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2.
Arthrosc Tech ; 13(5): 102966, 2024 May.
Article in English | MEDLINE | ID: mdl-38835442

ABSTRACT

As an important structure for maintaining the hoop tension of the medial meniscus of the knee joint, the posterior root is receiving increasing attention. Medial meniscus posterior root tear is an important reason for the occurrence, development, and kinematics changes of knee osteoarthritis. It is necessary to repair the posterior root of meniscus for restoring joint kinematics and improving clinical efficacy. This Technical Note reports a medial meniscus posterior root tear repair technique using arthroscopic transtibial pullout repair (ATPR) combined with tibial condylar valgus osteotomy. The aim of this technique is to repair the posterior root of the medial meniscus while correcting the force line through osteotomy, opening the joint gap, improving the joint surface fit, providing a good mechanical environment for meniscus repair, thereby improving the healing rate of the posterior root of the meniscus and reducing the risk of retear. Although clinical evidence is currently limited, we believe that this technology may have more clinical advantages compared with ATPR alone or ATPR combined with high tibial osteotomy.

3.
Commun Biol ; 7(1): 675, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824179

ABSTRACT

The three-dimensional (3D) organization of genome is fundamental to cell biology. To explore 3D genome, emerging high-throughput approaches have produced billions of sequencing reads, which is challenging and time-consuming to analyze. Here we present Microcket, a package for mapping and extracting interacting pairs from 3D genomics data, including Hi-C, Micro-C, and derivant protocols. Microcket utilizes a unique read-stitch strategy that takes advantage of the long read cycles in modern DNA sequencers; benchmark evaluations reveal that Microcket runs much faster than the current tools along with improved mapping efficiency, and thus shows high potential in accelerating and enhancing the biological investigations into 3D genome. Microcket is freely available at https://github.com/hellosunking/Microcket .


Subject(s)
Genomics , Software , Genomics/methods , High-Throughput Nucleotide Sequencing/methods , Humans , Sequence Analysis, DNA/methods , Data Analysis
4.
Bioact Mater ; 39: 317-335, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38827173

ABSTRACT

Biomaterials play an integral role in treatment of external auditory canal (EAC) diseases. Regarding the special anatomic structure and physiological characteristics of EAC, careful selection of applicable biomaterials was essential step towards effective management of EAC conditions. The bioactive materials can provide reasonable biocompatibility, reduce risk of host pro-inflammatory response and immune rejection, and promote the healing process. In therapeutic procedure, biomaterials were employed for covering or packing the wound, protection of the damaged tissue, and maintaining of normal structures and functions of the EAC. Therefore, understanding and application of biomaterials was key to obtaining great rehabilitation in therapy of EAC diseases. In clinical practice, biomaterials were recognized as an important part in the treatment of different EAC diseases. The choice of biomaterials was distinct according to the requirements of various diseases. As a result, awareness of property regarding different biomaterials was fundamental for appropriate selection of therapeutic substances in different EAC diseases. In this review, we firstly introduced the characteristics of EAC structures and physiology, and EAC pathologies were summarized secondarily. From the viewpoint of biomaterials, the different materials applied to individual diseases were outlined in categories. Besides, the underlying future of therapeutic EAC biomaterials was discussed.

