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1.
Biomed Pharmacother ; 170: 115975, 2024 Jan.
Article En | MEDLINE | ID: mdl-38070246

Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent low-grade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA. The cytotoxicity of DZ2002 was evaluated using the MTT assay on bone marrow-derived macrophages. The inhibitory impact of DZ2002 during the process of osteoclastogenesis was assessed using TRAP staining, analysis of bone resorption pits, and F-actin ring formation. Mechanistic insights were derived from qPCR and Western blot analyses. Through the intra-articular injection of monosodium iodoacetate (MIA), an experimental rat model of OA was successfully instituted. This was subsequently accompanied by a series of assessments including Von Frey filament testing, analysis of weight-bearing behaviors, and micro-CT imaging, all aimed at assessing the effectiveness of DZ2002. The findings emphasized the effectiveness of DZ2002 in mitigating osteoclastogenesis induced by M-CSF/RANKL, evident through a reduction in TRAP-positive OCs and bone resorption. Moreover, DZ2002 modulated bone resorption-associated gene and protein expression (CTSK, CTR, Integrin ß3) via the MEK/ERK pathway. Encouragingly, DZ2002 also alleviates MIA-induced pain, cartilage degradation, and bone loss. In conclusion, DZ2002 emerges as a potential therapeutic contender for OA, as evidenced by its capacity to hinder in vitro M-CSF/RANKL-induced osteoclastogenesis and mitigate in vivo osteoarthritis progression. This newfound perspective provides substantial support for considering DZ2002 as a compelling agent for osteoarthritis intervention.


Bone Resorption , Cartilage, Articular , Osteoarthritis , Rats , Animals , Iodoacetic Acid/adverse effects , Iodoacetic Acid/metabolism , Macrophage Colony-Stimulating Factor/metabolism , MAP Kinase Signaling System , Osteoarthritis/chemically induced , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Pain/drug therapy , Cartilage, Articular/metabolism , Bone Resorption/metabolism , Mitogen-Activated Protein Kinase Kinases/metabolism , Disease Models, Animal
2.
Orthop Surg ; 16(1): 140-148, 2024 Jan.
Article En | MEDLINE | ID: mdl-38086605

OBJECTIVE: Ankle joint fractures are often accompanied by medial deltoid ligament rupture. There is controversy over whether or how to treat deltoid ligament rupture. This study was aimed to explore the feasibility of repairing the medial deltoid ligament using Kirschner wire internal fixation of the medial tibiotalar joint combined with external fixation. METHODS: Forty-six patients with ankle fractures involving deltoid ligament rupture, treated between October 2012 and February 2021, were retrospectively evaluated. Twenty-five patients were treated with a Kirschner wire to fix the tibiotalar joint and indirectly repair the deltoid ligament as the repaired group. Twenty-one patients underwent reduction and fixation of internal and external malleolus fractures, and the deltoid ligament was not repaired in the unrepaired group. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale (VAS), Medical Outcomes Short Form 36-item questionnaire score (SF-36), and Medial clear space perpendicular (preoperative, postoperative, final follow-up) were used for functional evaluations and reduction assessments. Mann-Whitney test were used to compare the differences between the groups. RESULTS: The follow-up time was 13-112 months with a mean of 59.32 months for the repaired group and 11-94 months with a mean of 53.43 months for the unrepaired group. There was no significant difference in the operative time or intraoperative blood loss between the two groups (p > 0.05). At the last follow-up, the AOFAS ankle-hindfoot and SF-36 scores of the repaired group were significantly higher than those of the non-repaired group (p < 0.05). Moreover, the VAS pain score was significantly lower and the Medial clear space perpendicular was significantly narrower in the repaired group than that in the unrepaired group. CONCLUSION: Tibiotalar joint fixation using Kirschner wires is a simple and effective technique that can indirectly reduce and repair the deltoid ligament and stabilize the ankle.


