The impact of ankle-foot orthoses on mobility of dual-task walking in stroke patients? A cross-sectional two-factor factorial design clinical trial.

ABSTRACTTo assess the impact of ankle-foot orthoses (AFOs) on mobility and gait during dual-task walking in post-stroke survivors. In this cross-sectional, factorial design trial, stroke survivors performed four randomized tasks: (1) dual-task walking with AFOs, (2) single-task walking with AFOs, (3) dual-task walking without AFOs, and (4) single-task walking without AFOs. Primary outcome was the Timed Up and Go (TUG) test, with secondary outcomes including gait metrics, Tinetti scores, and auditory N-back tests. In the results, 48 subjects (38 males and 10 females; 19-65 years) completed the trial. Patients had a greater TUG score with AFOs compared with non-AFOs conditions (95% CI: 7.22-14.41, P < 0.001) in single-task and dual-task conditions. Secondary outcomes showed marked enhancement with AFOs during dual-task walking, with significant interaction effects in gait metrics, balance, and cognitive function (P < 0.05). Although not statistically significant, dual-task effects of TUG and walking speed were more pronounced during dual-task walking. In conclusion, AFOs enhance mobility and gait during both single and dual-task walking in post-stroke survivors.

Single-Cell RNA-Seq Reveals Changes in Cell Subsets in the Cortical Microenvironment during Acute Phase of Ischemic Stroke Rats.

BACKGROUND: Ischemic stroke, the most common stroke type, has threatened human life and health. Currently, intravenous thrombolysis and endovascular thrombectomy are the mainstream treatment methods, but they may cause cerebral ischemia-reperfusion injury (CIRI), which aggravates brain injury. Consequently, it is worthwhile to start with a study of CIRI mechanism to identify better prevention and treatment methods. Applying single-cell RNA sequencing (scRNA-seq) technology to further understand the biological functions of various cell types in CIRI will facilitate the intervention of CIRI. METHODS: This study aimed to establish a rat middle cerebral artery occlusion (MCAO) model to simulate cerebral ischemia-reperfusion, perform enzymatic hydrolysis, and suspend cerebral cortex tissue edema. Single-cell transcriptome sequencing was used, combined with cluster analysis, t-distributed stochastic neighbor embedding (t-SNE) visualization, and other bioinformatics methods to distinguish cell subgroups while using gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment to reveal the biological function of each cell subgroup. RESULTS: We identified 21 brain clusters with cell type-specific gene expression patterns and cell subpopulations, as well as 42 marker genes representing different cell subpopulations. The number of cells in clusters 0-3 increased significantly in MCAO group compared to that in the sham group, and nine-cell subpopulations exhibited remarkable differences in the number of genes. Subsequently, GO and KEGG analyses were performed on the top 40 differentially expressed genes (DEGs) in the six cell subpopulations with significant differences. These results indicate that biological processes and signaling pathways are involved in different cell subpopulations. CONCLUSIONS: ScRNA-seq revealed the diversity of cell differentiation and the unique information of cell subpopulations in the cortex of rats with acute ischemic stroke, providing novel insight into the pathological process and drug discovery in stroke.

Preliminary Study on Insecticidal Potential and Chemical Composition of Five Rutaceae Essential Oils against Thrips flavus (Thysanoptera: Thripidae).

