRACT

Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (TwHF). TG tablets are the representative TwHF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG.

5.
Nat Prod Res ; : 1-7, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752874

ABSTRACT

Two new withanolides named physaminilides L (1) and M (2), together with four known ones (3-6) were isolated from the Physalis minima L. The structures were established by analysis of the HR ESIMS, IR and NMR spectroscopic data. The absolute configurations were determined through NOESY and ECD spectra. For compounds 1-5 assayed at 20 µM and compound 6 at 10 µM, inhibition rates of hepatic fibrosis were 22.19%, 15.29%, 37.07%, 9.27%, 12.45%, and 37.03%, respectively.

6.
PLoS One ; 19(4): e0296945, 2024.
Article in English | MEDLINE | ID: mdl-38557758

ABSTRACT

COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020-2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers.


Subject(s)
COVID-19 , Colorectal Neoplasms , Humans , COVID-19/diagnosis , COVID-19/epidemiology , Early Detection of Cancer , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/therapy , Australia/epidemiology , Canada/epidemiology , COVID-19 Testing
7.
BMC Genomics ; 25(1): 369, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38622517

ABSTRACT

BACKGROUND: Pigeon circovirus infections in pigeons (Columba livia domestica) have been reported worldwide. Pigeons should be PiCV-free when utilized as qualified experimental animals. However, pigeons can be freely purchased as experimental animals without any clear guidelines to follow. Herein, we investigated the status quo of PiCV infections on a pigeon farm in Beijing, China, which provides pigeons for experimental use. RESULTS: PiCV infection was verified in at least three types of tissues in all forty pigeons tested. A total of 29 full-length genomes were obtained and deposited in GenBank. The whole genome sequence comparison among the 29 identified PiCV strains revealed nucleotide homologies of 85.8-100%, and these sequences exhibited nucleotide homologies of 82.7-98.9% as compared with those of the reference sequences. The cap gene displayed genetic diversity, with a wide range of amino acid homologies ranging from 64.5% to 100%. Phylogenetic analysis of the 29 full-genome sequences revealed that the PiCV strains in this study could be further divided into four clades: A (17.2%), B (10.4%), C (37.9%) and D (34.5%). Thirteen recombination events were also detected in 18 out of the 29 PiCV genomes obtained in this study. Phylogenetic research using the rep and cap genes verified the recombination events, which occurred between clades A/F, A/B, C/D, and B/D among the 18 PiCV strains studied. CONCLUSIONS: In conclusion, PiCV infection, which is highly genetically varied, is extremely widespread on pigeon farms in Beijing. These findings indicate that if pigeons are to be used as experimental animals, it is necessary to evaluate the impact of PiCV infection on the results.


Subject(s)
Bird Diseases , Circoviridae Infections , Circovirus , Animals , Columbidae , Phylogeny , Farms , Circovirus/genetics , Circoviridae Infections/veterinary , Nucleotides
8.
bioRxiv ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38645202

ABSTRACT

Pediatric low-grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding of pLGG biology is essential to identify novel, more effective, and less toxic therapies. We utilized single cell RNA sequencing (scRNA-seq), spatial transcriptomics, and cytokine analyses to characterize and understand tumor and immune cell heterogeneity across pLGG. scRNA-seq revealed tumor and immune cells within the tumor microenvironment (TME). Tumor cell subsets revealed a developmental hierarchy with progenitor and mature cell populations. Immune cells included myeloid and lymphocytic cells. There was a significant difference between the prevalence of two major myeloid subclusters between pilocytic astrocytoma (PA) and ganglioglioma (GG). Bulk and single-cell cytokine analyses evaluated the immune cell signaling cascade with distinct immune phenotypes among tumor samples. KIAA1549-BRAF tumors appeared more immunogenic, secreting higher levels of immune cell activators and chemokines, compared to BRAF V600E tumors. Spatial transcriptomics revealed the differential gene expression of these chemokines and their location within the TME. A multi-pronged analysis of pLGG demonstrated the complexity of the pLGG TME and differences between genetic drivers that may influence their response to immunotherapy. Further investigation of immune cell infiltration and tumor-immune interactions is warranted. Key points: There is a developmental hierarchy in neoplastic population comprising of both progenitor-like and mature cell types in both PA and GG.A more immunogenic, immune activating myeloid population is present in PA compared to GG. Functional analysis and spatial transcriptomics show higher levels of immune mobilizing chemokines in KIAA1549-BRAF fusion PA tumor samples compared to BRAF V600E GG samples. Importance of the Study: While scRNA seq provides information on cellular heterogeneity within the tumor microenvironment (TME), it does not provide a complete picture of how these cells are interacting or where they are located. To expand on this, we used a three-pronged approach to better understand the biology of pediatric low-grade glioma (pLGG). By analyzing scRNA-seq, secreted cytokines and spatial orientation of cells within the TME, we strove to gain a more complete picture of the complex interplay between tumor and immune cells within pLGG. Our data revealed a complex heterogeneity in tumor and immune populations and identified an interesting difference in the immune phenotype among different subtypes.

