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1.
Sensors (Basel) ; 24(6)2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38544077

RESUMEN

In recent computer vision research, the pursuit of improved classification performance often leads to the adoption of complex, large-scale models. However, the actual deployment of such extensive models poses significant challenges in environments constrained by limited computing power and storage capacity. Consequently, this study is dedicated to addressing these challenges by focusing on innovative methods that enhance the classification performance of lightweight models. We propose a novel method to compress the knowledge learned by a large model into a lightweight one so that the latter can also achieve good performance in few-shot classification tasks. Specifically, we propose a dual-faceted knowledge distillation strategy that combines output-based and intermediate feature-based methods. The output-based method concentrates on distilling knowledge related to base class labels, while the intermediate feature-based approach, augmented by feature error distribution calibration, tackles the potential non-Gaussian nature of feature deviations, thereby boosting the effectiveness of knowledge transfer. Experiments conducted on MiniImageNet, CIFAR-FS, and CUB datasets demonstrate the superior performance of our method over state-of-the-art lightweight models, particularly in five-way one-shot and five-way five-shot tasks.

2.
mBio ; : e0249223, 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37921493

RESUMEN

New approaches for combating microbial infections are needed. One strategy for disrupting pathogenesis involves developing compounds that interfere with bacterial virulence. A critical molecular determinant of virulence for Gram-negative bacteria are efflux pumps of the resistance-nodulation-division family, which includes AcrAB-TolC. We previously identified small molecules that bind AcrB, inhibit AcrAB-TolC, and do not appear to damage membranes. These efflux pump modulators (EPMs) were discovered in an in-cell screening platform called SAFIRE (Screen for Anti-infectives using Fluorescence microscopy of IntracellulaR Enterobacteriaceae). SAFIRE identifies compounds that disrupt the growth of a Gram-negative human pathogen, Salmonella enterica serotype Typhimurium (S. Typhimurium), in macrophages. We used medicinal chemistry to iteratively design ~200 EPM35 analogs and test them for activity in SAFIRE, generating compounds with nanomolar potency. Analogs were demonstrated to bind AcrB in a substrate binding pocket by cryo-electron microscopy. Despite having amphipathic structures, the EPM analogs do not disrupt membrane voltage, as monitored by FtsZ localization to the cell septum. The EPM analogs had little effect on bacterial growth in standard Mueller Hinton Broth. However, under broth conditions that mimic the micro-environment of the macrophage phagosome, acrAB is required for growth, the EPM analogs are bacteriostatic, and the EPM analogs increase the potency of antibiotics. These data suggest that under macrophage-like conditions, the EPM analogs prevent the export of a toxic bacterial metabolite(s) through AcrAB-TolC. Thus, compounds that bind AcrB could disrupt infection by specifically interfering with the export of bacterial toxic metabolites, host defense factors, and/or antibiotics.IMPORTANCEBacterial efflux pumps are critical for resistance to antibiotics and for virulence. We previously identified small molecules that inhibit efflux pumps (efflux pump modulators, EPMs) and prevent pathogen replication in host cells. Here, we used medicinal chemistry to increase the activity of the EPMs against pathogens in cells into the nanomolar range. We show by cryo-electron microscopy that these EPMs bind an efflux pump subunit. In broth culture, the EPMs increase the potency (activity), but not the efficacy (maximum effect), of antibiotics. We also found that bacterial exposure to the EPMs appear to enable the accumulation of a toxic metabolite that would otherwise be exported by efflux pumps. Thus, inhibitors of bacterial efflux pumps could interfere with infection not only by potentiating antibiotics, but also by allowing toxic waste products to accumulate within bacteria, providing an explanation for why efflux pumps are needed for virulence in the absence of antibiotics.