To meet the demand for novel pest management strategies to combat the development of insecticide resistance, plant essential oils may be a promising alternative source. This study investigated the insecticidal activity of five essential oils from the Rutaceae plant family against Thrips flavus Schrank (Thysanoptera: Thripidae) under laboratory conditions. The plant essential oils were citrus oil (Citrus reticulata Blanco), Chuan-shan pepper oil (Zanthoxylum piasezkii Maxim.), zanthoxylum oil (Zanthoxylum bungeanum Maxim.), pomelo peel oil (Citrus maxima (Burm.) Merr.) and orange leaf oil (Citrus sinensis (L.) Osbeck). Among the essential oils evaluated, orange leaf oil (LC50 = 0.26 g/L), zanthoxylum oil (LC50 = 0.27 g/L), and pomelo peel oil (LC50 = 0.44 g/L) resulted in a higher gastric toxicity under laboratory conditions. The results of the pot experiment also showed that orange leaf oil (93.06 ± 3.67% at 540.00 g a.i.·hm-2, 97.22 ± 1.39% at 720 g a.i.·hm-2, 100.00% at 900.00 g a.i.·hm-2) zanthoxylum oil (98.73 ± 1.27% at 900 g a.i.·hm-2), and pomelo peel oil (100.00% at 900 g a.i.·hm-2) exhibited a higher control efficacy, being the most effective against T. flavus after 7 days of treatment. The essential oil components were then identified by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of orange leaf oil, pomelo peel oil, and zanthoxylum oil could be attributed to their main constituents, such as methyl jasmonate (50.92%), D-limonene (76.96%), and linalool (52.32%), respectively. In the olfactory test, adult T. flavus were attracted by zanthoxylum oil and Chuan-shan pepper oil. We speculated that linalool might be the key signaling compound that attracts T. flavus. These results showed that orange leaf oil, zanthoxylum oil, and pomelo peel oil exhibited insecticidal activities under controlled conditions. They can be implemented as effective and low-toxicity botanical insecticides and synergistic agents against T. flavus.

Quadriceps strength is negatively associated with knee joint structural abnormalities-data from osteoarthritis initiative.

OBJECTIVE: The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA). METHODS: This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45-79. Quadriceps strength was measured by isometric knee extension testing at baseline. Knee joint structural abnormalities, including cartilage damage, bone marrow lesions (BMLs), effusion-synovitis and Hoffa-synovitis, were evaluated by Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) at baseline and 1-year follow-up. Generalized estimating equations were employed to examine the associations between quadriceps strength and knee structural abnormalities. All analyses were stratified by sex. RESULTS: One thousand three hundred thirty-eight participants (523 men and 815 women) with a mean age of 61.8 years and a mean BMI of 29.4 kg/m2 were included in this study. For men, no significantly longitudinal association of quadriceps strength with structural abnormalities was detected. In contrast, quadriceps strength was significantly and negatively associated with changes in cartilage damage and BMLs in lateral patellofemoral joint (PFJ) (cartilage damage: OR: 0.91, 95% CI 0.84 to 0.99, P = 0.023; BMLs: OR: 0.85, 95% CI 0.74 to 0.96, P = 0.011) and effusion-synovitis (OR = 0.88, 95% CI 0.78 to 0.99, P = 0.045) among females longitudinally. Higher quadriceps strength was significantly associated with less progression of lateral PFJ cartilage damage, BMLs and effusion-synovitis in females. CONCLUSIONS: Higher quadriceps strength was associated with changes in cartilage damage and BMLs within the lateral PFJ and effusion-synovitis among females, suggesting the potential protective role of quadriceps strength on joint structures in women.

Production of ß-carotene in Saccharomyces cerevisiae through altering yeast lipid metabolism.

Saccharomyces cerevisiae is a widely used cell factory for the production of fuels and chemicals. However, as a non-oleaginous yeast, S. cerevisiae has a limited production capacity for lipophilic compounds, such as ß-carotene. To increase its accumulation of ß-carotene, we engineered different lipid metabolic pathways in a ß-carotene producing strain and investigated the relationship between lipid components and the accumulation of ß-carotene. We found that overexpression of sterol ester synthesis genes ARE1 and ARE2 increased ß-carotene yield by 1.5-fold. Deletion of phosphatidate phosphatase (PAP) genes (PAH1, DPP1, and LPP1) also increased ß-carotene yield by twofold. Combining these two strategies resulted in a 2.4-fold improvement in ß-carotene production compared with the starting strain. These results demonstrated that regulating lipid metabolism pathways is important for ß-carotene accumulation in S. cerevisiae, and may also shed insights to the accumulation of other lipophilic compounds in yeast.

A three-dimensional dynamic DNA walker-mediated branching hybridization chain reaction for the ultrasensitive fluorescence sensing of ampicillin.

