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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 377-383, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38953261

ABSTRACT

Objective To analyze the research progress and hot topics in hypertrophic cardiomyopathy from 2018 to 2022.Methods The publications in the field of hypertrophic cardiomyopathy from January 1,2018 to December 31,2022 were retrieved from Web of Science core collection database and included for a bibliometric analysis.Results A total of 6355 publications were included,with an average citation frequency of 7 times.The year 2021 witnessed the most publications (1406).The analysis with VOSviewer showed that the research on sudden death related to hypertrophic cardiomyopathy,especially the predictive value of late gadolinium-enhanced cardiac MRI in sudden death,was a hot topic.In addition,gene detection and the new drug mavacamten became hot research topics.The United States was the country with the largest number of publications and the highest citation frequency in this field.Chinese scholars produced the second largest number of publications,which,however,included few high-quality research results.Conclusions Risk stratification and prevention of sudden death is still an important and hot research content in the field of hypertrophic cardiomyopathy.Chinese scholars should carry out multi-center cooperation in the future to improve the research results.


Subject(s)
Bibliometrics , Cardiomyopathy, Hypertrophic , Cardiomyopathy, Hypertrophic/epidemiology , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/diagnosis , Humans , Death, Sudden, Cardiac/epidemiology , Publications/statistics & numerical data , China/epidemiology
2.
J Control Release ; 371: 406-428, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38849093

ABSTRACT

Preventing the recurrence of melanoma after surgery and accelerating wound healing are among the most challenging aspects of melanoma management. Photothermal therapy has been widely used to treat tumors and bacterial infections and promote wound healing. Owing to its efficacy and specificity, it may be used for postoperative management of tumors. However, its use is limited by the uncontrollable distribution of photosensitizers and the likelihood of damage to the surrounding normal tissue. Hydrogels provide a moist environment with strong biocompatibility and adhesion for wound healing owing to their highly hydrophilic three-dimensional network structure. In addition, these materials serve as excellent drug carriers for tumor treatment and wound healing. It is possible to combine the advantages of both of these agents through different loading modalities to provide a powerful platform for the prevention of tumor recurrence and wound healing. This review summarizes the design strategies, research progress and mechanism of action of hydrogels used in photothermal therapy and discusses their role in preventing tumor recurrence and accelerating wound healing. These findings provide valuable insights into the postoperative management of melanoma and may guide the development of promising multifunctional hydrogels for photothermal therapy.


Subject(s)
Hydrogels , Melanoma , Photothermal Therapy , Wound Healing , Hydrogels/chemistry , Hydrogels/administration & dosage , Humans , Melanoma/therapy , Photothermal Therapy/methods , Animals , Wound Healing/drug effects , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/therapeutic use , Drug Carriers/chemistry , Neoplasm Recurrence, Local/prevention & control
3.
Schizophr Bull ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848516

ABSTRACT

BACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) and anorexia nervosa (AN) are 2 severe and highly heterogeneous disorders showing substantial familial co-aggregation. Genetic factors play a significant role in both disorders, but the shared genetic etiology between them is yet to be investigated. STUDY DESIGN: Using summary statistics from recent large genome-wide association studies on SCZ (Ncases = 53 386) and AN (Ncases = 16 992), a 2-sample Mendelian randomization analysis was conducted to explore the causal relationship between SCZ and AN. MiXeR was employed to quantify their polygenic overlap. A conditional/conjunctional false discovery rate (condFDR/conjFDR) framework was adopted to identify loci jointly associated with both disorders. Functional annotation and enrichment analyses were performed on the shared loci. STUDY RESULTS: We observed a cross-trait genetic enrichment, a suggestive bidirectional causal relationship, and a considerable polygenic overlap (Dice coefficient = 62.2%) between SCZ and AN. The proportion of variants with concordant effect directions among all shared variants was 69.9%. Leveraging overlapping genetic associations, we identified 6 novel loci for AN and 33 novel loci for SCZ at condFDR <0.01. At conjFDR <0.05, we identified 10 loci jointly associated with both disorders, implicating multiple genes highly expressed in the cerebellum and pituitary and involved in synapse organization. Particularly, high expression of the shared genes was observed in the hippocampus in adolescence and orbitofrontal cortex during infancy. CONCLUSIONS: This study provides novel insights into the relationship between SCZ and AN by revealing a shared genetic component and offers a window into their complex etiology.