5.
Pak J Med Sci ; 40(5): 1030-1034, 2024.
Article in English | MEDLINE | ID: mdl-38827862

ABSTRACT

Objective: To detect the continuous blood purification (CBP)'s application value in patients with urosepsis caused by ureteral calculi and heart failure after catheterization. Methods: This is a clinical comparative study. Sixty patients with ureteral calculi complicated with heart failure and urosepsis were admitted at Affiliated Hospital of Hebei University from January 2021 to March 2023 randomly split into control and experimental group(n=30). Based on conventional treatment after indwelling the DJ tube, the experimental group was treated with CBP therapy. The control group dealt with conventional anti-inflammatory, oxygen inhalation and other treatments only. Compared and analyzed in terms of alterations in blood inflammatory factors, cardiac function, BNP prior to and after therapy, blood pressure, blood WBC recovery time, and so on. Results: TNF-a, CRP, and PCT levels in the control and experimental groups were substantially more prominent than the average reference value prior to treatment. They decreased considerably at distinct time points after therapy, with substantial distinctions (p< 0.05). A more meaningful decrease was noticed in the experimental group in comparison with the control group (p< 0.05). BNP and cardiac function were improved in both groups prior to and after therapy, and the amelioration of indexes in the experimental group was more substantial than that in the control group after therapy, with statistically considerable distinctions. The improvement time in experimental group was earlier than in the control group, with statistically substantial differences. Conclusion: Patients with urosepsis complicated with heart failure after indwelling DJ tube have their inflammatory factors improved significantly, with more thorough excretion by using conventional treatment combined with CBP therapy.

6.
Heliyon ; 10(11): e30872, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38828305

ABSTRACT

Purpose: This retrospective study aims to evaluate the safety, practicality, and efficacy of the independent retrograde popliteal approach for recanalization superficial femoral artery (SFA) occlusions when the bilateral common femoral artery approach is unavailable, such as after endovascular aneurysm repair or common iliac artery stenting. Methods: This treatment was considered for patients with contralateral iliac artery occlusion, severe iliac tortuosity, or those who had previously undergone endovascular aneurysm repair or common iliac stenting. Patients with SFA lesions extending into the P1-P2 segment of the popliteal artery or with calcification in the P3 segment were excluded. Angioplasty and stenting were conducted via the popliteal artery approach, with hemostasis at the puncture site achieved using an EXOSEAL vascular closure device. Patients were routinely followed up at 3, 6, and 12 months, and annually thereafter. Results: Forty-eight consecutive patients with SFA occlusion who underwent endovascular treatment via the retrograde popliteal artery approach were included in this study. Retrograde puncture of the popliteal artery was successful in all cases. Six-French sheaths were utilized in all procedures. The EXOSEAL vascular closure device was successfully applied in all 48 cases. No instances of pseudoaneurysms, arteriovenous fistulas, major bleeding, or embolic complications were observed. The technical success rate for SFA recanalization was 100 %. All patients experienced clinical improvement. The ankle-brachial index significantly increased from an initial 0.33 ± 0.11 at admission to 0.81 ± 0.19 at discharge (P < 0.001). The mean follow-up period was 25.1 ± 11.7 months. Kaplan-Meier analysis revealed primary patency rates of 82.5 % at 12 months and 71.8 % at 24 months. No patients required major amputation during the follow-up period. Conclusion: The endovascular treatment of SFA occlusions via the independent retrograde popliteal approach is a viable alternative, demonstrating a low incidence of puncture-related complications and a high success rate of recanalization.

7.
Article in English | MEDLINE | ID: mdl-38829728

ABSTRACT

A novel therapeutic approach combining acupuncture and diclofenac sodium (DS) administration was established for the potential treatment for rheumatoid arthritis (RA). DS is a commonly used anti-inflammatory and analgesic drug but has short duration and adverse effects. Acupoints are critical linkages in the meridian system and are potential candidates for drug delivery. Herein, we fabricated a DS-loaded multilayer-modified acupuncture needle (DS-MMAN) and investigated its capacity for inhibiting RA. This DS-MMAN possesses sustained release properties and in vitro anti-inflammatory effects. Experimental results showed that the DS-MMAN with microdoses can enhance analgesia and efficiently relieve joint swelling compared to the oral or intra-articular administration of DS with gram-level doses. Moreover, the combination of acupoint and DS exerts a synergistic improvement in inflammation and joint damage. Cytokine and T cell analyses in the serum indicated that the application of DS-MMAN suppressed the levels of pro-inflammatory factors and increased the levels of anti-inflammatory factors. Furthermore, the acupoint administration via DS-MMAN could decrease the accumulation of DS in the liver and kidneys, which may express better therapeutic efficiency and low toxicity. The present study demonstrated that the acupuncture needle has the potential to build a bridge between acupuncture and medication, which would be a promising alternative to the combination of traditional and modern medicine.

