Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 234
Filter
1.
Front Cell Dev Biol ; 12: 1431558, 2024.
Article in English | MEDLINE | ID: mdl-39011392

ABSTRACT

Care for patients with peripheral nerve injury is multifaceted, as traditional methods are not devoid of limitations. Although the utilization of neural conduits shows promise as a therapeutic modality for peripheral nerve injury, its efficacy as a standalone intervention is limited. Hence, there is a pressing need to investigate a composite multifunctional neural conduit as an alternative treatment for peripheral nerve injury. In this study, a BDNF-loaded chitosan-based mimetic mussel polymer conduit was prepared. Its unique adhesion characteristics allow it to be suture-free, improve the microenvironment of the injury site, and have good antibacterial properties. Researchers utilized a rat sciatic nerve injury model to evaluate the progression of nerve regeneration at the 12-week postoperative stage. The findings of this study indicate that the chitosan-based mimetic mussel polymer conduit loaded with BDNF had a substantial positive effect on myelination and axon outgrowth. The observed impact demonstrated a favorable outcome in terms of sciatic nerve regeneration and subsequent functional restoration in rats with a 15-mm gap. Hence, this approach is promising for nerve tissue regeneration during peripheral nerve injury.

2.
BMC Plant Biol ; 24(1): 647, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977968

ABSTRACT

BACKGROUND: The ginseng endophyte Paenibacillus polymyxa Pp-7250 (Pp-7250) has multifaceted roles such as preventing ginseng diseases, promoting growth, increasing ginsenoside accumulation, and degrading pesticide residues, however, these effects still have room for improvements. Composite fungicides are an effective means to improve the biocontrol effect of fungicides, but the effect of Pp-7250 in combination with its symbiotic bacteria on ginseng needs to be further investigated, and its mechanism of action has not been elucidated. In this study, a series of experiments was conducted to elucidate the effect of Paenibacillus polymyxa and Bacillus cereus co-bacterial agent on the yield and quality of understory ginseng, and to investigate their mechanism of action. RESULTS: The results indicated that P. polymyxa and B. cereus co-bacterial agent (PB) treatment improved ginseng yield, ginsenoside accumulation, disease prevention, and pesticide degradation. The mechanism is that PB treatment increased the abundance of beneficial microorganisms, including Rhodanobacter, Pseudolabrys, Gemmatimonas, Bacillus, Paenibacillus, Cortinarius, Russula, Paecilomyces, and Trechispora, and decreased the abundance of pathogenic microorganisms, including Ellin6067, Acidibacter, Fusarium, Tetracladium, Alternaria, and Ilyonectria in ginseng rhizosphere soil. PB co-bacterial agents enhanced the function of microbial metabolic pathways, biosynthesis of secondary metabolites, biosynthesis of antibiotics, biosynthesis of amino acids, carbon fixation pathways in prokaryotes, DNA replication, and terpenoid backbone biosynthesis, and decreased the function of microbial plant pathogens and animal pathogens. CONCLUSION: The combination of P. polymyxa and B. cereus may be a potential biocontrol agent to promote the resistance of ginseng to disease and improve the yield, quality, and pesticide degradation.


Subject(s)
Ginsenosides , Paenibacillus polymyxa , Panax , Plant Diseases , Rhizosphere , Panax/microbiology , Panax/growth & development , Panax/drug effects , Plant Diseases/microbiology , Plant Diseases/prevention & control , Bacillus cereus/drug effects , Bacillus cereus/growth & development , Soil Microbiology , Endophytes/physiology , Endophytes/drug effects , Microbiota/drug effects
3.
Cell Death Differ ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060421

