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1.
Sci Total Environ ; 927: 172145, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38569974

ABSTRACT

Copper (Cu) has sparked widespread global concern as one of the most hazardous metals to aquatic animals. Ocean acidification (OA) and warming (OW) are expected to alter copper's bioavailability based on pH and temperature-sensitive effects; research on their effects on copper on marine organisms is still in its infancy. Therefore, under representative concentration pathways (RCP) 2.6, 4.5, and 8.5, we used the multiple linear regression-water quality criteria (MLR-WQC) method to assess the effects of OA and OW on the ecological risk posed by copper in the Ocean of East China (OEC), which includes the Bohai Sea, Yellow Sea, and East China Sea. The results showed that there was a positive correlation between temperature and copper toxicity, while there was a negative correlation between pH and copper toxicity. The short-term water quality criteria (WQC) values were 1.53, 1.41, 1.30 and 1.13 µg·L-1, while the long-term WQC values were 0.58, 0.48, 0.40 and 0.29 µg·L-1 for 2020, 2099-RCP2.6, 2099-RCP4.5 and 2099-RCP8.5, respectively. Cu in the OEC poses a moderate ecological risk. Under the current copper exposure situation, strict intervention (RCP2.6) only increases the ecological risk of copper exposure by 20 %, and no intervention (RCP8.5) will increase the ecological risk of copper exposure by nearly double. The results indicate that intervention on carbon emissions can slow down the rate at which OA and OW worsen the damage copper poses to marine creatures. This study can provide valuable information for a comprehensive understanding of the combined impacts of climate change and copper on marine organisms.


Subject(s)
Aquatic Organisms , Copper , Environmental Monitoring , Oceans and Seas , Seawater , Water Pollutants, Chemical , Copper/toxicity , Seawater/chemistry , Aquatic Organisms/drug effects , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity , Hydrogen-Ion Concentration , China , Climate Change , Global Warming , Animals , Ocean Acidification
2.
Int Rev Immunol ; : 1-14, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38661566

ABSTRACT

Research on the relationship between macrophages and neuropathic pain has flourished in the past two decades. It has long been believed that macrophages are strong immune effector cells that play well-established roles in tissue homeostasis and lesions, such as promoting the initiation and progression of tissue injury and improving wound healing and tissue remodeling in a variety of pathogenesis-related diseases. They are also heterogeneous and versatile cells that can switch phenotypically/functionally in response to the micro-environment signals. Apart from microglia (resident macrophages of both the spinal cord and brain), which are required for the neuropathic pain processing of the CNS, neuropathic pain signals in PNS are influenced by the interaction of tissue-resident macrophages and BM infiltrating macrophages with primary afferent neurons. And the current review looks at new evidence that suggests sexual dimorphism in neuropathic pain are caused by variations in the immune system, notably macrophages, rather than the neurological system.


Neuropathic pain is defined by the International Association for the Study of Pain as pain triggered or caused by primary damage to or dysfunction of the nervous system. Following intensive research into the mechanisms of neuropathic pain, macrophages have been revealed to play an important role in pathologic pain following nerve injury. Macrophages dynamically monitor the microenvironment to maintain tissue homeostasis. Once a macrophage is exposed to a pathologic stimulus, it in turn alters its functional phenotype and interacts with nociceptors, leading to neuropathic pain. This review wants to delve into the biology of macrophages in the central and peripheral nervous system, how they are related to play a role in neuropathic pain and whether there is sexual dimorphism in macrophages.