In this study, a novel, rapid and ultrasensitive fluorescence strategy using the three-dimensional (3D) dynamic DNA walker (DW)-induced branched hybridization chain reaction (bHCR) has been proposed for the detection of ampicillin (AMP). The sensing system was composed of an Nt·Bbvcl-powered DNA walker blocked by an AMP aptamer, hairpin-shaped DNA track probe (TP) and four kinds of metastable hairpin probes as the substrates of bHCR, which triggered the formation of the split G-quadruplex as the signal molecule. Due to the reasonable design, the specific binding between AMP and its aptamer activated the DW, and the DW moved on the surface of the gold nanoparticles (AuNPs) with the help of Nt·Bbvcl to produce primer probes (PPs), which induced bHCR. The products of the bHCR gathered two split G-quadruplex sequences together to form one complete G-quadruplex. The formed G-quadruplex emitted a strong fluorescence signal in the presence of thioflavin-T (ThT) to achieve the purpose of detecting AMP. The sensitivity of this method was greatly improved by the use of the 3D DNA walker and bHCR. The split G-quadruplex enhanced the signal-to-noise ratio (SNR). Under the optimal experimental conditions, a good correlation was obtained between the fluorescence intensity of the sensing system and the concentration of AMP ranging from 5 pM to 500 nM with a limit of detection (LOD) of 3.68 pM. Simultaneously, the method has been applied to the detection of antibiotics in spiked milk samples with satisfactory results.

Therapeutic potentials of the Rho kinase inhibitor Fasudil in experimental autoimmune encephalomyelitis and the related mechanisms.

Multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), and other neurodegenerative diseases of central nervous system (CNS) disorders are serious human health problems. Rho-kinase (ROCK) is emerging as a potentially important therapeutic target relevant to inflammatory neurodegeneration diseases. This is supported by studies showing the beneficial effects of fasudil, a ROCK inhibitor, in inflammatory neurodegeneration diseases. MS is an autoimmune disease resulting from inflammation and demyelination in the white matter of the CNS. It has been postulated that activation of Rho/ROCK causes neuropathological changes accompanied with related clinical symptoms, which are improved by treatment with ROCK inhibitors. Therefore, inhibition of abnormal activation of the Rho/ROCK signaling pathway appears to be a new mechanism for treating CNS diseases. In this review, we extensively discussed the role of ROCK inhibitors, summarized the efficacy of fasudil in the MS conventional animal model of experimental autoimmune encephalomyelitis (EAE), both in vivo and in vitro, and highlighted the mechanism involved. Overall, the findings collected in this review support the role of the ROCK signaling pathway in neurodegenerative diseases. Hence, ROCK inhibitors such as fasudil can be novel, and efficacious treatment for inflammatory neurodegenerative diseases.

An analysis of physiological responses as indicators of driver takeover readiness in conditionally automated driving.

By the year 2045, it is projected that Autonomous Vehicles (AVs) will make up half of the new vehicle market. Successful adoption of AVs can reduce drivers' stress and fatigue, curb traffic congestion, and improve safety, mobility, and economic efficiency. Due to the limited intelligence in relevant technologies, human-in-the-loop modalities are still necessary to ensure the safety of AVs at current or near future stages, because the vehicles may not be able to handle all emergencies. Therefore, it is important to know the takeover readiness of the drivers to ensure the takeover quality and avoid any potential accidents. To achieve this, a comprehensive understanding of the drivers' physiological states is crucial. However, there is a lack of systematic analysis of the correlation between different human physiological responses and takeover behaviors which could serve as important references for future studies to determine the types of data to use. This paper provides a comprehensive analysis of the effects of takeover behaviors on the common physiological indicators. A program for conditional automation was developed based on a game engine and applied to a driving simulator. The experiment incorporated three types of secondary tasks, three takeover events, and two traffic densities. Brain signals, Skin Conductance Level (SCL), and Heart Rate (HR) of the participants were collected while they were performing the driving simulations. The Frontal Asymmetry Index (FAI) (as an indicator of engagement) and Mental Workload (MWL) were calculated from the brain signals to indicate the mental states of the participants. The results revealed that the FAI of the drivers would slightly decrease after the takeover alerts were issued when they were doing secondary tasks prior to the takeover activities, and the higher difficulty of the secondary tasks could lead to lower overall FAI during the takeover periods. In contrast, The MWL and SCL increased during the takeover periods. The HR also increased rapidly at the beginning of the takeover period but dropped back to a normal level quickly. It was found that a fake takeover alert would lead to lower overall HR, slower increase, and lower peak of SCL during the takeover periods. Moreover, the higher traffic density scenarios were associated with higher MWL, and a more difficult secondary task would lead to higher MWL and HR during the takeover activities. A preliminary discussion of the correlation between the physiological data, takeover scenario, and vehicle data (that relevant to takeover readiness) was then conducted, revealing that although takeover event, SCL, and HR had slightly higher correlations with the maximum acceleration and reaction time, none of them dominated the takeover readiness. In addition, the analysis of the data across different participants was conducted, which emphasized the importance of considering standardization or normalization of the data when they were further used as input features for estimating takeover readiness. Overall, the results presented in this paper offer profound insights into the patterns of physiological data changes during takeover periods. These findings can be used as benchmarks for utilizing these variables as indicators of takeover preparedness and performance in future research endeavors.

