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1.
Brain Res ; : 149049, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38825161

ABSTRACT

BACKGROUND: Previous studies have revealed structural brain abnormalities in individuals with depression, but the causal relationship between depression and brain structure remains unclear. METHODS: A genetic correlation analysis was conducted using summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 1,265 brain structural imaging-derived phenotypes (IDPs, N = 33,224). Subsequently, a bidirectional two-sample Mendelian Randomization (MR) approach was employed to explore the causal relationships between depression and the IDPs that showed genetic correlations with depression. The main MR results were obtained using the inverse variance weighted (IVW) method, and other MR methods were further employed to ensure the reliability of the findings. RESULTS: Ninety structural IDPs were identified as being genetically correlated with depression and were included in the MR analyses. The IVW MR results indicated that reductions in the volume of several brain regions, including the bilateral subcallosal cortex, right medial orbitofrontal cortex, and right middle-posterior part of the cingulate cortex, were causally linked to an increased risk of depression. Additionally, decreases in surface area of the right middle temporal visual area, right middle temporal cortex, right inferior temporal cortex, and right middle-posterior part of the cingulate cortex were causally associated with a heightened risk of depression. Validation and sensitivity analyses supported the robustness of these findings. However, no evidence was found for a causal effect of depression on structural IDPs. CONCLUSIONS: Our findings reveal the causal influence of specific brain structures on depression, providing evidence to consider brain structural changes in the etiology and treatment of depression.

2.
Plant Commun ; : 100937, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38693694

ABSTRACT

The crosstalk between clathrin-mediated endocytosis (CME) and autophagy pathway has been reported in mammals. However, the interconnection of CME with autophagy has not been established in plants. In this report, we showed that Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopied the Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants both in auto-immunity and nutrient sensitivity. Accordingly, the autophagy pathway was significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, we demonstrated with multiple assays that CLC2 directly interacted with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP were subjected to autophagic degradation and the degradation of GFP-ATG8h was significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneously knocking out ATG8h and ATG8i by the CRISPR/CAS9 resulted in an enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results uncovered a link between the function of CLCs and the autophagy pathway in Arabidopsis.

3.
Science ; 384(6695): 579-584, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38696580

ABSTRACT

Fractional quantum Hall (FQH) states are known for their robust topological order and possess properties that are appealing for applications in fault-tolerant quantum computing. An engineered quantum platform would provide opportunities to operate FQH states without an external magnetic field and enhance local and coherent manipulation of these exotic states. We demonstrate a lattice version of photon FQH states using a programmable on-chip platform based on photon blockade and engineering gauge fields on a two-dimensional circuit quantum electrodynamics system. We observe the effective photon Lorentz force and butterfly spectrum in the artificial gauge field, a prerequisite for FQH states. After adiabatic assembly of Laughlin FQH wave function of 1/2 filling factor from localized photons, we observe strong density correlation and chiral topological flow among the FQH photons. We then verify the unique features of FQH states in response to external fields, including the incompressibility of generating quasiparticles and the smoking-gun signature of fractional quantum Hall conductivity. Our work illustrates a route to the creation and manipulation of novel strongly correlated topological quantum matter composed of photons and opens up possibilities for fault-tolerant quantum information devices.