4.
ACS Appl Mater Interfaces ; 16(24): 31304-31312, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38837961

ABSTRACT

The pursuit of high-quality phosphors exhibiting swift response to near-ultraviolet (n-UV) excitation, elevated quantum efficiency (QE), superior thermal stability, and impeccable light quality has been a focal point of investigation. In this research, we synthesized a novel K2La2B2O7:Ce3+,Tb3+ (KLBO:Ce3+,Tb3+) color-tunable phosphor that meets these requirements. KLBO:Ce3+ can be stimulated efficiently by the n-UV light and shows an intense blue emission centered at 437 nm. Notably, KLBO:0.04Ce3+ exhibits exceptional internal QE (IQE = 94%) and outstanding thermal stability (I423 K/I303 K = 88%). Optimization of doping compositions enables efficient Ce3+ → Tb3+ energy transfer, resulting in substantial enhancements in QE and thermal stability. Specifically, KLBO:0.04Ce3+,0.28Tb3+ achieves an IQE of 98% and a thermal stability of 97%, higher than those of most phosphors of the same type. White light-emitting diodes fabricated using phosphor samples emit warm white light characterized by high Ra (Ra = 96.6 and 93.4) and low CCT (CCT = 4886 and 4400 K). This study underscores the feasibility of enhancing phosphor QE and thermal stability through energy transfer mechanisms.

5.
Angew Chem Int Ed Engl ; : e202409862, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38866703

ABSTRACT

Isotopically labeled alkanes play a crucial role in organic and pharmaceutical chemistry. While some deuterated methylating agents are readily available, the limited accessibility of other deuteroalkyl reagents has hindered the synthesis of corresponding products. In this study, we introduce a nickel-catalyzed system that facilitates the synthesis of various deuterium-labeled alkanes through the hydrodeuteroalkylation of d2-labeled alkyl TT salts with unactivated alkenes. Diverging from traditional deuterated alkyl reagents, alkyl thianthrenium (TT) salts can effectively and selectively introduce deuterium at α position of alkyl chains using D2O as the deuterium source via a single-step pH-dependent hydrogen isotope exchange (HIE). Our method allows for high deuterium incorporation, and offers precise control over the site of deuterium insertion within an alkyl chain. This technique proves to be invaluable for the synthesis of various deuterium-labeled compounds, especially those of pharmaceutical relevance.

6.
Cancer Med ; 13(12): e7388, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38924330

ABSTRACT

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate , Biliary Tract Neoplasms , Biomarkers, Tumor , ROC Curve , Humans , Male , Female , Middle Aged , Biliary Tract Neoplasms/diagnosis , Biliary Tract Neoplasms/blood , Antigens, Tumor-Associated, Carbohydrate/blood , Biomarkers, Tumor/blood , Aged , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/blood , Liver Neoplasms/diagnosis , Liver Neoplasms/blood , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/blood , CA-19-9 Antigen/blood , Retrospective Studies , Sensitivity and Specificity
8.
ACS Nano ; 18(26): 17282-17292, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38904992

