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1.
Sensors (Basel) ; 24(13)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-39001121

RESUMEN

This paper proposes a solution to the problem of mobile robot navigation and trajectory interpolation in dynamic environments with large scenes. The solution combines a semantic laser SLAM system that utilizes deep learning and a trajectory interpolation algorithm. The paper first introduces some open-source laser SLAM algorithms and then elaborates in detail on the general framework of the SLAM system used in this paper. Second, the concept of voxels is introduced into the occupation probability map to enhance the ability of local voxel maps to represent dynamic objects. Then, in this paper, we propose a PointNet++ point cloud semantic segmentation network combined with deep learning algorithms to extract deep features of dynamic point clouds in large scenes and output semantic information of points on static objects. A descriptor of the global environment is generated based on its semantic information. Closed-loop completion of global map optimization is performed to reduce cumulative error. Finally, T-trajectory interpolation is utilized to ensure the motion performance of the robot and improve the smooth stability of the robot trajectory. The experimental results indicate that the combination of the semantic laser SLAM system with deep learning and the trajectory interpolation algorithm proposed in this paper yields better graph-building and loop-closure effects in large scenes at SIASUN large scene campus. The use of T-trajectory interpolation ensures vibration-free and stable transitions between target points.

2.
J Med Chem ; 67(14): 12248-12260, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38959374

RESUMEN

Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.


Asunto(s)
Antozoos , Colitis Ulcerosa , Sulfato de Dextran , Diterpenos , Animales , Colitis Ulcerosa/tratamiento farmacológico , Diterpenos/farmacología , Diterpenos/química , Diterpenos/uso terapéutico , Diterpenos/aislamiento & purificación , Ratones , Relación Estructura-Actividad , Antozoos/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/aislamiento & purificación , Células RAW 264.7 , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Descubrimiento de Drogas , Ratones Endogámicos C57BL , Humanos , Masculino , Óxido Nítrico/metabolismo
3.
J Psychiatr Res ; 176: 198-204, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38878647

RESUMEN

PURPOSE: Parents of children with cancer are exposed to risks of developing post-traumatic stress disorder (PTSD) symptoms, but few studies have explored PTSD symptoms of Chinese parents of children with acute lymphoblastic leukemia (ALL). Our study aimed to examine the association between social support and PTSD symptoms and to examine the mediating effect of positive expectations in this relationship among parents of children with ALL. METHODS: A cross-sectional study was conducted of consecutive parents of children with ALL in the Shengjing Hospital of China Medical University. A total of 177 parents eligible for this study completed questionnaires on PTSD symptoms, perceived social support, optimism and general self-efficacy anonymously. Asymptotic and resampling strategies were used to examine how positive expectations mediated the association between perceived social support and PTSD symptoms. RESULTS: Mean score of PTSD symptoms was 37.64 ± 14.44; 29.4% of the sample scored 44 and above, 19.8% scored 50 and above. After adjusting for covariates, perceived social support was negatively associated with the total score of PTSD symptoms (ß = -0.209, p < 0.01). Positive expectations were found to mediate the relationship between perceived social support and PTSD symptoms, especially for the symptoms of avoidance and hyperarousal. CONCLUSIONS: Optimism and general self-efficacy fully mediated the association between perceived social support and PTSD symptoms. Therefore, social support and positive expectations should be included in PTSD preventions and treatments targeting Chinese parents of children with ALL.


Asunto(s)
Padres , Leucemia-Linfoma Linfoblástico de Células Precursoras , Apoyo Social , Trastornos por Estrés Postraumático , Humanos , Femenino , Masculino , Padres/psicología , Estudios Transversales , Adulto , Niño , Persona de Mediana Edad , Autoeficacia , China , Optimismo , Adolescente
4.
Cell ; 187(15): 3973-3991.e24, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38897195

RESUMEN

The representation of odors in the locust antennal lobe with its >2,000 glomeruli has long remained a perplexing puzzle. We employed the CRISPR-Cas9 system to generate transgenic locusts expressing the genetically encoded calcium indicator GCaMP in olfactory sensory neurons. Using two-photon functional imaging, we mapped the spatial activation patterns representing a wide range of ecologically relevant odors across all six developmental stages. Our findings reveal a functionally ring-shaped organization of the antennal lobe composed of specific glomerular clusters. This configuration establishes an odor-specific chemotopic representation by encoding different chemical classes and ecologically distinct odors in the form of glomerular rings. The ring-shaped glomerular arrangement, which we confirm by selective targeting of OR70a-expressing sensory neurons, occurs throughout development, and the odor-coding pattern within the glomerular population is consistent across developmental stages. Mechanistically, this unconventional spatial olfactory code reflects the locust-specific and multiplexed glomerular innervation pattern of the antennal lobe.


