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Given the serious neurological complications and deaths associated with enterovirus 71 (EV71) infection, there is an urgent need to develop effective antivirals against this viral infection. In this study, we demonstrated that two Cathelicidin-derived peptides, LL-18 and FF-18 were more potent against EV71 infection than the parent peptide LL-37, which is the mature and processed form of Cathelicidin. These peptides could directly bind to the EV71 virus particles, but not to coxsackievirus, indicative of their high specificity. The binding of peptides with the virus surface occupied the viral canyon region in a way that could block virus-receptor interactions and inhibit viral uncoating. In addition, these peptide analogues could also relieve the deleterious effect of EV71 infection in vivo. Therefore, Cathelicidin-derived peptides might be excellent candidates for further development of antivirals to treat EV71 infection.

Honeybees play a major role in crop pollination, which supports the agricultural economy and international food supply. The colony health of honeybees is threatened by the parasitic mite Varroa destructor, which inflicts physical injury on the hosts and serves as the vector for variable viruses. Recently, it shows that V. destructor may also transmit bacteria through the feeding wound, yet it remains unclear whether the invading bacteria can exhibit pathogenicity to the honeybees. Here, we incidentally isolate Enterococcus faecalis, one of the most abundant bacteria in Varroa mites, from dead bees during our routine generation of microbiota-free bees in the lab. In vivo tests show that E. faecalis is only pathogenic in Apis mellifera but not in Apis cerana. The expression of antimicrobial peptide genes is elevated following infection in A. cerana. The gene-based molecular evolution analysis identifies positive selection of genes encoding Späetzle 4 (Spz4) in A. cerana, a signaling protein in the Toll pathway. The amino acid sites under positive selection are related to structural changes in Spz4 protein, suggesting improvement of immunity in A. cerana. The knock-down of Spz4 in A. cerana significantly reduces the survival rates under E. faecalis challenge and the expression of antimicrobial peptide genes. Our results indicate that bacteria associated with Varroa mites are pathogenic to adult bees, and the positively selected gene Spz4 in A. cerana is crucial in response to this mite-related pathogen.

Recently, Wang and Theeuwes used the additional singleton task and showed that attentional capture was reduced for the location that was likely to contain a distractor [1]. It is argued that due to statistical learning, the location that was likely to contain a distractor was suppressed relative to all other locations. The current study replicated these findings and by adding a search-probe condition, we were able to determine the initial distribution of attentional resources across the visual field. Consistent with a space-based resource allocation ("biased competition") model, it was shown that the representation of a probe presented at the location that was likely to contain a distractor was suppressed relative to other locations. Critically, the suppression of this location resulted in more attention being allocated to the target location relative to a condition in which the distractor was not suppressed. This suggests that less capture by the distractor results in more attention being allocated to the target. The results are consistent with the view that the location that is likely to contain a distractor is suppressed before display onset, modulating the first feed-forward sweep of information input into the spatial priority map.

The ambient temperature and relative humidity affect the metabolic and physiological responses of bees, thus affecting their life activities. However, the physiological changes in bee due to high temperature and high humidity remain poorly understood. In this study, we explored the effects of higher temperature and humidity on the epiphysiology of bees by evaluating the survival, tolerance and body water loss in two bee species (Apis cerana and Apis mellifera). We also evaluated the changes in the activity of antioxidant and detoxification enzymes in their body. We observed that under higher temperature and humidity conditions, the survival rate of A. mellifera was higher than that of A. cerana. On the other hand, a comparison of water loss between the two species revealed that A. mellifera lost more water. However, under extremely high temperature conditions, A. cerana was more tolerant than A. mellifera. Moreover, under higher temperature and humidity conditions, the activity of antioxidant and detoxification enzymes in bees was significantly increased. Overall, these results suggest that high temperatures can adversely affect bees. They not only affect the survival and water loss, but also stimulate oxidative stress in bees. However, unlike our previous understanding, high humidity can also adversely affect bees, although its effects are lower than that of temperature.

Chlorimuron-ethyl and atrazine are two herbicides with long half-lives in soil; their long-term and excessive application has led to a series of environmental problems. In this study, the strains Chenggangzhangella methanolivorans CHL1 and Arthrobacter sp. ART1 were combined and used for the remediation of chlorimuron-ethyl, atrazine and combined contaminated soils in a microcosm experiment. Changes in chlorimuron-ethyl and atrazine concentrations in soils were monitored, and variations in the soil microbial community were studied by phospholipid fatty acid (PLFA) analysis. The two inoculated degrading strains accelerated the degradation of chlorimuron-ethyl and atrazine in soil, especially in the combined contaminated soil. Addition of the two herbicides and their combination generally decreased the concentrations of total PLFAs, total bacterial PLFAs, Gram-negative and Gram-positive bacterial PLFAs and Shannon-Wiener indices, and changed microbial community composition, whilst stimulating fungal PLFA concentrations. In addition, the combined herbicide treatment had more impact on microbial biomass than the single herbicide treatments. Inoculation treatments significantly relieved the effects of herbicides on soil microbial biomass, diversity and community structure. This study demonstrated that strains CHL1 and ATR1 have the potential to remediate chlorimuron-ethyl, atrazine and combined contaminated soils, and provided valuable information for remediation of chlorimuron-ethyl, atrazine and combined contaminated soils in situ.