ABSTRACT

The transcription factor FOXM1, which plays critical roles in cell cycle progression and tumorigenesis, is highly expressed in rapidly proliferating cells and various tumor tissues, and high FOXM1 expression is related to a poor prognosis. However, the mechanism responsible for FOXM1 dysregulation is not fully understood. Here, we show that ABL1, a nonreceptor tyrosine kinase, contributes to the high expression of FOXM1 and FOXM1-dependent tumor development. Mechanistically, ABL1 directly binds FOXM1 and mediates FOXM1 phosphorylation at multiple tyrosine (Y) residues. Among these phospho-Y sites, pY575 is indispensable for FOXM1 stability as phosphorylation at this site protects FOXM1 from ubiquitin-proteasomal degradation. The interaction of FOXM1 with CDH1, a coactivator of the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), which is responsible for FOXM1 degradation, is significantly inhibited by Y575 phosphorylation. The phospho-deficient FOXM1(Y575F) mutant exhibited increased ubiquitination, a shortened half-life, and consequently a substantially decreased abundance. Compared to wild-type cells, a homozygous Cr-Y575F cell line expressing endogenous FOXM1(Y575F) that was generated by CRISPR/Cas9 showed obviously delayed mitosis progression, impeded colony formation and inhibited xenotransplanted tumor growth. Overall, our study demonstrates that ABL1 kinase is involved in high FOXM1 expression, providing clear evidence that ABL1 may act as a therapeutic target for the treatment of tumors with high FOXM1 expression.

4.
Huan Jing Ke Xue ; 45(6): 3446-3458, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38897765

ABSTRACT

Under the dual constraints of economic development and ecological carrying capacity, it is necessary to explore more technical means to achieve carbon neutrality and peak in China. Plants are important carriers of terrestrial and marine carbon sink systems, whereas phytoremediation is also a scientific method to remedy environmental pollution. However, the current studies mostly focus on the single aspect of plant carbon sequestration (including both the reduction of pollutant concentrations in environmental media and degradation of pollutants) or plant pollution reduction, without considering the dual benefits of plant pollution reduction and carbon sequestration. In order to explore the carbon neutral effect of plants, we focused on the pollution reduction and carbon sequestration effect of carbon neutral plants and its progress and evaluated the pollution reduction and carbon sequestration potential of carbon neutral plants and other organisms (such as animals and soil microorganisms) and environmental functional materials. The mechanisms underlying the synergistic coupling of carbon neutral plants and animals, microorganisms, and environmental functional materials and ecosystems in reducing pollution and carbon sequestration were also explored. Finally, we proposed constructive prospects for future research on the effects of carbon neutral plants on pollution reduction and carbon sink.


Subject(s)
Biodegradation, Environmental , Carbon Sequestration , Carbon , Environmental Pollution , Plants , Plants/metabolism , Carbon/metabolism , Environmental Pollution/prevention & control , China , Ecosystem
5.
Int J Mol Sci ; 25(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892109

ABSTRACT

Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which can induce neuroinflammation and oxidative stress (OS) and may increase the risk of neurodegenerative disease. As key regulators of inflammation and OS in the CNS, microglial cells may be involved in GCR-induced deficits, and therefore could be a target for neuroprotection. This study assessed the effects of exposure to helium (4He) and iron (56Fe) particles on inflammation and OS in microglia in vitro, to establish a model for testing countermeasure efficacy. Rat microglia were exposed to a single dose of 20 cGy (300 MeV/n) 4He or 2 Gy 56Fe (600 MeV/n), while the control cells were not exposed (0 cGy). Immediately following irradiation, fresh media was applied to the cells, and biomarkers of inflammation (cyclooxygenase-2 [COX-2], nitric oxide synthase [iNOS], phosphorylated IκB-α [pIκB-α], tumor necrosis factor-α [TNFα], and nitrite [NO2-]) and OS (NADPH oxidase [NOX2]) were assessed 24 h later using standard immunochemical techniques. Results showed that radiation did not increase levels of NO2- or protein levels of COX-2, iNOS, pIκB-α, TNFα, or NOX2 compared to non-irradiated control conditions in microglial cells (p > 0.05). Therefore, microglia in isolation may not be the primary cause of neuroinflammation and OS following exposures to helium or iron GCR particles.


Subject(s)
Biomarkers , Cosmic Radiation , Inflammation , Microglia , Oxidative Stress , Animals , Microglia/metabolism , Microglia/radiation effects , Cosmic Radiation/adverse effects , Oxidative Stress/radiation effects , Rats , Inflammation/metabolism , Inflammation/etiology , Biomarkers/metabolism , Nitric Oxide Synthase Type II/metabolism , Iron/metabolism , Cyclooxygenase 2/metabolism , Helium/pharmacology , Tumor Necrosis Factor-alpha/metabolism , NADPH Oxidase 2/metabolism
6.
Article in English | MEDLINE | ID: mdl-38751078