Asunto(s)
Antenas de Artrópodos , Odorantes , Neuronas Receptoras Olfatorias , Animales , Neuronas Receptoras Olfatorias/metabolismo , Antenas de Artrópodos/fisiología , Olfato/fisiología , Saltamontes/fisiología , Animales Modificados Genéticamente , Sistemas CRISPR-Cas/genética , Vías Olfatorias/fisiología , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Locusta migratoria/fisiología , Calcio/metabolismo
5.
Chem Biodivers ; : e202401146, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38772912

RESUMEN

Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. Sixteen cembranoids (1-16), including a new one named sinupedunol B (16), were isolated from the South China Sea Soft coral Sinularia pedunculata. The structure of the sinupedunol B (16) was determined through a combination of spectroscopic analysis and X-ray single-crystal diffraction. In this study, cembranoids isolated from Sinularia pedunculata were found of anti-HBV activity for the first time. Among them, flexilarin D (6) showed significant anti-HBV activity with an IC50 value of 5.57 µM without cytotoxicity. We then analyzed the structure-activity relationship (SAR). Furthermore, it is demonstrated that flexilarin D (6) can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti-HBV activity of 6 in HepG2-NTCP infection system. Finally, we demonstrated the anti-HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter.

6.
ACS Nano ; 18(20): 13298-13307, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38727530

RESUMEN

As a second-order nonlinear optical phenomenon, the bulk photovoltaic (BPV) effect is expected to break through the Shockley-Queisser limit of thermodynamic photoelectron conversion and improve the energy conversion efficiency of photovoltaic cells. Here, we have successfully induced a strong flexo-photovoltaic (FPV) effect, a form of BPV effect, in strained violet phosphorene nanosheets (VPNS) by utilizing strain engineering at the h-BN nanoedge, which was first observed in nontransition metal dichalcogenide (TMD) systems. This BPV effect was found to originate from the disruption of inversion symmetry induced by uniaxial strain applied to VPNS at the h-BN nanoedge. We have revealed the intricate relationship between the bulk photovoltaic effect and strain gradients in VPNS through thickness-dependent photovoltaic response experiments. A bulk photovoltaic coefficient of up to 1.3 × 10-3 V-1 and a polarization extinction ratio of 21.6 have been achieved by systematically optimizing the height of the h-BN nanoedge and the thickness of VPNS, surpassing those of reported TMD materials (typically less than 3). Our results have revealed the fundamental relationship between the FPV effect and the strain gradients in low-dimensional materials and inspired further exploration of optoelectronic phenomena in strain-gradient engineered materials.

7.
J Am Coll Cardiol ; 83(15): 1386-1398, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38599715

RESUMEN

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).


Asunto(s)
Compuestos de Bencidrilo , Conservación de los Recursos Hídricos , Diuresis , Glucósidos , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Anciano , Humanos , Persona de Mediana Edad , Diuréticos Osmóticos/farmacología , Diuréticos Osmóticos/uso terapéutico , Transportador 2 de Sodio-Glucosa , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Volumen Sistólico , Función Ventricular Izquierda , Agua
8.
JMIR Form Res ; 8: e54373, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669074