9.
Angew Chem Int Ed Engl ; : e202406069, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630112

ABSTRACT

The construction of C(sp3)-N bonds via direct N-centered radical addition with olefins under benign conditions is a desirable but challenging strategy. Herein, we describe an organo-photocatalytic approach to achieve anti-Markovnikov alkene hydroamidation with sulfonyl azides in a highly efficient manner under transition-metal-free and mild conditions. A broad range of substrates, including both activated and unactivated alkenes, are suitable for this protocol, providing a convenient and practical method to construct sulfonylamide derivatives. A synergistic experimental and computational mechanistic study suggests that the additive, Hantzsch ester (HE), might undergo a triplet-triplet energy transfer manner to achieve photosensitization by the organo-photocatalyst under visible light irradiation. Next, the resulted triplet excited state 3HE* could lead to a homolytic cleavage of C4-H bond, which triggers a straightforward H-atom transfer (HAT) style in converting sulfonyl azide to the corresponding key amidyl radical. Subsequently, the addition of the amidyl radical to alkene followed by HAT from p-toluenethiol could proceed to afford the desired anti-Markovnikov hydroamidation product. It is worth noting that mechanistic pathway bifurcation could be possible for this reaction. A feasible radical chain propagation mechanistic pathway is also proposed to rationalize the high efficiency of this reaction.

10.
Zhen Ci Yan Jiu ; 49(4): 424-433, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38649212

ABSTRACT

OBJECTIVES: To explore the rules of acupoint selection in the treatment of metabolic-associated fatty liver disease (MAFLD) with acupuncture and moxibustion by using data mining technology. METHODS: The clinical research literature on acupuncture treatment of MAFLD was collected from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database and China Biology Medicine from their inception to November 20, 2022. According to our inclusion and exclusion criteria, the literature was independently screened and re-screened by two research members, and the screened results were checked, followed by establishing an acupoint prescription database using Excel 2019. Descriptive statistics of acupoints applied frequency, involved meridians, locations and specific acupoints were perpormed. Then, SPSS Modeler18.0 software was used to conduct analysis about association rules, and the SPSS Statistics 26.0 software was used to perform cluster analysis on high-frequency acupoints, exploring the characteristics and rules of acupoint selection and combination in the treatment of MAFLD. RESULTS: Totally, 178 papers were collected, containing 130 acupoints, with a total application frequency of 1 305. The top five acupoints are Zusanli (ST36), Fenglong (ST40), Ganshu (BL18), Taichong (LR3) and Sanyinjiao (SP6). The commonly involved meridians are the Stomach Meridian of Foot Yangming, Bladder Meridian of Foot Taiyang, and Spleen Meridian of Foot Taiyin. The employed acupoints are mostly located in the lower limbs and abdomen, and the five Shu acupoints and crossing acupoints are in the majority. The association rule analysis of high frequency acupoints indicated that of the 16 qualified acupoint groups, the top 5 with close correlation degrees are ST36 and ST40, ST36 and LR3, ST36 and SP6, ST40 and LR3 and ST36, ST36 and SP6 and ST40. Further, 3 effective clusters were obtained by cluster analysis. CONCLUSIONS: Acupuncture and moxibustion treatment of MAFLD follows the therapeutic principles of soothing the liver, invigorating the spleen, tonifying the kidney, and resolving phlegm and removing dampness. The core acupoint group is ST36, ST40 and LR3, and the combination of acupoints is based on syndrome differentiation. These results may provide a useful reference for clinical practice.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Data Mining , Humans , Fatty Liver/therapy , Fatty Liver/metabolism , Meridians , Moxibustion
11.
Gels ; 10(4)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38667686