4.
Pathol Res Pract ; 257: 155312, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38663177

ABSTRACT

Current treatments for orthopaedic illnesses frequently result in poor prognosis, treatment failure, numerous relapses, and other unpleasant outcomes that have a significant impact on patients' quality of life. Cell-free therapy has emerged as one of the most promising options in recent decades for improving the status quo. As a result, using exosomes produced from various cells to modulate ferroptosis has been proposed as a therapeutic method for the condition. Exosomes are extracellular vesicles that secrete various bioactive chemicals that influence disease treatment and play a role in the genesis and progression of orthopaedic illnesses. Ferroptosis is a recently defined kind of controlled cell death typified by large iron ion buildup and lipid peroxidation. An increasing number of studies indicate that ferroptosis plays a significant role in orthopaedic illnesses. Exosomes, as intercellular information transfer channels, have been found to play a significant role in the regulation of ferroptosis processes. Furthermore, accumulating research suggests that exosomes can influence the course of many diseases by regulating ferroptosis in injured cells. In order to better understand the processes by which exosomes govern ferroptosis in the therapy of orthopaedic illnesses. This review discusses the biogenesis, secretion, and uptake of exosomes, as well as the mechanisms of ferroptosis and exosomes in the therapy of orthopaedic illnesses. It focuses on recent research advances and exosome mechanisms in regulating iron death for the therapy of orthopaedic illnesses. The present state of review conducted both domestically and internationally is elucidated and anticipated as a viable avenue for future therapy in the field of orthopaedics.

5.
Ecotoxicol Environ Saf ; 277: 116378, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38663191

ABSTRACT

Pesticide residues and microplastics (MPs) in agricultural soils are two major concerns for soil health and food safety. The degradation of chlorpyrifos (CPF), an organophosphorus pesticide, releases phosphates. This process may be affected by the presence of MPs in the soil. The combination of CPF and MPs presence in the soil may thus produce interaction effects that alter the soil phosphorus (P) balance. This study explores the degradation pathways of CPF (6 mg kg-1, 12 mg kg-1 of CPF addition) in soils with different levels of polylactic acid MPs (PLA-MPs) (0.0 %, 0.1 %, 0.5 %, 1.0 % w/w), and analyzes soil P fractions and phosphatase enzyme activities to investigate soil P bioavailability under different treatments. Results show that the degradation of CPF fits to a first-order decay model, with half-lives (DT50) ranging from 11.0 to 14.8 d depending on PLA-MPs treatment. The concentration of its metabolite 3, 5, 6-trichloropyridine 2-phenol (TCP) reached a peak of 0.93-1.67 mg kg-1 within 7-14 days. Similarly, the degradation of CPF led to a significant transient increase in P bioavailability within 3-7 days (p < 0.05), with a peak range of 22.55-26.01 mg kg-1 for Olsen-P content and a peak range of 4.63-6.76 % for the proportions of available P fractions (H2O-P+NaHCO3-P+NaOH-P), before returning to prior levels (Olsen-P: 11.28-19.52 mg kg-1; available soil P fractions: 4.15-5.61 %). CPF degradation (6 mg kg-1) was significantly inhibited in soil with 1.0 % PLA-MPs addition. The effects of MPs and CPF on soil P fractions occur at different time frames, implying that their modes of action and interactions with soil microbes differ.

6.
Nat Commun ; 15(1): 3495, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664399

ABSTRACT

Quantum annealing, which involves quantum tunnelling among possible solutions, has state-of-the-art applications not only in quickly finding the lowest-energy configuration of a complex system, but also in quantum computing. Here we report a single-crystal study of the frustrated magnet α-CoV2O6, consisting of a triangular arrangement of ferromagnetic Ising spin chains without evident structural disorder. We observe quantum annealing phenomena resulting from time-reversal symmetry breaking in a tiny transverse field. Below ~ 1 K, the system exhibits no indication of approaching the lowest-energy state for at least 15 hours in zero transverse field, but quickly converges towards that configuration with a nearly temperature-independent relaxation time of ~ 10 seconds in a transverse field of ~ 3.5 mK. Our many-body simulations show qualitative agreement with the experimental results, and suggest that a tiny transverse field can profoundly enhance quantum spin fluctuations, triggering rapid quantum annealing process from topological metastable Kosterlitz-Thouless phases, at low temperatures.

7.
3 Biotech ; 14(5): 134, 2024 May.
Article in English | MEDLINE | ID: mdl-38665879