RESUMEN

BACKGROUND: The growth in the capabilities of telehealth have made it possible to identify individuals with a higher risk of uncontrolled diabetes and provide them with targeted support and resources to help them manage their condition. Thus, predictive modeling has emerged as a valuable tool for the advancement of diabetes management. OBJECTIVE: This study aimed to conceptualize and develop a novel machine learning (ML) approach to proactively identify participants enrolled in a remote diabetes monitoring program (RDMP) who were at risk of uncontrolled diabetes at 12 months in the program. METHODS: Registry data from the Livongo for Diabetes RDMP were used to design separate dynamic predictive ML models to predict participant outcomes at each monthly checkpoint of the participants' program journey (month-n models) from the first day of onboarding (month-0 model) up to the 11th month (month-11 model). A participant's program journey began upon onboarding into the RDMP and monitoring their own blood glucose (BG) levels through the RDMP-provided BG meter. Each participant passed through 12 predicative models through their first year enrolled in the RDMP. Four categories of participant attributes (ie, survey data, BG data, medication fills, and health signals) were used for feature construction. The models were trained using the light gradient boosting machine and underwent hyperparameter tuning. The performance of the models was evaluated using standard metrics, including precision, recall, specificity, the area under the curve, the F1-score, and accuracy. RESULTS: The ML models exhibited strong performance, accurately identifying observable at-risk participants, with recall ranging from 70% to 94% and precision from 40% to 88% across the 12-month program journey. Unobservable at-risk participants also showed promising performance, with recall ranging from 61% to 82% and precision from 42% to 61%. Overall, model performance improved as participants progressed through their program journey, demonstrating the importance of engagement data in predicting long-term clinical outcomes. CONCLUSIONS: This study explored the Livongo for Diabetes RDMP participants' temporal and static attributes, identification of diabetes management patterns and characteristics, and their relationship to predict diabetes management outcomes. Proactive targeting ML models accurately identified participants at risk of uncontrolled diabetes with a high level of precision that was generalizable through future years within the RDMP. The ability to identify participants who are at risk at various time points throughout the program journey allows for personalized interventions to improve outcomes. This approach offers significant advancements in the feasibility of large-scale implementation in remote monitoring programs and can help prevent uncontrolled glycemic levels and diabetes-related complications. Future research should include the impact of significant changes that can affect a participant's diabetes management.

9.
Int Immunopharmacol ; 132: 111928, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38537540

RESUMEN

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by inflammation and fibrinoid necrosis of medium and small vessels, and its pathogenesis is closely related to inflammation and oxidative stress. Astaxanthin (ATX) is a carotenoid with anti-inflammatory, antioxidant, and immunomodulatory effects. We hypothesized that ATX could play a role in AAV treatment. This study aimed to investigate whether ATX has a protective effect against AAV and to elucidate its regulatory mechanism. METHODS: In vitro experiments, neutrophils isolated from healthy people were treated with ATX or not and cultured with serum from myeloperoxidase (MPO) -ANCA-positive patients and healthy persons. The levels of IL-6 and TNF-α in neutrophil culture supernatant before and after stimulation were measured. Neutrophil extracellular traps (NETs) and intracellular reactive oxygen species (ROS) in neutrophils were detected after stimulation. In vivo study, experimental autoimmune vasculitis (EAV) rat models were established and then treated with ATX via intragastric administration for 6 consecutive weeks. Urinary erythrocytes, urinary proteins, and serum creatinine were detected and HE staining was performed to assess renal injury in rats. Lung hemorrhage was observed by gross dissection and microscopic Prussian blue staining. The level of serum MPO-ANCA was detected. Serum IL-6, TNF-α, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in rats were measured to explore the effects of ATX on oxidative stress and inflammation in EAV rats. The deposition of MPO in kidney and lung of rats was detected by immunohistochemistry. RESULTS: ATX significantly inhibited neutrophil secretion of inflammatory factors IL-6 and TNF-α. ATX reduced the elevated levels of ROS in neutrophils stimulated by serum from AAV patients and alleviated the release of NETs. ATX administration was observed to reduce the degree of hematuria, proteinuria, and glomerular crescent formation in EAV rats. The degree of pulmonary hemorrhage was significantly reduced. Besides, the serum levels of IL-6 and TNF-α were attenuated, and antioxidant SOD and GSH-px increased in serum. Pathological results showed that MPO deposition was decreased in lung and kidney tissues after ATX treatment. CONCLUSION: ATX could ameliorate the organ damages in EAV rats. It could serve as a hopeful therapy for AAV by its anti-inflammatory and anti-oxidative feature as a unique nature carotenoid.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Interleucina-6 , Neutrófilos , Peroxidasa , Factor de Necrosis Tumoral alfa , Xantófilas , Animales , Xantófilas/farmacología , Xantófilas/uso terapéutico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/patología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Humanos , Masculino , Neutrófilos/inmunología , Neutrófilos/efectos de los fármacos , Ratas , Peroxidasa/metabolismo , Interleucina-6/metabolismo , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Femenino , Especies Reactivas de Oxígeno/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , Células Cultivadas , Trampas Extracelulares/efectos de los fármacos , Trampas Extracelulares/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Ratas Sprague-Dawley , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Persona de Mediana Edad
10.
Chin J Integr Med ; 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38212497

RESUMEN

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia. OBJECTIVE: To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN. METHODS: Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I2=99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I2=0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups. CONCLUSIONS: Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790).

