Validity and Reliability of a Smartphone Application for Home Measurement of Four-Meter Gait Speed in Older Adults.

The four-meter gait speed (4MGS) is a recommended physical performance test in older adults but is challenging to implement clinically. We developed a smartphone application (App) with a four-meter ribbon for remote 4MGS testing at home. This study aimed to assess the validity and reliability of this smartphone App-based assessment of the home 4MGS. We assessed the validity of the smartphone App by comparing it against a gold standard video assessment of the 4MGS conducted by study staff visiting community-dwelling older adults and against the stopwatch-based measurement. Moreover, we assessed the test-retest reliability in two supervised sessions and three additional sessions performed by the participants independently, without staff supervision. The 4MGS measured by the smartphone App was highly correlated with video-based 4MGS (r = 0.94), with minimal differences (mean = 0.07 m/s, ± 1.96 SD = 0.12) across a range of gait speeds. The test-retest reliability for the smartphone App 4MGS was high (ICC values: 0.75 to 0.93). The home 4MGS in older adults can be measured accurately and reliably using a smartphone in the pants pocket and a four-meter strip of ribbon. Leveraging existing technology carried by a significant portion of the older adult population could overcome barriers in busy clinical settings for this well-established objective mobility test.

Feasibility of High-Frequency Monitoring of the Home Environment and Health in Older Adults: Proof of Concept.

Technology provides new opportunities to understand and optimize the relationship between the home indoor environmental quality and health outcomes in older adults. We aimed to establish proof-of-concept and feasibility of remote, real-time, high-frequency, and simultaneous monitoring of select environmental variables and outcomes related to health and wellbeing in older adults. Thirty-four participants (27 were female) with an average age (SD) of 81 years (±7.1) were recruited from community and supportive housing environments. Environmental sensors were installed in each home and participants were asked to use a wearable device on their finger and answer smartphone-based questionnaires on a daily basis. Further, a subgroup of participants were asked to complete tablet-based cognitive tests on a daily basis. Average compliance with the wearable (time worn properly / total time with device) was 81%. Participants responded to 69% of daily smartphone surveys and completed 80% of the prescribed cognitive tests. These results suggest that it is feasible to study the impact of the home thermal environment and air quality on biological rhythms, cognition, and other outcomes in older adults. However, the success of non-passive data collection elements may be contingent upon baseline cognition.

Steatosis Quantification on Ultrasound Images by a Deep Learning Algorithm on Patients Undergoing Weight Changes.

INTRODUCTION: A deep learning algorithm to quantify steatosis from ultrasound images may change a subjective diagnosis to objective quantification. We evaluate this algorithm in patients with weight changes. MATERIALS AND METHODS: Patients (N = 101) who experienced weight changes ≥ 5% were selected for the study, using serial ultrasound studies retrospectively collected from 2013 to 2021. After applying our exclusion criteria, 74 patients from 239 studies were included. We classified images into four scanning views and applied the algorithm. Mean values from 3-5 images in each group were used for the results and correlated against weight changes. RESULTS: Images from the left lobe (G1) in 45 patients, right intercostal view (G2) in 67 patients, and subcostal view (G4) in 46 patients were collected. In a head-to-head comparison, G1 versus G2 or G2 versus G4 views showed identical steatosis scores (R2 > 0.86, p < 0.001). The body weight and steatosis scores were significantly correlated (R2 = 0.62, p < 0.001). Significant differences in steatosis scores between the highest and lowest body weight timepoints were found (p < 0.001). Men showed a higher liver steatosis/BMI ratio than women (p = 0.026). CONCLUSIONS: The best scanning conditions are 3-5 images from the right intercostal view. The algorithm objectively quantified liver steatosis, which correlated with body weight changes and gender.

Integrating Low-Order and High-Order Correlation Information for Identifying Phage Virion Proteins.