8.
Phytomedicine ; 130: 155542, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38823343

ABSTRACT

BACKGROUND: Malassezia globosa is a commensal basidiomycetous yeast occurring on the skin that causes pityriasis versicolor (PV) and seborrheic dermatitis, but that has also been implicated in other dermatoses. Cinnamaldehyde (CM) has antibacterial, antioxidant, and anti-inflammatory activities, but the effect of CM on M. globosa-infected PV has not been clarified. PURPOSE: The study aimed to investigate the possible antifungal and antibiofilm activities of CM against M. globosa-infected PV in vivo and in vitro. METHODS: The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of CM against M. globosa. The crystal violet staining assay and XTT assay were used to investigate the inhibition of CM on biofilm formation and the eradication of mature biofilms. The visualizations of the biofilm and cell distribution in the biofilm matrix were performed with a scanning electron microscope and confocal laser scanning microscope. The kits of antioxidant kinase were used to determine the activities of oxidative stress markers in M. globosa-stimulated HaCaT cells. Western blot assays were used to evaluate the role of TLR2/NF-κB in vitro. Furthermore, the protective effect of CM was assessed in M. globosa-associated PV mice. The expressions of inflammatory cytokines and apoptosis were screened using ELISA assays. The expressions of interleukin-6 and tumor necrosis factor-α were measured by an immunohistochemistry method in vivo. RESULTS: Our results showed that the MIC of CM against planktonic cells of M. globosa was 4 µg/ml and treatment with 20 × MIC CM eradicated mature biofilms of M. globosa. In vitro, after CM treatment the levels of oxidative stress indicators (i.e., superoxide dismutase, catalase, glutathione) significantly increased, while the levels of malondialdehyde decreased. In addition, the expression of TLR2/NF-κB in HaCaT cells was significantly reduced after CM treatment. On the other hand, an in vivo therapeutic effect of CM was assessed against M. globosa-infected mice. The fungal load on the skin decreased after treatment with CM compared to the M. globosa-infected group. In addition, the uninfected animals showed a normal skin structure, whereas, the M. globosa-infected mice showed extensive infiltration of neutrophils in skin tissues that improved after treatment with CM. Meanwhile, the levels of inflammatory and apoptotic factors improved after CM treatment. CONCLUSION: Our results showed that CM inhibits the biofilm formation of M. globosa and eradicates mature biofilms of M. globosa. Treatment with CM significantly decreased oxidative stress, apoptosis, and inflammatory markers in the skin tissue and HaCaT cells. Hence, this study suggests that CM is a good candidate therapeutic agent against M. globosa-induced PV infections because of its antifungal, antibiofilm, and anti-inflammatory properties.

10.
Article in English | MEDLINE | ID: mdl-38691432

ABSTRACT

Learning with noisy labels (LNL) has attracted significant attention from the research community. Many recent LNL methods rely on the assumption that clean samples tend to have a "small loss." However, this assumption often fails to generalize to some real-world cases with imbalanced subpopulations, that is, training subpopulations that vary in sample size or recognition difficulty. Therefore, recent LNL methods face the risk of misclassifying those "informative" samples (e.g., hard samples or samples in the tail subpopulations) into noisy samples, leading to poor generalization performance. To address this issue, we propose a novel LNL method to deal with noisy labels and imbalanced subpopulations simultaneously. It first leverages sample correlation to estimate samples' clean probabilities for label correction and then utilizes corrected labels for distributionally robust optimization (DRO) to further improve the robustness. Specifically, in contrast to previous works using classification loss as the selection criterion, we introduce a feature-based metric that takes the sample correlation into account for estimating samples' clean probabilities. Then, we refurbish the noisy labels using the estimated clean probabilities and the pseudo-labels from the model's predictions. With refurbished labels, we use DRO to train the model to be robust to subpopulation imbalance. Extensive experiments on a wide range of benchmarks demonstrate that our technique can consistently improve state-of-the-art (SOTA) robust learning paradigms against noisy labels, especially when encountering imbalanced subpopulations. We provide our code in https://github.com/chenmc1996/LNL-IS.