ABSTRACT

PURPOSE: The purpose of this study was to investigate whether double-level (femur + tibia) derotational osteotomy is superior to single-level femoral derotational osteotomy for recurrent patellar dislocation with severe femoral and tibial rotational deformities (femoral anteversion >30° and external tibial torsion >30°). METHODS: Between January 2015 and June 2020, a total of 115 knees with recurrent patellar dislocation treated with combined medial patellofemoral ligament reconstruction (MPFL-R) and derotational osteotomies were evaluated after a minimum follow-up of 2 years. Among these cases, 15 knees that underwent double-level derotational osteotomy were included in the double-level group, which was propensity-matched in a 1:2 ratio to a single-level group of patients who underwent single-level femoral derotational osteotomy (30 knees). The clinical and radiological outcomes were evaluated and compared between the groups. Furthermore, the foot progression angle was measured preoperatively and 2 years after surgery. RESULTS: The patient-specific variables did not differ significantly between the double- and the single-level groups after propensity score matching. The postoperative mean foot progression angle was significantly lower in the double-level group than in the single-level group (9° ± 8° vs. 15° ± 11°; p = 0.014); however, there were no statistically significant differences between the groups in terms of any other clinical and radiological assessments. CONCLUSION: For patients with severe femoral and tibial torsional deformities (femoral anteversion >30° and external tibial torsion >30°), the double-level derotational osteotomy is superior to single-level osteotomy in maintaining normal foot progression angle, but it does not show an advantage in terms of patient-reported outcomes, radiological results and redislocation rate at minimum 2 years of follow-up. Furthermore, concomitant excessive external tibial torsion (>30°) did not have an adverse effect on clinical outcomes in patients who underwent derotational distal femoral osteotomy with MPFL-R due to excessive femoral anteversion. LEVEL OF EVIDENCE: Level III.

7.
BMC Musculoskelet Disord ; 25(1): 370, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38730370

ABSTRACT

BACKGROUND: In this study, we present the unique case of a patient with knee osteoarthritis (OA) of the medial compartment and posterior cruciate ligament (PCL) deficiency who underwent simultaneous medial unicompartmental knee arthroplasty (UKA) and PCL reconstruction. CASE PRESENTATION: A 49-year-old male patient presented with a 1-year history of pain and instability in the left knee. The patient had previously experienced a trauma-related injury to the PCL of the left knee that was left untreated. Imaging and physical examination confirmed the presence of left medial knee OA along with PCL rupture. To address these issues, the patient underwent UKA combined with PCL reconstruction. The patient's Lysholm score was 47 before surgery and 81 three months after surgery, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 29 before surgery and 18 three months after surgery, and the International Knee Documentation Committee (IKDC) subjective score was 56.3 before surgery and 74.7 three months after surgery. Six months after surgery, the patient's gait returned to normal, and he was able to jog. CONCLUSION: This case report presents the first instance of UKA combined with PCL reconstruction and introduces a novel treatment approach for patients suffering from medial knee OA and ligament injury.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Posterior Cruciate Ligament Reconstruction , Posterior Cruciate Ligament , Humans , Male , Middle Aged , Arthroplasty, Replacement, Knee/methods , Osteoarthritis, Knee/surgery , Posterior Cruciate Ligament Reconstruction/methods , Posterior Cruciate Ligament/surgery , Posterior Cruciate Ligament/injuries , Treatment Outcome , Knee Joint/surgery , Knee Joint/diagnostic imaging
8.
Sci Bull (Beijing) ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38789326

ABSTRACT

The interplay between multi-atom assembly configurations and single atoms (SAs) has been gaining attention in research. However, the effect of long-term range interactions between SAs and multi-atom assemblies on the orbital filling characteristics has yet to be investigated. In this context, we introduced copper (Cu) doping to strengthen the interaction between cobalt (Co) nanoparticles (NPs) and Co SAs by promoting the spontaneous formation of Co-Cu alloy NPs that tends toward aggregation owing to its negative cohesive energy (-0.06454), instead of forming Cu SAs. The incorporation of Cu within the Co-Cu alloy NPs, compared to the pure Co NPs, significantly expedites the kinetics of peroxymonosulfate (PMS) oxidation processes on Co SAs. Unlike Co NPs, Co-Cu NPs facilitate electron rearrangement in the d orbitals (especially dz2 and dxz) near the Fermi level in Co SAs, thereby optimizing the dz2-O (PMS) and dxz-O (SO5-) orbital interaction. Eventually, the Co-Cu alloy NPs embedded in nitrogen-doped carbon (CC@CNC) catalysts rapidly eliminated 80.67% of 20 mg/L carbamazepine (CBZ) within 5 min. This performance significantly surpasses that of catalysts consisting solely of Co NPs in a similar matrix (C@CNC), which achieved a 58.99% reduction in 5 min. The quasi in situ characterization suggested that PMS acts as an electron donor and will transfer electrons to Co SAs, generating 1O2 for contaminant abatement. This study offers valuable insights into the mechanisms by which composite active sites formed through multi-atom assembly interact at the atomic orbital level to achieve high-efficiency PMS-based advanced oxidation processes at the atomic orbital level.

