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1.
J Hazard Mater ; 480: 135994, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39357355

RESUMO

The ultraviolet (UV)/chlorine process has been widely applied for water treatment. However, the transformation of microplastic-leached dissolved organic matter (MP-DOM) in advanced treatment of real wastewater remains unclear. Here, we investigated alterations in the photoproperties of MP-DOM leached from biodegradable and conventional microplastics (MPs) and their subsequent effects on the degradation of sulfamethazine (SMT) by the UV/chlorine process. Spectroscopy was used to assess photophysical properties, focusing on changes in light absorption capacity, functional groups, and fluorescence components, while photochemical properties were determined by calculating the apparent quantum yields of reactive intermediates (ΦRIs). For photophysical properties, our findings revealed that the degree of molecular structure modification, functional group changes, and fluorescence characteristics during UV/chlorine treatment are closely linked to the type of MPs. For photochemical properties, the ΦRIs increased with higher chlorine dosages due to the formation of new functionalities. Both singlet oxygen (1O2) and hydroxyl radicals (•OH) formation were strongly correlated with excited triplet state of DOM (3DOM*) in the UV/chlorine treatment. Additionally, we found that the four types of MP-DOM inhibit the degradation of SMT and elucidated the mechanisms behind this inhibition. We also proposed degradation pathways for SMT and assessed the ecotoxicity of the resulting intermediates. This study provides important insights into how the characteristics and transformation of MP-DOM affect contaminant degradation, which is critical for evaluating the practical application of UV-based advanced oxidation processes (UV-AOPs).

2.
Arch Public Health ; 82(1): 173, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358819

RESUMO

BACKGROUND: From January 2020 to June 2022, strict interventions against COVID-19 were implemented in Guangdong Province, China. However, the evolution of COVID-19 dynamics remained unclear in this period. OBJECTIVES: This study aims to investigate the evolution of within- and between-city COVID-19 dynamics in Guangdong, specifically during the implementation of rigorous prevention and control measures. The intent is to glean valuable lessons that can be applied to refine and optimize targeted interventions for future crises. METHODS: Data of COVID-19 cases and synchronous interventions from January 2020 to June 2022 in Guangdong Province were collected. The epidemiological characteristics were described, and the effective reproduction number (Rt) was estimated using a sequential Bayesian method. Endemic-epidemic multivariate time-series model was employed to quantitatively analyze the spatiotemporal component values and variations, to identify the evolution of within- and between-city COVID-19 dynamics. RESULTS: The incidence of COVID-19 in Guangdong Province was 12.6/100,000 population (15,989 cases) from January 2020 to June 2022. The Rt predominantly remained below 1 and increased to a peak of 1.39 in Stage 5. As for the evolution of variations during the study period, there were more spatiotemporal components in stage 1 and 5. All components were fewer from Stage 2 to Stage 4. Results from the endemic-epidemic multivariate time-series model revealed a strong follow-up impact from previous infections in Dongguan, Guangzhou and Zhanjiang, with autoregressive components of 0.48, 0.45 and 0.36, respectively. Local risk was relatively high in Yunfu, Shanwei and Shenzhen, with endemic components of 1.17, 1.04 and 0.71, respectively. The impact of the epidemic on the neighboring regions was significant in Zhanjiang, Shenzhen and Zhuhai, with epidemic components of 2.14, 1.92, and 1.89, respectively. CONCLUSION: The findings indicate the presence of spatiotemporal variation of COVID-19 in Guangdong Province, even with the implementation of strict interventions. It's significant to prevent transmissions within cities with dense population. Preventing spatial transmissions between cities is necessary when the epidemic is severe. To better cope with future crises, interventions including vaccination, medical resource allocation and coordinated non-pharmaceutical interventions were suggested.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39356279