3.
bioRxiv ; 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37786697

RESUMEN

New approaches for combatting microbial infections are needed. One strategy for disrupting pathogenesis involves developing compounds that interfere with bacterial virulence. A critical molecular determinant of virulence for Gram-negative bacteria are efflux pumps of the resistance-nodulation-division (RND) family, which includes AcrAB-TolC. We previously identified small molecules that bind AcrB, inhibit AcrAB-TolC, and do not appear to damage membranes. These efflux pump modulators (EPMs) were discovered in an in-cell screening platform called SAFIRE (Screen for Anti-infectives using Fluorescence microscopy of IntracellulaR Enterobacteriaceae). SAFIRE identifies compounds that disrupt the growth of a Gram-negative human pathogen, Salmonella enterica serotype Typhimurium (S. Typhimurium) in macrophages. We used medicinal chemistry to iteratively design ~200 EPM35 analogs and test them for activity in SAFIRE, generating compounds with nanomolar potency. Analogs were demonstrated to bind AcrB in a substrate binding pocket by cryo-electron microscopy (cryo-EM). Despite having amphipathic structures, the EPM analogs do not disrupt membrane voltage, as monitored by FtsZ localization to the cell septum. The EPM analogs had little effect on bacterial growth in standard Mueller Hinton Broth. However, under broth conditions that mimic the micro-environment of the macrophage phagosome, acrAB is required for growth, the EPM analogs are bacteriostatic, and increase the potency of antibiotics. These data suggest that under macrophage-like conditions the EPM analogs prevent the export of a toxic bacterial metabolite(s) through AcrAB-TolC. Thus, compounds that bind AcrB could disrupt infection by specifically interfering with the export of bacterial toxic metabolites, host defense factors, and/or antibiotics.

4.
PeerJ ; 11: e16270, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37842034

RESUMEN

The aim of this study was to investigate the association between physical activity (PA), problematic smartphone use (PSU), and burnout, as well as to identify whether there is a mediating role for PSU. We recruited 823 college students (Mage = 18.55, SD = 0.83) from Wuhan, China, in December 2022, including 499 males and 324 females. Demographic information, the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Smartphone Addiction Scale-Short Version (SAS-SV), and the Maslach Burnout Inventory-Student Survey (MBI-SS) were used for assessments. Pearson correlation analysis showed that PA was significantly associated with PSU (r = -0.151, p < 0.001), PSU was significantly associated with burnout (r = 0.421, p < 0.001), and the association between PA and burnout was not statistically significant (r = -0.046, p > 0.05). The results of the mediation model test showed that PA could not predict burnout directly; it instead predicted burnout entirely indirectly through PSU. Furthermore, PSU mediated the predictive effect of PA on exhaustion and cynicism. In conclusion, there is no direct connection between PA levels and burnout. PA indirectly affects burnout through PSU, but does not fully apply to the three different dimensions of exhaustion, cynicism, and professional efficacy.


Asunto(s)
Agotamiento Profesional , Teléfono Inteligente , Masculino , Femenino , Humanos , Adolescente , Psicometría , Agotamiento Psicológico/epidemiología , Estudiantes , Agotamiento Profesional/epidemiología , Ejercicio Físico
5.
Nat Commun ; 14(1): 6297, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37813902

RESUMEN

Conjugated polymers are generally featured with low structural order due to their aromatic and irregular structural units, which limits their light absorption and charge mobility in organic solar cells. In this work, we report a conjugated molecule INMB-F that can act as a molecular bridge via electrostatic force to enhance the intermolecular stacking of BDT-based polymer donors toward efficient and stable organic solar cells. Molecular dynamics simulations and synchrotron X-ray measurements reveal that the electronegative INMB-F adsorb on the electropositive main chain of polymer donors to increase the donor-donor interactions, leading to enhanced structural order with shortened π-π stacking distance and consequently enhanced charge transport ability. Casting the non-fullerene acceptor layer on top of the INMB-F modified donor layer to fabricate solar cells via layer-by-layer deposition evidences significant power conversion efficiency boosts in a range of photovoltaic systems. A power conversion efficiency of 19.4% (certified 18.96%) is realized in PM6/L8-BO binary devices, which is one of the highest reported efficiencies of this material system. The enhanced structural order of polymer donors by INMB-F also leads to a six-fold enhancement of the operational stability of PM6/L8-BO organic solar cells.