11.
World J Gastroenterol ; 29(44): 5919-5934, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38111505

RESUMEN

BACKGROUND: The role of Tousled-like kinase 1 (TLK1) in in gastric cancer (GC) remains unclear. AIM: To investigate the expression, biological function, and underlying mechanisms of TLK1 in GC. METHODS: We measured TLK1 protein expression levels and localized TLK1 in GC cells and tissues by western blot and immunofluorescence, respectively. We transfected various GC cells with lentiviruses to create TLK1 overexpression and knockdown lines and established the functional roles of TLK1 through in vitro colony formation, 5-ethynyl-2`-deoxyuridine, and Transwell assays as well as flow cytometry. We applied bioinformatics to elucidate the signaling pathways associated with TLK1. We performed in vivo validation of TLK1 functions by inducing subcutaneous xenograft tumors in nude mice. RESULTS: TLK1 was significantly upregulated in GC cells and tissues compared to their normal counterparts and was localized mainly to the nucleus. TLK1 knockdown significantly decreased colony formation, proliferation, invasion, and migration but increased apoptosis in GC cells. TLK1 overexpression had the opposite effects. Bioinformatics revealed, and subsequent experiments verified, that the tumor growth factor-beta signaling pathway was implicated in TLK1-mediated GC progression. The in vivo assays confirmed that TLK1 promotes tumorigenesis in GC. CONCLUSION: The findings of the present study indicated that TLK1 plays a crucial role in GC progression and is, therefore, promising as a therapeutic target against this disease.


Asunto(s)
Neoplasias Gástricas , Animales , Ratones , Humanos , Neoplasias Gástricas/patología , Ratones Desnudos , Transducción de Señal , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proliferación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Proteínas Serina-Treonina Quinasas/metabolismo
12.
Sensors (Basel) ; 23(20)2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37896595

RESUMEN

This paper studies the AWC (Active Wafer Centering) algorithm for the movement control and wafer calibration of the handling robot in semiconductor manufacturing to prevent wafer surface contact and contamination during the transfer process. The mechanical and software architecture of the wafer-handling robot is analyzed first, which is followed by a description of the experimental platform for semiconductor manufacturing methods. Secondly, the article utilizes the geometric method to analyze the kinematics of the semiconductor robot, and it decouples the motion control of the robot body from the polar coordinates and joint space. The wafer center position is calibrated using the generalized least-square inverse method for AWC correction. The AWC algorithm is divided into calibration, deviation correction, and retraction detection. These are determined by analyzing the robot's wafer calibration process. In conclusion, the semiconductor robot's motion control and AWC algorithm are verified through experiments for correctness, feasibility, and effectiveness. After the wafer correction, the precision of AWC is <± 0.15 mm, which meets the requirements for transferring robot wafers.

13.
ISME J ; 17(10): 1693-1704, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37479887

RESUMEN

Beauveria bassiana is a soil fungus that parasitizes a large number of arthropod species, including numerous crop pests, causing white muscardine disease and is therefore used as a biological insecticide. However, some insects, such as the cabbage aphid (Brevicoryne brassicae), defend themselves chemically by sequestering dietary pro-toxins (glucosinolates) from their Brassicales host plants. Glucosinolates are accumulated by cabbage aphids and activated to form toxic isothiocyanates when under attack. While isothiocyanate formation protects aphids against most attackers, B. bassiana is still able to infect the cabbage aphid under natural conditions. We therefore investigated how this fungus is able to circumvent the chemical defense system of the cabbage aphid. Here, we describe how B. bassiana infection activates the cabbage aphid defense system, but the resulting toxins are metabolized by B. bassiana via the mercapturic acid pathway, of which the first step is catalyzed by glutathione-S-transferases of low substrate specificity. This detoxification pathway enhances B. bassiana growth when isothiocyanates are present in natural concentrations, and so appears to be an important factor in fungal parasitization of these chemically defended aphids.