RESUMO

Na4MnV(PO4)3 (NMVP) has gained attention for its high redox potential, good cycling stability, and competitive price but suffers from poor intrinsic electronic conductivity and Jahn-Teller effect from Mn3+. In this work, cation/anion doping strategy was used for Aspergillus niger-bioderived carbon-coated NMVP (NMVP/AN) to improve the structural stability and electrochemical performance, where Al3+ doping inhibited the dissolution of Mn and enhanced the Mn3+/Mn2+ redox pair activity; besides, F- doping not only weakens the Na2-O bond but also endows the hierarchical and porous structure of NMVP/AN, which led to a more rapid and fluid transfer of Na+. The elaborately designed Na3.9Mn0.9Al0.1V(PO4)3/AN (NMAVP/AN) exhibits 105.9 mA h g-1 at 0.5 C, and the as-prepared Na3.1MnV(PO3.7F0.3)3/AN (NMVPF/AN) delivers 104.1 mA h g-1 at 5 C. Further demonstration of the hard carbon//NMAVP/AN full cell manifests the good potential of Al3+-doped NMVP/AN for practical applications (100.6 mA h g-1 at 1 C). These findings open up the possibility of unlocking the high-performance Na superionic conductor (NASICON).

4.
Eur J Neurol ; : e16501, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352122

RESUMO

BACKGROUND AND PURPOSE: Elevated serum lipoprotein(a) (Lp[a]) levels have been linked to an increased incidence of stroke. This systematic review and meta-analysis aimed to evaluate the impact of serum Lp(a) on the functional outcomes of patients with ischemic stroke (IS). METHODS: We conducted a comprehensive search of the MEDLINE, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure databases to identify relevant cohort studies. A random effects model was utilized to synthesize the data, accounting for study heterogeneity. RESULTS: The analysis included 11 cohort studies comprising 11,958 patients with IS. Pooled results indicated that high baseline Lp(a) levels were associated with an increased risk of poor functional outcomes during follow-up (odds ratio [OR] = 2.13, 95% confidence interval = 1.67-2.71, p < 0.001, I2 = 62%). Subgroup analyses revealed that the relationship between high Lp(a) levels and the risk of poor functional outcomes was more pronounced at discharge (OR = 3.25), 3 months (OR = 2.02), and 6 months (OR = 2.11) poststroke, compared to 12 months (OR = 1.25, p for subgroup difference < 0.001). Furthermore, the association was attenuated yet remained significant in studies adjusting for low-density lipoprotein cholesterol (LDL-C) compared to those that did not adjust for LDL-C (OR = 1.69 vs. 2.63, p for subgroup difference = 0.03). CONCLUSIONS: High serum Lp(a) levels at baseline are significantly associated with poor functional outcomes in patients with IS.

5.
J Dig Dis ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227029

RESUMO

OBJECTIVES: Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled-off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. METHODS: Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure-related adverse events, and clinical outcomes were investigated. RESULTS: Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure-related adverse events, and seven (6.9%) died during the treatment period. During a median follow-up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new-onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure-related adverse event rate, and long-term follow-up outcomes were not significantly different among the three groups. High APACHE-II scores (≥15) and organ failure were identified as factors related to treatment failure. CONCLUSIONS: A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short-term and long-term outcomes.

6.
Mol Neurobiol ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230866

RESUMO

Spinal cord injury (SCI) is a severe neurological disorder that can lead to paralysis or death. Oxidative stress during SCI is a critical phase causing extensive nerve cell damage and apoptosis, thereby impairing spinal cord healing. Thus, a primary goal of SCI drug therapy is to mitigate oxidative stress. Curculigoside (CUR), a phenolic glucoside extracted from the dried root and rhizome of Curculigo orchioides Gaertn, possesses neuroprotective and antioxidant properties. This study aimed to investigate whether CUR effectively promotes the recovery of spinal cord tissue following SCI and elucidate its mechanism. We employed a hydrogen peroxide (H2O2)-induced PC12 cell model and an SCI rat model to observe the effects of CUR on oxidation and apoptosis. The results demonstrated that CUR significantly reduced the expression of apoptosis-related proteins (Bax and Caspase-3), Annexin V/propidium iodide (PI), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while increasing the expression of the anti-apoptotic protein Bcl-2. Moreover, CUR effectively enhanced levels of antioxidants (glutathione [GSH)] and decreased reactive oxygen species (ROS) in vitro. Furthermore, CUR facilitated functional recovery through its anti-apoptotic and anti-oxidative stress effects on spinal cord tissues in SCI rats. These effects were mediated via the Nrf2/NQO1 signaling pathway. Therefore, our study showed that CUR acted as an anti-apoptotic and anti-oxidative stress agent, inhibiting astrocyte activation and promoting neuronal reconstruction and functional recovery. These findings may contribute significantly to the development of SCI treatments and advance the field of SCI drug therapy.