Phage virion proteins (PVPs) play an important role in the host cell. Fast and accurate identification of PVPs is beneficial for the discovery and development of related drugs. Although wet experimental approaches are the first choice to identify PVPs, they are costly and time-consuming. Thus, researchers have turned their attention to computational models, which can speed up related studies. Therefore, we proposed a novel machine-learning model to identify PVPs in the current study. First, 50 different types of physicochemical properties were used to denote protein sequences. Next, two different approaches, including Pearson's correlation coefficient (PCC) and maximal information coefficient (MIC), were employed to extract discriminative information. Further, to capture the high-order correlation information, we used PCC and MIC once again. After that, we adopted the least absolute shrinkage and selection operator algorithm to select the optimal feature subset. Finally, these chosen features were fed into a support vector machine to discriminate PVPs from phage non-virion proteins. We performed experiments on two different datasets to validate the effectiveness of our proposed method. Experimental results showed a significant improvement in performance compared with state-of-the-art approaches. It indicates that the proposed computational model may become a powerful predictor in identifying PVPs.

An Educational Program for Remote Training and Supervision of Home-Based Transcranial Electrical Stimulation: Feasibility and Preliminary Effectiveness.

OBJECTIVES: There has been recent interest in the administration of transcranial electrical stimulation (tES) by a caregiver, family member, or patient themselves while in their own homes (HB-tES). The need to properly train individuals in the administration of HB-tES is essential, and the lack of a uniform training approach across studies has come to light. The primary aim of this paper is to present the HB-tES training and supervision program, a tele-supervised, instructional, and evaluation program to teach laypersons how to administer HB-tES to a participant and to provide a standardized framework for remote monitoring of participants by teaching staff. The secondary aim is to present early pilot data on the feasibility and effectiveness of the training portion of the program based on its implementation in 379 sessions between two pilot clinical trials. MATERIALS AND METHODS: The program includes instructional materials, standardized tele-supervised hands-on practice sessions, and a system for remote supervision of participants by teaching staff. Nine laypersons completed the training program. Data on the feasibility and effectiveness of the program were collected. RESULTS: No adverse events were reported during the training or any of the HB-tES sessions after the training. All laypersons successfully completed the training. The nine laypersons reported being satisfied with the training program and confident in their tES administration capabilities. This was consistent with laypersons requiring technical assistance from teaching staff very infrequently during the 379 completed sessions. The average adherence rate between all administrators was >98%, with seven of nine administrators having 100% adherence to the scheduled sessions. CONCLUSIONS: These findings indicate that the HB-tES program is effective and is associated with participant satisfaction. SIGNIFICANCE: We hope that the remote nature of this training program will facilitate increased accessibility to HB-tES research for participants of different demographics and locations. This program, designed for easy adaptation to different HB-tES research applications and devices, also is accessible online. The adoption of this program is expected to facilitate uniformity of study methods among future HB-tES studies and thereby accelerate the pace of tES intervention discovery.

A shape-memory poly(ε-caprolactone) hybridized TiO2/poly(l-lactide) composite with antibacterial properties.

Organic-inorganic composites as an efficient strategy to upgrade the structural and functional properties of synthetic polymers are attracting extensive attentions. However, there are few studies on the shape memory (SM) behavior of organic-inorganic composites. In the work, poly(ε-caprolactone) hybridized TiO2 nanomaterial (PCL-TiO2) is made as the switching phase and integrated into poly (l-lactide) (PLLA) to construct an SM composite. PCL-TiO2/PLLA shows "sea-island" structure and better interfacial adhesion than PCL/PLLA, which facilitates the transmission of elastic power between the switching phase and the fixing phase. PCL-TiO2 as switching phase exhibits lower enthalpy at 57 °C than PCL, and PCL-TiO2 also acts as "heat dispersion pump station", which builds a dynamically responsive system and initiates shape change. The shape fixing and recovery ratio of PCL-TiO2/PLLA are 93.9 % and 94.4 %, respectively, and go back to the original shape within 15 s at 57 °C. At the same time, PCL-TiO2 endows SMP with good antibacterial properties. Then this work provides a well-placed way for developing SM materials with structure-function integration.