Drought limits vegetation carbon sequestration by affecting photosynthetic capacity of semi-arid ecosystems on the Loess Plateau.

Drought is the driver for ecosystem production in semi-arid areas. However, the response mechanism of ecosystem productivity to drought remains largely unknown. In particular, it is still unclear whether drought limits the production via photosynthetic capacity or phenological process. Herein, we assess the effects of maximum seasonal photosynthesis, growing season length, and climate on the annual gross primary productivity (GPP) in vegetation areas of the Loess Plateau using multi-source remote sensing and climate data from 2001 to 2021. We found that maximum seasonal photosynthesis rather than growing season length dominates annual GPP, with above 90 % of the study area showing significant and positive correlation. GPP and maximum seasonal photosynthesis were positively correlated with self-calibrating Palmer Drought Severity Index (scPDSI), standardized precipitation and evapotranspiration index (SPEI) in >95 % of the study area. Structural equation model demonstrated that both drought indices contributed to the annual GPP by promoting the maximum seasonal photosynthesis. Total annual precipitation had a positive and significant effect on two drought indices, whereas the effects of temperature and radiation were not significant. Evidence from wood formation data also confirmed that low precipitation inhibited long-term carbon sequestration by decreasing the maximum growth rate in forests. Our findings suggest that drought limits ecosystem carbon sequestration by inhibiting vegetation photosynthetic capacity rather than phenology, providing a support for assessing the future dynamics of the terrestrial carbon cycle and guiding landscape management in semi-arid ecosystems.

Novel Hsp90-Targeting PROTACs: Enhanced synergy with cisplatin in combination therapy of cervical cancer.

The development of effective drugs for cervical cancer is urgently required because of its high mortality rate and the limited treatment options. Herein, we report the design, synthesis, and evaluation of a series of novel and effective Hsp90-targeting PROTACs. These compounds exhibited potent anti-proliferative activity against cervical cancer cells with low IC50 values. Compound lw13 effectively degraded Hsp90 at a concentration of only 0.05 µM. In addition, it can inhibit the metastasis of cancer cells and induce significant cell cycle arrest and apoptosis. Furthermore, lw13 demonstrated remarkable antitumor activity both in vitro and in vivo, and has a synergistic effect in combination with cisplatin. Moreover, lw13 can prevent the activation of the HER2/AKT/mTOR signaling pathway by indirectly reducing the levels of HER2 and AKT. This study paves the way for cancer treatment and provides valuable insights into the combination therapy of cervical cancer.

BMSC-Exosomes attenuate ALP dysfunction by restoring lysosomal function via the mTOR/TFEB Axis to reduce cerebral ischemia-reperfusion injury.