ABSTRACT

Epitaxial growth stands as a key method for integrating semiconductors into heterostructures, offering a potent avenue to explore the electronic and optoelectronic characteristics of cutting-edge materials, such as transition metal dichalcogenide (TMD) and perovskites. Nevertheless, the layer-by-layer growth atop TMD materials confronts a substantial energy barrier, impeding the adsorption and nucleation of perovskite atoms on the 2D surface. Here, we epitaxially grown an inorganic lead-free perovskite on TMD and formed van der Waals (vdW) heterojunctions. Our work employs a monomolecular membrane-assisted growth strategy that reduces the contact angle and simultaneously diminishing the energy barrier for Cs3Sb2Br9 surface nucleation. By controlling the nucleation temperature, we achieved a reduction in the thickness of the Cs3Sb2Br9 epitaxial layer from 30 to approximately 4 nm. In the realm of inorganic lead-free perovskite and TMD heterojunctions, we observed long-lived interlayer exciton of 9.9 ns, approximately 36 times longer than the intralayer exciton lifetime, which benefited from the excellent interlayer coupling brought by direct epitaxial growth. Our research introduces a monomolecular membrane-assisted growth strategy that expands the diversity of materials attainable through vdW epitaxial growth, potentially contributing to future applications in optoelectronics involving heterojunctions.

9.
Front Microbiol ; 15: 1332105, 2024.
Article in English | MEDLINE | ID: mdl-38800758

ABSTRACT

Introduction: Research on the mechanism of marine polysaccharide utilization by Bacteroides thetaiotaomicron has drawn substantial attention in recent years. Derived from marine algae, the marine algae polysaccharides could serve as prebiotics to facilitate intestinal microecological balance and alleviate colonic diseases. Bacteroides thetaiotaomicron, considered the most efficient degrader of polysaccharides, relates to its capacity to degrade an extensive spectrum of complex polysaccharides. Polysaccharide utilization loci (PULs), a specialized organization of a collection of genes-encoded enzymes engaged in the breakdown and utilization of polysaccharides, make it possible for Bacteroides thetaiotaomicron to metabolize various polysaccharides. However, there is still a paucity of comprehensive studies on the procedure of polysaccharide degradation by Bacteroides thetaiotaomicron. Methods: In the current study, the degradation of four kinds of marine algae polysaccharides, including sodium alginate, fucoidan, laminarin, and Pyropia haitanensis polysaccharides, and the underlying mechanism by Bacteroides thetaiotaomicron G4 were investigated. Pure culture of Bacteroides thetaiotaomicron G4 in a substrate supplemented with these polysaccharides were performed. The change of OD600, total carbohydrate contents, and molecular weight during this fermentation were determined. Genomic sequencing and bioinformatic analysis were further performed to elucidate the mechanisms involved. Specifically, Gene Ontology (GO) annotation, Clusters of Orthologous Groups (COG) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized to identify potential target genes and pathways. Results: Underlying target genes and pathways were recognized by employing bioinformatic analysis. Several PULs were found that are anticipated to participate in the breakdown of these four polysaccharides. These findings may help to understand the interactions between these marine seaweed polysaccharides and gut microorganisms. Discussion: The elucidation of polysaccharide degradation mechanisms by Bacteroides thetaiotaomicron provides valuable insights into the utilization of marine polysaccharides as prebiotics and their potential impact on gut health. Further studies are warranted to explore the specific roles of individual PULs and their contributions to polysaccharide metabolism in the gut microbiota.

10.
Eur J Pharmacol ; 972: 176551, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38570082

ABSTRACT

Fibroblast-like synoviocytes (FLS) play an important role in rheumatoid arthritis (RA)-related swelling and bone damage. Therefore, novel targets for RA therapy in FLS are urgently discovered for improving pathologic phenomenon, especially joint damage and dyskinesia. Here, we suggested that pyruvate kinase M2 (PKM2) in FLS represented a pharmacological target for RA treatment by antimalarial drug artemisinin (ART). We demonstrated that ART selectively inhibited human RA-FLS and rat collagen-induced arthritis (CIA)-FLS proliferation and migration without observed toxic effects. In particular, the identification of targets revealed that PKM2 played a crucial role as a primary regulator of the cell cycle, leading to the heightened proliferation of RA-FLS. ART exhibited a direct interaction with PKM2, resulting in an allosteric modulation that enhances the lactylation modification of PKM2. This interaction further promoted the binding of p300, ultimately preventing the nuclear translocation of PKM2 and inducing cell cycle arrest at the S phase. In vivo, ART obviously suppressed RA-mediated synovial hyperplasia, bone damage and inflammatory response to further improve motor behavior in CIA-rats. Taken together, these findings indicate that directing interventions towards PKM2 in FLS could offer a hopeful avenue for pharmaceutical treatments of RA through the regulation of cell cycle via PKM2 lactylation.