To evaluate the association of acromial morphology and subacromial impingement.Bilateral shoulder computed tomography was performed in 138 patients who received shoulder arthroscopy. Measured parameters included: acromial tilt (AT), modified acromial tilt (mAT), acromial slope (AS), acromiohumeral interval (AHI), lateral acromial angle (LAA), acromial index (AI), critical shoulder angle (CSA), acromial anterior protrusion (AAP), and acromial inferior protrusion (AIP). Acromial morphological characteristics were compared between groups. Side-to-side differences were assessed between affected and non-affected shoulders. Intra- and inter-observer agreements for each parameter were calculated.AT (25.90 vs. 29.41°), mAT (18.88 vs. 22.64°), and AHI (5.46 vs. 6.47 mm) were significantly smaller in impinged patients. The impingement group demonstrated significantly larger AI (63.50 vs. 59.84%), CSA (31.78 vs. 28.74°), AAP (7.13 vs. 5.32 mm), and AIP (5.51 vs. 4.04 mm). Regarding side-to-side comparison, the acromial morphology was significantly different between the affected and non-affected shoulders in impinged patients, while the difference was slight and insignificant in control patients. All, except AS and LAA, measured parameters demonstrated good intra- and inter-observer agreements.Three-dimensional reconstructed CT scan is a reliable method to measure shoulder morphology. The acromial morphological variation is related with sub acromial impingement, however, the causal relationship of them should be further explored.

Microbial communities play critical roles in soil nitrogen (N) cycle; however, we have limited understanding of the distribution of N-cycling microbial groups in deeper soil horizons. In this study, we used quantitative PCR to characterize the changes of microbial populations (16S rRNA and 18S rRNA) and five key N-cycling gene abundances involved in N fixation (nifH), ammonia oxidation (amoA) by ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA), and nitrite reduction (nirS and nirK) along profiles (0-100 cm depth) of different paddy soils from three regions (Hailun, Changshu, Yingtan) across China from north to south. We found that most microbial and N-cycling functional genes significantly decreased with soil depth; however, AOA were enriched in deeper soil layers (20-40 cm). The abundances of microbial and N-cycling functional genes generally decreased by one to two orders of magnitude in the deeper horizons relative to topsoils. The AOA gene abundance was higher than that of AOB in the paddy soil profile, and the nirS and nirK abundances were dominant in topsoil and deeper soil, respectively. All N functional genes except AOA were more abundant in Changshu than Hailun and Yingtan. High abundances and low vertical changes of N-cycling genes in Changshu suggest more dynamic N-transformations in this region. Correlation analysis showed that soil properties and climate parameters had a significant relationship with N-cycling gene abundances. Moreover, the abundance of different N-cycling genes was affected by different environmental parameters, which should be studied further to explore their roles in N cycling for sustainable agriculture and environmental management.

Alarm communication is a key adaptation that helps social groups resist predation and rally defenses. In Asia, the world's largest hornet, Vespa mandarinia, and the smaller hornet, Vespa velutina, prey upon foragers and nests of the Asian honey bee, Apis cerana. We attacked foragers and colony nest entrances with these predators and provide the first evidence, in social insects, of an alarm signal that encodes graded danger and attack context. We show that, like Apis mellifera, A. cerana possesses a vibrational "stop signal," which can be triggered by predator attacks upon foragers and inhibits waggle dancing. Large hornet attacks were more dangerous and resulted in higher bee mortality. Per attack at the colony level, large hornets elicited more stop signals than small hornets. Unexpectedly, stop signals elicited by large hornets (SS large hornet) had a significantly higher vibrational fundamental frequency than those elicited by small hornets (SS small hornet) and were more effective at inhibiting waggle dancing. Stop signals resulting from attacks upon the nest entrance (SS nest) were produced by foragers and guards and were significantly longer in pulse duration than stop signals elicited by attacks upon foragers (SS forager). Unlike SS forager, SS nest were targeted at dancing and non-dancing foragers and had the common effect, tuned to hornet threat level, of inhibiting bee departures from the safe interior of the nest. Meanwhile, nest defenders were triggered by the bee alarm pheromone and live hornet presence to heat-ball the hornet. In A. cerana, sophisticated recruitment communication that encodes food location, the waggle dance, is therefore matched with an inhibitory/alarm signal that encodes information about the context of danger and its threat level.

We consider a cheap-talk setting that mimics the situation where an incumbent firm (the sender) is endowed with incentives to understate the true size of the market demand to two potential entrants (the receivers). Although our experimental data reveals that the senders' messages convey truthful information and this is picked up by the receivers, this overcommunication (relative to standard theoretical prediction) does not enhance efficient entry levels (and payoffs) to beyond what can be achieved without communication. The reason is that receivers fail to optimally translate the information received in their entry decision, possibly due to overcautiousness.

Although a growing number of empirical studies have revealed that activating mate-related motives might exert a specific set of consequences for human cognition and behaviors, such as attention and memory, little is known about whether mate-related motives affect self-regulated learning. The present study examined the effects of mate-related motives (mate-search and mate-guarding) on study-time allocation to faces varying in attractiveness. In two experiments, participants in mate-related priming conditions (Experiment 1: mate-search; Experiment 2: mate-guarding) or control conditions studied 20 female faces (10 highly attractive, 10 less attractive) during a self-paced study task, and then were given a yes/no face recognition task. The finding of Experiment 1 showed that activating a mate-search motive led the male participants to allocate more time to highly attractive female faces (i.e., perceived potential mates) than to less attractive ones. In Experiment 2, female participants in the mate-guarding priming condition spent more time studying highly attractive female faces (i.e., perceived potential rivals) than less attractive ones, compared to participants in the control condition. These findings illustrate the highly specific consequences of mate-related motives on study-time allocation, and highlight the value of exploring human cognition and motivation within evolutionary and self-regulated learning frameworks.

Long-term and excessive application of chlorimuron-ethyl has led to a series of environmental problems. Strain Hansschlegelia sp. CHL1, a highly efficient chlorimuron-ethyl degrading bacterium isolated in our previous study, was employed in the current soil bioremediation study. The residues of chlorimuron-ethyl in soils were detected, and the changes of soil microbial communities were investigated by phospholipid fatty acid (PLFA) analysis. The results showed that strain CHL1 exhibited significant chlorimuron-ethyl degradation ability at wide range of concentrations between 10μg kg-1 and 1000μg kg-1. High concentrations of chlorimuron-ethyl significantly decreased the total concentration of PLFAs and the Shannon-Wiener indices and increased the stress level of microbes in soils. The inoculation with strain CHL1, however, reduced the inhibition on soil microbes caused by chlorimuron-ethyl. The results demonstrated that strain CHL1 is effective in the remediation of chlorimuron-ethyl-contaminated soil, and has the potential to remediate chlorimuron-ethyl contaminated soils in situ.