4.
Natl Sci Rev ; 11(5): nwae113, 2024 May.
Article in English | MEDLINE | ID: mdl-38698903

ABSTRACT

Precise and efficient therapy of malignant tumors is always a challenge. Herein, gold nanoclusters co-modified by aggregation-induced-emission (AIE) molecules, copper ion chelator (acylthiourea) and tumor-targeting agent (folic acid) were fabricated to perform AIE-guided and tumor-specific synergistic therapy with great spatio-temporal controllability for the targeted elimination and metastasis inhibition of malignant tumors. During therapy, the functional gold nanoclusters (AuNTF) would rapidly accumulate in the tumor tissue due to the enhanced permeability and retention effect as well as folic acid-mediated tumor targeting, which was followed by endocytosis by tumor cells. After that, the overexpressed copper ions in the tumor cells would trigger the aggregation of these intracellular AuNTF via a chelation process that not only generated the photothermal agent in situ to perform the tumor-specific photothermal therapy damaging the primary tumor, but also led to the copper deficiency of tumor cells to inhibit its metastasis. Moreover, the copper ions were reduced to cuprous ions along with the chelation, which further catalysed the excess H2O2 in the tumor cells to produce cytotoxic reactive oxygen species, resulting in additional chemodynamic therapy for enhanced antitumor efficiency. The aggregation of AuNTF also activated the AIE molecules to present fluorescence, which not only imaged the therapeutic area for real-time monitoring of this tumor-specific synergistic therapy, but also allowed us to perform near-infrared radiation at the correct time point and location to achieve optimal photothermal therapy. Both in vitro and in vivo results revealed the strong tumor elimination, effective metastasis inhibition and high survival rate of tumor-bearing mice after treatment using the AuNTF nanoclusters, indicating that this AIE-guided and tumor-specific synergistic strategy could offer a promising approach for tumor therapy.

5.
Phys Rev Lett ; 132(16): 165002, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38701476

ABSTRACT

We report the experimental measurement of millijoule terahertz (THz) radiation emitted in the backward direction from laser wakefields driven by a femtosecond laser pulse of few joules interacting with a gas target. By utilizing frequency-resolved energy measurement, it is found that the THz spectrum exhibits two peaks located at about 4.5 and 9.0 THz, respectively. In particular, the high frequency component emerges when the drive laser energy exceeds 1.26 J, at which electron acceleration in the forward direction is detected simultaneously. Theoretical analysis and particle-in-cell simulations indicate that the THz radiation is generated via mode conversion from the laser wakefields excited in plasma with an up-ramp profile, where radiations both at the local electron plasma frequency and its harmonics are produced. Such intense THz sources may find many applications in ultrafast science, e.g., manipulating the transient states of matter.

6.
Curr Mol Med ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38726777

ABSTRACT

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease characterized by the degradation of articular cartilage. Polyphyllin I (PPI) has anti-inflammatory effects in many diseases. However, the mechanism of PPI in OA remains unclear.

Methods: HC-a cells treated with IL-1ß were identified by immunofluorescence staining and microscopic observation. The expression of collagen II and DAPI in HC-a cells was detected by immunofluorescence. The effects of gradient concentration of PPI on IL-1ß-induced cell viability, apoptosis, senescence, and inflammatory factor release were detected by MTT, flow cytometry, SA-ß-Gal assay and ELISA, respectively. Expressions of apoptosis-related genes, extracellular matrix (ECM)- related genes, and TWIST1 were determined by qRT-PCR and western blot as needed. The above-mentioned experiments were conducted again after TWIST1 overexpression in IL-1ß-induced chondrocytes.

Results: IL-1ß reduced the number of chondrocytes and the density of collagen II. PPI (0.25, 0.5, 1 µmol/L) had no effect on cell viability, but it dose-dependently elevated the inhibition of cell viability regulated by IL-1ß. The elevation of cell apoptosis, senescence and expression of IL-6 and TNF-α were suppressed by PPI in a dosedependent manner. Additionally, PPI reduced the expression of cleaved caspase-3, bax, MMP-3, and MMP-13 and promoted the expression of collagen II. TWIST1 expression was diminished by PPI. TWIST1 overexpression reversed the abovementioned effects of PPI on chondrocytes.

Conclusion: PPI suppressed apoptosis, senescence, inflammation, and ECM degradation of OA chondrocytes by downregulating the expression of TWIST1.