Subject(s)
Arthritis, Rheumatoid , Cell Proliferation , Synoviocytes , Synoviocytes/drug effects , Synoviocytes/metabolism , Synoviocytes/pathology , Arthritis, Rheumatoid/pathology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Animals , Cell Proliferation/drug effects , Humans , Rats , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Pyruvate Kinase/metabolism , Thyroid Hormone-Binding Proteins , Male , Thyroid Hormones/metabolism , Arthritis, Experimental/pathology , Arthritis, Experimental/drug therapy , Arthritis, Experimental/metabolism , Cell Movement/drug effects , Molecular Targeted Therapy , Membrane Proteins/metabolism , Carrier Proteins/metabolism , Small Molecule Libraries/pharmacology , Small Molecule Libraries/chemistry
11.
J Med Chem ; 67(9): 7635-7646, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38661304

ABSTRACT

The T-cell receptor (TCR) is a crucial molecule in cellular immunity. The single-chain T-cell receptor (scTCR) is a potential format in TCR therapeutics because it eliminates the possibility of αß-TCR mispairing. However, its poor stability and solubility impede the in vitro study and manufacturing of therapeutic applications. In this study, some conserved structural motifs are identified in variable domains regardless of germlines and species. Theoretical analysis helps to identify those unfavored factors and leads to a general strategy for stabilizing scTCRs by substituting residues at exact IMGT positions with beneficial propensities on the consensus sequence of germlines. Several representative scTCRs are displayed to achieve stability optimization and retain comparable binding affinities with the corresponding αß-TCRs in the range of µM to pM. These results demonstrate that our strategies for scTCR engineering are capable of providing the affinity-enhanced and specificity-retained format, which are of great value in facilitating the development of TCR-related therapeutics.


Subject(s)
Receptors, Antigen, T-Cell , Humans , Receptors, Antigen, T-Cell/chemistry , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/immunology , Protein Stability , Receptors, Antigen, T-Cell, alpha-beta/chemistry , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Amino Acid Sequence , Models, Molecular , Protein Engineering , Protein Binding
12.
Nanotechnology ; 35(30)2024 May 07.
Article in English | MEDLINE | ID: mdl-38631322

ABSTRACT

The growth kinetics of colloidal lead halide perovskite nanomaterials are an integral part of their applications, remains poorly understood due to complex nucleation processes and lack ofin situsize monitoring method. Here we demonstrated that absorption spectra can be used to observein situgrowth processes of ultrathin CsPbBr3nanowires in solution with reference to the effective mass infinite deep square potential well model. By means of this method, we have found that the ultrathin nanowires, fabricated by hot injection method, were firstly formed within one minute. Subsequently, they merge with each other into a thicker structure with increasing reaction time. We revealed that the nucleation, growth, and merging of the CsPbBr3nanowires are determined by the acid concentration and ligand chain length. At lower acidity, the critical nucleation size of the nanowire is smaller, while the shorter the ligand chain length, the faster the merging among the nanowires. Moreover, the merging mode between nanowires changed with their nucleation size. This growth kinetics of CsPbBr3nanowires provides a reference for optimizing the synthesis conditions to obtain the one-dimensional CsPbBr3with desired size, thus enabling accurate control of the nanowire shape.