A potential association between diabetes and Guillain-Barré syndrome (GBS) has been indicated by a few case studies. We retrospectively analyzed the clinical features of a large cohort of GBS patients to explore the relationship between the level of fasting plasma glucose (FPG) obtained in the acute phase at admission and the severity of GBS.Three hundred and four GBS patients were divided into two groups, one with normal FPG and the other with high FPG levels according to the international standards of FPG.The GBS disability scale score was positively, the Medical Research Council (MRC) sum score was negatively correlated to the level of FPG, but not to blood HBA1c or CSF glucose concentrations. A relatively higher FPG level was observed in older and younger GBS patients, and more often in those with cranial nerve involvement, autonomic deficit, dyspnea and ventilator dependence than in patients without these clinical characteristics. Importantly, higher levels of FPG at admission were associated with poorer short-term prognosis measured by the MRC sum score and the GBS disability scale at discharge.Our data demonstrates that FPG in the acute phase of GBS correlates with the severity of GBS and may predict the short-term prognosis of GBS.

PurposeTo investigate the associations of single nucleotide polymorphisms (SNPs) of three genes (IL-12B, IL-12Rβ1 and IL-12Rβ2) in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.MethodsA total of 806 BD cases, 820 VKH patients, and 1600 healthy controls were involved in this study. The first investigation included 400 BD patients, 400 VKH cases, and 600 healthy individuals. A second confirmatory study included a separate set of 406 BD patients, 420 VKH cases and another 1000 normal controls. Genotyping was carried out by PCR-restriction fragment length polymorphism assay and results were validated by using direct sequencing. The χ2 test was performed to compare the allele and genotype frequencies between cases and healthy controls.ResultsThis study comprised two phases. In the first phase study, a significantly increased frequency of the rs3212227/IL-12B genotype CC and C allele was found in BD patients as compared to controls (Bonferroni corrected p value (pc) = 0.009, OR 1.8; pc = 0.024, OR 1.3, respectively). Moreover, the frequency of the C allele of rs3212227/IL-12B was also significantly increased in VKH patients (pc = 0.012, OR 1.3, 95% CI 1.1 to 1.6). No associations were found for the other seven tested SNPs either in BD or VKH disease. The second study as well as the combined data confirmed the significant association of rs3212227/IL-12B with BD (CC genotype: combined pc = 6.3×10(-7), OR = 1.8; C allele: combined pc = 2.0×10(-5), OR = 1.3, respectively) and the C allele frequency of rs3212227/IL-12B as the risk factor to VKH patients (combined pc = 2.5×10(-5), OR 1.3, 95% CI 1.2 to 1.5).ConclusionsOur study revealed that the IL-12B gene is involved both in the susceptibility to BD as well as VKH syndrome.

As the pandemic (H1N1) 2009 progressed, the Ministry of Health of China advised cases with mild symptoms to remain home for isolation and observation, which may have increased the risk for infection among other household members. Describing the transmission characteristics of this novel virus is indispensable to effectively controlling the spread of disease; thus, the aim of this study was to assess risk factors associated with household transmission of pandemic H1N1 from self-quarantined patients in Beijing, the capital city of China. A 1:2 case-control study with 54 case households and 108 control households was conducted between August 1 and September 30, 2009 in Beijing. Cases were households with a self-quarantined index patient and a secondary case, while controls were households with a self-quarantined index patient and a close contact. Controls were also matched to cases for sex and age of index case-patient. A structured interview guide was used to collect the data. Conditional logistical models were employed to estimate Odds Ratios (OR) with 95% confidence intervals (95% CI). Results indicated that higher education level (OR 0.42; 95% CI 0.22-0.83), sharing room with an index case-patient (OR 3.29; 95%CI 1.23-8.78), daily room ventilation (OR 0.28; 95%CI 0.08-0.93), and hand washing ≥ 3/d (OR 0.71; 95%CI 0.48-0.94) were related to the household transmission of pandemic H1N1 from self-quarantined patients. These results highlight that health education, as well as the quarantine of the index case-patient immediately after infection, frequent hand hygiene, and ventilation are critical to mitigating household spread of pandemic H1N1 virus and minimizing its impact. Household contacts should be educated to promote these in-home practices to contain transmission, particularly when household members are quarantined at home.

To investigate the risk factors of scrub typhus infection in Beijing, China, a case-control study was carried out. Cases (n = 56) were defined as persons who were diagnosed by PCR and serological method within three years. Three neighborhood control subjects were selected by matching for age and occupation. Living at the edge of the village, living in the houses near grassland, vegetable field or ditch, house yard without cement floor, piling weeds in the house or yard, all of these were risk factors for scrub typhus infection. Working in vegetable fields and hilly areas, and harvesting in autumn posed the highest risks, with odds ratios (ORs) and 95% confidence intervals (CIs) of 3.7 (1.1-11.9), 8.2 (1.4-49.5), and 17.2 (5.1-57.9), respectively. These results would be useful for the establishment of a detail control strategy for scrub typhus infection in Beijing, China.

BackgroundTuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates and adverse outcomes. However, the existing evidence on the epidemiology and treatment of TB-COVID co-infection remains limited.MethodsThis updated systematic review aimed to investigate the prevalence, fatality rates, and treatment outcomes of TB-COVID co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, to January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk of bias of included studies, and meta-analysis estimated co-infection fatality rates and relative risk.ResultsFrom 5,095 studies screened, 17 were included. TB-COVID co-infection prevalence was reported in 38 countries or regions, spanning both high and low TB prevalence areas. Prevalence estimates were approximately 0.06% in West Cape Province, South Africa, and 0.02% in California, USA. Treatment approaches for TB-COVID co-infection displayed minimal evolution since 2021. Converging findings from diverse studies underscored increased hospitalization risks, extended recovery periods, and accelerated mortality compared to single COVID-19 cases. The pooled fatality rate among co-infected patients was 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital co-infected patients faced a mean fatality rate of 11.4% (95%CI: 5.6% ~ 18.8%). The pooled relative risk of in-hospital fatality was 0.8 (95% CI, 0.18-3.68) for TB-COVID patients versus single COVID patients.ConclusionTB-COVID co-infection is increasingly prevalent worldwide, with fatality rates gradually declining but remaining higher than COVID-19 alone. This underscores the urgency of continued research to understand and address the challenges posed by TB-COVID co-infection.

Miscanthus lutarioriparia is a promising energy crop that is used for abandoned mine soil phytoremediation because of its high biomass yield and strong tolerance to heavy metals. However, the biological mechanism of heavy metal resistance is limited, especially for applications in the soil restoration of mining areas. Here, through the investigation of soil cadmium(Cd) in different mining areas and soil potted under Cd stress, the adsorption capacity of Miscanthus lutarioriparia was analyzed. The physiological and transcriptional effects of Cd stress on M. lutarioriparia leaves and roots under hydroponic conditions were analyzed. The results showed that M. lutarioriparia could reduce the Cd content in mining soil by 29.82%. Moreover, different Cd varieties have different Cd adsorption capacities in soils with higher Cd concentration. The highest cadmium concentrations in the aboveground and belowground parts of the plants were 185.65 mg/kg and 186.8 mg/kg, respectively. The total chlorophyll content, superoxide dismutase and catalase activities all showed a trend of increasing first and then decreasing. In total, 24,372 differentially expressed genes were obtained, including 7735 unique to leaves, 7725 unique to roots, and 8912 unique to leaves and roots, which showed differences in gene expression between leaves and roots. These genes were predominantly involved in plant hormone signal transduction, glutathione metabolism, flavonoid biosynthesis, ABC transporters, photosynthesis and the metal ion transport pathway. In addition, the number of upregulated genes was greater than the number of downregulated genes at different stress intervals, which indicated that M. lutarioriparia adapted to Cd stress mainly through positive regulation. These results lay a solid foundation for breeding excellent Cd resistant M. lutarioriparia and other plants. The results also have an important theoretical significance for further understanding the detoxification mechanism of Cd stress and the remediation of heavy metal pollution in mining soil.

Autophagy and Cell wall integrity (CWI) signaling are critical stress-responsive processes during fungal infection of host plants. In the rice blast fungus Magnaporthe oryzae, autophagy-related (ATG) proteins phosphorylate CWI kinases to regulate virulence; however, how autophagy interplays with CWI signaling to coordinate such regulation remains unknown. Here, we have identified the phosphorylation of ATG protein MoAtg4 as an important process in the coordination between autophagy and CWI in M. oryzae. The ATG kinase MoAtg1 phosphorylates MoAtg4 to inhibit the deconjugation and recycling of the key ATG protein MoAtg8. At the same time, MoMkk1, a core kinase of CWI, also phosphorylates MoAtg4 to attenuate the C-terminal cleavage of MoAtg8. Significantly, these two phosphorylation events maintain proper autophagy levels to coordinate the development and pathogenicity of the rice blast fungus.

The emergence of fungicide resistance severely threatens crop production by limiting the availability and application of established fungicides. Therefore, it is urgent to identify new fungicidal targets for controlling plant diseases. Here, we characterized the function of a conserved homoserine O-acetyltransferase (HOA) from the rice blast fungus Magnaporthe oryzae that could serve as the candidate antifungal target. Deletion of the MoMET2 and MoCYS2 genes encoding HOAs perturbed the biosynthesis of methionine and S-adenyl methionine, a methyl group donor for epigenetic modifications, and severely attenuated the development and virulence of M. oryzae. The ∆Momet2 mutant is significantly increased in 5-methylcytosine (5mC) modification that represses the expression of genes required for pathogenicity, including MoGLIK and MoCDH-CYT. We further showed that host-induced gene silencing (HIGS) targeting MoMET2 and MoCYS2 effectively controls rice blasts. Our studies revealed the importance of HOA in the development and virulence of M. oryzae, which suggests the potential feasibility of HOA as new targets for novel anti-rice blast measurements.

The rice blast fungus Magnaporthe oryzae forms specialized infectious structures called appressoria that breach host cells to initiate infection. Previous studies demonstrated that the regulator of G-protein signaling (RGS)-like protein MoRgs7 undergoes endocytosis upon fungal sensing of hydrophobic environmental cues to activate cAMP signaling required for appressorium formation. However, the mechanism by which MoRgs7 internalizes and its fate remains undetermined. We here show that MoSep1, a conserved protein kinase of Mitotic Exit Network (MEN), phosphorylates MoRgs7 to regulate its function. MoRgs7 phosphorylation determines its interaction with MoCrn1, a coronin-like actin-binding protein homolog that also modulates the internalization of MoRgs7. Importantly, the endocytic transport of MoRgs7 is critical for its GTPase-activating protein (GAP) function important in cAMP signaling. Together, our findings revealed a novel mechanism by which M. oryzae activates MoRgs7-mediated hydrophobic cue-sensing signal transduction involving protein phosphorylation and endocytic transport to govern appressorium formation and fungal pathogenicity.

Magnaporthe oryzae causes rice blasts posing serious threats to food security worldwide. During infection, M. oryzae utilizes several transmembrane receptor proteins that sense cell surface cues to induce highly specialized infectious structures called appressoria. However, little is known about the mechanisms of intracellular receptor tracking and their function. Here, we described that disrupting the coat protein complex II (COPII) cargo protein MoErv14 severely affects appressorium formation and pathogenicity as the ΔMoerv14 mutant is defective not only in cAMP production but also in the phosphorylation of the mitogen-activated protein kinase (MAPK) MoPmk1. Studies also showed that either externally supplementing cAMP or maintaining MoPmk1 phosphorylation suppresses the observed defects in the ΔMoerv14 strain. Importantly, MoErv14 is found to regulate the transport of MoPth11, a membrane receptor functioning upstream of G-protein/cAMP signaling, and MoWish and MoSho1 function upstream of the Pmk1-MAPK pathway. In summary, our studies elucidate the mechanism by which the COPII protein MoErv14 plays an important function in regulating the transport of receptors involved in the appressorium formation and virulence of the blast fungus.