11.
JMIR Med Inform ; 12: e56909, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38801705

ABSTRACT

Background: Predicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes. Objective: The aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes. Methods: We assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose<54 mg/dL) levels. The validation data set of 427 patients of European-American ancestry in the United States was used to validate the models and examine their generalizations. The predictive performance of the models was evaluated according to the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results: For the difficult-to-predict mild hypoglycemia events, the LSTM model consistently achieved AUC values greater than 97% in the primary data set, with a less than 3% AUC reduction in the validation data set, indicating that the model was robust and generalizable across populations. AUC values above 93% were also achieved when the LSTM model was applied to both type 1 and type 2 diabetes in the validation data set, further strengthening the generalizability of the model. Under different satisfactory levels of sensitivity for mild and severe hypoglycemia prediction, the LSTM model achieved higher specificity than the SVM and RF models, thereby reducing false alarms. Conclusions: Our results demonstrate that the LSTM model is robust for hypoglycemia prediction and is generalizable across populations or diabetes subtypes. Given its additional advantage of false-alarm reduction, the LSTM model is a strong candidate to be widely implemented in future CGM devices for hypoglycemia prediction.

12.
Neurosci Lett ; 833: 137827, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38777104

ABSTRACT

OBJECTIVE: SET domain-containing protein 1A (SETD1A) histone lysine N-methyltransferase may serve as a biomarker for the auxiliary diagnosis and treatment assessment of schizophrenia (SCZ). The aim of this study was to compare serum levels of SETD1A protein between patients with SCZ and health controls. METHODS: Patients with SCZ and health controls were recruited from the Sixth Hospital of Changchun and the 'Survey on Chronic Diseases and Risk Factors among Adults in Jilin Province', respectively. The quantifications of lysine N-methyltransferase in peripheral serum were conducted by the ELISA method, and data was analyzed using the R software. RESULTS: Forty patients with SCZ (mean age: 33.97 ± 5.99 years) and forty healthy controls (mean age: 39.07 ± 4.62 years) were included. There was significantly lower concentration of SETD1A protein in the SCZ group compared with the control group (P < 0.001). This significant difference still exists after stratification by sex (P < 0.05). CONCLUSION: Our study demonstrates that decreased levels of serum SETD1A protein may be utilized as a possible peripheral biomarker for schizophrenia.


Subject(s)
Biomarkers , Histone-Lysine N-Methyltransferase , Schizophrenia , Humans , Schizophrenia/blood , Schizophrenia/diagnosis , Male , Female , Histone-Lysine N-Methyltransferase/blood , Adult , Biomarkers/blood , Case-Control Studies , Middle Aged
13.
Sci Rep ; 14(1): 12439, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816443

ABSTRACT

With the large-scale construction of oil and gas pipelines, the safety issues of long-distance buried pipelines in the service and construction have become increasingly prominent. The complex geological and topographical conditions of the special zone will put forwards extremely high requirements on pipe trench laying backfill materials and construction technology. For example, pipelines are inevitable to cross the active fault, while the trench backfilled with soil has limitations in protecting them from failure under the active fault displacement caused by the earthquake. Therefore, it is necessary to study the pipe-soil interaction mechanism, determine the stress state of the pipeline and propose a new backfilling material that can protect the pipeline from failure. Foam concrete (FC) provides a new choice to backfill the buried pipeline trench due to its high-homogeneity, lightweight, controllable-strength, and self-compacting. To further determine the applicability of the FC, the pipe-FC interaction mechanism is studied. Then, a FE model of the FC-pipeline-soil interaction system is established by Abaqus to quantitatively analyze the applicability of the FC based on the experimental data of the mechanical performance of the FC. It proves that using FC as trench backfill material has a noticeable protective effect on the pipeline under the earthquake-induced displacement of the normal fault. Furthermore, FC has a better protective effect on the pipeline subjected to compressive than tensile. Therefore, the reference for applying FC in trench backfilling of pipelines crossing normal fault is provided.