9.
Ecotoxicol Environ Saf ; 278: 116400, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38718725

ABSTRACT

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.


Subject(s)
Molybdenum , Molybdenum/urine , Molybdenum/toxicity , Molybdenum/analysis , Humans , China/epidemiology , Female , Male , Adult , Middle Aged , Environmental Exposure/statistics & numerical data , Environmental Exposure/analysis , Cystatin C , Risk Assessment , Environmental Pollutants/urine , Environmental Pollutants/analysis , Young Adult , Bayes Theorem , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/chemically induced , Aged , Chemical Industry , Kidney/drug effects , Glomerular Filtration Rate/drug effects
10.
Knee Surg Sports Traumatol Arthrosc ; 32(7): 1650-1659, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38651601

ABSTRACT

PURPOSE: To explore the relationship between preoperative J-sign grading and structural bone abnormalities in patients with recurrent patellar dislocation (RPD). METHODS: A retrospective study was conducted on RPD patients over 5 years. Patients were categorised based on J-sign grade into low (J- and J1+), moderate (J2+) and high groups (J3+). Trochlear dysplasia (TD) and osseous structures (femoral anteversion angle [FAA], knee torsion, tibial tuberosity-trochlear groove [TT-TG] distance, Caton-Deschamps index) were assessed and grouped according to risk factor thresholds. The χ2 test was used to compare composition ratio differences of structural bone abnormalities among the groups. RESULTS: A total of 256 patients were included, with 206 (80.5%) females. The distribution of J-sign grade was as follows: 89 knees (34.8%) of low grade, 86 moderate (33.6%) and 81 high (31.6%). Among the five structural bone abnormalities, TD was the most common with a prevalence of 78.5%, followed by increased TT-TG at 47.4%. Excessive tibiofemoral rotation had the lowest occurrence at 28.9%. There were 173 (67.6%) patients who had two or more abnormalities, while 45 (17.6%) had four to five bony abnormalities. Among patients with any bony abnormality, the proportion of high-grade J-sign surpassed 40%. Patients with moderate and high-grade J-sign had more increased FAA and more pronounced patella alta (all p < 0.001). The proportion of excessive knee torsion and TD increased with increasing each J-sign grade, with the more notable tendency in knee torsion (high vs. moderate vs. low-grade: 61% vs. 22% vs 7%, p < 0.001). Furthermore, the higher J-sign grade was also associated with more combined bony abnormalities (p < 0.001). In the high-grade J-sign group, 90.2% of the knees had two or more bony risk factors and 40.7% had four or more, which were significantly higher than the moderate and low-grade J-sign groups (40.7% vs. 11.6% vs. 2.2%, p < 0.001). CONCLUSION: In patients with a high-grade J-sign, over 90% of the lower limbs had two or more structural bone risk factors, and more than 40% had four or more. These proportions were significantly higher compared to knees with low-grade and moderate J-sign. In clinical practice, when treating high-grade patellar mal-tracking, it is important to focus on and correct these strongly correlated abnormal bone structures. LEVEL OF EVIDENCE: Level III.