7.
Adv Sci (Weinh) ; : e2409081, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258781

RESUMO

Peptide-based drugs hold great potential for cancer treatment, and their effectiveness is driven by mechanisms on how peptides target cancer cells and escape from potential lysosomal entrapment post-endocytosis. Yet, the mechanisms remain elusive, which hinder the design of peptide-based drugs. Here hendeca-arginine peptides (R11) are synthesized for targeted delivery in bladder carcinoma (BC), investigated the targeting efficiency and elucidated the mechanism of peptide-based delivery, with the aim of refining the design and efficacy of peptide-based therapeutics. It is demonstrated that the over-activated Piezo1/integrin ß1 (ITGB1) signaling axis significantly facilitates tumor-targeted delivery of R11 peptides via macropinocytosis. Furthermore, R11 peptides formed hydrogen bonds with integrin ß1, facilitating targeting and penetration into tumor cells. Additionally, R11 peptides protected integrin ß1 from lysosome degradation, promoting its recycling from cytoplasm to membrane. Moreover, this findings establish a positive feedback loop wherein R11 peptides activate Piezo1 by increasing membrane fusion, promoting Ca2+ releasing and resulting in enhanced integrin ß1-mediated endocytosis in both orthotopic models and clinical tissues, demonstrating effective tumor-targeted delivery. Eventually, the Piezo1/integrin ß1 signaling axis promoted cellular uptake and transport of peptides, establishing a positive feedback loop, promoting mechanical delivery to cancer and offering possibilities for drug modification in cancer therapy.

8.
Bone Joint Res ; 13(9): 474-484, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39253760

RESUMO

Aims: Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration. Methods: Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results: We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion: This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT.

9.
Theranostics ; 14(14): 5551-5570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39310099

RESUMO

Rationale: Epilepsy affects over 70 million people globally, with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) often progressing to a drug-resistant state. Recent research has highlighted the role of reactive astrocytes and glutamate dysregulation in epilepsy pathophysiology. This study aims to investigate the involvement of astrocytic xCT, a glutamate-cystine antiporter, and its regulation by the m6A reader protein YTHDC2 in TLE-HS. Methods: A pilocarpine-induced epilepsy model in mice was used to study the role of xCT in reactive astrocytes. The expression of xCT and its regulation by YTHDC2 were assessed through various molecular and cellular techniques. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure mRNA and protein levels of xCT and YTHDC2, respectively; immunofluorescence was utilized to visualize their localization and expression in astrocytes. In vivo glutamate measurements were conducted using microdialysis to monitor extracellular glutamate levels in the hippocampus. RNA immunoprecipitation-qPCR (RIP-qPCR) was performed to investigate the binding of YTHDC2 to SLC7A11 mRNA, while methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) was performed to quantify m6A modifications on SLC7A11 mRNA. A dual-luciferase reporter assay was conducted to assess the effect of m6A modifications on SLC7A11 mRNA translation, and polysome profiling was employed to evaluate the translational efficiency of SLC7A11 mRNA. Inhibition experiments involved shRNA-mediated knockdown of SLC7A11 (commonly known as xCT) and YTHDC2 expression in astrocytes. Video-electroencephalogram (EEG) recordings were used to monitor seizure activity in mice. Results: The xCT transporter in reactive astrocytes significantly contributes to elevated extracellular glutamate levels, enhancing neuronal excitability and seizure activity. Increased xCT expression is influenced by the m6A reader protein YTHDC2, which regulates its expression through m6A methylation. Inhibition of xCT or YTHDC2 in astrocytes reduces glutamate levels and effectively controls seizures in a mouse model. Specifically, mice with SLC7A11- or YTHDC2-knockdown astrocytes showed decreased glutamate concentration in the hippocampus and reduced frequency and duration of epileptic seizures. Conclusions: This study highlights the therapeutic potential of targeting YTHDC2 and xCT in reactive astrocytes to mitigate epilepsy. The findings provide a novel perspective on the mechanisms of glutamate dysregulation and their implications in seizure pathophysiology, suggesting that modulation of YTHDC2 and xCT could be a promising strategy for treating TLE.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Astrócitos , Modelos Animais de Doenças , Epilepsia do Lobo Temporal , Ácido Glutâmico , Animais , Astrócitos/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/fisiopatologia , Camundongos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Ácido Glutâmico/metabolismo , Masculino , Hipocampo/metabolismo , Pilocarpina , Camundongos Endogâmicos C57BL , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Humanos
10.
Orthop Surg ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313843