Nighttime ambient temperature and sleep in community-dwelling older adults.

This longitudinal study examines the association between bedroom nighttime temperature and sleep quality in a sample of community dwelling older adults. Using wearable sleep monitors and environmental sensors, we assessed sleep duration, efficiency, and restlessness over an extended period within participants' homes while controlling for potential confounders and covariates. Our findings demonstrated that sleep was most efficient and restful when nighttime ambient temperature ranged between 20 and 25 °C, with a clinically relevant 5-10 % drop in sleep efficiency when the temperature increased from 25 °C to 30 °C. The associations were primarily nonlinear, and substantial between-subject variations were observed. These results highlight the potential to enhance sleep quality in older adults by optimizing home thermal environments and emphasize the importance of personalized temperature adjustments based on individual needs and circumstances. Additionally, our study underscores the potential impact of climate change on sleep quality in older adults, particularly those with lower socioeconomic status, and supports increasing their adaptive capacity in the face of a changing climate.

Tele-supervised home-based transcranial alternating current stimulation (tACS) for Alzheimer's disease: a pilot study.

Background: Over 55 million people worldwide are currently diagnosed with Alzheimer's disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS). Methods: Eight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2-3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2-3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD. Results: All participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus -0.64 ± 3.28 and Taper -2.56 ± 5.03 Phases. Conclusion: This pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04783350?term=NCT04783350&draw=2&rank=1, identifier NCT04783350.

RAD21 is the core subunit of the cohesin complex involved in directing genome organization.

BACKGROUND: The ring-shaped cohesin complex is an important factor for the formation of chromatin loops and topologically associating domains (TADs) by loop extrusion. However, the regulation of association between cohesin and chromatin is poorly understood. In this study, we use super-resolution imaging to reveal the unique role of cohesin subunit RAD21 in cohesin loading and chromatin structure regulation. RESULTS: We directly visualize that up-regulation of RAD21 leads to excessive chromatin loop extrusion into a vermicelli-like morphology with RAD21 clustered into foci and excessively loaded cohesin bow-tying a TAD to form a beads-on-a-string-type pattern. In contrast, up-regulation of the other four cohesin subunits results in even distributions. Mechanistically, we identify that the essential role of RAD21 is attributed to the RAD21-loader interaction, which facilitates the cohesin loading process rather than increasing the abundance of cohesin complex upon up-regulation of RAD21. Furthermore, Hi-C and genomic analysis reveal how RAD21 up-regulation affects genome-wide higher-order chromatin structure. Accumulated contacts are shown at TAD corners while inter-TAD interactions increase after vermicelli formation. Importantly, we find that in breast cancer cells, the expression of RAD21 is aberrantly high with poor patient survival and RAD21 forms beads in the nucleus. Up-regulated RAD21 in HeLa cells leads to compartment switching and up-regulation of cancer-related genes. CONCLUSIONS: Our results provide key insights into the molecular mechanism by which RAD21 facilitates the cohesin loading process and provide an explanation to how cohesin and loader work cooperatively to promote chromatin extrusion, which has important implications in construction of three-dimensional genome organization.

The age-related contribution of cognitive function to dual-task gait in middle-aged adults in Spain: observations from a population-based study.