ABSTRACT

Tubal inflammation, endometritis, and uterine adhesions due to post-pelvic inflammatory disease (SPID) are important causes of infertility. Chronic endometritis (CE) belongs to SPID, which seriously affects women's reproductive health, quality of life, and family harmony, and is a hot and difficult problem in clinical research. The efficacy of Pen Yan Kang Fu Decoction (PYKFD) has been verified in long-term clinical practice for chronic endometritis infertility caused by the SPID. Numerous studies have confirmed that the LIF/JAK2/STAT3 signaling pathway is important in embryo implantation and development, and endometritis infertility is close to LIF/JAK2/STAT3. In vivo results showed that PYKFD increased endometrial receptivity, repaired uterine tissue damage, and regulates the expression of endometrial receptivity-related factors ER (estrogen receptor), PR (progesterone receptor), CD31, and integrin αvß3, and induced the transduction of LIF/JAK2/STAT3 signaling pathway. PYKFD can also regulate the expression of IL-6. The results of in vitro experiments showed that PYKFD regulates the behavior of rat endometrial epithelial cells (REECs) involving LIF. In conclusion, PYKFD can improve endometrial receptivity and promote endometrial repair by LIF/JAK2/STAT3 signaling pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03981-0.

8.
BMC Oral Health ; 24(1): 452, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622579

ABSTRACT

OBJECTIVES: To compare the changes in condylar position after mandibular reconstruction with free fibular flap(FFF) and the differences between computer-assisted techniques and traditional methods on CT images. METHODS: Thirty-four patients who underwent mandibular reconstruction with free fibular flap were selected according to the inclusion and exclusion criteria. In the 3D group, virtual surgical planning (VSP) with osteotomy cutting plate and placement guiding plate were used, while the traditional group underwent freehand reconstruction. The CT data of 68 temporomandibular joints (TMJs) were recorded before and immediately after surgery. The condylar position was evaluated by measuring the anterior space (AS), posterior space (PS) and superior space (SS), and the ln (PS/AS) was calculated according to the method proposed by Pullinger and Hollender. RESULTS: In the patients included in the 3D group, the condyle on the ipsilateral side moved slightly backward; however, in the patients in the traditional group, the ipsilateral side moved considerably anteroinferior. No obvious changes on the contralateral side were noted. In the 3D group, 33% of ipsilateral condyles were in the posterior position postoperatively when compared with the preoperative position (13%). In the traditional group, the number of ipsilateral condyles in the anterior position increased from 4 to 10, accounting for 53% postoperatively. Contrary to the traditional group, the 3D group presented less condylar displacement on the ipsilateral side postoperatively. CONCLUSIONS: This study showed a decreased percentage of change in condylar position postoperatively when VSP was used. Virtual surgical planning improved the accuracy of FFF mandibular reconstruction and made the condylar position more stable.


Subject(s)
Free Tissue Flaps , Mandibular Reconstruction , Humans , Mandibular Reconstruction/methods , Temporomandibular Joint/diagnostic imaging , Temporomandibular Joint/surgery , Free Tissue Flaps/surgery , Bone and Bones , Computers , Mandible/diagnostic imaging , Mandible/surgery
9.
Heliyon ; 10(7): e29271, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38623219

ABSTRACT

Low fertilization rate (LFR) and total fertilization failure (TFF) are often encountered in routine in vitro fertilization (IVF) procedure. To solve this problem, multivariate analyses on the relationship between male factors and in vitro fertilization rate were performed, and a nomogram for prediction of LFR was constructed. This retrospective study contained 2011 couples who received IVF treatment from January 2017 to December 2021. Man factors and in vitro fertilization rate were collected. Among these couples, 1347 cases had in vitro fertilization rates ≥30 % (control group), and 664 cases had in vitro fertilization rates <30 % (LFR group). Univariate analyses of male factors found that between the two groups there were significant differences (p < 0.05) in sperm progressive motility (SPR), sperm concentration (SC), total sperm number, normal sperm morphology rate (NSMR), DNA fragmentation index (DFI), sperm acrosin activity (SAA) and the clinical diagnosis of primary or secondary infertility. Multivariate logistic regression analyses showed that SPR, SAA, and SC were independent risk factors for LFR. An algorithm and a correspondent nomogram for predicting high LFR risk were constructed using data from the training cohort. The LFR nomogram exhibited an excellent discrimination power and a high fitting degree in both the training cohort (AUC = 0.90, 95 % CI: 0.88-0.92), (H-L: x2 = 5.43, p = 0.71) and validation cohort (AUC = 0.89, 95 % CI:0.87-0.92), (H-L: x2 = 7.85, p = 0.45), respectively. The decision curve analysis (DCA) demonstrated a high efficiency of the LFR nomogram for clinical utility. SPR, SAA, and SC are independent risk factors for LFR. The LFR nomogram established based on these factors could be a useful tool to predict high risk of LFR, and patients with high risk of LFR can be guided to direct ICSI procedure. Clinical application of the LFR nomogram may increase the in vitro fertilization rate by facilitating the decision making in IVF service.