Real-time and accurate detection of ships plays a vital role in ensuring navigation safety and ship supervision. Aiming at the problems of large parameters, large computation quantity, poor real-time performance, and high requirements for memory and computing power of the current ship detection model, this paper proposes a ship target detection algorithm MC-YOLOv5s based on YOLOv5s. First, the MobileNetV3-Small lightweight network is used to replace the original feature extraction backbone network of YOLOv5s to improve the detection speed of the algorithm. And then, a more efficient CNeB is designed based on the ConvNeXt-Block module of the ConvNeXt network to replace the original feature fusion module of YOLOv5s, which improves the spatial interaction ability of feature information and further reduces the complexity of the model. The experimental results obtained from the training and verification of the MC-YOLOv5s algorithm show that, compared with the original YOLOv5s algorithm, MC-YOLOv5s reduces the number of parameters by 6.98 MB and increases the mAP by about 3.4%. Even compared with other lightweight detection models, the improved model proposed in this paper still has better detection performance. The MC-YOLOv5s has been verified in the ship visual inspection and has great application potential. The code and models are publicly available at https://github.com/sakura994479727/datas.

Objective To evaluate the efficacy and safety of cilostazol, pentoxifylline, beraprost for intermittent claudication due to lower extremity arterial occlusive disease. Methods Randomized controlled clinical trials were identified from PubMed, Scopus, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, Wanfang and Chongqing VIP databases, from the database inception to 31/12/2021. The outcome measures were walking distance measured by treadmill (maximum and pain-free walking distance), ankle-brachial index and adverse events. The quality of included studies was assessed by the Cochrane bias risk assessment tool. A network meta-analysis was carried out with Stata 16.0 software. Results There were 29 RCTs included in the study, covering total 5352 patients. Cilostazol was ranked first for both maximum and pain-free walking distance, followed by beraprost and pentoxifylline. For cilostazol, pentoxifylline and beraprost, maximum walking distance increased by 62.93 95%CI(44.06, 81.79), 32.72 95%CI(13.51, 55.79) and 43.90 95%CI(2.10, 85.71) meters, respectively relative to placebo, and pain-free walking distance increased by 23.92 95%CI(11.24, 36.61), 15.16 95%CI(2.33, 27.99) and 19.78 95%CI(-3.07, 42.62) meters. For cilostazol, pentoxifylline, beraprost and cilostazol combined with beraprost, ankle-brachial index increased by 0.06 95%CI(0.04, 0.07), -0.01 95%CI(-0.08, 0.05), 0.18 95%CI(0.12, 0.23) and 0.23 95%CI(0.18, 0.27), respectively relative to placebo. The pentoxifylline and cilostazol was associated with a lower ratio of adverse events than beraprost and cilostazol combined with beraprost. Conclusion Cilostazol, pentoxifylline and beraprost were all effective treatments for intermittent claudication; cilostazol with good tolerance was likely to be the most effective in walking distance, while beraprost and cilostazol combined with beraprost were more prominent in the ankle-brachial index.

In order to find out the optimized technological parameters of rice straw bowl tray, the forming test was carried out with the slurry made of rice straw as the main raw material and the pneumatic molding machine as the equipment. The orthogonal rotational combination test of ternary quadratic regression and response surface analysis method were used to study the effect of 3 molding factors (vacuum degree, pressure preservation time and adsorption time) on 3 molding technical indices (bowl hole molding rate, relaxation density and rupture-resisting strength). Design-Expert data analysis software was used to establish regression models between rice straw bowl tray molding factors and molding properties so as to obtain optimal technological parameters, which were as follows: vacuum degree: -0.09 MPa; holding time: 14 s; adsorption time: 5 s. At the moment, theoretical bowl hole molding rate was 98.62%, relaxation density was 5.8 g/cm3 and rupture-resisting strength was 27.48 N, the experimental results show that the theoretical analysis is correct, and the model fitting is better. This study can provide a theoretical basis for optimization of pneumatic molding technological of rice straw bowl tray and lay a foundation for realizing industrialized production of biomass seeding tray.

The special width approach lane (SWAL) is a newly proposed unconventional design, whereby a wide approach lane is divided into two narrower lanes. The design entails the use of a single lane by two passenger cars or one heavy vehicle. Such design has been applicated at signalized intersections of Karlsruhe, Germany. This paper focuses on the saturation flow rate analysis since most existing studies on such design rely on the default highway capacity manual (HCM) values. Saturation flow rate data was collected at four SWAL design based signalized intersections with procedural steps of the HCM 2010 using the video camera. The two-sample t-test was performed to explore the potential influencing factors, and then the non-linear regression analysis was conducted to estimate the saturation flow rate of SWAL. The proposed model can effectively depict the saturation flow rate with lane marking, presence of cyclists, and rainfall being the influencing factors. The overall accuracy of the proposed model is about 95%. The results indicate that the three influencing factors are independent of each other. The existence of cyclists and rainfall lead to a decrease in the saturation flow rate, while the lane markings can improve the saturation flow rate. Moreover, the SWAL works well in Karlsruhe, Germany. The model predicts a base saturation flow rate value of 1652 pcu/h/ln, which is plausible with comparison of the base saturation flow rate recommended in the German Highway Capacity Manual.