13.
Dalton Trans ; 53(16): 6941-6949, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38567552

ABSTRACT

Phosphors with intrinsic white light emission are of great potential in constructing high-quality white LEDs (WLEDs). In this work, we propose the use of energy transfer from Bi3+ to Eu3+ ions for white light emission. A unique Bi3+-activated phosphor LaGdO3 (LGO):Bi3+ was generated using the conventional high-temperature solid-state process. An energy transfer was established by introducing Eu3+ into the phosphor composition. The emission colour of LGO:Bi3+,Eu3+ phosphors changes from cyan to white to orange-red depending on the Bi3+/Eu3+ doping proportion. The energy transfer between the Bi3+ and Eu3+ ions results from the dipole-dipole interaction. The LGO:Bi3+,Eu3+ phosphors were combined with a near-ultraviolet chip to successfully create a single-component WLED device with a colour-rendering index of 92.4. Our work demonstrates the energy transfer as a route for single-component white light emission and makes LGO:Bi3+,Eu3+ phosphors one of the candidate materials for near-ultraviolet lighting.

14.
Sensors (Basel) ; 24(8)2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38676112

ABSTRACT

Micromechanical resonators have aroused growing interest as biological and chemical sensors, and microcantilever beams are the main research focus. Recently, a resonant microcantilever with an integrated heater has been applied in on-chip thermogravimetric analysis (TGA). However, there is a strong relationship between the mass sensitivity of a resonant microcantilever and the location of adsorbed masses. Different sampling positions will cause sensitivity differences, which will result in an inaccurate calculation of mass change. Herein, an integrated H-shaped resonant beam with uniform mass sensitivity and temperature distribution is proposed and developed to improve the accuracy of bio/chemical sensing and TGA applications. Experiments verified that the presented resonant beam possesses much better uniformity of sensitivity and temperature distribution compared with resonant microcantilevers. Gas-sensing and TGA experiments utilizing the integrated resonant beam were also carried out and exhibited good measurement accuracy.

15.
Pharm Res ; 41(4): 807-817, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38443629

ABSTRACT

OBJECTIVE: Current gene therapy of inherited retinal diseases is achieved mainly by subretinal injection, which is invasive with severe adverse effects. Intravitreal injection is a minimally invasive alternative for gene therapy of inherited retinal diseases. This work explores the efficacy of intravitreal delivery of PEGylated ECO (a multifunctional pH-sensitive amphiphilic amino lipid) plasmid DNA (pGRK1-ABCA4-S/MAR) nanoparticles (PEG-ELNP) for gene therapy of Stargardt disease. METHODS: Pigmented Abca4-/- knockout mice received 1 µL of PEG-ELNP solution (200 ng/uL, pDNA concentration) by intravitreal injections at an interval of 1.5 months. The expression of ABCA4 in the retina was determined by RT-PCR and immunohistochemistry at 6 months after the second injection. A2E levels in the treated eyes and untreated controls were determined by HPLC. The safety of treatment was monitored by scanning laser ophthalmoscopy and electroretinogram (ERG). RESULTS: PEG-ELNP resulted in significant ABCA4 expression at both mRNA level and protein level at]6 months after 2 intravitreal injections, and a 40% A2E accumulation reduction compared with non-treated controls. The PEG-ELNP also demonstrated excellent safety as shown by scanning laser ophthalmoscopy, and the eye function evaluation from electroretinogram. CONCLUSIONS: Intravitreal delivery of the PEG-ELNP of pGRK1-ABCA4-S/MAR is a promising approach for gene therapy of Stargardt Disease, which can also be a delivery platform for gene therapy of other inherited retinal diseases.


Subject(s)
Nanoparticles , Retina , Mice , Animals , Stargardt Disease/genetics , Stargardt Disease/metabolism , Stargardt Disease/therapy , Retina/metabolism , Genetic Therapy/methods , Plasmids/genetics , DNA/metabolism , Mice, Knockout , Polyethylene Glycols/metabolism , Intravitreal Injections , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism
16.
Eur J Radiol ; 175: 111416, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38460443