10.
BMC Bioinformatics ; 25(1): 158, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643066

ABSTRACT

BACKGROUND: Motif finding in Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data is essential to reveal the intricacies of transcription factor binding sites (TFBSs) and their pivotal roles in gene regulation. Deep learning technologies including convolutional neural networks (CNNs) and graph neural networks (GNNs), have achieved success in finding ATAC-seq motifs. However, CNN-based methods are limited by the fixed width of the convolutional kernel, which makes it difficult to find multiple transcription factor binding sites with different lengths. GNN-based methods has the limitation of using the edge weight information directly, makes it difficult to aggregate the neighboring nodes' information more efficiently when representing node embedding. RESULTS: To address this challenge, we developed a novel graph attention network framework named MMGAT, which employs an attention mechanism to adjust the attention coefficients among different nodes. And then MMGAT finds multiple ATAC-seq motifs based on the attention coefficients of sequence nodes and k-mer nodes as well as the coexisting probability of k-mers. Our approach achieved better performance on the human ATAC-seq datasets compared to existing tools, as evidenced the highest scores on the precision, recall, F1_score, ACC, AUC, and PRC metrics, as well as finding 389 higher quality motifs. To validate the performance of MMGAT in predicting TFBSs and finding motifs on more datasets, we enlarged the number of the human ATAC-seq datasets to 180 and newly integrated 80 mouse ATAC-seq datasets for multi-species experimental validation. Specifically on the mouse ATAC-seq dataset, MMGAT also achieved the highest scores on six metrics and found 356 higher-quality motifs. To facilitate researchers in utilizing MMGAT, we have also developed a user-friendly web server named MMGAT-S that hosts the MMGAT method and ATAC-seq motif finding results. CONCLUSIONS: The advanced methodology MMGAT provides a robust tool for finding ATAC-seq motifs, and the comprehensive server MMGAT-S makes a significant contribution to genomics research. The open-source code of MMGAT can be found at https://github.com/xiaotianr/MMGAT , and MMGAT-S is freely available at https://www.mmgraphws.com/MMGAT-S/ .


Subject(s)
Chromatin Immunoprecipitation Sequencing , Genomics , Humans , Animals , Mice , Binding Sites , Protein Binding , Genomics/methods , Chromatin/genetics , Transcription Factors/metabolism
11.
Eur J Med Res ; 29(1): 244, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643140

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Catheter ablation has become a crucial treatment for AF. However, there is a possibility of atrial fibrillation recurrence after catheter ablation. Our study sought to elucidate the role of lncRNA‒mRNA regulatory networks in late AF recurrence after catheter ablation. METHODS: We conducted RNA sequencing to profile the transcriptomes of 5 samples from the presence of recurrence after AF ablation (P-RAF) and 5 samples from the absence of recurrence after AF ablation (A-RAF). Differentially expressed genes (DEGs) and long noncoding RNAs (DE-lncRNAs) were analyzed using the DESeq2 R package. The functional correlations of the DEGs were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein‒protein interaction (PPI) network was constructed using STRING and Cytoscape. We also established a lncRNA‒mRNA regulatory network between DE-lncRNAs and DEGs using BEDTools v2.1.2 software and the Pearson correlation coefficient method. To validate the high-throughput sequencing results of the hub genes, we conducted quantitative real-time polymerase chain reaction (qRT‒PCR) experiments. RESULTS: A total of 28,528 mRNAs and 42,333 lncRNAs were detected. A total of 96 DEGs and 203 DE-lncRNAs were identified between the two groups. GO analysis revealed that the DEGs were enriched in the biological processes (BPs) of "regulation of immune response" and "regulation of immune system process", the cellular components (CCs) of "extracellular matrix" and "cell‒cell junction", and the molecular functions (MFs) of "signaling adaptor activity" and "protein-macromolecule adaptor activity". According to the KEGG analysis, the DEGs were associated with the "PI3K-Akt signaling pathway" and "MAPK signaling pathway." Nine hub genes (MMP9, IGF2, FGFR1, HSPG2, GZMB, PEG10, GNLY, COL6A1, and KCNE3) were identified through the PPI network. lncRNA-TMEM51-AS1-201 was identified as a core regulator in the lncRNA‒mRNA regulatory network, suggesting its potential impact on the recurrence of AF after catheter ablation through the regulation of COL6A1, FGFR1, HSPG2, and IGF2. CONCLUSIONS: The recurrence of atrial fibrillation after catheter ablation may be associated with immune responses and fibrosis, with the extracellular matrix playing a crucial role. TMEM51-AS1-201 has been identified as a potential key target for AF recurrence after catheter ablation.