14.
J Cell Mol Med ; 28(11): e18365, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38818577

ABSTRACT

Traditional Chinese medicine, particularly Zhi-zi-chi decoction (ZZCD), is gaining recognition as a potential treatment for depression. This study aimed to uncover the molecular mechanisms behind ZZCD's antidepressant effects, focusing on lncRNA Six3os1 and histone H3K4 methylation at the BDNF promoter. Network pharmacology and in vivo experiments were conducted to identify ZZCD targets and evaluate its impact on depression-related behaviours and neuron injury. The role of Six3os1 in recruiting KMT2A to the BDNF promoter and its effects on oxidative stress and neuron injury were investigated. ZZCD reduced depression-like behaviours and neuron injury in mice subjected to chronic stress. It upregulated Six3os1, which facilitated KMT2A recruitment to the BDNF promoter, leading to increased histone H3K4 methylation and enhanced BDNF expression. ZZCD also inhibited CORT-induced neuron injury, inflammatory response and oxidative stress in vitro. ZZCD's antidepressant properties involve Six3os1 upregulation, which exerts neuroprotective effects by inhibiting oxidative stress and neuron injury, thereby alleviating depressive symptoms. Targeting Six3os1 upregulation may offer a potential therapeutic intervention for depression.


Subject(s)
Brain-Derived Neurotrophic Factor , Depression , Drugs, Chinese Herbal , Histones , Oxidative Stress , Promoter Regions, Genetic , RNA, Long Noncoding , Animals , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Histones/metabolism , Depression/drug therapy , Depression/genetics , Depression/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Mice , Drugs, Chinese Herbal/pharmacology , Male , Oxidative Stress/drug effects , Methylation/drug effects , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Gene Expression Regulation/drug effects , Mice, Inbred C57BL , Neurons/metabolism , Neurons/drug effects , Disease Models, Animal
15.
Neuropharmacology ; 254: 109988, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38744401

ABSTRACT

Neuropathic pain (NP) is usually treated with analgesics and symptomatic therapy with poor efficacy and numerous side effects, highlighting the urgent need for effective treatment strategies. Recent studies have reported an important role for peroxisome proliferator-activated receptor alpha (PPARα) in regulating metabolism as well as inflammatory responses. Through pain behavioral assessment, we found that activation of PPARα prevented chronic constriction injury (CCI)-induced mechanical allodynia and thermal hyperalgesia. In addition, PPARα ameliorated inflammatory cell infiltration at the injury site and decreased microglial activation, NOD-like receptor protein 3 (NLRP3) inflammasome production, and spinal dendritic spine density, as well as improved serum and spinal cord metabolic levels in mice. Administration of PPARα antagonists eliminates the analgesic effect of PPARα agonists. PPARα relieves NP by inhibiting neuroinflammation and functional synaptic plasticity as well as modulating metabolic mechanisms, suggesting that PPARα may be a potential molecular target for NP alleviation. However, the effects of PPARα on neuroinflammation and synaptic plasticity should be further explored.


Subject(s)
Mice, Inbred C57BL , Neuralgia , PPAR alpha , Spinal Cord , Animals , PPAR alpha/metabolism , Neuralgia/drug therapy , Neuralgia/metabolism , Male , Mice , Spinal Cord/metabolism , Spinal Cord/drug effects , Hyperalgesia/drug therapy , Hyperalgesia/metabolism , Metabolomics , Microglia/drug effects , Microglia/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Dendritic Spines/drug effects , Dendritic Spines/metabolism , Dendritic Spines/pathology , Inflammasomes/metabolism , Inflammasomes/drug effects
16.
Int Immunopharmacol ; 135: 112298, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38776854