ABSTRACT

Aerogel fibers, characterized by their ultra-low density and ultra-low thermal conductivity, are an ideal candidate for personal thermal management as they hold the potential to effectively reduce the energy consumption of room heating and significantly contribute to energy conservation. However, most aerogel fibers have weak mechanical properties or require complex manufacturing processes. In this study, simple continuous silk fibroin-agarose composite aerogel fibers (SCAFs) were prepared by mixing agarose with silk fibroin through wet spinning and rapid gelation, followed by solvent replacement and supercritical carbon dioxide treatment. Among them, the rapid gelation of the SCAFs was achieved using agarose physical methods with heat-reversible gel properties, simplifying the preparation process. Hydrophobic silk fibroin-agarose composite aerogel fibers (HSCAFs) were prepared using a simple chemical vapor deposition (CVD) method. After CVD, the HSCAFs' gel skeletons were uniformly coated with a silica layer containing methyl groups, endowing them with outstanding radial elasticity. Moreover, the HSCAFs exhibited low density (≤0.153 g/cm3), a large specific surface area (≥254.0 m2/g), high porosity (91.1-94.7%), and excellent hydrophobicity (a water contact angle of 136.8°). More importantly, they showed excellent thermal insulation performance in low-temperature (-60 °C) or high-temperature (140 °C) environments. The designed HSCAFs may provide a new approach for the preparation of high-performance aerogel fibers for personal thermal management.

12.
J Clin Lab Anal ; 38(8): e25033, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38563457

ABSTRACT

BACKGROUND: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc. METHODS: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820). CONCLUSIONS: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice.


Subject(s)
Immunoglobulin G , Luminescent Measurements , Humans , Immunoglobulin G/blood , Female , Male , Middle Aged , Immunoassay/methods , Luminescent Measurements/methods , Adult , ROC Curve , Nephelometry and Turbidimetry/methods , Case-Control Studies , China , Aged , Sjogren's Syndrome/blood , Sjogren's Syndrome/diagnosis , Asian People , Immunoglobulin G4-Related Disease/blood , Immunoglobulin G4-Related Disease/diagnosis , East Asian People
13.
Zhongguo Zhong Yao Za Zhi ; 49(4): 961-967, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38621903

ABSTRACT

The chemical composition of the aqueous part of the extract from Lindera aggregata was studied, which was separated and purified by the macroporous resin column chromatography, MCI medium pressure column chromatography, semi-preparative high-performance liquid phase and other methods. The structures of the compounds were identified according to physical and chemical properties and spectroscopic data. Thirteen compounds were isolated and identified from the aqueous extracts, which were identified as(1S,3R,5R,6R,8S,10S)-epi-lindenanolide H(1), tachioside(2), lindenanolide H(3), leonuriside A(4), 3,4-dihydroxyphenyl ethyl ß-D-glucopyranoside(5), 3,4,5-trimethoxyphenol-1-O-6-α-L-rhamnose-(1→6)-O-ß-D-glucoside(6), 5-hydroxymethylfurfural(7),(+)-lyoniresin-4-yl-ß-D-glucopyranoside(8), lyoniside(9), norboldine(10), norisopordine(11), boldine(12), reticuline(13). Among them, compound 1 was a new one, and compounds 2, 5, 6, 8, 9 were obtained from L. aggregata for the first time. The inflammatory model was induced by lipopolysaccharide(LPS) in the RAW264.7 cells. The results showed that compounds 1, 8, 10 and 12 had significant anti-inflammatory activity.