Ankle Fractures , Bone Wires , Humans , Retrospective Studies , Treatment Outcome , Ligaments , Fracture Fixation, Internal/methods , Ankle Fractures/complications , Ankle Joint/surgery , Ligaments, Articular/surgery
3.
Acta Pharmacol Sin ; 45(1): 166-179, 2024 Jan.
Article En | MEDLINE | ID: mdl-37605050

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.


Corneal Neovascularization , Dry Eye Syndromes , Rats , Humans , Mice , Animals , Female , Corneal Neovascularization/drug therapy , Corneal Neovascularization/metabolism , Corneal Neovascularization/pathology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Rodentia/metabolism , Endothelial Cells/metabolism , Angiogenesis , Inflammation/drug therapy , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/chemically induced , STAT3 Transcription Factor/metabolism
4.
Sensors (Basel) ; 23(13)2023 Jun 21.
Article En | MEDLINE | ID: mdl-37447644

The transportation control infrastructure serves as the foundation for regional traffic signal control. However, in practice, this infrastructure is often imperfect and complex, characterized by factors such as heterogeneity and uncertainty, which pose significant challenges to existing methods and systems. Therefore, this paper proposes a novel approach to coordinated traffic signal control that emphasizes flexibility. To achieve this flexibility, we combine the flexible model of complex networks with robust fuzzy control methods. This approach enables us to overcome the complexity of the transportation control infrastructure and ensure efficient management of traffic signals. Additionally, to ensure long-term operational ease, we develop a regional traffic signal control system using steam computing technology, which provides high scalability and compatibility. Finally, computational experiments are performed to validate adaptability and performance of our proposed approach.

5.
Eur J Gastroenterol Hepatol ; 35(7): 761-768, 2023 07 01.
Article En | MEDLINE | ID: mdl-37272505

INTRODUCTION: Microwave ablation (MWA) is an effective local treatment for malignant liver tumors; however, its efficacy and safety for liver tumors adjacent to important organs are debatable. PATIENTS AND METHODS: Forty-three cases with liver tumors adjacent to important organs were the risk group and 66 cases were the control group. The complications between two groups were compared by chi-square test and t-test. Local tumor recurrence (LTR) was analyzed by log-rank test. Factors affecting complications were analyzed by logistic regression and Spearman analyses. Factors affecting LTR were analyzed by Cox regression analysis. A receiver operating characteristic curve predicted pain treated with drugs and LTR. RESULTS: We found no significant difference in complications and LTR between two groups. The risk group experienced lower ablation energy and more antennas per tumor than control group. Necrosis volume after MWA was positively correlated with pain; necrosis volume and ablation time were positively correlated with recovery duration. Major diameter of tumor >3 cm increased risk of LTR by 3.319-fold, good lipiodol deposition decreased risk of LTR by 73.4%. The area under the curve (AUC) for necrosis volume in predicting pain was 0.74, with a 69.1 cm3 cutoff. AUC for major diameter of tumor in predicting LTR was 0.68, with a 27.02 mm cutoff. CONCLUSION: MWA on liver tumors in at-risk areas is safe and effective, this is largely affected by proper ablation energy, antennas per tumor, and experienced doctors. LTR is primarily determined by major diameter of tumor and lipiodol deposition status.


Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Humans , Retrospective Studies , Ethiodized Oil , Microwaves/therapeutic use , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Treatment Outcome , Necrosis , Catheter Ablation/adverse effects
6.
Sensors (Basel) ; 23(9)2023 May 07.
Article En | MEDLINE | ID: mdl-37177756

Public transportation is a crucial component of urban transportation systems, and improving passenger sharing rates can help alleviate traffic congestion. To enhance the punctuality and supply-demand balance of dedicated buses, we propose a hierarchical multi-objective optimization model to optimize bus guidance speeds and bus operation schedules. Firstly, we present an intelligent decision-making method for bus driving speed based on the mathematical description of bus operation states and the application of the Lagrange multiplier method, which improves the overall punctuality rate of the bus line. Secondly, we propose an optimization method for bus operation schedules that respond to passenger needs by optimizing departure time intervals and station schedules for supply-demand balance. The experiments were conducted in Future Science City, Beijing, China. The results show that the bus line's punctuality rate has increased to 90.53%, while the retention rate for platform passengers and the intersection stop rate have decreased by 36.22% and 60.93%, respectively. These findings verify the effectiveness and practicality of the proposed hierarchical multi-objective optimization model.