7.
Metabolism ; : 155933, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38729601

ABSTRACT

AIMS/HYPOTHESIS: cGAS (cyclic GMP-AMP synthase) has been implicated in various cellular processes, but its role in ß-cell proliferation and diabetes is not fully understood. This study investigates the impact of cGAS on ß-cell proliferation, particularly in the context of diabetes. METHODS: Utilizing mouse models, including cGAS and STING (stimulator of interferon genes) knockout mice, we explored the role of cGAS in ß-cell function. This involved ß-cell-specific cGAS knockout (cGASßKO) mice, created by breeding cGAS floxed mice with transgenic mice expressing Cre recombinase under the insulin II promoter. We analyzed cGAS expression in diabetic mouse models, evaluated the effects of cGAS deficiency on glucose tolerance, and investigated the molecular mechanisms underlying these effects through RNA sequencing. RESULTS: cGAS expression is upregulated in the islets of diabetic mice and by high glucose treatment in MIN6 cells. Both global cGAS deficiency and ß-cell-specific cGAS knockout mice lead to improved glucose tolerance by promoting ß-cell mass. Interestingly, STING knockout did not affect pancreatic ß-cell mass, suggesting a STING-independent mechanism for cGAS's role in ß-cells. Further analyses revealed that cGAS- but not STING-deficiency leads to reduced expression of CEBPß, a known suppressor of ß-cell proliferation, concurrently with increased ß-cell proliferation. Moreover, overexpression of CEBPß reverses the upregulation of Cyclin D1 and D2 induced by cGAS deficiency, thereby regulating ß-cell proliferation. These results confirm that cGAS regulation of ß-cell proliferation via a CEBPß-dependent but STING-independent mechanism. CONCLUSIONS/INTERPRETATION: Our findings highlight the pivotal role of cGAS in promoting ß-cell proliferation and maintaining glucose homeostasis, potentially by regulating CEBPß expression in a STING-independent manner. This study uncovers the significance of cGAS in controlling ß-cell mass and identifies a potential therapeutic target for enhancing ß-cell proliferation in the treatment of diabetes.

8.
Colloids Surf B Biointerfaces ; 238: 113928, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692175

ABSTRACT

In this research, four water-insoluble flavonoid compounds were utilized and reacted with arginine to prepare four carbonized polymer dots with good water-solubility in a hydrothermal reactor. Structural characterization demonstrated that the prepared carbonized polymer dots were classic core-shell structure. Effect of the prepared carbonized polymer dots on protein amyloid aggregation was further investigated using hen egg white lysozyme and human lysozyme as model protein in aqueous solution. All of the prepared carbonized polymer dots could retard the amyloid aggregation of hen egg white lysozyme and human lysozyme in a dose-depended manner. All measurements displayed that the inhibition ratio of luteolin-derived carbonized polymer dots (CPDs-1) was higher than that of the other three carbonized polymer dots under the same dosage. This result may be interpreted by the highest content of phenolic hydroxyl groups on the periphery. The inhibition ratio of CPDs-1 on hen egg white lysozyme and human lysozyme reached 88 % and 83 % at the concentration of 0.5 mg/mL, respectively. CPDs-1 also could disaggregate the formed mature amyloid fibrils into short aggregates.


Subject(s)
Amyloid , Flavonoids , Muramidase , Polymers , Protein Aggregates , Muramidase/chemistry , Muramidase/metabolism , Humans , Polymers/chemistry , Polymers/pharmacology , Amyloid/chemistry , Amyloid/antagonists & inhibitors , Flavonoids/chemistry , Flavonoids/pharmacology , Protein Aggregates/drug effects , Animals , Chickens , Carbon/chemistry
9.
Gut Microbes ; 16(1): 2347725, 2024.
Article in English | MEDLINE | ID: mdl-38722028

ABSTRACT

The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.


Subject(s)
Feces , Gastrointestinal Microbiome , Humans , Feces/microbiology , Clostridiales/genetics , Clostridiales/metabolism , Clostridiales/isolation & purification , Clostridiales/classification , Probiotics/metabolism , Metabolomics , Genomics , Male , Phylogeny , Female , Genome, Bacterial
10.
Article in English | MEDLINE | ID: mdl-38716548