GTP-binding protein (G-protein) and regulator of G-protein signaling (RGS) mediated signal transduction are critical in the growth and virulence of the rice blast pathogen Magnaporthe oryzae. We have previously reported that there are eight RGS and RGS-like proteins named MoRgs1 to MoRgs8 playing distinct and shared regulatory functions in M. oryzae and that MoRgs1 has a more prominent role compared to others in the fungus. To further explore the unique regulatory mechanism of MoRgs1, we screened a M. oryzae cDNA library for genes encoding MoRgs1-interacting proteins and identified MoCkb2, one of the two regulatory subunits of the casein kinase (CK) 2 MoCk2. We found that MoCkb2 and the sole catalytic subunit MoCka1 are required for the phosphorylation of MoRgs1 at the plasma membrane (PM) and late endosome (LE). We further found that an endoplasmic reticulum (ER) membrane protein complex (EMC) subunit, MoEmc2, modulates the phosphorylation of MoRgs1 by MoCk2. Interestingly, this phosphorylation is also essential for the GTPase-activating protein (GAP) function of MoRgs1. The balance among MoRgs1, MoCk2, and MoEmc2 ensures normal operation of the G-protein MoMagA-cAMP signaling required for appressorium formation and pathogenicity of the fungus. This has been the first report that an EMC subunit is directly linked to G-protein signaling through modulation of an RGS-casein kinase interaction.

The fungal cell wall plays an essential role in maintaining cell morphology, transmitting external signals, controlling cell growth, and even virulence. Relaxation and irreversible stretching of the cell wall are the prerequisites of cell division and development, but they also inevitably cause cell wall stress. Both Mitotic Exit Network (MEN) and Cell Wall Integrity (CWI) are signaling pathways that govern cell division and cell stress response, respectively, how these pathways cross talk to govern and coordinate cellular growth, development, and pathogenicity remains not fully understood. We have identified MoSep1, MoDbf2, and MoMob1 as the conserved components of MEN from the rice blast fungus Magnaporthe oryzae. We have found that blocking cell division results in abnormal CWI signaling. In addition, we discovered that MoSep1 targets MoMkk1, a conserved key MAP kinase of the CWI pathway, through protein phosphorylation that promotes CWI signaling. Moreover, we provided evidence demonstrating that MoSep1-dependent MoMkk1 phosphorylation is essential for balancing cell division with CWI that maintains the dynamic stability required for virulence of the blast fungus.

Large-scale breeding environments often lead to oxidative stress. Macrophages play an important role in the immune system and are vulnerable to reactive oxygen species (ROS), which result in macrophage death. Curcumin is the main active component of turmeric and exerts antioxidant effects. Here, we measured the activity of some antioxidant enzymes and chose the Nrf2-Keap1 signaling pathway to study the protective effects of curcumin on macrophages under oxidative stress in vitro. We used RAW264.7 cells as a research model, and oxidative damage was induced by hydrogen peroxide (H2O2). Cell viability was measured by an MTT assay. Flow cytometry was used to measure cellular ROS and apoptosis. The effect of curcumin on Nrf2-Keap1 signaling pathway-related genes was analyzed by qRT-PCR. Furthermore, the translocation of Nrf2 protein was also investigated by Western blot analysis of total and nuclear proteins. All curcumin-treated groups exhibited increased activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Low- and middle-dose curcumin decreased malondialdehyde (MDA) and ROS levels, but high-dose curcumin increased MDA and ROS production. We found that low-dose curcumin protected cells from apoptosis, while apoptosis in the middle- and high-dose curcumin-treated groups were stagnant in the early stage. Furthermore, middle-dose curcumin upregulated Nrf2 expression after H2O2 treatment for 4 h. Low- and middle-dose curcumin could activate Nrf2 and promote it to migrate into nuclei. The translocation of Nrf2 to the nucleus to upregulate the expression of haemoxygenase-1 (HO-1) was promoted in the low- and middle-dose curcumin-treated groups. The middle-dose curcumin-treated group also exhibited enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), but inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). Curcumin resisted oxidants by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway, which could potentially promote cell survival.

The accumulation of the reactive oxygen species (ROS) in rice is important in its interaction with the rice blast fungus Magnaporthe oryzae during which the pathogen scavenges ROS through the production of extracellular enzymes that promote blast. We previously characterized the MoYvh1 protein phosphatase from M. oryzae that plays a role in scavenging of ROS. To understand the underlying mechanism, we found that MoYvh1 is translocated into the nucleus following oxidative stress and that this translocation is dependent on MoSsb1 and MoSsz1 that are homologous to heat-shock protein 70 (Hsp70) proteins. In addition, we established a link between MoYvh1 and MoMrt4, a ribosome maturation factor homolog whose function also involves shuttling between the cytoplasm and the nucleus. Moreover, we found that MoYvh1 regulates the production of extracellular proteins that modulate rice-immunity. Taking together, our evidence suggests that functions of MoYvh1 in regulating ROS scavenging require its nucleocytoplasmic shuttling and the partner proteins MoSsb1 and MoSsz1, as well as MoMrt4. Our findings provide novel insights into the mechanism by which M. oryzae responds to and subverts host immunity through the regulation of ribosome biogenesis and protein biosynthesis.

We previously demonstrated that transient receptor potential vanilloid subfamily 5 (TRPV5) expression was decreased in renal cell carcinoma (RCC) compared with that in normal kidney tissues, a finding that was correlated with vitamin D receptor (VDR) expression, but further investigations is warranted. The aim of this study was to elucidate whether VDR could regulate the expression of TRPV5 and affect proliferation and metastasis in RCC. In this study, we used lentivirus to conduct the model of VDR overexpression and knockdown caki-1 and 786-O RCC cell lines in vitro. The results demonstrated that VDR overexpression significantly inhibited RCC cells proliferation, migration and invasion, and promoted apoptosis by the MTT, transwell cell migration/invasion and flow cytometry assays, respectively. However, VDR knockdown in RCC cells had the opposite effect. The RNA-sequence assay, which was assessed in caki-1 cells after VDR overexpression and knockdown, also indicated that significantly differentially expressed genes were associated with cell apoptotic, differentiation, proliferation and migration. RT-PCR and western blot analysis showed that VDR knockdown increased TRPV5 expression and VDR overexpression decreased TRPV5 expression in caki-1 cells. Furthermore, knockdown of TRPV5 expression suppressed the VDR knockdown-induced change in the proliferation, migration and invasion in caki-1 cells. Taken together, these findings confirmed that VDR functions as a tumour suppressor in RCC cells and suppresses the proliferation, migration and invasion of RCC through regulating the expression of TRPV5.