8.
IEEE Trans Image Process ; 32: 6183-6194, 2023.
Article En | MEDLINE | ID: mdl-37022902

Pseudo supervision is regarded as the core idea in semi-supervised learning for semantic segmentation, and there is always a tradeoff between utilizing only the high-quality pseudo labels and leveraging all the pseudo labels. Addressing that, we propose a novel learning approach, called Conservative-Progressive Collaborative Learning (CPCL), among which two predictive networks are trained in parallel, and the pseudo supervision is implemented based on both the agreement and disagreement of the two predictions. One network seeks common ground via intersection supervision and is supervised by the high-quality labels to ensure a more reliable supervision, while the other network reserves differences via union supervision and is supervised by all the pseudo labels to keep exploring with curiosity. Thus, the collaboration of conservative evolution and progressive exploration can be achieved. To reduce the influences of the suspicious pseudo labels, the loss is dynamic re-weighted according to the prediction confidence. Extensive experiments demonstrate that CPCL achieves state-of-the-art performance for semi-supervised semantic segmentation.

9.
J Orthop Surg Res ; 18(1): 167, 2023 Mar 04.
Article En | MEDLINE | ID: mdl-36871013

OBJECTIVE: To investigate the efficacy of the minimally invasive clamp reduction technique via the anterior approach in the treatment of irreducible intertrochanteric femoral fractures. METHODS: From January 2015 to January 2021, 115 patients (48 males and 67 females) with irreducible intertrochanteric femoral fractures were treated. The average age of the patients was 78.7 (45-100 years old). The types of injuries were falls (91 cases), traffic accidents (12 cases), smashing (6 cases), and high falling (6 cases). The duration between injury and surgery ranged from 1 to 14 days, with an average of 3.9 days. The distribution of AO classification was as follows: 31-A1 in 15 cases, type 31-A2 in 67 cases and 31-A3 in 33 cases. RESULTS: All patients achieved good reduction, with fracture reduction times ranging from 10 to 32 min (mean of 18 min), and were followed up for 12-27 months after surgery (mean of 17.9 months). Two patients with pronation displacement of the proximal fracture segment died of infection or hypostatic pneumonia after internal fixation failure; one patient with failed internal fixation switched to joint replacement. After internal fixation, the lateral wall of six reversed intertrochanteric femoral fractures showed repronation and abduction displacement, but all fractures achieved bony healing. The rest of the patients did not lose fracture reduction, and all fractures achieved bony healing with a healing time ranging from 3 to 9 months (mean of 5.7 months). While two patients died and one patient exhibited failed internal fixation and thus switched to joint replacement, 91 of the remaining 112 patients had an excellent Harris score of the hip joint function at the final follow-up, while 21 patients had a good Harris score. CONCLUSION: The minimally invasive clamp reduction technique via the anterior approach for the treatment of irreducible intertrochanteric femoral fractures is simple, effective and minimally invasive. In the case of irreducible intertrochanteric femoral fractures associated with lateral wall displacement, the lateral wall needs to be strengthened after clamp reduction and intramedullary nail fixation to avoid loss of reduction and failure of internal fixation.