Subject(s)
Femur , Patellar Dislocation , Recurrence , Humans , Female , Male , Patellar Dislocation/diagnostic imaging , Retrospective Studies , Adult , Adolescent , Femur/abnormalities , Femur/diagnostic imaging , Young Adult , Tibia/abnormalities , Tibia/diagnostic imaging , Risk Factors , Patella/abnormalities , Patella/diagnostic imaging
11.
Water Sci Technol ; 89(7): 1757-1770, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38619901

ABSTRACT

The water reuse facilities of industrial parks face the challenge of managing a growing variety of wastewater sources as their inlet water. Typically, this clustering outcome is designed by engineers with extensive expertise. This paper presents an innovative application of unsupervised learning methods to classify inlet water in Chinese water reuse stations, aiming to reduce reliance on engineer experience. The concept of 'water quality distance' was incorporated into three unsupervised learning clustering algorithms (K-means, DBSCAN, and AGNES), which were validated through six case studies. Of the six cases, three were employed to illustrate the feasibility of the unsupervised learning clustering algorithm. The results indicated that the clustering algorithm exhibited greater stability and excellence compared to both artificial clustering and ChatGPT-based clustering. The remaining three cases were utilized to showcase the reliability of the three clustering algorithms. The findings revealed that the AGNES algorithm demonstrated superior potential application ability. The average purity in six cases of K-means, DBSCAN, and AGNES were 0.947, 0.852, and 0.955, respectively.


Subject(s)
Bays , Unsupervised Machine Learning , Reproducibility of Results , Algorithms , Cluster Analysis
12.
Chemosphere ; 356: 141962, 2024 May.
Article in English | MEDLINE | ID: mdl-38614399

ABSTRACT

The impact of shale gas extraction on surrounding environmental media remains unclear. In this study, the current state of contamination by polycyclic aromatic hydrocarbons (PAHs), which are high-frequency contaminants of shale gas, was investigated in the soil surrounding emerging shale gas development sites. The source analysis of PAHs was conducted in the soils of shale gas extraction sites using positive matrix factorization (PMF). The health risk assessment (HRA) was calculated for ingestion, dermal contact, and inhalation exposures, and the priority sources of PAHs in the soil were jointly identified by PMF and HRA to refine the contribution level of different individual PAHs to the carcinogenic risk. The results showed that both Sichuan and Chongqing mining site soils were contaminated to different degrees. Shale gas extraction has an impact on the surrounding soil, and the highest contributing source of PAHs in the mining site soil of Sichuan was anthropogenic activity, accounting for 31.6%, whereas that in the mining site soil of Chongqing was biomass combustion and mixed automobile combustion, accounting for 35.9%. At the two mining sites in Sichuan and Chongqing, none of the three exposure pathways (ingestion, dermal contact, and inhalation) posed a carcinogenic risk to children, whereas the dermal exposure pathway posed a carcinogenic risk to adults. Health risk assessments based on specific source assignments indicate that when managing soil pollution, the control of fossil fuel combustion and vehicular emissions should be prioritized.


Subject(s)
Environmental Monitoring , Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Soil , Polycyclic Aromatic Hydrocarbons/analysis , Soil Pollutants/analysis , Risk Assessment , Humans , Environmental Monitoring/methods , Soil/chemistry , China , Mining , Natural Gas/analysis
13.
Sci Total Environ ; 929: 172646, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38653417

ABSTRACT

Agroforestry waste and cow manure pollute the environment, of which, agroforestry waste is difficult to degrade. Compost is an effective way to dispose agroforestry waste; however, the low degradation efficiency of lignocellulose in agroforestry waste affects the process of composting humification. This study investigated lignocellulose degradation and composting humification in full-size apple wood and cow manure composting processes by applying different pretreatments (acidic, alkaline, and high-temperature) to apple wood. Simultaneously, physicochemical characterization and metagenome sequencing were combined to analyze the function of carbohydrate-active enzymes database (CAZy). Therefore, microbial communities and functions were linked during the composting process and the lignocellulose degradation mechanism was elaborated. The results showed that the addition of apple wood increased the compost humus (HS) yield, and pretreatment of apple wood enhanced the lignocellulose degradation during composting processes. In addition, pretreatment improved the physicochemical properties, such as temperature, pH, electric conductivity (EC), ammonium nitrogen (NH4+), and nitrate nitrogen (NO3-) in the compost, of which, acid treated apple wood compost (AcAWC) achieved the highest temperature of 58.4 °C, effectively promoting nitrification with NO3- ultimately reaching 0.127 g/kg. In all composts, microbial networks constructed a high proportion of positively correlated connections, and microorganisms promoted the composting process through cooperation. The proportions of glycosyltransferase (GT) and glycoside hydrolase (GH) promoted the separation and degradation of lignocellulose during composting to form HS. Notably, the adverse effects of the alkali-treated apple wood compost on bacteria were greater. AcAWC showed significant correlations between bacterial and fungal communities and both lignin and hemicellulose, and had more biomarkers associated with lignocellulose degradation and humification. The lignin degradation rate was 24.57 % and the HS yield increased by 27.49 %. Therefore, AcAWC has been confirmed to enhance lignocellulose degradation and promote compost humification by altering the properties of the apple wood and establishing a richer microbial community.