Subject(s)
Lindera , Sesquiterpenes , Lindera/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Glucosides
14.
ACS Biomater Sci Eng ; 10(4): 2523-2533, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38445444

ABSTRACT

Regenerating the pulp-dentin complex remains a decisive factor during apexification for immature permanent teeth. Peptide KN-17, which was modified based on the structure of cecropin B, could effectively interfere with bacterial growth and induce the migration of human bone marrow stromal cells (hBMSCs). This study aimed to investigate the effect of KN-17 on the tissue regeneration. To our surprise, KN-17 can significantly stimulate angiogenesis in vitro and in vivo, which may provide a guarantee for apical closure. Herein, a novel peptide/KN-17 coassembled hydrogel is developed via a heating-cooling process. Npx-FFEY/KN-17 supramolecular hydrogel can induce vessel development, stimulate odontogenic differentiation of human dental pulp stem cells (hDPSCs), and exert an antibacterial effect on Enterococcus faecalis (E. faecalis). Furthermore, coronal pulp excised rat molars are supplied with KN-17 or KN-17-loaded hydrogel and transplanted subcutaneously in BALB/c-nu mice. After 4 weeks, the hydrogel Npx-FFEY/KN-17 stimulates the formation of multiple odontoblast-like cells and dentin-like structures. Our findings demonstrate that the KN-17-loaded hydrogel can promote the regeneration of the pulp-dentin complex for continued root development.


Subject(s)
Hydrogels , Mesenchymal Stem Cells , Mice , Rats , Humans , Animals , Hydrogels/pharmacology , Hydrogels/chemistry , Peptides , Odontoblasts , Dentin , Dental Pulp
15.
Mol Psychiatry ; 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38486048

ABSTRACT

Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex (PFC) activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in PFC activity during early life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the PFC of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the PFC during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the PFC we performed single-nucleus RNA-sequencing. Maternal separation led to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life PFC inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of PFC activity during early life in behavioral expression in adulthood.

16.
School Psych Rev ; 53(1): 1-16, 2024.
Article in English | MEDLINE | ID: mdl-38487040

ABSTRACT

Many racial-ethnic minoritized individuals are repeatedly exposed to subtle actions reflecting racial slights, termed racial microaggressions (RMAs), which are associated with adjustment problems in early adult and adult populations. Early adolescence represents a unique developmental period when minoritized youth begin their racial-ethnic identity exploration and are subjected to stereotypes and prejudice, thereby making them vulnerable to RMAs. Based upon the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, a systematic literature search, screening and review of RMA literature focusing on high schoolers and younger youth was conducted and yielded 54 publications. This paper reviewed the publications and identified gaps in the field such as the need for systematic research on early adolescents including the frequency and severity of RMAs and the important contributions of peers, parents and teachers for RMA victims, and the need for more evidence-based programming for middle schoolers. Findings suggest that developing school-based microaggression anti-racism programs is clearly needed for minoritized and White youth.

17.
J Control Release ; 368: 623-636, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479445

ABSTRACT

Chemoresistance to cisplatin remains a significant challenge affecting the prognosis of advanced oral squamous cell carcinoma (OSCC). However, the specific biomarkers and underlying mechanisms responsible for cisplatin resistance remain elusive. Through comprehensive bioinformatic analyses, we identified a potential biomarker, BCL2 associated athanogene-1 (BAG1), showing elevated expression in head and neck squamous cell carcinoma (HNSCC). Since OSCC represents the primary pathological type of HNSCC, we investigated BAG1 expression in human tumor tissues and cisplatin resistant OSCC cell lines, revealing that silencing BAG1 induced apoptosis in cisplatin-resistant cells both in vitro and in vivo. This effect led to impaired cell viability of cisplatin resistant OSCC cells and indicated a positive correlation between BAG1 expression and the G1/S transition during cell proliferation. Based on these insights, the administration of a CDK4/6 inhibitor in combination with cisplatin effectively overcame cisplatin resistance in OSCC through the CDK4/6-BAG1 axis. Additionally, to enable simultaneous drug delivery and enhance synergistic antitumor efficacy, we developed a novel supramolecular nanodrug LEE011-FFERGD/CDDP, which was validated in an OSCC orthotopic mouse model. In summary, our study highlights the potential of a combined administration of CDK4/6 inhibitor and cisplatin as a promising therapeutic regimen for treating advanced or cisplatin resistant OSCC.