ABSTRACT

BACKGROUND: Differentiating seminomas from nonseminomas is crucial for formulating optimal treatment strategies for testicular germ cell tumors (TGCTs). Therefore, our study aimed to develop and validate a clinical-radiomics model for this purpose. METHODS: In this study, 221 patients with TGCTs confirmed by pathology from four hospitals were enrolled and classified into training (n = 126), internal validation (n = 55) and external test (n = 40) cohorts. Radiomics features were extracted from the CT images. After feature selection, we constructed a clinical model, radiomics models and clinical-radiomics model with different machine learning algorithms. The top-performing model was chosen utilizing receiver operating characteristic (ROC) curve analysis. Decision curve analysis (DCA) was also conducted to assess its practical utility. RESULTS: Compared with those of the clinical and radiomics models, the clinical-radiomics model demonstrated the highest discriminatory ability, with AUCs of 0.918 (95 % CI: 0.870 - 0.966), 0.909 (95 % CI: 0.829 - 0.988) and 0.839 (95 % CI: 0.709 - 0.968) in the training, validation and test cohorts, respectively. Moreover, DCA confirmed that the combined model had a greater net benefit in predicting seminomas and nonseminomas. CONCLUSION: The clinical-radiomics model serves as a potential tool for noninvasive differentiation between testicular seminomas and nonseminomas, offering valuable guidance for clinical treatment.


Subject(s)
Machine Learning , Seminoma , Testicular Neoplasms , Humans , Male , Testicular Neoplasms/diagnostic imaging , Seminoma/diagnostic imaging , Adult , Diagnosis, Differential , Middle Aged , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Tomography, X-Ray Computed/methods , Retrospective Studies , Young Adult , Reproducibility of Results , Radiomics
17.
J Neurosci ; 44(17)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38453467

ABSTRACT

Pain perception arises from the integration of prior expectations with sensory information. Although recent work has demonstrated that treatment expectancy effects (e.g., placebo hypoalgesia) can be explained by a Bayesian integration framework incorporating the precision level of expectations and sensory inputs, the key factor modulating this integration in stimulus expectancy-induced pain modulation remains unclear. In a stimulus expectancy paradigm combining emotion regulation in healthy male and female adults, we found that participants' voluntary reduction in anticipatory anxiety and pleasantness monotonically reduced the magnitude of pain modulation by negative and positive expectations, respectively, indicating a role of emotion. For both types of expectations, Bayesian model comparisons confirmed that an integration model using the respective emotion of expectations and sensory inputs explained stimulus expectancy effects on pain better than using their respective precision. For negative expectations, the role of anxiety is further supported by our fMRI findings that (1) functional coupling within anxiety-processing brain regions (amygdala and anterior cingulate) reflected the integration of expectations with sensory inputs and (2) anxiety appeared to impair the updating of expectations via suppressed prediction error signals in the anterior cingulate, thus perpetuating negative expectancy effects. Regarding positive expectations, their integration with sensory inputs relied on the functional coupling within brain structures processing positive emotion and inhibiting threat responding (medial orbitofrontal cortex and hippocampus). In summary, different from treatment expectancy, pain modulation by stimulus expectancy emanates from emotion-modulated integration of beliefs with sensory evidence and inadequate belief updating.


Subject(s)
Anticipation, Psychological , Anxiety , Magnetic Resonance Imaging , Humans , Male , Female , Anxiety/psychology , Anxiety/physiopathology , Adult , Anticipation, Psychological/physiology , Young Adult , Pain Perception/physiology , Pain/psychology , Pain/physiopathology , Bayes Theorem , Emotions/physiology , Brain/diagnostic imaging , Brain/physiopathology , Brain/physiology , Pleasure/physiology , Brain Mapping
18.
Bioconjug Chem ; 35(3): 381-388, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38446033