6.
Proc Natl Acad Sci U S A ; 120(39): e2306480120, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37725645

RESUMEN

Kinesin-5 motor proteins play essential roles during mitosis in most organisms. Their tetrameric structure and plus-end-directed motility allow them to bind to and move along antiparallel microtubules, thereby pushing spindle poles apart to assemble a bipolar spindle. Recent work has shown that the C-terminal tail is particularly important to kinesin-5 function: The tail affects motor domain structure, ATP hydrolysis, motility, clustering, and sliding force measured for purified motors, as well as motility, clustering, and spindle assembly in cells. Because previous work has focused on presence or absence of the entire tail, the functionally important regions of the tail remain to be identified. We have therefore characterized a series of kinesin-5/Cut7 tail truncation alleles in fission yeast. Partial truncation causes mitotic defects and temperature-sensitive growth, while further truncation that removes the conserved BimC motif is lethal. We compared the sliding force generated by cut7 mutants using a kinesin-14 mutant background in which some microtubules detach from the spindle poles and are pushed into the nuclear envelope. These Cut7-driven protrusions decreased as more of the tail was truncated, and the most severe truncations produced no observable protrusions. Our observations suggest that the C-terminal tail of Cut7p contributes to both sliding force and midzone localization. In the context of sequential tail truncation, the BimC motif and adjacent C-terminal amino acids are particularly important for sliding force. In addition, moderate tail truncation increases midzone localization, but further truncation of residues N-terminal to the BimC motif decreases midzone localization.


Asunto(s)
Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Cinesinas/genética , Huso Acromático/genética , Microtúbulos , Alelos , Ciclo Celular , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética
7.
ACS Appl Mater Interfaces ; 15(35): 41647-41655, 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37621155

RESUMEN

Interfacial modification is crucial for achieving efficient and stable organic solar cells (OSCs). Herein, an N,N-dimethylformamide (DMF) solution-cast poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) interlayer was applied to enhance the efficiency and stability of a range of OSCs, and the underlying mechanism was revealed via morphological and device physics studies. DMF rinse during the P(VDF-TrFE) interlayer casting process strengthens π-π stacking of the active layer with fibril aggregation, optimized phase separation, and vertical component distribution, while the P(VDF-TrFE) interlayer with rich diploes contributes to increased surface potential and internal electric field. The synergistic effect of the P(VDF-TrFE) interlayer and DMF rinse increases the PCEs of PM6:IT-4F, PM6:C5-16, and PM6:L8-BO OSCs from 12.7, 17.9, and 18.2% to 13.1, 18.7, and 18.8%, respectively. Additionally, OSCs containing the P(VDF-TrFE) interlayer also showed improved storage stability.

8.
Adv Mater ; 35(41): e2304921, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37468168

RESUMEN

Organic semiconductors are generally featured with low structure order in solid-state films, which leads to low charge-transport mobility and strong charge recombination in their photovoltaic devices. In this work, a "polycrystal-induced aggregation" strategy orders the polymer donor (PM6) and non-fullerene acceptor (L8-BO) molecules during solution casting with the assistance of PM6 polycrystals that are incubated through a vapor diffusion method, toward improved solar cell efficiency with either thin or thick photoactive layers. These PM6 polycrystals are redissolved in chloroform to prepare PM6 pre-aggregates (PM6-PA), and further incorporated into the conventional PM6:L8-BO blend solutions, which is found to prolong the molecular organization process and enhance the aggregation of both the PM6 and the L8-BO components. As the results, with the assistance of 10% PM6-PA, PM6:L8-BO solar cell devices obtain power conversion efficiencies (PCEs) from 18.0% and 16.2% to 19.3% and 17.2% with a 100 nm-thick and 300 nm-thick photoactive layer, respectively.

9.
bioRxiv ; 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37205432

RESUMEN

Kinesin-5 motor proteins play essential roles during mitosis in most organisms. Their tetrameric structure and plus-end-directed motility allow them to bind to and move along antiparallel microtubules, thereby pushing spindle poles apart to assemble a bipolar spindle. Recent work has shown that the C-terminal tail is particularly important to kinesin-5 function: the tail affects motor domain structure, ATP hydrolysis, motility, clustering, and sliding force measured for purified motors, as well as motility, clustering, and spindle assembly in cells. Because previous work has focused on presence or absence of the entire tail, the functionally important regions of the tail remain to be identified. We have therefore characterized a series of kinesin-5/Cut7 tail truncation alleles in fission yeast. Partial truncation causes mitotic defects and temperature-sensitive growth, while further truncation that removes the conserved BimC motif is lethal. We compared the sliding force generated by cut7 mutants using a kinesin-14 mutant background in which some microtubules detach from the spindle poles and are pushed into the nuclear envelope. These Cut7-driven protrusions decreased as more of the tail was truncated, and the most severe truncations produced no observable protrusions. Our observations suggest that the C-terminal tail of Cut7p contributes to both sliding force and midzone localization. In the context of sequential tail truncation, the BimC motif and adjacent C-terminal amino acids are particularly important for sliding force. In addition, moderate tail truncation increases midzone localization, but further truncation of residues N terminal to the BimC motif decreases midzone localization.