ABSTRACT

BACKGROUND: Uncontrolled inflammation plays an important role in the initiation and progression of tumors. The repeated circulation and continuous stimulation of gallbladder epithelium caused by gallstones is an important risk factor for gallbladder cancer. METHODS: To study pathogenesis, samples were collected for chronic cholecystitis caused by gallstones and early and advanced gallbladder cancer with gallstones and subjected to RNA-seq analysis. Gene Ontology and Kyoto Gene and Genome Encyclopedia analyses were used to elucidate the protein-protein interaction network and identify differentially expressed genes. RESULTS: Nine potential molecular markers, VTN, CHAD, AKR1C4, ABCC2, AOX1, ADH1A, ADH1C, PLA2G2A, and CYP4F3, with elevated expression gradients in cholecystitis and early and advanced gallbladder cancer, were identified. Using qPCR and immunohistochemistry on clinical tissues, we confirmed three factors, VTN, CYP4F3, and AOX1, to be worthy of further research. To demonstrate that these three genes are potential molecular markers for gallbladder cancer, their cellular biological functions were confirmed in gallbladder cancer cell lines through siRNA transfection. CONCLUSION: The potential molecular markers CYP4F3, VTN, and AOX1 for cholecystitis and different stages of gallbladder cancer were identified. Further studies on differentially expressed genes vital in gallbladder cancer progression can help provide potential targets for the early diagnosis and treatment of gallbladder cancer.

11.
Pathol Res Pract ; 258: 155314, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38696855

ABSTRACT

Nasopharyngeal carcinoma (NPC) arises from the epithelium of the nasopharynx and is characterized by geography-dependent incidence. Despite the high mortality rate, specifically in some ethnic groups, the mechanisms underlying NPC pathogenesis are not thoroughly understood and there is an urgent need to detect the potential and clinically applicable biomarkers to ameliorate the overall survival rate and improve the prognosis of patients. In recent years, research has increasingly focused on the importance of long non-coding RNAs (LncRNAs) in cancer progression. LncRNAs play critical roles in regulating gene expression through mechanisms such as competitively binding to microRNAs (CeRNA). While numerous LncRNAs have been studied in nasopharyngeal carcinoma (NPC), their potential as diagnostic and prognostic biomarkers have not been systematically examined. In the present study, we delve into elucidating the biological functions, molecular mechanisms, and clinical significance of newly identified LncRNAs that serve as sponges for different microRNAs in NPC. We highlight their regulatory mechanisms in promoting cell proliferation, invasion, and metastasis, and discuss their implications in diverse cancer-related signaling pathways. Our overall goal is to emboss the fundamental roles of LncRNA-mediated CeRNA networks in NPC progression, which may open up new avenues for determining the pathogenesis of NPC and developing effective prevention and treatment strategies.


Subject(s)
Gene Expression Regulation, Neoplastic , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , Gene Expression Regulation, Neoplastic/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Regulatory Networks , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , RNA, Competitive Endogenous
12.
Jpn J Clin Oncol ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711392

ABSTRACT

BACKGROUND: The incidence and risk factors of peripherally inserted central catheter-related thrombosis in patients with breast cancer have not been fully elucidated. METHOD: Meta-analysis was performed by searching all studies on the incidence of peripherally inserted central catheter-associated thrombosis and risk factors for its formation in breast cancer patients from the establishment of the database to May 2023, including PubMed, Embase, Web of Science, China Knowledge Network, China Biomedical Literature Service System (SinoMed) and Wanfang databases. Then the incidence of peripherally inserted central catheter-related thrombosis and risk factors for its formation were analyzed in breast cancer patients. RESULTS: A total of 15 articles were included, involving 8635 patients. The total incidence of peripherally inserted central catheter-related thrombosis in breast cancer patients was 7.0% (95% confidence interval: 4.0-13.0%) and 12.9% (95% confidence interval: 7.0-22.5%) after correction. Thirty-two risk factors were included, and eight risk factors could be combined. Among these risk factors, there were statistically significant differences (P < 0.05) in body mass index ≥ 25 (odds ratio = 6.319, 95% confidence interval: 2.733-14.613; P < 0.001), D-dimer >500 ng/ml (odds ratio = 1.436, 95% confidence interval: 1.113-1.854; P = 0.005), increased fibrinogen (odds ratio = 4.733, 95% confidence interval: 1.562-14.346; P = 0.006), elevated platelet count (odds ratio = 4.134, 95% confidence interval: 2.694-6.346; P < 0.001) and catheter malposition (odds ratio = 8.475, 95% confidence interval: 2.761-26.011; P < 0.001). CONCLUSION: The incidence rate of peripherally inserted central catheter-related thrombosis in breast cancer patients was 7.0% (95% confidence interval: 4.0-13.0%). Body mass index ≥ 25, D-dimer >500 ng/ml, elevated fibrinogen, elevated platelet count and catheter malposition were risk factors for peripherally inserted central catheter-related thrombosis in breast cancer patients.