Hip Fractures , Plastic Surgery Procedures , Aged , Aged, 80 and over , Female , Humans , Male , Accidents, Traffic , Fracture Fixation, Internal , Wound Healing , Middle Aged
10.
PLoS One ; 18(3): e0279950, 2023.
Article En | MEDLINE | ID: mdl-36996144

Given the ban on antibiotic growth promoters, the effects of nonantibiotic alternative growth promoter combinations (NAGPCs) on the growth performance, nutrient utilization, digestive enzyme activity, intestinal morphology, and cecal microflora of broilers were evaluated. All birds were fed pellets of two basal diets-starter (0-21 d) and grower (22-42 d)-with either enramycin (ENR) or NAGPC supplemented. 1) control + ENR; 2) control diet (CON, basal diet); 3) control + mannose oligosaccharide (MOS) + mannanase (MAN) + sodium butyrate (SB) (MMS); 4) control + MOS + MAN + Bacillus subtilis (BS) (MMB); 5) control + MOS + fruit oligosaccharide (FOS) + SB (MFS); 6) control + FOS + BS (MFB); 7) control + MOS + FOS + MAN (MFM); 8) control + MOS + BS + phytase (PT) (MBP). ENR, MOS, FOS, SB, MAN, PT, and BS were added at 100, 2,000, 9,000, 1,500, 300, 37, and 500 mg/kg, respectively. The experiment used a completely random block design with six replicates per group: 2400 Ross 308 broilers in the starter phase and 768 in the grower phase. All NAGPCs significantly improved body weight gain (P < 0.01), utilization of dry matter, organic matter, and crude protein (P < 0.05), villus height and villus height/crypt depth in the jejunum and ileum (P < 0.01), and decreased the feed conversion ratio (P < 0.01) at d 21 and 42. MMS, MMB, MFB, and MFM duodenum trypsin, lipase, and amylase activities increased significantly (P < 0.05) at d 21 and 42. On d 21 and 42, MMS, MMB, and MBP increased the abundance of Firmicutes and Bacteroides whereas MMB, MFB, and MBP decreased the abundance of Proteobacteria, compared to ENR and CON. Overall, the NAGPCs were found to have some beneficial effects and may be used as effective antibiotic replacements in broilers.


Animal Feed , Chickens , Gastrointestinal Microbiome , Animals , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Anti-Bacterial Agents/pharmacology , Chickens/growth & development , Chickens/microbiology , Diet/veterinary , Dietary Supplements/analysis , Gastrointestinal Agents , Nutrients , Oligosaccharides/pharmacology
11.
Poult Sci ; 102(4): 102502, 2023 Apr.
Article En | MEDLINE | ID: mdl-36739801

Mycotoxins, including aflatoxin B1 (AFB1), zearalenone (ZEN) and deoxynivalenol (DON), are common contaminants of moldy feeds. Mycotoxins can cause deleterious effects on the health of chickens and can be carried over in poultry food products. This study was conducted to investigate the effects of moldy corn (containing AFB1, ZEN, and DON) on the performance, health, and mycotoxin residues of laying hens. One hundred and eighty 400-day-old laying hens were divided into 4 treatments: basal diet (Control), basal diet containing 20% moldy corn (MC20), 40% moldy corn (MC40) and 60% moldy corn (MC60). At d 20, 40, and 60, the performance, oxidative stress, immune function, metabolism, and mycotoxin residues in eggs were determined. At d 60, mycotoxin residues in muscle and edible viscera were measured. Results showed the average daily feed intake (ADFI) and laying performance of laying hens were decreased with moldy corn treatments. All the moldy corn treatments also induced significant oxidative stress and immunosuppression, reflected by decreased antioxidase activities, contents of cytokines, immunoglobulins, and increased malonaldehyde level. Moreover, the activities of aspartate aminotransferase and alanine transaminase were increased by moldy corn treatments. The lipid metabolism was influenced in laying hens receiving moldy corn, reflected by lowered levels of total protein, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, and increased total triglyceride as well as uric acid. The above impairments were aggravated with the increase of mycotoxin levels. Furthermore, AFB1 and ZEN residues were found in eggs, muscle, and edible viscera with moldy corn treatments, but the residues were below the maximum residue limits. In conclusion, moldy corn impaired the performance, antioxidant capacity, immune function, liver function, and metabolism of laying hens at d 20, 40, and 60. Moldy corn also led to AFB1 residue in eggs at d 20, 40, and 60, and led to both AFB1 and ZEN residues in eggs at days 40 and 60, and in muscle and edible viscera at d 60. The toxic effects and mycotoxin residues were elevated with the increase of moldy corn levels in feed.