ABSTRACT

BACKGROUND: Excessive activation of colonic fibroblasts and differentiation of T helper 17 (Th17) cells are the key steps for intestinal fibrogenesis in the process of inflammatory bowel disease (IBD). Although both transforming growth factor-beta (TGF-ß)/Mothers Against Decapentaplegic Homolog (SMAD) 3-induced fibroblasts activation and interleukin (IL)-6/signal transducer and activator of transcription (STAT) 3-induced Th17 differentiation have been well studied, the crosstalk between fibroblasts and Th17 cells in the process of intestinal fibrogenesis needs to be unveiled. METHODS: In this study, the activation of colonic fibroblasts was induced with dextran sulfate sodium salt (DSS) and TGF-ß in vivo and in vitro respectively. P-SMAD3 and its downstream targets were quantified using RT-PCR, western blot and immunofluorescence. The differentiation of programmed death 1 (PD-1) + Th17 and activation of fibroblasts were quantified by FACS. PD-1+ Th17 cells and fibroblasts were co-cultured and cytokines in the supernatant were tested by ELISA. The anti-fibrosis effects of different chemical compounds were validated in vitro and further confirmed in vivo. RESULTS: The colonic fibroblasts were successfully activated by DSS and TGF-ß in vivo and in vitro respectively, as activation markers of fibroblasts (p-SMAD3 and its downstream targets such as Acta2, Col1a1 and Ctgf) were significantly increased. The activated fibroblasts produced more IL-6 compared with their inactivated counterparts in vivo and in vitro. The proinflammatory cytokine IL-6 induced PD-1+ Th17 differentiation and TGF-ß that in return promoted the activation of colonic fibroblasts. Fraxinellone inhibited TGF-ß+ PD-1+ Th17 cells via deactivating STAT3. CONCLUSIONS: The reciprocal stimulation constructed a circuit of PD-1+ Th17 cells and fibroblasts that accelerated the fibrosis process. Fraxinellone was selected as the potential inhibitor of the circuit of PD-1+ Th17 cells and fibroblasts in vivo and in vitro. Inhibiting the circuit of PD-1+ Th17 cells and fibroblasts could be a promising strategy to alleviate intestinal fibrosis.

17.
J Leukoc Biol ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814954

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. ß-amyloid (Aß) is one of the typical pathological features of AD, and its accumulation leads to neuronal death from oxidative stress. Here, we found that hederagenin (HG), a natural product, exhibits anti-tumor, anti-inflammatory, anti-depressant, anti-neurodegenerative biological activities. However, whether HG has anti-Aß activity remains unclear. Based on the characteristics of HG, it is hypothesized that HG has biological activity against Aß injury. Therefore, Aß-injured SH-SY5Y cells were constructed, and the protective effect of HG against Aß injury was further evaluated using C. elegans. The results showed that HG increased superoxide dismutase activity, effectively reduced Aß-induced oxidative damage, and reduced apoptosis via the PI3 K/Akt signaling pathway. HG inhibited Aß deposition and delayed senescence and paralysis in the C. elegans strain, CL4176. HG showed inhibitory effects on Aß; therefore, more natural active products are expected to be applied in AD therapy.

18.
Pharmacol Res ; 205: 107236, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38797358

ABSTRACT

The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here, we show that ketamine rapidlyalleviated depression-like behaviors and normalized abnormal expression of pTyr1472NR2B and striatal-enriched protein tyrosine phosphatase (STEP) 61 within and outside synapses in the medial prefrontal cortex (mPFC) induced by chronic unpredictable stress (CUS) and conditional knockdown of STEP 61, a key phosphatase of NR2B, within 1 hour after administration Together, our results delineate the rapid initiation of ketamine's antidepressant effects results from the restoration of NR2B phosphorylation homeostasis within and outside synapses. The dynamic regulation of phosphorylation of NR2B provides a new perspective for developing new antidepressant strategies.