BACKGROUND: Poor dual-task gait performance is associated with a risk of falls and cognitive decline in adults aged 65 years or older. When and why dual-task gait performance begins to deteriorate is unknown. This study aimed to characterise the relationships between age, dual-task gait, and cognitive function in middle age (ie, aged 40-64 years). METHODS: We conducted a secondary analysis of data from community-dwelling adults aged 40-64 years that took part in the Barcelona Brain Health Initiative (BBHI) study, an ongoing longitudinal cohort study in Barcelona, Spain. Participants were eligible for inclusion if they were able to walk independently without assistance and had completed assessments of both gait and cognition at the time of analysis and ineligble if they could not understand the study protocol, had any clinically diagnosed neurological or psychiatric diseases, were cognitively impaired, or had lower-extremity pain, osteoarthritis, or rheumatoid arthritis that could cause abnormal gait. Stride time and stride time variability were measured under single-task (ie, walking only) and dual-task (ie, walking while performing serial subtractions) conditions. Dual-task cost (DTC; the percentage increase in the gait outcomes from single-task to dual-task conditions) to each gait outcome was calculated and used as the primary measure in analyses. Global cognitive function and composite scores of five cognitive domains were derived from neuropsychological testing. We used locally estimated scatterplot smoothing to characterise the relationship between age and dual-task gait, and structural equation modelling to establish whether cognitive function mediated the association between observed biological age and dual tasks. FINDINGS: 996 people were recruited to the BBHI study between May 5, 2018, and July 7, 2020, of which 640 participants completed gait and cognitive assessments during this time (mean 24 days [SD 34] between first and second visit) and were included in our analysis (342 men and 298 women). Non-linear associations were observed between age and dual-task performance. Starting at 54 years, the DTC to stride time (ß=0·27 [95% CI 0·11 to 0·36]; p<0·0001) and stride time variability (0·24 [0·08 to 0·32]; p=0·0006) increased with advancing age. In individuals aged 54 years or older, decreased global cognitive function correlated with increased DTC to stride time (ß=-0·27 [-0·38 to -0·11]; p=0·0006) and increased DTC to stride time variability (ß=-0·19 [-0·28 to -0·08]; p=0·0002). INTERPRETATION: Dual-task gait performance begins to deteriorate in the sixth decade of life and, after this point, interindividual variance in cognition explains a substantial portion of dual-task performance. FUNDING: La Caixa Foundation, Institut Guttmann, and Fundació Abertis.

Fabrication and characterization of hybrid eco-friendly high methoxyl pectin/gelatin/TiO2/curcumin (PGTC) nanocomposite biofilms for salmon fillet packaging.

Hybrid eco-friendly nanocomposite films were fabricated by blending high-methoxyl pectin, gelatin, TiO2, and curcumin through the solution casting method. Various concentrations (0-5 wt%) of TiO2 nanoparticles (TNPs) and curcumin as an organic filler were added to the blend solutions. A high TNP concentration affected the surface morphology, roughness, and compactness of the films. Additionally, 3D mapping revealed the nanoparticle distribution in the film layers. Moisture content, water solubility, and light transmittance reduced dramatically with increasing TNP content, in accordance with the water vapor and oxygen permeabilities. X-ray diffraction revealed that the films were semicrystalline nanocomposites, and the thermal properties of the films increased when 5 wt% of TNPs was incorporated into the blend solution. Fourier-transform infrared and Raman analyses revealed interactions among biopolymers, nanoparticles, and organic fillers through hydrogen bonding. The shelf life of fresh salmon fillets was prolonged to six days for all groups, revealed by total viable counts and psychrotrophic bacteria counts, and the pH of the salmon fillets could be extended until the sixth day for all groups. Biodegradation assays demonstrated a significant weight loss in the nanocomposite films. Therefore, a nanocomposite film with 5 wt% TNPs could potentially be cytotoxic to NIH 3T3 cells.

The Predictive Value of Midscalp Hair Density and Terminal Hair Percentage in the Severity Evaluation of FPHL Assessed by Trichoscan in a Sample of Chinese Population.