Subject(s)
Composting , Lignin , Malus , Manure , Wood , Lignin/metabolism , Animals , Cattle , Biomass , Humic Substances , Biodegradation, Environmental
14.
J Virol ; 98(4): e0156523, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38445884

ABSTRACT

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of SARS-CoV-2, a conserved helicase for coronavirus replication, both in cells and in lung tissues subjected to SARS-CoV-2 infection. The ATPase and helicase activity of viral nsp13 were shown to be potentiated by CREB1 association, as well as by Protein kinase A (PKA)-mediated CREB1 activation. SARS-CoV-2 replication is significantly suppressed by PKA Cα, cAMP-activated protein kinase catalytic subunit alpha (PRKACA), and CREB1 knockdown or inhibition. Consistently, the CREB1 inhibitor 666-15 has shown significant antiviral effects against both the WIV04 strain and the Omicron strain of the SARS-CoV-2. Our findings indicate that the PKA-CREB1 signaling axis may serve as a novel therapeutic target against coronavirus infection. IMPORTANCE: In this study, we provide solid evidence that host transcription factor cAMP-responsive element-binding protein (CREB1) interacts directly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helicase non-structural protein 13 (nsp13) and potentiate its ATPase and helicase activity. And by live SARS-CoV-2 virus infection, the inhibition of CREB1 dramatically impairs SARS-CoV-2 replication in vivo. Notably, the IC50 of CREB1 inhibitor 666-15 is comparable to that of remdesivir. These results may extend to all highly pathogenic coronaviruses due to the conserved nsp13 sequences in the virus.


Subject(s)
Coronavirus RNA-Dependent RNA Polymerase , Cyclic AMP Response Element-Binding Protein , Cyclic AMP-Dependent Protein Kinases , Host Microbial Interactions , SARS-CoV-2 , Viral Nonstructural Proteins , Virus Replication , Humans , Adenosine Triphosphatases/metabolism , Antiviral Agents/pharmacology , Coronavirus RNA-Dependent RNA Polymerase/metabolism , COVID-19/virology , Cyclic AMP Response Element-Binding Protein/antagonists & inhibitors , Cyclic AMP Response Element-Binding Protein/deficiency , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , DNA Helicases/metabolism , Inhibitory Concentration 50 , RNA Helicases/metabolism , SARS-CoV-2/classification , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , SARS-CoV-2/growth & development , Signal Transduction/drug effects , Viral Nonstructural Proteins/metabolism , Virus Replication/drug effects , Female , Animals , Mice
15.
Quant Imaging Med Surg ; 14(3): 2213-2224, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38545056