Mycotoxins , Trichothecenes , Zearalenone , Animals , Female , Mycotoxins/toxicity , Mycotoxins/metabolism , Antioxidants/metabolism , Trichothecenes/toxicity , Zea mays/metabolism , Chickens/physiology , Viscera/chemistry , Viscera/metabolism , Zearalenone/toxicity , Fungi/metabolism , Diet/veterinary , Eggs/analysis , Animal Feed/analysis , Muscles/metabolism , Immunity
12.
BMC Microbiol ; 22(1): 242, 2022 10 06.
Article En | MEDLINE | ID: mdl-36203160

The current methods for detecting pathogenic bacteria in feed require high technique and take a long time. The Micro Biological Survey (MBS) rapid detection system is a simple, economical and rapid microbial detection method. The purpose of this experiment was to compare the detection of Escherichia coli (E. coli), Salmonella, Staphylococcus aureus (S. aureus), Listeria monocytogenes (LM), coliform (COLI) and total viable count (TVC) in feed by the MBS rapid microbial detection system and plate counting method (PCM). The results showed that the limit of quantitation, recovery rate and coefficient of variation of the MBS microbial rapid detection system are better than the plate counting method. When detecting the pathogenic bacteria content in artificially contaminated feed, the MBS rapid microbial detection system was positively correlated with the PCM. When the MBS microbial rapid detection system and PCM were used to detect the collected real feed samples, there was no significant difference in the detection results of the two methods in most of the feed samples. In summary, the MBS microbial rapid detection system is the most convenient and rapid detection method and is suitable for promotion and application in production lines.


Escherichia coli O157 , Listeria monocytogenes , Staphylococcal Infections , Colony Count, Microbial , Food Microbiology , Humans , Salmonella , Staphylococcus aureus
13.
Front Pharmacol ; 13: 849014, 2022.
Article En | MEDLINE | ID: mdl-36120344

Intestinal barrier disruption due to the intestinal epithelial cells' (IECs) death is one of the critical pathological features of inflammatory bowel diseases (IBDs). SM934, an artemisinin analog, has previously been proven to ameliorate colitis induced by dextran sulfate sodium (DSS) in mice by suppressing inflammation response. In this study, we investigated the protective effects of SM934 on the epithelial barrier and the underlying mechanism in trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We demonstrated that SM934 restored the body weight and colon length, and improved the intestine pathology. Furthermore, SM934 treatment preserved the intestinal barrier function via decreasing the intestinal permeability, maintaining epithelial tight junction (TJ) protein expressions, and preventing apoptosis of epithelial cells, which were observed both in the colon tissue and the tumor necrosis factor-α (TNF-α)-induced human colonic epithelial cell line HT-29. Specifically, SM934 reduced the pyroptosis of IECs exposed to pathogenic signaling and inhibited pyroptosis-related factors such as NOD-like receptor family pyrin domain containing 3 (NLRP3), adapter apoptosis-associated speck-like protein (ASC), cysteine protease-1 (caspase-1), gasdermin (GSDMD), interleukin-18 (IL-18), and high-mobility group box 1 (HMGB1) both in colon tissue and lipopolysaccharide (LPS) and adenosine triphosphate (ATP) co-stimulated HT-29 cells in vitro. Moreover, SM934 interdicted pyroptosis via blocking the transduction of mitogen-activated protein kinase (MAPK) and nuclear factor-kB (NF-kB) signaling pathways. In conclusion, SM934 protected TNBS-induced colitis against intestinal barrier disruption by inhibiting the apoptosis and pyroptosis of epithelial cells via the NLRP3/NF-κB/MAPK signal axis, and intestinal barrier protection in company with an anti-inflammatory strategy might yield greater benefits in IBD treatment.