Subject(s)
Atrial Fibrillation , Catheter Ablation , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Gene Regulatory Networks , Atrial Fibrillation/genetics , Atrial Fibrillation/surgery , RNA, Messenger/genetics , Phosphatidylinositol 3-Kinases , MicroRNAs/genetics
12.
J Transl Med ; 22(1): 368, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637886

ABSTRACT

In this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-ɑ during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Receptors, Chimeric Antigen , Humans , Animals , Mice , Carcinoma, Renal Cell/therapy , T-Lymphocytes , Cell Line, Tumor , Kidney Neoplasms/therapy , Immunotherapy, Adoptive , Xenograft Model Antitumor Assays , CD27 Ligand
13.
Emerg Microbes Infect ; 13(1): 2339946, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38578304

ABSTRACT

Streptococcus suis is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for S. suis human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of S. suis ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 S. suis ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of S. suis strains.


Subject(s)
Genome, Bacterial , Genomic Islands , Phylogeny , Streptococcal Infections , Streptococcus suis , Streptococcus suis/genetics , Streptococcus suis/pathogenicity , Streptococcus suis/classification , Streptococcus suis/isolation & purification , Streptococcal Infections/microbiology , Streptococcal Infections/veterinary , Streptococcal Infections/epidemiology , China/epidemiology , Humans , Virulence , Animals , Mice , Female , Genomics , Virulence Factors/genetics
14.
Mol Nutr Food Res ; 68(8): e2300720, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38581348

ABSTRACT

SCOPE: The global prevalence of obesity has significantly increased, presenting a major health challenge. High-fat diet (HFD)-induced obesity is closely related to the disease severity of psoriasis, but the mechanism is not fully understood. METHODS AND RESULTS: The study utilizes the HFD-induced obesity model along with an imiquimod (IMQ)-induced psoriasis-like mouse model (HFD-IMQ) to conduct transcriptomics and metabolomic analyses. HFD-induced obese mice exhibits more severe psoriasis-like lesions compared to normal diet (ND)-IMQ mice. The expression of genes of the IL-17 signaling pathway (IL-17A, IL-17F, S100A9, CCL20, CXCL1) is significantly upregulated, leading to an accumulation of T cells and neutrophils in the skin. Moreover, the study finds that there is an inhibition of the branched-chain amino acids (BCAAs) catabolism pathway, and the key gene branched-chain amino transferase 2 (Bcat2) is significantly downregulated, and the levels of leucine, isoleucine, and valine are elevated in the HFD-IMQ mice. Furthermore, the study finds that the peroxisome proliferator-activated receptor gamma (PPAR γ) is inhibited, while STAT3 activity is promoted in HFD-IMQ mice. CONCLUSION: HFD-induced obesity significantly amplifies IL-17 signaling and exacerbates psoriasis, with a potential role played by Bcat2-mediated BCAAs metabolism. The study suggests that BCAA catabolism and PPAR γ-STAT3 exacerbate inflammation in psoriasis with obesity.