ABSTRACT

Background: There is an increasing evidence that pulmonary vein (PV) enlargement is associated with atrial fibrillation (AF); however, the predictive value of PV enlargement in AF recurrence remains unclear. This study sought to evaluate whether PV volume quantification derived from cardiac computed tomographic angiography (CCTA) could serve as a predictive indicator of the success of the catheter ablation (CA) procedure. Methods: The data of 160 patients diagnosed with AF who underwent both CCTA and CA treatments from January to June 2020 were retrospectively examined; the CCTA was conducted before the CA surgery. The study focused on documenting the PV structure, and the volume of the PV and left atrium (LA). The clinical, CCTA, and echocardiographic predictors of the recurrence and no-recurrence groups were compared. A multivariable logistic regression analysis was performed to adjust for confounders. Receiver operating characteristic (ROC) curves were analyzed to assess the predictive performance of the predictors of AF recurrence. Results: Of the 160 patients [55.6% male, 62.00 (55.25-68.00) years, 23.1% with persistent AF], 45 (28.1%) experienced AF recurrence within a one-year period. Notably, patients with AF recurrence had elevated CHADS2 scores (P=0.020) and increased LA and PV volumes (P<0.05). Patients with persistent AF (n=37) had significantly larger LA volume indexes (P<0.001) than those with paroxysmal AF, but there was no difference between the two groups in terms of the PV maximum volume index (P=0.200). Moreover, the PV maximum volume index [odds ratio (OR): 1.244, 95% confidence interval (CI): 1.008-1.536, P=0.042] and the LA minimum volume index (OR: 1.026, 95% CI: 1.001-1.052, P=0.038) were found to be significant predictors of AF recurrence. The ROC curves revealed that the PV maximum volume index threshold for predicting AF recurrence was 7.13 mL/m2, with a sensitivity of 84.4% and a specificity of 34.8% [area under the curve (AUC): 0.635, 95% CI: 0.540-0.730, P=0.008], and the LA minimum volume index threshold for predicting AF recurrence was 46.16 mL/m2, with a sensitivity of 88.9% and a specificity of 31.3% (AUC: 0.629, 95% CI: 0.534-0.723, P=0.012). A sub-analysis of patients with a lower left atrial dimension (LAD ≤38 mm in females, LAD ≤40 mm in males, n=120) demonstrated that the PV maximum volume index was a noteworthy indicator of AF recurrence (OR: 1.443: 95% CI: 1.145-1.820, P=0.002). Conversely, no significant correlation between AF recurrence and the LA volume index was found. The AUC value for the PV maximum volume index predictive of recurrent AF was 0.680 (95% CI: 0.577-0.781, P=0.003), with a sensitivity of 75.8%, specificity of 54%, and the cut-off value of the maximum AUC was 7.89 mL/m2. Conclusions: PV volume, derived from CCTA, may help to predict the recurrence of AF after CA, and is superior to the LA size in patients with less pronounced LA enlargement.

16.
Thorax ; 79(7): 615-623, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38388490

ABSTRACT

BACKGROUND: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation. METHODS: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively. RESULTS: Overall, there were negative associations between forced expiratory volume in 1 s (FEV1) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV1/FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV1 and FVC within the model, respectively. CONCLUSION: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health.


Subject(s)
Environmental Exposure , Trace Elements , Humans , Cross-Sectional Studies , Male , Female , Middle Aged , Environmental Exposure/adverse effects , Environmental Exposure/analysis , China/epidemiology , Trace Elements/urine , Adult , Forced Expiratory Volume , Spirometry , Vital Capacity , Lung/physiopathology , Aged
17.
Polymers (Basel) ; 16(3)2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38337244

ABSTRACT

Monodisperse mesoporous carbon spheres (MCS) were synthesized and their potential applications in ethylene propylene diene monomer (EPDM) foam were evaluated. The obtained MCS exhibited a high specific surface area ranging from 621-to 735 m2/g along with large pore sizes. It was observed that the incorporation of MCS into EPDM foam rubber significantly enhances its mechanical properties. The prepared MCS-40 rubber composites exhibit the highest tear strength of 210 N/m and tensile strength of 132.72 kPa, surpassing those of other samples. The enhancement mechanism was further investigated by employing computer simulation technology. The pores within the MCS allowed for the infiltration of EPDM molecular chains, thereby strengthening the interaction forces between the filler and matrix. Moreover, a higher specific surface area resulted in greater adsorption of molecular chains onto the surface of these carbon spheres. This research offers novel insights for understanding the enhancement mechanism of monodisperse mesoporous particles/polymer composites (MCS/EPDM) and highlights their potential application in high-performance rubber composites.

18.
ACS Appl Mater Interfaces ; 16(6): 7904-7916, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38302102

ABSTRACT

Noncontact triboelectric sensors (TESs) have the potential to enhance self-powered sensing performance by eliminating the need for physical contact. This study demonstrates a strategy to construct noncontact TES that enables self-powered sensing and vibration signal acquisition with high sensitivity and wide bandwidth. The incorporation of carbon nanotubes into nitrocellulose (CNTs/NC) endows the tribopositive layer with larger inner micro/nanocapacitances, consequently augmenting the charge storage capacity. As a result, the contactless sensing performance of CNTs/NC-based TES (CNTs/NC-TES) was enhanced by 146%. Correspondingly, the related theory and working mechanism of noncontact sensing were demonstrated. Furthermore, the CNTs/NC-TES exhibits optimal distance response sensitivity of 57.10 V mm-1, a wide-bandwidth response from 0.1 to 4000 Hz, and relative humidity (RH) stability. This contactless CNTs/NC-TES has the potential for high sensitivity and wide frequency vibration monitoring in a high-RH environment.