Background: Female pattern hair loss (FPHL) is the most common hair loss disorder in women, which may impair patient's self-identity. It presents as a diffuse reduction in hair density at the mid and frontal regions of the scalp with preservation of the frontal hairline. TrichoScan can be used as a diagnostic tool and for monitoring patients in male pattern hair loss, but little is known in FPHL with Chinese population. Objective: To explore the predictive value of various TrichoScan characteristics at different areas of the scalp in the diagnosis and evaluation of FPHL. Materials and Methods: A total of 261 FPHL subjects were divided into three groups according to Ludwig classification. Together with 108 healthy controls, they were evaluated by computer-assisted TrichoScan. Various hair parameters were analyzed in the frontal, midscalp, vertex, parietal, and occipital areas of the scalp. Results: Declining hair densities, terminal hair percentage, hair follicular unit density, mean hair diameter, and average hair/unit combined with increased intermediate hair percentage, and vellus hair percentage were observed across all areas of the scalp for FPHL subjects. Hair density and terminal hair percentage in the midscalp area were the factors most affecting Ludwig classification. The two parameters combined achieved 85.12% correct classification rate and an area under the ROC curve of 0.88 in the diagnosis of FPHL. Additionally, we reported a unique type of FPHL which mostly affected the parietal area, occurring with or without traditional midline changes. Conclusion: FPHL in a Chinese population presented characteristics of reduced hair density and miniaturization of hair follicles in the midline scalp and to a lesser extent in the parietal area. Hair density and terminal hair percentage in the midscalp exhibited the greatest predictive value of Ludwig classification. Our results may further provide the basis for quantitative classification of FPHL.

A Comprehensive Survey of Abstractive Text Summarization Based on Deep Learning.

With the rapid development of the Internet, the massive amount of web textual data has grown exponentially, which has brought considerable challenges to downstream tasks, such as document management, text classification, and information retrieval. Automatic text summarization (ATS) is becoming an extremely important means to solve this problem. The core of ATS is to mine the gist of the original text and automatically generate a concise and readable summary. Recently, to better balance and develop these two aspects, deep learning (DL)-based abstractive summarization models have been developed. At present, for ATS tasks, almost all state-of-the-art (SOTA) models are based on DL architecture. However, a comprehensive literature survey is still lacking in the field of DL-based abstractive text summarization. To fill this gap, this paper provides researchers with a comprehensive survey of DL-based abstractive summarization. We first give an overview of abstractive summarization and DL. Then, we summarize several typical frameworks of abstractive summarization. After that, we also give a comparison of several popular datasets that are commonly used for training, validation, and testing. We further analyze the performance of several typical abstractive summarization systems on common datasets. Finally, we highlight some open challenges in the abstractive summarization task and outline some future research trends. We hope that these explorations will provide researchers with new insights into DL-based abstractive summarization.

Accurate and generalizable quantitative scoring of liver steatosis from ultrasound images via scalable deep learning.

BACKGROUND: Hepatic steatosis is a major cause of chronic liver disease. Two-dimensional (2D) ultrasound is the most widely used non-invasive tool for screening and monitoring, but associated diagnoses are highly subjective. AIM: To develop a scalable deep learning (DL) algorithm for quantitative scoring of liver steatosis from 2D ultrasound images. METHODS: Using multi-view ultrasound data from 3310 patients, 19513 studies, and 228075 images from a retrospective cohort of patients received elastography, we trained a DL algorithm to diagnose steatosis stages (healthy, mild, moderate, or severe) from clinical ultrasound diagnoses. Performance was validated on two multi-scanner unblinded and blinded (initially to DL developer) histology-proven cohorts (147 and 112 patients) with histopathology fatty cell percentage diagnoses and a subset with FibroScan diagnoses. We also quantified reliability across scanners and viewpoints. Results were evaluated using Bland-Altman and receiver operating characteristic (ROC) analysis. RESULTS: The DL algorithm demonstrated repeatable measurements with a moderate number of images (three for each viewpoint) and high agreement across three premium ultrasound scanners. High diagnostic performance was observed across all viewpoints: Areas under the curve of the ROC to classify mild, moderate, and severe steatosis grades were 0.85, 0.91, and 0.93, respectively. The DL algorithm outperformed or performed at least comparably to FibroScan control attenuation parameter (CAP) with statistically significant improvements for all levels on the unblinded histology-proven cohort and for "= severe" steatosis on the blinded histology-proven cohort. CONCLUSION: The DL algorithm provides a reliable quantitative steatosis assessment across view and scanners on two multi-scanner cohorts. Diagnostic performance was high with comparable or better performance than the CAP.