ABSTRACT

Long noncoding RNA (lncRNA) differentiation antagonizing noncoding RNA (DANCR) is overexpressed in human triple-negative breast cancer (TNBC) and promotes cell migration and proliferation. TNBC is limited in treatment options relative to hormone-receptor-positive breast cancer and is commonly treated with chemotherapy, which is often compromised by acquired resistance. DANCR has been implicated in the development of chemoresistance across multiple cancer types. Here, we applied magnetic resonance molecular imaging (MRMI) with a targeted contrast agent, MT218, specific to extradomain-B fibronectin (EDB-FN), a marker for epithelial-to-mesenchymal transition, to assess the therapeutic efficacy of the combination of paclitaxel and ZD2-PEG-ECO/siDANCR nanoparticles (ZD2-siDANCR-ELNP) to treat TNBC. The treatment of orthotopic MDA-MB-231 TNBC in mice with paclitaxel significantly suppressed tumor growth but with a significant increase of EDB-FN in the tumor, as revealed by MRMI and immunohistochemistry. Combining ZD2-siDANCR-ELNP with paclitaxel further reduced tumor sizes, along with reduced EDB-FN expression. Interestingly, MT218-MRMI revealed a lower reduction of tumor signal enhancement with the combination treatment than that with the siDANCR treatment alone, which was supported by higher cell density in the tumors treated with the combination therapy, as shown by histochemical analysis. MT218-MRMI clearly revealed the changes of the tumor microenvironment in response to various therapies and is effective to noninvasively assess the response of TNBC tumors to the therapies. Regulating oncogenic lncRNA DANCR is an effective strategy for improving the outcomes of chemotherapy in TNBC.


Subject(s)
RNA, Long Noncoding , Triple Negative Breast Neoplasms , Humans , Animals , Mice , Triple Negative Breast Neoplasms/diagnostic imaging , Triple Negative Breast Neoplasms/drug therapy , RNA, Long Noncoding/genetics , RNA Interference , Cell Line, Tumor , Paclitaxel/therapeutic use , Magnetic Resonance Spectroscopy , Molecular Imaging/methods , Cell Proliferation , Tumor Microenvironment
19.
ACS Appl Mater Interfaces ; 16(12): 14902-14911, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38484086

ABSTRACT

Li-rich Mn-based layered oxides (LMLOs) are expected to be the most promising high-capacity cathodes for the next generation of lithium-ion batteries (LIBs). However, the poor cycling stability and kinetics performance of polycrystalline LMLOs restrict their practical applications due to the anisotropic lattice stress and crack propagation during cycling. Herein, B-doped micron-sized single-crystal Co-free LMLOs were obtained by molten-salt (LiNO3 and H3BO3)-assisted sintering. The results reveal that the low-melting-point molten salt can serve as liquid-phase media to improve the efficiency of atomic mass transfer and crystal nucleation and growth. The modified single-crystal LMLO cathodes can resist the accumulation of anisotropic stress and strain during the cycling and reduce interface side reactions, thus achieving excellent high-voltage stability and kinetics performance. The reversible specific capacity of the single crystals is 210.8 mAh g-1 at 1C with a voltage decay rate of 1.95 mV/cycle and up to 161.1 mAh g-1 at 10C with a capacity retention of 81.06% after 200 cycles.

20.
Heliyon ; 10(5): e26767, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38463829

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is a multistep process involving sophisticated genetic, epigenetic, and transcriptional changes. However, studies on microRNA (miRNA)'s regulatory effects of N6-methyladenosine (m6A) modifications on HCC progression are limited. Methods: Cell Counting Kit-8 (CCK-8), clone formation, and Transwell assays were used to investigate changes in cancer cell proliferation, invasion, and migration. RNA m6A levels were verified using methylated RNA immunoprecipitation. Luciferase reporter assay was used to study the potential binding between miRNAs and mRNA. A mouse tumor transplant model was established to study the changes in tumor progression. Results: Follistatin-like 5 (FSTL5) was significantly downregulated in HCC and inhibited its further progression. Additionally, methyltransferase-like 3 (METTL3) reduced FSTL5 mRNA stability in an m6A-YTH domain family 2(YTHDF2)-dependent manner. Functional experiments revealed that METTL3 downregulation inhibited HCC progression by upregulating FSTL5 in vitro and in vivo. Luciferase reporter assay verified that miR-186-5p directly targets METTL3. Additionally, miR-186-5p inhibits the proliferation, migration, and invasion of HCC cells by downregulating METTL3 expression. Conclusions: The miR-186-5p/METTL3/YTHDF2/FSTL5 axis may offer new directions for targeted HCC therapy.

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