Asunto(s)
Áfidos , Beauveria , Insecticidas , Animales , Glucosinolatos , Insectos , Isotiocianatos
14.
Phytomedicine ; 114: 154772, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37015187

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is a common malignancy that can significantly diminish patients' quality of life. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (AC) is an ancient Chinese medicinal combination used for the treatment of CRC. However, the core ingredients and targets involved in regulating lipid and amino acid metabolism in CRC remain unknown. We aimed to explore the key components and pharmacological mechanisms of AC in the treatment of CRC through a comprehensive analysis of network metabolomics, network pharmacology, molecular docking, and biological methods. METHODS: Ultra-performance liquid chromatography/mass spectrometry (MS) was used for quality control. Gas chromatography/MS and liquid chromatography/MS were used to detect metabolites in the feces and serum of CRC mice. A network pharmacology approach and molecular docking were used to explore the potential genes involved in the CRC-target-component network. The effect of AC on tumor immunity was investigated using flow cytometry and polymerase chain reaction. RESULTS: AC, high-dose AC, and 5-fluorouracil treatment reduced liver metastasis and tumor mass. Compared with the CRC group, 2 amino acid metabolites and 14 lipid metabolites (LPC, PC, PE) were upregulated and 15 amino acid metabolites and 9 lipid metabolites (TG, PE, PG, 12-HETE) were downregulated. Subsequently, through network analysis, four components and six hub genes were identified for molecular docking. AC can bind to ALDH1B1, ALDH2, CAT, GOT2, NOS3, and ASS1 through beta-Elemene, canavanine, betaine, and chrysanthemaxanthin. AC promoted the responses of M1 macrophages and down-regulated the responses of M2 macrophages, Treg cells, and the gene expression of related factors. CONCLUSION: Our research showed that AC effectively inhibited the growth and metastasis of tumors and regulated metabolism and immunity in a CRC mouse model. Thus, AC may be an effective alternative treatment option for CRC.


Asunto(s)
Neoplasias Colorrectales , Medicamentos Herbarios Chinos , Ratones , Animales , Astragalus propinquus/química , Curcuma/química , Simulación del Acoplamiento Molecular , Calidad de Vida , Metabolómica/métodos , Aminoácidos , Neoplasias Colorrectales/patología , Lípidos , Medicamentos Herbarios Chinos/farmacología
15.
Chem Biodivers ; 20(4): e202300214, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36896990

RESUMEN

A new cembranolide, namely, sinupendunculide A (1), along with eight known related compounds (2-9), was isolated from the South China Sea Soft coral Sinularia pendunculata. The structure of sinupendunculide A (1) was established by extensive spectroscopic analysis and X-ray diffraction experiments. In a bioassay, anti-colorectal cancer (CRC) activity was performed, and the results showed that several compounds exhibited cytotoxicity against RKO cells, and a preliminary structure-activity relationship was analysed. Meanwhile, the most effective compound 7 was proven to increase reactive oxygen species levels, which promoted cell apoptosis and inhibited cell proliferation.


Asunto(s)
Antozoos , Antineoplásicos , Diterpenos , Neoplasias , Animales , Antozoos/química , China , Diterpenos/farmacología , Diterpenos/química , Estructura Molecular , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/prevención & control
16.
Curr Cancer Drug Targets ; 23(4): 293-306, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35713129

RESUMEN

BACKGROUND: Novel therapeutic strategies are urgently required to improve clinical outcomes of gastric cancer (GC). KIF15 cooperates with KIF11 to promote bipolar spindle assembly and formation, which is essential for proper sister chromatid segregation. Therefore, we speculated that the combined inhibition of KIF11 and KIF15 might be an effective strategy for GC treatment. Hence, to test this hypothesis, we aimed to evaluate the combined therapeutic effect of KIF15 inhibitor KIF15- IN-1 and KIF11 inhibitor ispinesib in GC. METHODS: We validated the expression of KIF11 and KIF15 in GC tissues using immunohistochemistry and immunoblotting. Next, we determined the effects of KIF11 or KIF15 knockout on the proliferation of GC cell lines. Finally, we investigated the combined effects of the KIF11 and KIF15 inhibitors both in vitro and in vivo. RESULTS: KIF11 and KIF15 were overexpressed in GC tissues than in the adjacent normal tissues. Knockout of either KIF11 or KIF15 inhibited the proliferative and clonogenic abilities of GC cells. We found that the KIF15 knockout significantly increased ispinesib sensitivity in GC cells, while its overexpression showed the opposite effect. Further, using KIF15-IN-1 and ispinesib together had a synergistic effect on the antitumor proliferation of GC both in vitro and in vivo. CONCLUSION: This study shows that the combination therapy of inhibiting KIF11 and KIF15 might be an effective therapeutic strategy against gastric cancer.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Cinesinas/genética , Cinesinas/metabolismo , Benzamidas/farmacología , Quinazolinas , Línea Celular Tumoral
17.
Work ; 74(1): 129-136, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36214013