Subject(s)
Amino Acids, Branched-Chain , Diet, High-Fat , Imiquimod , Inflammation , Mice, Inbred C57BL , Obesity , Psoriasis , Animals , Psoriasis/metabolism , Amino Acids, Branched-Chain/metabolism , Obesity/metabolism , Obesity/complications , Diet, High-Fat/adverse effects , Male , Inflammation/metabolism , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Interleukin-17/metabolism , Interleukin-17/genetics , Mice , PPAR gamma/metabolism , PPAR gamma/genetics , Disease Models, Animal , Mice, Obese , Signal Transduction , Transaminases/metabolism , Skin/metabolism
15.
Aging (Albany NY) ; 16(7): 6566-6587, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38604164

ABSTRACT

Traumatic brain injury (TBI) and its resulting complications pose a major challenge to global public health, resulting in increased rates of disability and mortality. Cerebrovascular dysfunction is nearly universal in TBI cases and is closely associated with secondary injury after TBI. Transcranial direct current stimulation (tDCS) shows great potential in the treatment of TBI; however, the exact mechanism remains elusive. In this study, we performed in vivo and in vitro experiments to explore the effects and mechanisms of tDCS in a controlled cortical impact (CCI) rat model simulating TBI. In vivo experiments show that tDCS can effectively reduce brain tissue damage, cerebral edema and neurological deficits. The potential mechanism may be that tDCS improves the neurological function of rats by increasing orexin A (OXA) secretion, upregulating the TF-AKT/ERK signaling pathway, and promoting angiogenesis at the injury site. Cellular experiments showed that OXA promoted HUVEC migration and angiogenesis, and these effects were counteracted by the ERK1/2 inhibitor LY3214996. The results of Matrigel experiment in vivo showed that TNF-a significantly reduced the ability of HUVEC to form blood vessels, but OXA could rescue the effect of TNF-a on the ability of HUVEC to form blood vessels. However, LY3214996 could inhibit the therapeutic effect of OXA. In summary, our preliminary study demonstrates that tDCS can induce angiogenesis through the OXA-TF-AKT/ERK signaling pathway, thereby improving neurological function in rats with TBI.


Subject(s)
Brain Injuries, Traumatic , MAP Kinase Signaling System , Neovascularization, Physiologic , Proto-Oncogene Proteins c-akt , Transcranial Direct Current Stimulation , Animals , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/therapy , Proto-Oncogene Proteins c-akt/metabolism , Rats , Male , Neovascularization, Physiologic/drug effects , Rats, Sprague-Dawley , Humans , Human Umbilical Vein Endothelial Cells , Disease Models, Animal , Signal Transduction , 60489
16.
Sci Rep ; 14(1): 8940, 2024 04 18.
Article in English | MEDLINE | ID: mdl-38637536

ABSTRACT

An abnormality of structures and functions in the hippocampus may have a key role in the pathophysiology of major depressive disorder (MDD). However, it is unclear whether structure factors of the hippocampus effectively impact antidepressant responses by hippocampal functional activity in MDD patients. We collected longitudinal data from 36 MDD patients before and after a 3-month course of antidepressant pharmacotherapy. Additionally, we obtained baseline data from 43 healthy controls matched for sex and age. Using resting-state functional magnetic resonance imaging (rs-fMRI), we estimated the dynamic functional connectivity (dFC) of the hippocampal subregions using a sliding-window method. The gray matter volume was calculated using voxel-based morphometry (VBM). The results indicated that patients with MDD exhibited significantly lower dFC of the left rostral hippocampus (rHipp.L) with the right precentral gyrus, left superior temporal gyrus and left postcentral gyrus compared to healthy controls at baseline. In MDD patients, the dFC of the rHipp.L with right precentral gyrus at baseline was correlated with both the rHipp.L volume and HAMD remission rate, and also mediated the effects of the rHipp.L volume on antidepressant performance. Our findings suggested that the interaction between hippocampal structure and functional activity might affect antidepressant performance, which provided a novel insight into the hippocampus-related neurobiological mechanism of MDD.


Subject(s)
Depressive Disorder, Major , Motor Cortex , Humans , Gray Matter/diagnostic imaging , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/drug therapy , Magnetic Resonance Imaging/methods , Hippocampus/diagnostic imaging , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Brain
17.
Sci Adv ; 10(16): eadl1856, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640241