Porcine circovirus-associated disease is caused by porcine circovirus type 2 (PCV2) infection, which targets iliac artery endothelial cells (PIECs); it leads to severe immunopathologies and is associated with major economic losses in the porcine industry. Here, we report that in vitro PCV2 infection of PIECs causes cell injury, which affects DC function as well as adaptive immunity. Specifically, PCV2 infection downregulated PIEC antigen-presenting molecule expression, upregulated cytokines involved in the immune and inflammatory response causing cell damage and repair, and altered the migratory capacity of PIECs. In addition, PCV2-infected PIECs inhibited DC maturation, enhanced the endocytic ability of DCs, and weakened the stimulatory effect of DCs on T lymphocytes. Together, these findings indicate that profound functional impairment of DCs in the presence of PCV2-infected PIECs may be a potential pathogenic mechanism associated with PCV2-induced porcine disease.

[This corrects the article DOI: 10.1371/journal.pone.0162243.].

Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals.

Adenylate kinase (AK) from Escherichia coli was used as both solubility and affinity tag for recombinant protein production. When fused to the N-terminus of a target protein, an AK fusion protein could be expressed in soluble form and purified to near homogeneity in a single step from Blue-Sepherose via affinity elution with micromolar concentration of P1, P5- di (adenosine-5') pentaphosphate (Ap5A), a transition-state substrate analog of AK. Unlike any other affinity tags, the level of a recombinant protein expression in soluble form and its yield of recovery during each purification step could be readily assessed by AK enzyme activity in near real time. Coupled to a His-Tag installed at the N-terminus and a thrombin cleavage site at the C terminus of AK, the streamlined method, here we dubbed AK-TAG, could also allow convenient expression and retrieval of a cleaved recombinant protein in high yield and purity via dual affinity purification steps. Thus AK-TAG is a new addition to the arsenal of existing affinity tags for recombinant protein expression and purification, and is particularly useful where soluble expression and high degree of purification are at stake.

Co-clustering, often called biclustering for two-dimensional data, has found many applications, such as gene expression data analysis and text mining. Nowadays, a variety of multi-dimensional arrays (tensors) frequently occur in data analysis tasks, and co-clustering techniques play a key role in dealing with such datasets. Co-clusters represent coherent patterns and exhibit important properties along all the modes. Development of robust co-clustering techniques is important for the detection and analysis of these patterns. In this paper, a co-clustering method based on hyperplane detection in singular vector spaces (HDSVS) is proposed. Specifically in this method, higher-order singular value decomposition (HOSVD) transforms a tensor into a core part and a singular vector matrix along each mode, whose row vectors can be clustered by a linear grouping algorithm (LGA). Meanwhile, hyperplanar patterns are extracted and successfully supported the identification of multi-dimensional co-clusters. To validate HDSVS, a number of synthetic and biological tensors were adopted. The synthetic tensors attested a favorable performance of this algorithm on noisy or overlapped data. Experiments with gene expression data and lineage data of embryonic cells further verified the reliability of HDSVS to practical problems. Moreover, the detected co-clusters are well consistent with important genetic pathways and gene ontology annotations. Finally, a series of comparisons between HDSVS and state-of-the-art methods on synthetic tensors and a yeast gene expression tensor were implemented, verifying the robust and stable performance of our method.

N-linked glycosylation is a way of glycosylation for newly synthesized protein, which plays a key role in the maturation and transport of proteins. Glycoside hydrolases (GHs) are essential in this process, and are involved in processing of N-linked glycoproteins or degradation of carbohydrate structures. Here, we identified and characterized MoGls2 in Magnaporthe oryzae, which is a yeast glucosidase II homolog Gls2 and is required for trimming the final glucose in N-linked glycans and normal cell wall synthesis. Target deletion of MoGLS2 in M. oryzae resulted in a reduced mycelial growth, an increased conidial production, delayed conidial germination and loss the ability of sexual reproduction. Pathogenicity assays revealed that the ΔMogls2 mutant showed significantly decreased in virulence and infectious growth. Further studies showed that the mutant was less sensitive to salt and osmotic stress, and increased sensitivity to cell wall stresses. Additionally, the ΔMogls2 mutant showed a defect in cell wall integrity. Our results indicate that MoGls2 is a key protein for the growth and development of M. oryzae, involving in the regulation of asexual/sexual development, stress response, cell wall integrity and infectious growth.

This paper proposes an optimization algorithm, the dimension-down iterative algorithm (DDIA), for solving a mixed transportation network design problem (MNDP), which is generally expressed as a mathematical programming with equilibrium constraint (MPEC). The upper level of the MNDP aims to optimize the network performance via both the expansion of the existing links and the addition of new candidate links, whereas the lower level is a traditional Wardrop user equilibrium (UE) problem. The idea of the proposed solution algorithm (DDIA) is to reduce the dimensions of the problem. A group of variables (discrete/continuous) is fixed to optimize another group of variables (continuous/discrete) alternately; then, the problem is transformed into solving a series of CNDPs (continuous network design problems) and DNDPs (discrete network design problems) repeatedly until the problem converges to the optimal solution. The advantage of the proposed algorithm is that its solution process is very simple and easy to apply. Numerical examples show that for the MNDP without budget constraint, the optimal solution can be found within a few iterations with DDIA. For the MNDP with budget constraint, however, the result depends on the selection of initial values, which leads to different optimal solutions (i.e., different local optimal solutions). Some thoughts are given on how to derive meaningful initial values, such as by considering the budgets of new and reconstruction projects separately.