10.
J Cell Sci ; 136(5)2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36655493

RESUMEN

Kinesin-5 motors are essential to separate mitotic spindle poles and assemble a bipolar spindle in many organisms. These motors crosslink and slide apart antiparallel microtubules via microtubule plus-end-directed motility. However, kinesin-5 localization is enhanced away from antiparallel overlaps. Increasing evidence suggests this localization occurs due to bidirectional motility or trafficking. The purified fission-yeast kinesin-5 protein Cut7 moves bidirectionally, but bidirectionality has not been shown in cells, and the function of the minus-end-directed movement is unknown. Here, we characterized the motility of Cut7 on bipolar and monopolar spindles and observed movement toward both plus- and minus-ends of microtubules. Notably, the activity of the motor increased at anaphase B onset. Perturbations to microtubule dynamics only modestly changed Cut7 movement, whereas Cut7 mutation reduced movement. These results suggest that the directed motility of Cut7 contributes to the movement of the motor. Comparison of the Cut7 mutant and human Eg5 (also known as KIF11) localization suggest a new hypothesis for the function of minus-end-directed motility and spindle-pole localization of kinesin-5s.


Asunto(s)
Proteínas de Schizosaccharomyces pombe , Anafase , Cinesinas/genética , Cinesinas/metabolismo , Microtúbulos/metabolismo , Mitosis , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Huso Acromático/metabolismo
11.
Adv Mater ; 35(6): e2208211, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36418914

RESUMEN

The structural order and aggregation of non-fullerene acceptors (NFA) are critical toward light absorption, phase separation, and charge transport properties of their photovoltaic blends with electron donors, and determine the power conversion efficiency (PCE) of the corresponding organic solar cells (OSCs). In this work, the fibrillization of small molecular NFA L8-BO with the assistance of fused-ring solvent additive 1-fluoronaphthalene (FN) to substantially improve device PCE is demonstrated. Molecular dynamics simulations show that FN attaches to the backbone of L8-BO as the molecular bridge to enhance the intermolecular packing , inducing 1D self-assembly of L8-BO into fine fibrils with a compact polycrystal structure. The L8-BO fibrils are incorporated into a pseudo-bulk heterojunction (P-BHJ) active layer with D18 as a donor, and show enhanced light absorption, charge transport, and collection properties, leading to enhanced PCE from 16.0% to an unprecedented 19.0% in the D18/L8-BO binary P-BHJ OSC, featuring a high fill factor of 80%. This work demonstrates a strategy for fibrillating NFAs toward the enhanced performance of OSCs.

12.
Front Aging Neurosci ; 14: 1040828, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36570542

RESUMEN

Purpose: This study aimed to examine whether aerobic exercise exerts mood-modulating effects through an estrogen signaling mechanism. Method: The experiment was divided into two parts. The first part is to compare the three modeling methods to obtain the most obvious method of depression-like phenotype for further study in the second part. The first part of ovariectomized rats (age, 13 weeks) was tested when rats were 14 or 22 weeks old or in the sixth week after 3 weeks of chronic restraint stress. The second part was to treat the animals with the most obvious depression-like phenotype in different ways, placebo treatment or estradiol (E2) replacement therapy was administered, aerobic training, or estrogen receptor antagonist treatment. The cognitive (Barnes maze and 3-chamber social tests), anxiety-like (open-field and elevated plus maze tests) and depression-like (sucrose preference and forced swim tests) behaviors of rats in both parts were analyzed to study the effects of estrogen depletion and aerobic exercise. Results: Rats did not develop depressive symptoms immediately after ovariectomy, however, the symptoms became more pronounced with a gradual decrease in ovarian hormone levels. Compared with the placebo or control groups, the exercise and E2 groups showed improved performance in all behavioral test tasks, and the antidepressant effects of aerobic exercise were comparable to those of estrogen. Moreover, the estrogen receptor antagonist has markedly inhibited the antidepressant effects of aerobic exercise. Conclusion: Estrogen receptors may mediate the antidepressant effects of aerobic exercise. In addition, an increasingly fragile ovarian hormonal environment may underlies chronic restraint stress-induced depression.