1+1>2: Fiber Synergy in Aggregation-Induced Emission.

Mesoscopic aggregate is important to transfer or even amplify the molecular information in macroscopic materials. As an important branch of aggregate science, aggregation-induced emissive luminogens (AIEgens) often show slight or even no emission in solutions but exhibit bright emission when they aggregate, which open a new avenue for the practical applications. Due to the flexible and rotor structure of AIEgens, the aggregate structure of AIEgens is highly sensitive to the surrounding microenvironment, resulting in adjustable optical properties. Fibers integrated of a multiplicity of functional components are ideal carriers to control the aggregation processes, further assembly of fibers produces large-scale fabrics with amplified functions and practical values. In this Concept article, we focus on the latest advances on the synergy between "AIE+Fiber" for the boosted performance that beyond AIE, and their applications are presented and abstracted out to stimulate new ideas for developing "AIE+Fiber" systems.

Transcranial magnetic stimulation (TMS) for geriatric depression.

BACKGROUND: The prevalence of treatment-resistant geriatric depression (GD) highlights the need for treatments that preserve cognitive functions and recognize polypharmacy in elderly, yet effectively reduce symptom burden. Transcranial magnetic stimulation (TMS) is a proven intervention for treatment-resistant depression in younger adults but the efficacy of TMS to treat depressed older adults is still unclear. This review provides an updated view on the efficacy of TMS treatment for GD, discusses methodological differences between trials in TMS application, and explores avenues for optimization of TMS treatment in the context of the ageing brain. METHODS: A systematic review was conducted to identify published literature on the antidepressant efficacy of TMS for GD. Databases PubMed, Embase, and PsycINFO were searched for English language articles in peer-reviewed journals in March 2021. RESULTS: Seven randomized controlled trials (RCTs) (total n = 260, active n = 148, control n = 112) and seven uncontrolled trials (total n = 160) were included. Overall, we found substantial variability in the clinical response, ranging from 6.7% to 54.3%. CONCLUSIONS: The reviewed literature highlights large heterogeneity among studies both in terms of the employed TMS dosage and the observed clinical efficacy. This highlights the need for optimizing TMS dosage by recognizing the unique clinical features of GD. We showcase a set of novel approaches for the optimization of the TMS protocol for depression and discuss the possibility for a standardized TMS protocol tailored for the treatment of GD.

Effects of Continuous LPS Induction on Oxidative Stress and Liver Injury in Weaned Piglets.

Due to imperfections in their immune and digestive systems, weaned piglets are susceptible to invasions of the external environment and diseases, especially bacterial infections, which lead to slow growth, tissue damage, and even the death of piglets. Here, a model of weaned piglets induced by Escherichia coli lipopolysaccharide (LPS) was established to explore the effects of continuous low-dose LPS induction on the mechanism of liver injury. A total of forty-eight healthy 28-day-old weaned piglets (weight = 6.65 ± 1.19 kg) were randomly divided into two groups: the CON group and LPS group. During the experimental period of thirteen days, the LPS group was injected intraperitoneally with LPS (100 µg/kg) once per day, and the CON group was treated with the same volume of 0.9% NaCl solution. On the 1st, 5th, 9th, and 13th days, the serum and liver of the piglets were collected for the determination of serum biochemical indexes, an antioxidant capacity evaluation, and histopathological examinations. In addition, the mRNA expression levels of the TLR4 pathway and inflammatory cytokines were detected. The results showed that the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in the serum increased after LPS induction. The activities of total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) in the serum and liver homogenate of the LPS group were lower than those of the CON group, while the malondialdehyde (MDA) content in the serum and the activities of catalase (CAT) and superoxide dismutase (SOD) in the liver of the LPS group were higher than those in the CON group. At the same time, morphological impairment of the livers occurred, including hepatocyte caryolysis, hepatocyte vacuolization, karyopycnosis, and inflammatory cell infiltration, and the mRNA expression levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-10 were upregulated in the livers after LPS induction. The above results were more obvious on the 1st and 5th days of LPS induction, while the trend during the later period was not significant. It was concluded that the oxidative stress and liver injury occurred at the early stage of LPS induction, while the liver damage weakened at the later stage. The weaned piglets probably gradually developed tolerance to the endotoxin after the continuous low-dose induction of LPS.

Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis.

Porcine circovirus 2 (PCV2), considered one of the most globally important porcine pathogens, causes postweaning multisystemic wasting syndrome (PMWS). This virus is localized in the mitochondria in pigs with PMWS. Here, we identified, for the first time, a mitochondrial localization signal (MLS) in the PCV2 capsid protein (Cap) at the N-terminus. PK-15 cells showed colocalization of the MLS-EGFP fusion protein with mitochondria. Since the PCV2 Cap also contained a nuclear localization signal (NLS) that mediated entry into the nucleus, we inferred that the subcellular localization of the PCV2 Cap is inherently complex and dependent on the viral life cycle. Furthermore, we also determined that deletion of the MLS attenuated Cap-induced apoptosis. More importantly, the MLS was essential for PCV2 replication, as absence of the MLS resulted in failure of virus rescue from cells infected with infectious clone DNA. In conclusion, the MLS of the PCV2 Cap plays critical roles in Cap-induced apoptosis, and MLS deletion of Cap is lethal for virus rescue.

Targeted tDCS Mitigates Dual-Task Costs to Gait and Balance in Older Adults.

OBJECTIVE: Among older adults, the ability to stand or walk while performing cognitive tasks (ie, dual-tasking) requires coordinated activation of several brain networks. In this multicenter, double-blinded, randomized, and sham-controlled study, we examined the effects of modulating the excitability of the left dorsolateral prefrontal cortex (L-DLPFC) and the primary sensorimotor cortex (SM1) on dual-task performance "costs" to standing and walking. METHODS: Fifty-seven older adults without overt illness or disease completed 4 separate study visits during which they received 20 minutes of transcranial direct current stimulation (tDCS) optimized to facilitate the excitability of the L-DLPFC and SM1 simultaneously, or each region separately, or neither region (sham). Before and immediately after stimulation, participants completed a dual-task paradigm in which they were asked to stand and walk with and without concurrent performance of a serial-subtraction task. RESULTS: tDCS simultaneously targeting the L-DLPFC and SM1, as well as tDCS targeting the L-DLPFC alone, mitigated dual-task costs to standing and walking to a greater extent than tDCS targeting SM1 alone or sham (p < 0.02). Blinding efficacy was excellent and participant subjective belief in the type of stimulation received (real or sham) did not contribute to the observed functional benefits of tDCS. INTERPRETATION: These results demonstrate that in older adults, dual-task decrements may be amenable to change and implicate L-DPFC excitability as a modifiable component of the control system that enables dual-task standing and walking. tDCS may be used to improve resilience and the ability of older results to walk and stand under challenging conditions, potentially enhancing everyday functioning and reducing fall risks. ANN NEUROL 2021;90:428-439.

DELLA-NAC Interactions Mediate GA Signaling to Promote Secondary Cell Wall Formation in Cotton Stem.

Gibberellins (GAs) promote secondary cell wall (SCW) development in plants, but the underlying molecular mechanism is still to be elucidated. Here, we employed a new system, the first internode of cotton, and the virus-induced gene silencing method to address this problem. We found that knocking down major DELLA genes via VIGS phenocopied GA treatment and significantly enhanced SCW formation in the xylem and phloem of cotton stems. Cotton DELLA proteins were found to interact with a wide range of SCW-related NAC proteins, and virus-induced gene silencing of these NAC genes inhibited SCW development with downregulated biosynthesis and deposition of lignin. The findings indicated a framework for the GA regulation of SCW formation; that is, the interactions between DELLA and NAC proteins mediated GA signaling to regulate SCW formation in cotton stems.