19.
Appl Microbiol Biotechnol ; 108(1): 186, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38300290

ABSTRACT

Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space-time yields, but byproducts are frequently observed during the bioprocessing. In this study, the catabolic switch between the C19- and C22-steroidal subpathways was investigated in resting cells of Mycobacterium neoaurum NRRL B-3805, and a dose-dependent transcriptional response toward the induction of phytosterol with increased concentrations was found in the putative node enzymes including ChoM2, KstD1, OpccR, Sal, and Hsd4A. Aldolase Sal presented a dominant role in the C22 steroidal side-chain cleavage, and the byproduct was eliminated after sequential deletion of opccR and sal. Meanwhile, the molar yield of androst-1,4-diene-3,17-dione (ADD) was increased from 59.4 to 71.3%. With the regard of insufficient activity of rate-limiting enzymes may also cause byproduct accumulation, a chromosomal integration platform for target gene overexpression was established supported by a strong promoter L2 combined with site-specific recombination in the engineered cell. Rate-limiting steps of ADD bioconversion were further characterized and overcome. Overexpression of the kstD1 gene further strengthened the bioconversion from AD to ADD. After subsequential optimization of the bioconversion system, the directed biotransformation route was developed and allowed up to 82.0% molar yield with a space-time yield of 4.22 g·L-1·day-1. The catabolic diversion elements and the genetic overexpression tools as confirmed and developed in present study offer new ideas of M. neoaurum cell factory development for directed biotransformation for C19- and C22-steroidal drug intermediates from phytosterol. KEY POINTS: • Resting cells exhibited a catabolic switch between the C19- and C22-steroidal subpathways. • The C22-steroidal byproduct was eliminated after sequential deletion of opccR and sal. • Rate-limiting steps were overcome by promoter engineering and chromosomal integration.


Subject(s)
Aldehyde-Lyases , Phytosterols , Androstadienes , Cell Differentiation , Polyenes
20.
Neurol Sci ; 45(7): 3191-3200, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38340219

ABSTRACT

BACKGROUND: Spinocerebellar ataxia 2 (SCA2) with a low range of CAG repeat expansion of ATXN2 gene can present with predominant or isolated parkinsonism that closely resembles Parkinson's disease (PD). This study is aimed at comparing clinical features, disease progression, and nuclear imaging between ATXN2-related parkinsonism (ATXN2-P) and PD. METHODS: Three hundred and seventy-seven clinically diagnosed PD with family history were screened by multiplex ligation-dependent probe amplification, whole-exome sequencing or target sequencing, and dynamic mutation testing of 10 SCA subtypes. The baseline and longitudinal clinical features as well as the dual-tracer positron emission tomography (PET) imaging were compared between ATXN2-P and genetically undefined familial PD (GU-fPD). RESULTS: Fifteen ATXN2-P patients from 7 families and 50 randomly selected GU-fPD patients were evaluated. Significantly less resting tremor and more symmetric signs were observed in ATXN2-P than GU-fPD. No significant difference was found in motor progression and duration from onset to occurrence of fluctuation, dyskinesia, and recurrent falls between the two groups. Cognitive impairment and rapid-eye-movement sleep behavior disorder were more common in ATXN2-P. During follow-up, olfaction was relatively spared, and no obvious progression of cognition dysfunction evaluated by Mini-Mental State Examination scores was found in ATXN2-P. PET results of ATXN2-P demonstrated a symmetric, diffuse, and homogenous dopamine transporter loss of bilateral striatum and a glucose metabolism pattern inconsistent with that in PD. CONCLUSIONS: Symmetric motor signs and unique nuclear imaging might be the clues to distinguish ATXN2-P from GU-fPD.


Subject(s)
Ataxin-2 , Disease Progression , Parkinsonian Disorders , Positron-Emission Tomography , Humans , Male , Female , Ataxin-2/genetics , Middle Aged , Longitudinal Studies , Parkinsonian Disorders/genetics , Parkinsonian Disorders/diagnostic imaging , Adult , Aged , Spinocerebellar Ataxias/diagnostic imaging , Spinocerebellar Ataxias/genetics , Cohort Studies
SELECTION OF CITATIONS
SEARCH DETAIL