RESUMO

OBJECTIVE: The incidence of degenerative diseases of the lumbar spine has increased in recent years. Unilateral pedicle screw combined with contralateral translaminar facet screw fixation offers the advantages of less trauma, better stability, and fewer complications. However, the surgical difficulty and suboptimal pinning accuracy of translaminar facet screw placement in clinical practice limit its use. Therefore, in this study, we designed a novel suspended 3D-printed navigation module to facilitate fast and accurate intraoperative screw placement. The aim of this study is to investigate the digital design, precise implementation, and evaluation methods for placing unilateral pedicle screws in the lumbar spine combined with translaminar facet screw placement using a new suspended 3D navigation module. METHODS: This retrospective study included 46 patients with single-level lumbar lesions who underwent spine surgery at the Affiliated Hospital of Putian University between June 2022 and December 2023. The suspended navigation module was designed digitally. Preoperative screw placement was simulated using 3D printed models, followed by an intraoperative accurate screw placement facilitated by the navigation module and a postoperative evaluation of the accuracy of screw placement. The absolute difference in three-dimensional coordinates of the inlet and outlet points of the preoperative design and the postoperative screw-nail channel served as the precision index. RESULTS: In a study involving 46 patients, surgery was successful with 92 pedicle screws and 46 translaminar facet screws placed without any penetration of the cortex. The difference in coordinates before and after screw insertion was minimal, with entry points varying between 1.21 to 1.36 mm and exit points between 1.97 to 2.46 mm. When screw accuracy met certain thresholds, there was no significant difference between preoperative design and postoperative coordinates, indicating precise replication of the surgical plan. CONCLUSION: The new suspended 3D navigation module enables the precise placement of unilateral pedicle screws in the lumbar spine combined with translaminar pedicle screws for precise surgery.

11.
Curr Mol Med ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39313904

RESUMO

AIM: Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model. METHODS: The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice. RESULTS: Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/ß-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor. CONCLUSION: Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/ß- catenin pathway.