13.
Materials (Basel) ; 17(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38730771

ABSTRACT

With the continuous integration of semiconductor devices, the requirements of the size accuracy and surface quality of etched lead frames are stricter. The etchant is a key factor in the etching process and etched surface quality, while the effects of the difference in etchants on the etched surface morphology of Cu alloy have not been directly studied. In this study, aqua regia, acidic FeCl3 and two CuCl2 solutions were used as etchants, and different CuCrSn specimens were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocations have significant influences on the local etching rate. The preferential etching of some atomic planes forms steps between the grains with different orientations, and preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For the surfaces etched by the FeCl3 and CuCl2 etchants, the steps and grooves are blurred; thus, they are less rough. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high-density Cr-rich particles remain on the surfaces etched by the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism, rate and the etched surface morphology.

14.
Materials (Basel) ; 17(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38730822

ABSTRACT

Thermal deformation behavior of Cu-Cr-Sn alloy ingots under deformation temperatures ranging from 600 °C to 950 °C and strain rates from 0.01 s-1 to 10 s-1 was investigated in detail. The thermal deformation constitutive equation and thermal processing map of the alloy were established, respectively. The activation energy Q was determined as 430.61 KJ/mol. The optimal deformation system corresponding to the hot working diagram was a deformation temperature of 900 °C and strain rate of 0.1 s-1. Under these deformation conditions, twin dynamic recrystallization (TDRX), continuous dynamic recrystallization (CDRX), and discontinuous dynamic recrystallization (DDRX) occurred simultaneously, with the twinning process causing the stress-strain curve to exhibit a wavy change. The thermal deformation microstructure of the alloy is co-regulated by different recrystallization mechanisms, with DDRX occurring mainly at low deformation temperatures, and both CDRX and DDRX occurring at high deformation temperatures.

15.
Article in English | MEDLINE | ID: mdl-38739685

ABSTRACT

An oval to rod-shaped, Gram-stain-positive, strictly anaerobic bacterium, designated LFL-14T, was isolated from the faeces of a healthy Chinese woman. Cells of the strain were non-spore-forming, grew optimally at 37 °C (growth range 30-45 °C) and pH 7.0 (growth range 6.0-9.0) under anaerobic conditions in the liquid modified Gifu anaerobic medium (mGAM). The result of 16S rRNA gene-based analysis indicated that LFL-14T shared an identity of 94.7 0% with Eubacterium ventriosum ATCC 27560T, indicating LFL-14T represented a novel taxon. The results of genome-based analysis revealed that the average nucleotide identity (ANI), the digital DNA-DNA hybridisation (dDDH) and average amino acid identity (AAI) between LFL-14T and its phylogenetically closest neighbour, Eubacterium ventriosum ATCC 27560T, were 77.0 %, 24.6 and 70.9 %, respectively, indicating that LFL-14T represents a novel species of the genus Eubacterium. The genome size of LFL-14T was 2.92 Mbp and the DNA G+C content was 33.14 mol%. We analysed the distribution of the genome of LFL-14T in cohorts of healthy individuals, type 2 diabetes patients (T2D) and patients with non-alcoholic fatty liver disease (NAFLD). We found that its abundance was higher in the T2D cohort, but it had a low average abundance of less than 0.2 % in all three cohorts. The percentages of frequency of occurrence in the T2D, healthy and NAFLD cohorts were 48.87 %, 16.72 % and 13.10 % respectively. The major cellular fatty acids of LFL-14T were C16 : 0 (34.4 %), C17 : 0 2-OH (21.4 %) and C14 : 0 (11.7 %). Additionally, the strain contained diphosphatidylglycerol (DPG) and phosphatidylethanolamine (PE), as well as unidentified phospholipids and unidentified glycolipids. The glucose fermentation products of LFL-14T were acetate and butyrate. In summary, On the basis of its chemotaxonomic, phenotypic, phylogenetic and phylogenomic properties, strain LFL-14T (= CGMCC 1.18005T = KCTC 25580T) is identified as representing a novel species of the genus Eubacterium, for which the name Eubacterium album sp. nov. is proposed.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Eubacterium , Fatty Acids , Feces , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Humans , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Female , Eubacterium/genetics , Eubacterium/isolation & purification , Eubacterium/classification , Feces/microbiology , Butyrates/metabolism , Genome, Bacterial , China , Adult
16.
Article in English | MEDLINE | ID: mdl-38755472