ABSTRACT

Continuous glucose monitoring systems (CGMs) are critical toward closed-loop diabetes management. The field's progress urges next-generation CGMs with enhanced antinoise ability, reliability, and wearability. Here, we propose a coin-sized, fully integrated, and wearable CGM, achieved by holistically synergizing state-of-the-art interdisciplinary technologies of biosensors, minimally invasive tools, and hydrogels. The proposed CGM consists of three major parts: (i) an emerging biochemical signal amplifier, the organic electrochemical transistor (OECT), improving the signal-to-noise ratio (SNR) beyond traditional electrochemical sensors; (ii) a microneedle array to facilitate subcutaneous glucose sampling with minimized pain; and (iii) a soft hydrogel to stabilize the skin-device interface. Compared to conventional CGMs, the OECT-CGM offers a high antinoise ability, tunable sensitivity and resolution, and comfort wearability, enabling personalized glucose sensing for future precision diabetes health care. Last, we discuss how OECT technology can help push the limit of detection of current wearable electrochemical biosensors, especially when operating in complicated conditions.


Subject(s)
Biosensing Techniques , Diabetes Mellitus , Humans , Blood Glucose Self-Monitoring , Blood Glucose , 60431 , Reproducibility of Results , Glucose , Diabetes Mellitus/diagnosis
18.
Medicine (Baltimore) ; 103(16): e37792, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640281

ABSTRACT

Currently, few studies have demonstrated the relationship between total serum IgE (T-IgE) and acute exacerbation chronic obstructive pulmonary disease (AECOPD). In this study, T-IgE in AECOPD patients were investigated and jointly analyzed with the clinical characteristics. AECOPD patients hospitalized from July 2018 to July 2019 were included in this study. In this patient cohort, clinical information was investigated. Routine blood tests, C-reactive protein and T-IgE levels of patients were determined along with blood gas analysis. The length of hospital stays, mechanical ventilation during hospitalization, ICU admission, glucocorticoid related clinical information were recorded. A total of 285 AECOPD patients were included in this study, which consisted of a high proportion of males. Of all patients, 49.82% patients exhibited higher T-IgE levels. Based on the reference T-IgE value 60 kU/L, patients were divided into high T-IgE group with T-IgE > 60 kU/L, and low T-IgE group with T-IgE ≤ 60 kU/L. There was no significant difference in the dosage of glucocorticoid between the two groups. Patients in the high T-IgE group had shorter hospital stays and lower probability of mechanical ventilation compared to the low T-IgE group. After adjustment for confounding factors, T-IgE was negatively correlated with the length of hospital stays. AECOPD patients with elevated T-IgE had shorter hospital stays and lower risks of mechanical ventilation and ICU admission. Our results showed that T-IgE might play an important role on evaluating the condition and guiding for treatment decisions in AECOPD patients.


Subject(s)
Glucocorticoids , Pulmonary Disease, Chronic Obstructive , Male , Humans , Retrospective Studies , Glucocorticoids/therapeutic use , Hospitalization , Pulmonary Disease, Chronic Obstructive/therapy , Immunoglobulin E , Disease Progression
19.
iScience ; 27(5): 109668, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38655196

ABSTRACT

Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

20.
World J Gastrointest Oncol ; 16(4): 1227-1235, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38660665

ABSTRACT

BACKGROUND: Postoperative delirium, particularly prevalent in elderly patients after abdominal cancer surgery, presents significant challenges in clinical management. AIM: To develop a synthetic minority oversampling technique (SMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer patients. METHODS: In this retrospective cohort study, we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between September 2020 and October 2022. The incidence of postoperative delirium was recorded for 7 d post-surgery. Patients were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not. A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative delirium. The SMOTE technique was applied to enhance the model by oversampling the delirium cases. The model's predictive accuracy was then validated. RESULTS: In our study involving 611 elderly patients with abdominal malignant tumors, multivariate logistic regression analysis identified significant risk factors for postoperative delirium. These included the Charlson comorbidity index, American Society of Anesthesiologists classification, history of cerebrovascular disease, surgical duration, perioperative blood transfusion, and postoperative pain score. The incidence rate of postoperative delirium in our study was 22.91%. The original predictive model (P1) exhibited an area under the receiver operating characteristic curve of 0.862. In comparison, the SMOTE-based logistic early warning model (P2), which utilized the SMOTE oversampling algorithm, showed a slightly lower but comparable area under the curve of 0.856, suggesting no significant difference in performance between the two predictive approaches. CONCLUSION: This study confirms that the SMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of traditional methods, effectively addressing data imbalance.

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