14.
Biomed Pharmacother ; 153: 113399, 2022 Sep.
Article En | MEDLINE | ID: mdl-35834986

Aberrant microbe-immune cell interaction is a predisposing factor in inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Cortex Periplocae is a famous traditional Chinese medicine with putative anti-rheumatoid arthritis and anti-dyspepsia effects. Here, we show that the Periploca sepium periplosides (PePs), a cardiac glycosides-free pregnane glycosides extract from root bark of Cortex Periplocae, alleviates colon inflammation, improves intestinal epithelial barrier function, and prevents colitis-associated tumorigenesis in mice with colitis and CAC. Mechanistically, PePs treatment modulates abnormal gut microbiota composition in model mice, especially enriches an anti-inflammatory commensal bacterium A. muciniphila BAA-835. We further demonstrate that the altered gut microbiota following PePs treatment plays an important role in modulation of intestinal Type 17 immunity in both colitis and CAC mouse model. Our results indicate that PePs may be used as a potential gut microbiota modulator to treat IBD and CAC.


Colitis-Associated Neoplasms , Colitis , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Animals , Colitis/complications , Colitis/drug therapy , Colitis/microbiology , Dextran Sulfate , Disease Models, Animal , Mice , Mice, Inbred C57BL , Th17 Cells/pathology
15.
Front Vet Sci ; 9: 898121, 2022.
Article En | MEDLINE | ID: mdl-35685341

Fumonisin B1 (FB1), produced by Fusarium, is among the most abundant and toxic mycotoxin contaminations in feed, causing damages to the health of livestock. However, the mechanisms of FB1 toxicity in chickens are less understood. As splenic lymphocytes play important roles in the immune system, the aim of this study was to investigate the immunotoxic effects and mechanisms of FB1 on chicken splenic lymphocytes. In the present study, the chicken primary splenic lymphocytes were harvested and treated with 0, 2.5, 5, 10, 20 and 40 µg/mL FB1. Then, the cell proliferation, damage, ultrastructure, inflammation and apoptosis were evaluated. Results showed that the proliferation rate of splenic lymphocytes was decreased by FB1 treatments. The activity of lactate dehydrogenase (LDH) was increased by FB1 treatments in a dose-dependent manner, implying the induction of cell damage. Consistently, the ultrastructure of splenic lymphocytes showed that FB1 at all the tested concentrations caused cell structure alterations, including nuclear vacuolation, mitochondrial swelling and mitochondrial crest fracture. Besides, immunosuppressive effects of FB1 were observed by the decreased concentrations of interleukin-2 (IL-2), IL-4, IL-12 and interferon-γ (IFN-γ) in the cell culture supernatant. Furthermore, apoptosis was observed in FB1-treated cells by flow cytometry. The mRNA expressions of apoptosis-related genes showed that the expression of Bcl-2 was decreased, while the expressions of the P53, Bax, Bak-1, and Caspase-3 were increased with FB1 treatment. Similar results were found in the concentrations of apoptosis-related proteins in the cell supernatant by ELISA assay. Moreover, regression analysis indicated that increasing FB1 concentration increased LDH activity, concentrations of Bax, Bak-1 and mRNA expression of Bak-1 linearly, increased M1 area percentage quadratically, decreased concentration of IFN-γ, mRNA expression of Bcl-2 linearly, and decreased concentrations of IL-2 and IL-4 quadratically. Besides, regression analysis also showed reciprocal relationships between IL-12 concentration, Caspase-3 mRNA expression and increasing FB1 concentration. The increasing FB1 concentration could decrease IL-12 concentration and increase Caspase-3 mRNA expression. Altogether, this study reported that FB1 induced the immunotoxicity of chicken splenic lymphocytes and caused splenic lymphocytes apoptosis by the Bcl-2 family-mediated mitochondrial pathway of caspase activation.