ABSTRACT

The large-scale integration of renewable power poses great challenges to grid stability. Among flexible resources, demand response (DR) stands out for its advantages in cost and efficiency. To identify key factors influencing DR, this study adopted the modified theory of planned behavior (TPB) to establish the conceptual model. Social norms were included as a front-end variable, and institutional factors and electricity consumption habits served as moderating variables. The model was subsequently tested and modified using the structural equation modelling (SEM). Results indicated that social norms can exert a substantial indirect effect on DR behavior. However, due to the deficiency of such norms, the formation of the positive attitude towards DR was hindered, resulting in a low standard coefficient of 0.16. Moreover, the influence of subjective norm on response intention was rejected due to limited perceived external pressure. Perceived behavior control exhibited the most significant direct influence on response intention (0.76). Additionally, the positive effects of situational factors and personal habits on the conversion from response intention to behavior were supported. Based on these findings, several policy suggestions including enhancing publicity and incentive policies were proposed.

17.
Nanoscale ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38757536

ABSTRACT

Gene therapy is a promising disease treatment approach by editing target genes, and thus plays a fundamental role in precision medicine. To ensure gene therapy efficacy, the effective delivery of therapeutic genes into specific cells is a key challenge. Electroporation utilizes short electric pulses to physically break the cell membrane barrier, allowing gene transfer into the cells. It dodges the off-target risks associated with viral vectors, and also stands out from other physical-based gene delivery methods with its high-throughput and cargo-accelerating features. In recent years, with the help of advanced micro/nanotechnology, micro/nanostructure-integrated electroporation (micro/nano-electroporation) techniques and devices have significantly improved cell viability, transfection efficiency and dose controllability of the electroporation strategy, enhancing its application practicality especially in vivo. This technical advancement makes micro/nano-electroporation an effective and versatile tool for gene therapy. In this review, we first introduce the evolution of electroporation technique with a brief explanation of the perforation mechanism, and then provide an overview of the recent advancements and prospects of micro/nano-electroporation technology in the field of gene therapy. To comprehensively showcase the latest developments of micro/nano-electroporation technology in gene therapy, we focus on discussing micro/nano-electroporation devices and current applications at both in vitro and in vivo levels. Additionally, we outline the ongoing clinical studies of gene electrotransfer (GET), revealing the tremendous potential of electroporation-based gene delivery in disease treatment and healthcare. Lastly, the challenges and future directions in this field are discussed.