Subject(s)
Carcinoma, Squamous Cell , Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Drug Resistance, Neoplasm , Mouth Neoplasms , Nanoparticles , Animals , Humans , Mice , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Proliferation , Cisplatin/pharmacology , Cisplatin/therapeutic use , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Head and Neck Neoplasms/drug therapy , Mouth Neoplasms/drug therapy , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck/drug therapy , Cyclin-Dependent Kinase 6/antagonists & inhibitors
18.
Brain Res ; 1831: 148822, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38408558

ABSTRACT

Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, holds potential for applications in the treatment of Alzheimer's disease (AD). This study aims to compare the therapeutic effects of rTMS at different frequencies on Alzheimer's disease and explore the alterations in neuronal electrophysiological properties throughout this process. APP/PS1 AD mice were subjected to two rTMS treatments at 0.5 Hz and 20 Hz, followed by assessments of therapeutic outcomes through the Novel Object Recognition (NOR) and Morris Water Maze (MWM) tests. Following this, whole-cell patch-clamp techniques were used to record action potential, voltage-gated sodium channel currents, and voltage-gated potassium channel currents in dentate gyrus granule neurons. The results show that AD mice exhibit significant cognitive decline compared to normal mice, along with a pronounced reduction in neuronal excitability and ion channel activity. Both frequencies of rTMS treatment partially reversed these changes, demonstrating similar therapeutic efficacy. Furthermore, the investigation indicates that low-frequency magnetic stimulation inhibited the concentrated firing of early action potentials in AD.


Subject(s)
Alzheimer Disease , Mice , Animals , Alzheimer Disease/therapy , Transcranial Magnetic Stimulation/methods , Neurons/physiology , Hippocampus , Action Potentials/physiology , Disease Models, Animal
19.
Pest Manag Sci ; 80(6): 2668-2678, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38411319

ABSTRACT

BACKGROUND: The Angoumois grain moth, Sitotroga cerealella, is a destructive pest of maize, wheat, and rice, causing economic losses and threatening food security. This study aimed to develop and characterize microcapsules of mesoporous silica nanospheres (MSN) and cyclodextrin-modified mesoporous silica nanospheres (CDMSN) containing two aldehydes, nonanal and decanal, found in plant essential oils, to assess their attractiveness to S. cerealella populations. RESULTS: Microcapsules with 2:1 ratio of nonanal and decanal exhibited an average encapsulation efficiency of 39.82% for MSN loaded with nonanal and decanal (MSN-ND) and 46.10% for CDMSN loaded with nonanal and decanal (CDMSN-ND). They have an elliptical shape with particle sizes of 115 nm for MSN and 175 nm for CDMSN. Gas chromatography-mass spectrometry analysis revealed in vitro release of nonanal in MSN at 96.24% and decanal at 96.42% by the 36th day. CDMSN showed releases of 93.83% for nonanal and 93.74% for decanal by the 50th day. CDMSN-ND attracted adult S. cerealella for 43 days, while MSN-ND remained effective for 29 days. In mass trapping assays in simulated grain warehouse, both MSN-ND and CDMSN-ND trapped over 50% of the adult population within 7 days, significantly reducing grain infestation rates below 10% by inhibiting F1 adult emergence. At temperatures ranging from 20 °C to 35 °C, both microcapsules exhibited significant and effective attraction rates for S. cerealella. Stored wheat seeds treated with CDMSN and CDMSN-ND over 1 year showed no significant differences in key germination parameters. CONCLUSION: Microencapsulated nonanal and decanal offer a promising, sustainable approach for controlling S. cerealella infestation in stored grains, contributing to global food security. © 2024 Society of Chemical Industry.


Subject(s)
Capsules , Cyclodextrins , Edible Grain , Silicon Dioxide , Silicon Dioxide/chemistry , Animals , Cyclodextrins/chemistry , Edible Grain/chemistry , Aldehydes/chemistry , Moths/growth & development , Insect Control/methods , Food Storage
20.
Head Neck ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38344842

ABSTRACT

BACKGROUND: Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease-free survival (DFS) in patients with OCSCC treated by primary neck surgery. METHODS: This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment-naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism-corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome. RESULTS: Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR [aHR]: 0.73, 95% CI: 0.54-0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49-0.95), and regional failure (aHR: 0.61, 95% CI: 0.39-0.93). CONCLUSIONS: Our study findings suggested high LNY to be a strong independent predictor of various patient-level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice.

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