12.
BMC Genomics ; 25(1): 885, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304826

RESUMO

MicroRNAs (miRNAs) have been demonstrated to be closely related to human diseases. Studying the potential associations between miRNAs and diseases contributes to our understanding of disease pathogenic mechanisms. As traditional biological experiments are costly and time-consuming, computational models can be considered as effective complementary tools. In this study, we propose a novel model of robust orthogonal non-negative matrix tri-factorization (NMTF) with self-paced learning and dual hypergraph regularization, named SPLHRNMTF, to predict miRNA-disease associations. More specifically, SPLHRNMTF first uses a non-linear fusion method to obtain miRNA and disease comprehensive similarity. Subsequently, the improved miRNA-disease association matrix is reformulated based on weighted k-nearest neighbor profiles to correct false-negative associations. In addition, we utilize L 2 , 1 norm to replace Frobenius norm to calculate residual error, alleviating the impact of noise and outliers on prediction performance. Then, we integrate self-paced learning into NMTF to alleviate the model from falling into bad local optimal solutions by gradually including samples from easy to complex. Finally, hypergraph regularization is introduced to capture high-order complex relations from hypergraphs related to miRNAs and diseases. In 5-fold cross-validation five times experiments, SPLHRNMTF obtains higher average AUC values than other baseline models. Moreover, the case studies on breast neoplasms and lung neoplasms further demonstrate the accuracy of SPLHRNMTF. Meanwhile, the potential associations discovered are of biological significance.


Assuntos
Biologia Computacional , MicroRNAs , MicroRNAs/genética , Humanos , Biologia Computacional/métodos , Algoritmos , Predisposição Genética para Doença , Aprendizado de Máquina , Neoplasias Pulmonares/genética
13.
Light Sci Appl ; 13(1): 258, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300070

RESUMO

Neural stimulation and modulation at high spatial resolution are crucial for mediating neuronal signaling and plasticity, aiding in a better understanding of neuronal dysfunction and neurodegenerative diseases. However, developing a biocompatible and precisely controllable technique for accurate and effective stimulation and modulation of neurons at the subcellular level is highly challenging. Here, we report an optomechanical method for neural stimulation and modulation with subcellular precision using optically controlled bio-darts. The bio-dart is obtained from the tip of sunflower pollen grain and can generate transient pressure on the cell membrane with submicrometer spatial resolution when propelled by optical scattering force controlled with an optical fiber probe, which results in precision neural stimulation via precisely activation of membrane mechanosensitive ion channel. Importantly, controllable modulation of a single neuronal cell, even down to subcellular neuronal structures such as dendrites, axons, and soma, can be achieved. This bio-dart can also serve as a drug delivery tool for multifunctional neural stimulation and modulation. Remarkably, our optomechanical bio-darts can also be used for in vivo neural stimulation in larval zebrafish. This strategy provides a novel approach for neural stimulation and modulation with sub-cellular precision, paving the way for high-precision neuronal plasticity and neuromodulation.

14.
Joint Bone Spine ; : 105776, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39303941

RESUMO

OBJECTIVES: This systematic review aims to (1) summarize the clinical, laboratory, and imaging characteristics of Palmar Fasciitis and Polyarthritis Syndrome (PFPAS) patients and (2) evaluate the effectiveness of different treatments. METHODS: We conducted a systematic search of three electronic databases (Scopus, Embase, and PubMed) from inception to December 31, 2023. We presented demographic and clinical features, along with laboratory factors and imaging examinations of PFPAS patients. Additionally, we outline main treatments and evaluate therapeutic effectiveness. RESULTS: A total of 121 patients were included in the analysis, with a mean onset age of 61.4 years. Swelling or thickening (49.6%, n=60/121) and pain (41.3%, n=50/121) were characteristic musculoskeletal symptoms of the hands. The median time between onset of PFPAS symptoms and detection of malignancy was 4 months, with a median survival of 13.0 months (range = 2 to 69). The abnormal rate of ultrasound, magnetic resonance imaging, and bone scan of the musculoskeletal system was more than 80%. Effective therapeutic responses were observed in 66.0% (n=33/50) of cases treated with chemotherapies and 79.2% (n=19/24) with operations. Two patients who received biologics achieved partial remission. CONCLUSION: PFPAS is a rare paraneoplastic condition, and early recognition of its distinctive symptoms may lead to the detection of underlying malignancy and timely treatments, potentially saving lives.