Genome dynamics of pathogenic organisms are driven by pathogen and host co-evolution, in which pathogen genomes are shaped to overcome stresses imposed by hosts with various genetic backgrounds through generation of a variety of isolates. This same principle applies to the rice blast pathogen Magnaporthe oryzae and the rice host; however, genetic variations among different isolates of M. oryzae remain largely unknown, particularly at genome and transcriptome levels. Here, we applied genomic and transcriptomic analytical tools to investigate M. oryzae isolate 98-06 that is the most aggressive in infection of susceptible rice cultivars. A unique 1.4 Mb of genomic sequences was found in isolate 98-06 in comparison to reference strain 70-15. Genome-wide expression profiling revealed the presence of two critical expression patterns of M. oryzae based on 64 known pathogenicity-related (PaR) genes. In addition, 134 candidate effectors with various segregation patterns were identified. Five tested proteins could suppress BAX-mediated programmed cell death in Nicotiana benthamiana leaves. Characterization of isolate-specific effector candidates Iug6 and Iug9 and PaR candidate Iug18 revealed that they have a role in fungal propagation and pathogenicity. Moreover, Iug6 and Iug9 are located exclusively in the biotrophic interfacial complex (BIC) and their overexpression leads to suppression of defense-related gene expression in rice, suggesting that they might participate in biotrophy by inhibiting the SA and ET pathways within the host. Thus, our studies identify novel effector and PaR proteins involved in pathogenicity of the highly aggressive M. oryzae field isolate 98-06, and reveal molecular and genomic dynamics in the evolution of M. oryzae and rice host interactions.

The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1) and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes.

Clinical use of CHADS2 and CHA2DS2-VASc scoring systems for predicting AF following cardiac surgery have been reported in previous studies and demonstrated well-validated predictive value. We sought to investigate whether the two scoring systems are effective for predicting new-onset of AF following cardiac valve surgery and to demonstrate its potential utility of clinical assessment.Medical records of all patients underwent cardiac valve surgeries during the period of January 2003 and December 2013 without preoperative AF at the cardiac center of our university were reviewed. The main outcome end point of our study was the early new-onset of AF following cardiac valve surgery.There were overall 518 patients involved in this study, with 234 (45.17%) developed POAF following valve surgery. Patients with POAF had older age (P=0.23) and higher BMI (P=0.013) than those without POAF. History of heart failure (P=0.025), hypertension (P=0.021), previous stroke or TIA (P=0.032), coronary artery disease (P=0.001), carotid artery disease (P=0.024) and preoperative medication of statins (P=0.021) were significantly more recorded in POAF group. Patients with POAF also had higher LAD (P=0.013) and E/e' ratio (P

AIM:To explore the association of lipid ratios and triglyceride (TG) with insulin resistance (IR) in a Chinese population. We also provide the clinical utility of lipid ratios to identify men and women with IR. METHODS:This cross-sectional study included 614 men and 1055 women without diabetes. Insulin resistance was defined by homeostatic model assessment of IR > 2.69. Lipid ratios included the TG/ high density lipoprotein cholesterol (HDL-C), the total cholesterol (TC)/HDL-C and the low density lipoprotein cholesterol (LDL-C)/HDL -C. Logistic regression models and accurate estimates of the area under the receiver operating characteristic (AUROC) curves were obtained. RESULTS:In normal-weight men, none of lipid ratios nor TG was associated with IR. In overweight/obese men, normal-weight women and overweight/obese women, the TG/HDL-C, the TC/HDL-C and TG were significantly associated with IR, and the associations were independent of waist circumference. All of the AUROCs for the TG/HDL-C and TG were > 0.7. The AUROCs for TC/HDL-C ratio were 0.69-0.77. The optimal cut-offs for TG/HDL-C were 1.51 in men and 0.84 in women. The optimal cut-offs for TG were 1.78 mmol/L in men and 1.49 mmol/L in women, respectively. In men, the optimal cut-off for LDL-C/HDL-C is 3.80. In women, the optimal cut-off for LDL-C/HDL-C is 3.82. CONCLUSION:The TG/HDL-C, the TC/HDL-C and TG are associated with IR in overweight/obese men, normal-weight and overweight/obese women. The LDL-C/HDL-C is only associated with IR in normal-weight women. The TG/HDL-C and TG might be used as surrogate markers for assessing IR.

Exercise tolerance is impaired in hypoxia. The aim of this study was to evaluate the effects of myricetin, a dietary flavonoid compound widely found in fruits and vegetables, on acute hypoxia-induced exercise intolerance in vivo and in vitro.Male rats were administered myricetin or vehicle for 7 days and subsequently spent 24 hours at a barometric pressure equivalent to 5000 m. Exercise capacity was then assessed through the run-to-fatigue procedure, and mitochondrial morphology in skeletal muscle cells was observed by transmission electron microscopy (TEM). The enzymatic activities of electron transfer complexes were analyzed using an enzyme-linked immuno-sorbent assay (ELISA). mtDNA was quantified by real-time-PCR. Mitochondrial membrane potential was measured by JC-1 staining. Protein expression was detected through western blotting, immunohistochemistry, and immunofluorescence.Myricetin supplementation significantly prevented the decline of run-to-fatigue time of rats in hypoxia, and attenuated acute hypoxia-induced mitochondrial impairment in skeletal muscle cells in vivo and in vitro by maintaining mitochondrial structure, mtDNA content, mitochondrial membrane potential, and activities of the respiratory chain complexes. Further studies showed that myricetin maintained mitochondrial biogenesis in skeletal muscle cells under hypoxic conditions by up-regulating the expressions of mitochondrial biogenesis-related regulators, in addition, AMP-activated protein kinase(AMPK) plays a crucial role in this process.Myricetin may have important applications for improving physical performance under hypoxic environment, which may be attributed to the protective effect against mitochondrial impairment by maintaining mitochondrial biogenesis.