RESUMEN

BACKGROUND: The Indigenous workforce in Canada is challenged by a history of Euro-Canadian colonialism that has presented deleterious health outcomes, including those in the workplace. OBJECTIVE: The aim of this study was to describe the mental health of Indigenous workers in the workplace. METHODS: We used the Canadian Community Health Survey (CCHS) between 2015 to 2016. Data were analyzed using the Public Use Microdata Files to profile the workplace mental health characteristics of First Nation Canadians (n = 6,297) and Canadians (n = 84,155). We utilized secondary data analysis design. The analyses included descriptive statistics (e.g., means and standard deviations) of self-reported mood disorders (depression, bipolar, mania, dysthymia), anxiety (phobia, OCD, panic) and occupational factors (e.g., demographic, days off work due to an acute mental health condition, job type, and job stress) in indigenous peoples living off-reserve and other Aboriginal settlements in the provinces. RESULTS: We examined the indigenous cohort between the ages of 18-64 who were employed. The sample was 53.1% male, married (34.8%), and obtained a post-secondary diploma or university degree (57.9%). The study reported statistically significant gender and age differences across mood and anxiety disorders (p < 0.05), job stress (p < 0.05) and workload (p < 0.05). CONCLUSION: To the best of our knowledge, this is the first study to describe the work profile of indigenous populations in Canada across various occupational mental health (e.g., mood disorders, anxiety) and demographic (e.g., age, education attainment) outcomes.


Asunto(s)
Salud Mental , Estrés Laboral , Humanos , Masculino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Canadá/epidemiología , Lugar de Trabajo , Recursos Humanos
18.
Environ Pollut ; 315: 120328, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36202267

RESUMEN

Large quantities of lead/zinc (Pb/Zn) mine tailings were deposited at tailings impoundments without proper management, which have posed considerable risks to the local ecosystem and residents in mining areas worldwide. Therefore, the geochemical behaviors of potentially toxic elements (PTEs) in tailings were in-depth investigated in this study by a coupled use of batch kinetic tests, statistical analysis and mineralogical characterization. The results indicated that among these studied PTEs, Cd concentration fluctuated within a wide range of 0.83-6.91 mg/kg, and showed the highest spatial heterogeneity. The mean Cd concentrations generally increased with depth. Cd were mainly partitioned in the exchangeable and carbonate fractions. The release potential of PTEs from tailings was ranged as: Cd > Mn > Zn > Pb > As, Cd > Pb > Zn > Mn > As and Cd > Pb > Mn > Zn > As, respectively, under the assumed environmental scenarios, i.e. acid rain, vegetation restoration, human gastrointestinal digestion. The results from mineralogical characterization indicated that quartz, sericite, calcite and pyrite were typical minerals, cumulatively accounting for over 80% of the tailings. Sulfides (arsenopyrite, galena, and sphalerite), carbonates (calcite, dolomite, cerussite and kutnahorite), oxides (limonite) were identified as the most relevant PTEs-bearing phases, which significantly contributed to PTEs release from tailings. A combined result of statistical, geochemical and mineralogical approaches would be provided valuable information for the alteration characteristics and contaminant release of Pb/Zn mine tailings.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Humanos , Zinc/análisis , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Cadmio/análisis , Monitoreo del Ambiente/métodos , Ecosistema , Plomo/análisis , Carbonato de Calcio/análisis
20.
Food Chem ; 395: 133581, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-35777213

RESUMEN

Highland barley (HB) has become popular due to its nutritional benefits, and pearling as a necessary process that could broaden its applications. The influence of pearling on the composition, microstructure, water migration and cooking characteristics of HB was investigated. With different degrees of pearling (DOPs), the levels of nutritious components except for starch and ß-glucan, decreased, and the ß-glucan content gradually increased and reached a plateau when the DOP was over 15%. Pearling can significantly shorten the cooking time by removing different tissues, and removal of the pericarp layer had significant influence by reducing the cooking time by 17 min (i.e., HB with DOP 5%). From the result of Peleg model fitting and low-field nuclear magnetic resonance spectroscopy, the saturated water absorption of HB did not differ for a DOP 5% and above, and cooking mainly increased the amount of moderately bound water and added small amount of bound water.


Asunto(s)
Hordeum , beta-Glucanos , Culinaria , Hordeum/química , Almidón , Agua , beta-Glucanos/química
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