13.
Front Psychol ; 13: 1006007, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36425826

RESUMEN

Inconsistency between intention and behavior is very common in daily life. This study explored the intention-behavior relationship in exercise, focusing on the mediating effect of action planning and the moderating effects of habit strength and gender. For the purpose of providing theoretical reference for the implementation of intervention strategies in the volitional phase, a total of 489 college students (M-age = 20.61, 57.46% female) from Hubei Province, China, were recruited to complete the questionnaire at two time points. The findings showed that exercise intention could positively predict exercise behavior via the mediating effect of action planning, with the mediating effect accounting for 48.52% of the total effect. The predictive effect of action planning × habit strength interaction on exercise behavior was statistically significant. As individuals' levels of habitual strength increased, so did the relationship between action plans and exercise behavior. The action planning-exercise behavior relationship was stronger in males than in females. In summary, action planning is a very important predictor of the post-intentional phase and has many advantages. For individuals whose exercise has become habitualized, forming a plan is not counterproductive and can still promote more exercise rather than in a mutually compensating manner.

14.
Front Aging Neurosci ; 14: 981002, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36092802

RESUMEN

Background: Emerging evidence suggests that exercise is a simple and effective method for maintaining brain function. Aims: This review evaluates the effects of five physical exercises, including aerobic training (AT), high-intensity interval training (HIIT), combined training (CT), resistance training (RT), and AT+RT, on the serum level of brain-derived neurotrophic factor (BDNF) in healthy and non-healthy populations. Methods: We searched CNKI, PubMed, Embase, Scopus, Medline, Web of Science, and Cochrane Library databases to review randomized controlled studies on exercise interventions for BDNF. Quantitative merging analysis of the resulting data using Bayesian network meta-analysis. Results: The screening and exclusion of the searched literature resulted in the inclusion of 39 randomized controlled trials containing 5 exercise interventions with a total of 2031 subjects. The AT, RT, AT+RT, HIIT, and CT groups (intervention groups) and the CG group (conventional control group) were assigned to 451, 236, 102, 84, 293, and 865 subjects, respectively. The Bayesian network meta-analysis ranked the effect of exercise on BDNF level improvement in healthy and non-healthy subjects as follows: RT > HIIT > CT > AT+RT > AT > CG. Better outcomes were observed in all five intervention groups than in the CG group, with RT having the most significant effect [MD = 3.11 (0.33, 5.76), p < 0.05]. Conclusions: RT at moderate intensity is recommended for children and older adults in the case of exercise tolerance and is effective in maintaining or modulating BDNF levels for promoting brain health. Systematic Review Registration: https://inplasy.com, INPLASY202250164.

15.
J Virol Methods ; 151(1): 24-9, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18499276

RESUMEN

Reverse transcriptase polymerase chain reaction (RT-PCR) for the diagnosis of rabbit hemorrhagic disease virus (RHDV) was developed by examining sensitivity and specificity. Samples from rabbits infected with rabbit hemorrhagic disease (RHD) were examined to investigate the distribution of the virus in the body. The results showed that the RT-PCR method had good specificity. The sensitivity of the RT-PCR was 1 x 10(4) times higher than that of the hemagglutination assay (HA). RT-PCR was able to detect RHDV in all viscera, but not in feces. In the second part of the study, in order to investigate the prevalence of RHDV, 400 meat samples from the Entry-exit Inspection and Quarantine Bureau and 512 nasal secretion samples from rabbits in three provinces of China were collected and tested by RT-PCR. The results showed significant differences in the prevalence of RHDV in rabbits of different ages, but no significant differences among different provinces and years. Some random isolates were sequenced and compared. The homology of sequences among three new isolates and other isolates ranged between 93.7% and 99.6%. It is recommended that RHD vaccine should be used in China to protect rabbits against RHDV.


Asunto(s)
Infecciones por Caliciviridae , Virus de la Enfermedad Hemorrágica del Conejo/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Animales , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/virología , China/epidemiología , Pruebas de Hemaglutinación , Virus de la Enfermedad Hemorrágica del Conejo/genética , Carne/virología , Filogenia , Prevalencia , Conejos , Sensibilidad y Especificidad , Organismos Libres de Patógenos Específicos , Vísceras/virología
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