BACKGROUND: The complex pathophysiological changes following cerebral ischemia-reperfusion injury (CIRI) include the accumulation of defective proteins and damaged organelles, which cause massive neuron demise. To preserve cellular homeostasis, the autophagy-lysosomal pathway (ALP) is crucial for neurons to dispose of these substances. Many studies have shown that bone mesenchymal stem cell exosomes (BMSC-Exos) can reduce CIRI. However, the specific mechanisms have not been well elucidated, a fact that limits its widespread clinical use. This study aimed to clarify whether BMSC-Exos could attenuate ALP dysfunction by restoring lysosomal function after CIRI via inhibiting mTOR and then activating TFEB nucleus translocation. METHODS: In this study, Flow cytometry, Nanoparticle tracking analysis (NTA), Transmission electron microscope (TEM), and Western blot were used to identify the BMSCs and BMSC-Exos used in this experiment as conforming to the requirements. In vivo experiments, SD rats were modeled with temporary middle cerebral artery occlusion (tMCAO), and BMSC-Exos was injected into the tail vein 2 h after modeling. Triphenyl tetrazolium chloride (TTC) staining, modified neurological severity scores (mNSS), corner turn test, and rotating rod test were used to detect neurological deficits in rats after BMSC-Exos intervention. Western blot and Immunofluorescence were used to detect ALP, transcription factor EB(TFEB) nucleus translocation, and mammalian target of rapamycin (mTOR) change at different time points after modeling and after BMSC-Exos intervention. In vitro experiments, pheochromocytoma cells (PC12) cells were subjected to oxygen-glucose deprivation and reperfusion (OGD/R) modeling to mimic CIRI, and were respectively intervened with BMSC-Exos, BMSC-Exos + MHY 1485 (the mTOR agonist), Rapamycin (the mTOR inhibitor). CCK8, Western blot, and Immunofluorescence were used to detect PC12 cell survival, TFEB nucleus translocation, and cathepsin B(CTSB) Immunofluorescence intensity. RESULTS: We found that ALP dysfunction occurred 72 h after tMCAO, and BMSC-Exos can attenuate ALP dysfunction by restoring lysosomal function. Next, we examined TFEB nucleus translocation and the expression of mTOR, a key regulator of translocation. We found that BMSC-Exos could inhibit mTOR and activate TFEB nucleus translocation. Additional in vitro tests revealed that BMSC-Exos could increase PC12 cell survival after OGD/R, activating TFEB nucleus translocation and enhancing the fluorescence intensity of CTSB, which in turn could be reversed by the mTOR agonist, MHY1485. This effect was similar to another mTOR inhibitor, Rapamycin. CONCLUSION: BMSC-Exos could attenuate ALP dysfunction by restoring lysosomal function after CIRI by inhibiting mTOR and then promoting TFEB nucleus translocation.

Multivariate Assessment of Vaccine Equity in Cambodia: A Longitudinal VERSE Tool Case Study Using Demographic and Health Survey 2004, 2010, and 2014.

Cambodia has exhibited great progress in achieving high coverage in nationally recommended immunizations. As vaccination program managers plan interventions to reach last-mile children, it is important to consider issues of equity immunization priority setting. In this analysis, we apply the VERSE Equity Tool to Cambodia's Demographic and Health Survey for the years 2004, 2010, and 2014 to evaluate multivariate equity in vaccine coverage for 11 vaccination statuses, emphasizing the results of the 2014 survey for MCV1, DTP3, fully immunized for age (FULL), and zero dose (ZERO). The largest drivers of vaccination inequity are socioeconomic status and the educational attainment of the child's mother. MCV1, DTP3, and FULL exhibit increasing levels of both coverage and equity with increasing survey years. The national composite Wagstaff concentration index values from the 2014 survey for DTP3, MCV1, ZERO, and FULL are 0.089, 0.068, 0.573, and 0.087, respectively. The difference in vaccination status coverage between the most and least advantaged quintiles of Cambodia's population, using multivariate ranking criteria, is 23.5% for DTP3, 19.5% for MCV1, 9.1% for ZERO, and 30.3% for FULL. By utilizing these VERSE Equity Tool outputs, immunization program leaders in Cambodia can identify subnational regions in need of targeted interventions.

Protein engineering of invertase for enhancing yeast dough fermentation under high-sucrose conditions.