17.
Virol Sin ; 37(2): 256-265, 2022 Apr.
Article En | MEDLINE | ID: mdl-35305922

The hepatitis B virus (HBV) is a global public health challenge due to its highly contagious nature. It is estimated that almost 300 million people live with chronic HBV infection annually. Although nucleoside analogs markedly reduce the risk of liver disease progression, the analogs do not fully eradicate the virus. As such, new treatment options and drugs are urgently needed. Psoralen is a nourishing monomer of Chinese herb and is known to inhibit virus replication and inactivate viruses. In this study, we evaluated the potential of psoralen as an anti-HBV agent. Quantitative PCR and Southern blot analysis revealed that psoralen inhibited HBV replication in HepG2.2.15 â€‹cells in a concentration-dependent manner. Moreover, psoralen was also active against the 3TC/ETV-dual-resistant HBV mutant. Further investigations revealed that psoralen suppressed both HBV RNA transcription and core protein expression. The transcription factor FOXO1, a known target for PGC1α co-activation, binds to HBV pre-core/core promoter enhancer II region and activates HBV RNA transcription. Co-immunoprecipitation showed that psoralen suppressed the expression of FOXO1, thereby decreasing the binding of FOXO1 co-activator PGC1α to the HBV promoter. Overall, our results demonstrate that psoralen suppresses HBV RNA transcription by down-regulating the expression of FOXO1 resulting in a reduction of HBV replication.


Ficusin , Hepatitis B , Virus Replication , Antiviral Agents/pharmacology , Ficusin/pharmacology , Hep G2 Cells , Hepatitis B virus/drug effects , Hepatitis B virus/physiology , Humans , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Promoter Regions, Genetic , RNA, Viral , Transcription, Genetic , Virus Replication/drug effects
18.
IEEE Trans Cybern ; 52(11): 11397-11406, 2022 Nov.
Article En | MEDLINE | ID: mdl-34232903

Calibration of agent-based models (ABM) is an essential stage when they are applied to reproduce the actual behaviors of distributed systems. Unlike traditional methods that suffer from the repeated trial and error and slow convergence of iteration, this article proposes a new ABM calibration approach by establishing a link between agent microbehavioral parameters and systemic macro-observations. With the assumption that the agent behavior can be formulated as a high-order Markovian process, the new approach starts with a search for an optimal transfer probability through a macrostate transfer equation. Then, each agent's microparameter values are computed using mean-field approximation, where his complex dependencies with others are approximated by an expected aggregate state. To compress the agent state space, principal component analysis is also introduced to avoid high dimensions of the macrostate transfer equation. The proposed method is validated in two scenarios: 1) population evolution and 2) urban travel demand analysis. Experimental results demonstrate that compared with the machine-learning surrogate and evolutionary optimization, our method can achieve higher accuracies with much lower computational complexities.

19.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(9): 1086-1092, 2021 Sep 15.
Article Zh | MEDLINE | ID: mdl-34523271