15.
Life Sci ; : 123057, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39277132

RESUMO

AIMS: Microglia activation after spinal cord injury (SCI) is a double-edged sword, modulation of the activated microglia populations toward pro-regenerative phenotypes highlights the potential therapeutic implications. P2Y12, a microglia-specific marker, remains underexplored in its capacity to polarize microglial activation populations in SCI repair. We aimed to explore the effects of modulating P2Y12 on microglia function after spinal cord injury, and further on axonal regeneration and motor recovery after spinal cord injury. MATERIALS AND METHODS: The study employed both in vitro and in vivo models, using BV2 cells and a mouse model of SCI, respectively. Ticagrelor, a P2Y12 antagonist, was administered via a collagen scaffold to ensure stable and sustained release. Transcriptome sequencing analysis, immunofluorescence staining, and Basso Mouse Scale (BMS) scores were used to assess microglial activation, axonal regeneration, and functional recovery. KEY FINDINGS: Herein, we observed P2Y12+ microglia localized predominantly at the lesion periphery within 3 days post injury (dpi), manifesting a pro-inflammatory phenotype, but not anti-inflammatory phenotype. In vitro investigations revealed that P2Y12 inhibition of the activated microglia curtailed pro-inflammatory differentiation while augmenting anti-inflammatory differentiation. SIGNIFICANCE: Leveraging this insight, we engineered a collagen scaffold-based delivery system for sustained release of the P2Y12 antagonist, ticagrelor, at the injury site in a mouse complete SCI model. Notably, P2Y12 suppression markedly enhanced axonal regeneration within the injured site and ameliorated lower limb motor functions in SCI mice. Collectively, our findings illuminate P2Y12-targeted microglial modulation as a promising therapeutic approach for SCI.

16.
Int J Antimicrob Agents ; : 107320, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293772

RESUMO

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker, whose advantages as a potent acid suppressor in Helicobacter pylori (H. pylori) eradication has not yet been demonstrated. This study aimed to evaluate the efficacy of Keverprazan as a component of bismuth quadruple therapy in H. pylori treatment. METHODS: Adult patients with H. pylori infection were enrolled and randomized to take Keverprazan (KEV group) or Esomeprazole (ESO group)-quadruple therapy (regimen contains Keverprazan 20 mg or Esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, bismuth potassium citrate 240 mg) twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment. RESULTS: Full analysis set showed the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for KEV group and ESO group, respectively (difference: 5.29%; 95% CI: -0.55% to 11.18%). Superiority of Keverprazan over Esomeprazole in terms of eradication rate was observed in the per-protocol set (P=0.0382). The eradication rates for patients resistant or not resistant to clarithromycin were both numerically higher in KEV group than ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 96.67 vs. 93.38% for clarithromycin-nonresistance). The incidence of adverse events was similar in KEV and ESO group (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity and leading to no deaths. CONCLUSIONS: Keverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy provided effective H. pylori eradication and was non-inferior to Esomeprazole-based regimen.

17.
Bioresour Technol ; 413: 131513, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39313009

RESUMO

Rural sewage treatment facilitates nitrogen and phosphorus removal yet can be costly. To address this challenge, a cost-effective embedding material mainly consisting of heterotrophic nitrifying bacteria, activated alumina (AA), and a solid carbon source (HPMC) was applied to a tidal flow constructed wetlands (TFCWs); aimed at stable nitrogen and phosphorus removal under low carbon-to-nitrogen (C/N) ratios. The TFCWs could be shortened to 16 d of startup duration time compared with the control group; and improved the ammonia nitrogen (NH4+-N), total nitrogen (TN), and total phosphorus (TP) removal efficiencies to 98 %, 93 %, and 68 %, respectively. Also, effluent NH4+-N, TN, and TP in the enhanced TFCWs could be stable at 0.52 ± 0.18, 1.23 ± 0.45, and 0.75 ± 0.25 mg/L, respectively. Microbial community analysis revealed that AA and HPMC were enriched Pseudomonas sp., which potentially accelerated the NH4+-N assimilation pathway and phosphate biological removal. Embedding materials-TFCWs can provide new solutions for integrated rural sewage technology.