During yeast dough fermentation, such as the high-sucrose bread-making process, the yeast cells are subjected to considerable osmotic stress, resulting in poor outcomes. Invertase is important for catalyzing the irreversible hydrolysis of sucrose to free glucose and fructose, and decreasing the catalytic activity of the invertase may reduce the glucose osmotic stress on the yeast. In this study, we performed structural design and site-directed mutagenesis (SDM) on the Saccharomyces cerevisiae invertase (ScInV) in an Escherichia coli expression system to study the catalytic activity of ScInV mutants in vitro. In addition, we generated the same mutation sites in the yeast endogenous genome and tested their invertase activity in yeast and dough fermentation ability. Our results indicated that appropriately reduced invertase activity of yeast ScInV can enhance dough fermentation activity under high-sucrose conditions by 52%. Our systems have greatly accelerated the engineering of yeast endogenous enzymes both in vitro and in yeast, and shed light on future metabolic engineering of yeast.

Histone demethylases in the regulation of immunity and inflammation.

Pathogens or danger signals trigger the immune response. Moderate immune response activation removes pathogens and avoids excessive inflammation and tissue damage. Histone demethylases (KDMs) regulate gene expression and play essential roles in numerous physiological processes by removing methyl groups from lysine residues on target proteins. Abnormal expression of KDMs is closely associated with the pathogenesis of various inflammatory diseases such as liver fibrosis, lung injury, and autoimmune diseases. Despite becoming exciting targets for diagnosing and treating these diseases, the role of these enzymes in the regulation of immune and inflammatory response is still unclear. Here, we review the underlying mechanisms through which KDMs regulate immune-related pathways and inflammatory responses. In addition, we also discuss the future applications of KDMs inhibitors in immune and inflammatory diseases.

Pain-Related Risk Factors Among Radiologic Stages of Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: To investigate whether risk factors related to pain vary at different stages of knee osteoarthritis (OA). METHODS: Individuals from the Osteoarthritis Initiative with available Kellgren/Lawrence (K/L) grade and numerical rating scale (NRS) data at baseline were included in this study. Pain severity was classified into 3 categories based on NRS scores: no pain, mild pain, and moderate/severe pain. Knee OA severity was stratified into 4 categories according to the K/L system. Pain risk factors were evaluated using generalized ordinal logistic regression analysis, and a heatmap was created to compare differences in standardized regression coefficients between subgroups of patients with different knee OA severities. RESULTS: A total of 4,446 subjects were included in this study: 1,574 individuals without pain (35.4%), 1,138 individuals with mild pain (25.6%), and 1,734 individuals with moderate/severe pain (39.0%). For the entire population and subjects in the premorbid-stage subgroup, knee injury history, diabetes mellitus, depression, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and valgus malaligned knees were associated with more severe pain. Older age and stronger quadriceps muscles were associated with milder pain. As the disease progressed, the number of significant risk factors decreased. Only age and quadriceps muscle force remained significant in end-stage disease. CONCLUSION: Multiple factors are associated with pain in patients with knee OA. As the disease progresses, the number of significant risk factors gradually reduces. These findings suggest that strategies for managing pain related to knee OA should vary depending on radiographic grades.

Fasudil alleviates cerebral ischemia­reperfusion injury by inhibiting inflammation and improving neurotrophic factor expression in rats.

The Rho kinase inhibitor fasudil exerts neuroprotective effects. We previously showed that fasudil can regulate M1/M2 microglia polarization and inhibit neuroinflammation. Here, the therapeutic effect of fasudil on cerebral ischemia­reperfusion (I/R) injury was investigated using the middle cerebral artery occlusion and reperfusion (MCAO/R) model in Sprague­Dawley rats. The effect of fasudil on the phenotype of microglia and neurotrophic factors in the I/R brain and its potential molecular mechanism was also explored. It was found that fasudil ameliorated neurological deficits, neuronal apoptosis, and inflammatory response in rats with cerebral I/R injury. Fasudil also promoted the polarization of microglia into the M2 phenotype, in turn promoting the secretion of neurotrophic factors. Furthermore, fasudil significantly inhibited the expression of TLR4 and NF­κB. These findings suggest that fasudil could inhibit the neuroinflammatory response and reduce brain injury after I/R injury by regulating the shift of microglia from an inflammatory M1 phenotype to an anti­inflammatory M2 phenotype, which may be related to the regulation of the TLR4/ NF­κB signal pathway.

The Association Between Quadriceps Strength and Synovitis in Knee Osteoarthritis: An Exploratory Study From the Osteoarthritis Initiative.