OBJECTIVE: To formulate the classification criteria of femoral intertrochanteric fractures based on irreducibility or not in order to predict the difficulty of fracture recovery. METHODS: A clinical data of 244 patients with closed femoral intertrochanteric fractures admitted between January 2017 and March 2020 was retrospectively analyzed. There were 116 males and 128 females with an average age of 77.9 years (range, 45-100 years). The cause of injury included falling in 190 cases, traffic accident in 36 cases, smashing in 13 cases, and falling from height in 5 cases. The time from injury to operation was 1-14 days (mean, 3.6 days). According toAO/Orthopaedic Trauma Association (AO/OTA) classification, the fractures were classified as type 31-A1 in 38 cases, type 31-A2 in 160 cases, and type 31-A3 in 46 cases. According to whether the recovery difficulty occurred after intraoperative closed traction reset, the patients were divided into reducible-group and irreducible-group; combined with the literature and preoperative imaging data of two groups, the classification criteria of femoral intertrochanteric fractures was formulated based on the irreducibility or not. The 244 fractures were classified by the doctors who did not attend the operation according to the classification criteria, predicted the difficulty of fracture reduction, and compared with the actual intraoperative reduction situation. RESULTS: The 244 patients were divided into reducible-group ( n=164, 67.21%) and irreducible-group ( n=80, 32.79%) according to the intraoperative difficulty of reduction. Comparing the imaging data and characteristics of the two groups, and formulating the classification criteria of femoral intertrochanteric fractures based on irreducibility or not, the fractures were mainly divided into two categories of irreducibility and reducibility. The fractures of irreducibility category was divided into typesⅠ-Ⅴ, among which type Ⅲ was divided into subtypes 1-4; the fractures of reducibility category was divided into typesⅠand Ⅱ. Compared with the actual intraoperative evaluation results, the total accuracy rate of the doctors who did not attend the operation was 81.15% (198/244) based on the classification criteria of femoral intertrochanteric fractures. The accuracy rate of irreducibility category was 65.74% (71/108), and the reducibility category was 93.38% (127/136). All patients were followed up 13-25 months, with an average of 17.6 months. All fractures healed except 2 cases died of infection. CONCLUSION: The classification criteria of femoral intertrochanteric fractures based on irreducibility or not can accurately predict the reducible cases preoperatively, and most of the irreducible cases can be correctly predicted in a wider way. But the classification criteria still need to be further improved and supplemented.


Femoral Fractures , Fracture Fixation, Intramedullary , Hip Fractures , Aged , Bone Nails , Female , Femoral Fractures/surgery , Hip Fractures/surgery , Humans , Male , Retrospective Studies , Treatment Outcome
20.
Sci Total Environ ; 792: 148361, 2021 Oct 20.
Article En | MEDLINE | ID: mdl-34153772

The influences of polyether sulfone (PES) microplastics and different structures aromatic carboxylic acids such as benzoic acid (BA), phthalic acid (PA), hemimellitic acid (HA), and 1-naphthoic acid (1-NA) on the performances and characteristics of anaerobic granular sludge as well as the microbial community were investigated. The chemical oxygen demand (COD) removal efficiency was the highest in the experimental group with 40 mg/L BA, reaching 90.1%. The inhibitory effect of aromatic carboxylic acids addition on the 2,3,5-triphenyltetrazolium chloride (TTC) activity was more obvious than that on 2-para (iodo-phenyl)-3(nitrophenyl)-5(phenyl) tetrazolium chloride (INT) activity. Compared with the control group (only 0.5 g/L PES microplastics, 60.6 mg TF·g TSS·h-1), the inhibition effect of TTC activity was 32.5 mg TF·g TSS·h-1 and 44.3 mg TF·g TSS·h-1 in the 40 mg/L HA and 40 mg/L 1-NA experimental groups, respectively. When aromatic carboxylic acids were added, the activities of acetate kinase and coenzyme F420 in the anaerobic granular sludge decreased. The excitation-emission matrix (EEM) fluorescence spectra indicated that loosely bound extracellular polymeric substances (LB-EPS) began to decay. After the addition of different aromatic carboxylic acids, the CC and CH functional groups of the anaerobic granular sludge increased, suggesting that aromatic carboxylic acids migrated to the surface of anaerobic granular sludge, such a transfer would lead to changes in anaerobic granular sludge performance. High-throughput sequencing technology showed that the dominant microbial communities in the anaerobic granular sludge were Proteobacteria, Methanothrix, and Methanomicrobia. After the addition of aromatic carboxylic acids, the relative abundances of Proteobacteria, Methanobacterium, and Methanospirillum increased. In the presence of PES, 1-NA had the most serious toxicity to the anaerobic granular sludge.


Microbiota , Sewage , Anaerobiosis , Carboxylic Acids/toxicity , Microplastics , Plastics , Waste Disposal, Fluid
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