18.
Am J Kidney Dis ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38750878

ABSTRACT

RATIONALE & OBJECTIVE: Light and heavy chain deposition disease (LHCDD) is a rare form of monoclonal immunoglobulin deposition disease (MIDD), and limited clinical data are available characterizing this condition. We described the clinicopathological characteristics and outcomes of LHCDD. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 13 patients with biopsy-proven LHCDD, diagnosed between January 2008 to December 2022, at two Chinese medical centers. FINDINGS: Among the 13 patients described, 6 were men and 7 were women, with a mean age of 52.6 ± 8.0 years. Patients presented with hypertension (76.9%), anemia (84.6%), elevated serum creatinine (84.6%, median serum creatinine 1.7 mg/dL), proteinuria (100%, average urine protein 3.0g/24h), nephrotic syndrome (30.8%) and microscopic hematuria (76.9%). Serum immunofixation electrophoresis showed monoclonal immunoglobulin for 11 (84.6%) patients. Serum free light chain (FLC) ratios were abnormal in 11 (84.6%) patients, and heavy/light chain (HLC) ratios were abnormal in 9 of 10 (90%) patients with available data. Five patients were diagnosed with multiple myeloma. A histological diagnosis of nodular mesangial sclerosis was made in 10 (76.9%) patients. Immunofluorescence demonstrated deposits of IgG subclass (γ-κ/γ-λ:4/3) in 7 patients, and IgA (α-κ/α-λ:2/3) in 5 patients. Six patients underwent IgG subclass staining (γ1/γ2/γ3:3/2/1). The deposits of IgD-κ were confirmed by mass spectrometry in 1 patient. Among 12 patients for whom data were available over a median of 26.5 months, 11 received chemotherapy, and 1 received conservative treatment. One patient died. Three (25%) patients progressed to kidney failure. Among the 9 patients evaluable for hematological and kidney disease progression, five (56%) had a hematologic response and one (11%) achieved improvement in kidney disease. LIMITATIONS: Retrospective descriptive study, limited number of patients, UPEP or UIFE missing for most patients. CONCLUSIONS: In this case series of LHCDD, light and heavy chain deposition in kidney tissues were most frequent with monoclonal IgG1-κ. Among patients with evaluable data, more than half had hematologic response but a kidney response was uncommon.

19.
bioRxiv ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38746474

ABSTRACT

High Frequency Oscillations (HFOs) is an important biomarker that can potentially pinpoint the epileptogenic zones (EZs). However, the duration of HFO is short with around 4 cycles, which might be hard to recognize when embedded within signals of lower frequency oscillatory background. In addition, annotating HFOs manually can be time-consuming given long-time recordings and up to hundreds of intracranial electrodes. We propose to leverage a Switching State Space Model (SSSM) to identify the HFOs events automatically and instantaneously without relying on extracting features from sliding windows. The effectiveness of the SSSM for HFOs detection is fully validated in the intracranial EEG recording from human subjects undergoing the presurgical evaluations and showed improved accuracy when capturing the HFOs occurrence and their duration.

20.
PLoS One ; 19(5): e0302651, 2024.
Article in English | MEDLINE | ID: mdl-38743758

ABSTRACT

Since the COVID-19, cough sounds have been widely used for screening purposes. Intelligent analysis techniques have proven to be effective in detecting respiratory diseases. In 2021, there were up to 10 million TB-infected patients worldwide, with an annual growth rate of 4.5%. Most of the patients were from economically underdeveloped regions and countries. The PPD test, a common screening method in the community, has a sensitivity of as low as 77%. Although IGRA and Xpert MTB/RIF offer high specificity and sensitivity, their cost makes them less accessible. In this study, we proposed a feature fusion model-based cough sound classification method for primary TB screening in communities. Data were collected from hospitals using smart phones, including 230 cough sounds from 70 patients with TB and 226 cough sounds from 74 healthy subjects. We employed Bi-LSTM and Bi-GRU recurrent neural networks to analyze five traditional feature sets including the Mel frequency cepstrum coefficient (MFCC), zero-crossing rate (ZCR), short-time energy, root mean square, and chroma_cens. The incorporation of features extracted from the speech spectrogram by 2D convolution training into the Bi-LSTM model enhanced the classification results. With traditional futures, the best TB patient detection result was achieved with the Bi-LSTM model, with 93.99% accuracy, 93.93% specificity, and 92.39% sensitivity. When combined with a speech spectrogram, the classification results showed 96.33% accuracy, 94.99% specificity, and 98.13% sensitivity. Our findings underscore that traditional features and deep features have good complementarity when fused using Bi LSTM modelling, which outperforms existing PPD detection methods in terms of both efficiency and accuracy.


Subject(s)
Cough , Neural Networks, Computer , Tuberculosis, Pulmonary , Humans , Cough/diagnosis , Tuberculosis, Pulmonary/diagnosis , Male , Female , Adult , Middle Aged , COVID-19/diagnosis , Aged , Sensitivity and Specificity
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