OBJECTIVE: The aim of this study was to explore the association between quadriceps strength and synovitis in knee osteoarthritis (KOA). METHODS: This study was derived from the Osteoarthritis Initiative (OAI), which recruited adults from the OAI cohort with or at risk of KOA. Knees with complete records of isometric quadriceps strength and effusion-synovitis and Hoffa-synovitis assessments were included. Quadriceps strength was measured isometrically at baseline. Effusion-synovitis and Hoffa-synovitis were measured using the Magnetic Resonance Imaging Osteoarthritis Knee Score at baseline and at 1-year and 2-year follow-ups. Generalized estimating equations were used to analyze the associations of baseline quadriceps strength with changes in effusion-synovitis and Hoffa-synovitis in multivariable analyses. Additionally, analyses were stratified by synovitis-driven inflammatory phenotypes. RESULTS: A total of 1513 knees were included in this study. In total, 61% of the subjects were female; subjects had an average age of 61.9 (SD 8.8) years and a mean BMI of 29.4 (SD 4.7). Regarding the whole population, baseline quadriceps strength was negatively associated with baseline effusion-synovitis and follow-up changes in effusion-synovitis (odds ratio [OR] 0.77-0.86), but no significant association was observed in terms of Hoffa-synovitis. Stratified by synovitis-driven inflammatory phenotype, baseline quadriceps strength was significantly associated with follow-up changes in effusion-synovitis-but not in Hoffa-synovitis-in the population with existing effusion-synovitis (OR 0.75-0.79). CONCLUSION: Higher baseline quadriceps strength was negatively associated with changes in effusion-synovitis-but not in Hoffa-synovitis-especially in the population with existing effusion-synovitis. Our findings suggested a potential protective role of the quadriceps in effusion-synovitis.

Nanoplastics dominate the cotransport of small-scale plastics in seawater-saturated porous media.

The transport of microplastics (MP) or nanoplastics (NP) in porous media has been widely reported. However, their mutual interaction and effect on cotransport remain unclear. Here, we investigated the colloidal interaction between NP (50 nm), submicroplastics (SP, 300 nm), and MP (1000 nm) in seawater and their cotransport in saturated natural sea sands. In the single-component suspension, the recovered mass percentage (Meff) of colloids was as follows: MP (47.81%) > NP (24.18%) > SP (21.66%). SP and MP remained monodispersed. MP had the highest mobility due to the strongest electrostatic repulsion with sand surface, whereas NP formed homoaggregates and was characterized by ripening phenomena. In the SP-MP mixture, SP and MP kept independent mobility without mutual effect. In the NP-SP-MP mixture, the Meff of MP was reduced by 10% because unstable NP induced MP to form heteroaggregates with SP, which could not pass through the pores. In addition, NP attached to the sand surface could form additional retention sites to retain MP. By contrast, SP showed a 13% increase in Meff because MP became an indirect carrier of SP through the bridging of NP. Overall, this study demonstrates the dominant role of unstable NP in the cotransport of NP-SP-MP in the marine sedimentary environment.

Alexithymia and post-traumatic stress disorder symptoms in Chinese undergraduate students during the COVID-19 national lockdown: The mediating role of sleep problems and the moderating role of self-esteem.

Objective: This study examined whether sleep disturbance was a mediator between alexithymic traits and post-traumatic stress disorder (PTSD) COVID-19 pandemic-related stress symptoms, and explored whether self-esteem moderated the alexithymic contribution to poor sleep and PTSD symptoms. Method: A representative sample of young adults (N = 2,485) from six universities in Southwest China completed online self-report surveys on alexithymia, sleep, PTSD, self-esteem, sociodemographic information, and health-related behaviors. Results: High alexithymic young adults were found to be more likely to have higher sleep problems and higher PTSD symptoms. The moderated mediation model showed that sleep problems mediated the associations between alexithymia and PTSD symptoms. Alexithymic people with lower self-esteem were more likely to have elevated PTSD symptoms and sleep problems than those with higher self-esteem. Conclusion: Targeted psychological interventions for young people who have difficulty expressing and identifying emotions are recommended as these could assist in reducing their post-traumatic psychophysical and psychological problems. Improving self-esteem could also offer some protection for trauma-exposed individuals.

Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research.

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.