18.
Urol Case Rep ; 57: 102842, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39319222

RESUMO

Pheochromocytoma is a neuroendocrine tumor for which surgical resection is the main treatment.Malignant pheochromocytoma is very rare. Here,we present a case of adrenal pheochromocytoma invading the ureteral wall muscle layer, which resulted in left adrenal and left nephrectomy.

19.
Environ Int ; 192: 109026, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39321539

RESUMO

Nanoplastics (NPs) are ubiquitous in daily life, posing potential risks to the environment and human. While their negative effects on parental organisms have been extensively studied, intergenerational effects are still in the early stages of investigation. Here, we aimed to investigate the impact of maternal exposure to an environmentally relevant level of polystyrene NPs (PSNPs, 100 nm) during gestation and lactation (∼32 days, 50 µg/mouse/day) on neurotoxicity mediated by the microbe-gut-brain axis in offspring mice. Maternal PSNPs exposure significantly increased brain TNF-α level and microglia by 1.43 and 1.48 folds respectively, compared to control, accompanied by nuclear pyknosis and cell vacuolization in cortex and hippocampus. Targeted neurotransmitter metabolomics analysis revealed dysregulation in dopamine and serotonin metabolism. Specifically, dopamine levels increased significantly from 0.007 ng/L to 0.015 ng/L, while N-acetylseroton and 3,4-dihydroxyphenylacetic acid decreased significantly from 0.002 and 0.929 ng/L to 0.001 and 0.680 ng/L, respectively. Through a combination of 16S rRNA sequencing and biochemical analysis, we discovered that maternal PSNPs exposure led to a depletion of anti-inflammatory bacteria and an enrichment of pro-inflammatory bacteria resulting in intestinal barrier damage, elevated levels of lipopolysaccharide in blood, and subsequent activation of neuroinflammation. Meanwhile, gut bacteria dysbiosis interfered with communication between gut and brain by dysregulating neurotransmitter synthesis, as evidenced by significant associations between neurotransmitter-related bacteria (Akkermansia, Family_XIII_AD3011_group, Lachnoclostridium) and dopamine/serotonin related metabolites. Furthermore, transcriptional alterations in dopamine and serotonin related pathways were observed in the enteric nervous system, suggesting abnormal signal transduction from gut to brain contributes to neurotoxicity. This study provides new insights into NPs-induced neurotoxicity within the context of microbe-gut-brain axis and highlights the risk of cerebral dysfunction in offspring with maternal NPs exposure.

20.
J Environ Manage ; 370: 122653, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39340882

RESUMO

Different soil microbial communities play distinct key roles in regulating forest ecosystem processes and functions. However, the differences in spatial variability and assembly mechanisms of various taiga forest soil microbial taxa remain poorly understood. Here, we assessed the spatial patterns of bacterial and fungal communities, their assembly processes, and the influencing factors in taiga forest ecosystems in Xinjiang, China. A significant distance decay pattern was observed in the similarity of bacterial and fungal communities, with bacterial communities exhibiting a more pronounced pattern than fungal communities. Stochastic and deterministic processes governed together to drive soil bacterial community assembly, whereas stochastic processes dominated fungal community assembly. The coexistence networks revealed that the interactions of bacterial and fungal networks in the four regions are primarily based on interspecies symbiosis, with fungal coexistence networks demonstrating greater stability than bacterial networks. Additionally, the study identified a positive relationship between the modularity of bacterial networks and dispersal limitation. Analysis of environmental factors revealed that soil pH primarily affects the characteristics and assembly mechanisms of bacterial communities, while vegetation conditions primarily affect fungal diversity and composition, with other unconsidered environmental variables influencing the fungal community assembly process. This study emphasized the distinct ways in which bacteria and fungi respond to environmental factors and interspecies interactions. Our results suggested that distinct restoration measures should be implemented for bacteria and fungi in future conservation efforts for forest soil microorganisms.

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