19.
Discov Med ; 36(184): 1030-1040, 2024 May.
Article in English | MEDLINE | ID: mdl-38798262

ABSTRACT

BACKGROUND: Since 2019, the incidence of anthrax in the Ningxia Hui Autonomous Region has increased significantly compared with previous years, so in this situation the anthrax in the Ningxia region not only had a detrimental impact on public health, but also inflicted significant economic repercussions. Therefore, we conducted a molecular epidemiological study of 20 strains from 2019-2023 isolates. This study investigated the origin of Bacillus anthracis and its genetic diversity. METHODS: We conducted canonical single-nucleotide polymorphisms (CanSNPs) typing and whole genome sequencing based on the extracted nucleic acid of Bacillus anthracis. Based on the whole genome drafts, we studied the genomic characteristics of 20 isolates. Meanwhile, we performed phylogenetic studies based on genome-wide core single-nucleotide polymorphisms (SNPs) using MEGA's Maximum Likelihood (ML) method and core-genome-based multilocus sequence typing (cgMLST) of the core genomes of these strains using BioNumerics' minimum spanning tree (MST) model. RESULTS: The 20 isolates were categorized into sub-lineages A.Br.001/002, and comparative genomic analyses of these strains with other isolates from other parts of the world showed that the strains from Ningxia were correlated with isolates from Europe, Indonesia, Georgia (USA), and Beijing (China). For the 20 isolates in Ningxia, the genetic relationship of the isolates isolated from the same year or region was relatively close. CONCLUSION: The A.Br.001/002 subgroup was the dominant endemic strain in Ningxia. The genetic relationship and phylogenesis between isolates from Ningxia and strains from Europe and Indonesia suggest that anthrax spread around the globe through ancient trade routes.


Subject(s)
Anthrax , Bacillus anthracis , Genome, Bacterial , Phylogeny , Polymorphism, Single Nucleotide , Whole Genome Sequencing , Bacillus anthracis/genetics , Bacillus anthracis/isolation & purification , Whole Genome Sequencing/methods , China/epidemiology , Anthrax/microbiology , Anthrax/epidemiology , Genome, Bacterial/genetics , Humans , Multilocus Sequence Typing/methods
20.
J Environ Sci (China) ; 144: 185-198, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38802230

ABSTRACT

There is a large surface-groundwater exchange downstream of wastewater treatment plants (WWTPs), and antibiotics upstream may influence sites downstream of rivers. Thus, samples from 9 effluent-receiving urban rivers (ERURs) and 12 groundwater sites were collected in Shijiazhuang City in December 2020 and April 2021. For ERURs, 8 out of 13 target quinolone antibiotics (QNs) were detected, and the total concentration of QNs in December and April were 100.6-4,398 ng/L and 8.02-2,476 ng/L, respectively. For groundwater, all target QNs were detected, and the total QNs concentration was 1.09-23.03 ng/L for December and 4.54-170.3 ng/L for April. The distribution of QNs was dissimilar between ERURs and groundwater. Most QN concentrations were weakly correlated with land use types in the system. The results of a positive matrix factorization model (PMF) indicated four potential sources of QNs in both ERURs and groundwater, and WWTP effluents were the main source of QNs. From December to April, the contribution of WWTP effluents and agricultural emissions increased, while livestock activities decreased. Singular value decomposition (SVD) results showed that the spatial variation of most QNs was mainly contributed by sites downstream (7.09%-88.86%) of ERURs. Then, a new method that combined the results of SVD and PMF was developed for a specific-source-site risk quotient (SRQ), and the SRQ for QNs was at high level, especially for the sites downstream of WWTPs. Regarding temporal variation, the SRQ for WWTP effluents, aquaculture, and agricultural emissions increased. Therefore, in order to control the antibiotic pollution, more attention should be paid to WWTP effluents, aquaculture, and agricultural emission sources for the benefit of sites downstream of WWTPs.


Subject(s)
Anti-Bacterial Agents , Environmental Monitoring , Groundwater , Quinolones , Rivers , Wastewater , Water Pollutants, Chemical , Groundwater/chemistry , Water Pollutants, Chemical/analysis , China , Rivers/chemistry , Quinolones/analysis , Anti-Bacterial Agents/analysis , Wastewater/chemistry , Cities , Waste Disposal, Fluid/methods
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