Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.

BACKGROUND: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels. METHODS: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25. RESULTS: A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).

Compound heterozygous variants in SLC45A1 might cause syndromic intellectual disability by localization failure and activity attenuation in cells.

Intellectual disability (ID) is a kind of nervous developmental disorder and affects more than 1% of people worldwide. SLC45A1 as a transmembrane protein is implicated in the regulation of glucose homoeostasis. Through trio-based exome sequencing, the missense mutations of SLC45A1 c.103G>A (p.V35M) and c.1211T>G (p.F404C) were identified in the proband with syndromic ID. The distribution, expression and activity of SLC45A1 wild-type (WT) and variants were assayed in transfected COS7 cells. In SLC45A1 variants, the hydrogen bonds surrounding the 35th and 404th amino acid were changed, location on the cytomembrane was failed, their activity to transport glucose was also significantly decreased to contrast with SLC45A1-WT. No difference was observed at the mRNA and protein level. In conclusion, the compound heterozygous variants of SLC45A1 might be the genetic etiology for syndromic ID. These novel mutations probably attenuated its activity to transport glucose by the alteration of tertiary structure and failure of intracellular location.

Whole-brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice.

Corticotropin-releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus-based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.

Simultaneous reconstruction of 3D fluorescence distribution and object surface using structured light illumination and dual-camera detection.

Fluorescence molecular tomography (FMT) serves as a noninvasive modality for visualizing volumetric fluorescence distribution within biological tissues, thereby proving to be an invaluable imaging tool for preclinical animal studies. The conventional FMT relies upon a point-by-point raster scan strategy, enhancing the dataset for subsequent reconstruction but concurrently elongating the data acquisition process. The resultant diminished temporal resolution has persistently posed a bottleneck, constraining its utility in dynamic imaging studies. We introduce a novel system capable of simultaneous FMT and surface extraction, which is attributed to the implementation of a rapid line scanning approach and dual-camera detection. The system performance was characterized through phantom experiments, while the influence of scanning line density on reconstruction outcomes has been systematically investigated via both simulation and experiments. In a proof-of-concept study, our approach successfully captures a moving fluorescence bolus in three dimensions with an elevated frame rate of approximately 2.5 seconds per frame, employing an optimized scan interval of 5 mm. The notable enhancement in the spatio-temporal resolution of FMT holds the potential to broaden its applications in dynamic imaging tasks, such as surgical navigation.

Adaptive real-time single-pixel imaging.

For most imaging systems, there is a trade-off between spatial resolution, temporal resolution, and signal-to-noise ratio. Such a trade-off is particularly severe in single-pixel imaging systems, given the limited throughput of the only one available pixel. Here we report a real-time single-pixel imaging method that can adaptively balance the spatial resolution, temporal resolution, and signal-to-noise ratio of the imaging system according to the changes in the target scene. When scene changes are detected, the dynamic imaging mode will be activated. The temporal resolution will be given high priority and real-time single-pixel imaging will be conducted at a video frame rate (30 frames/s) to visualize the object motion. When no scene changes are detected, the static imaging mode will be activated. The spatial resolution and the signal-to-noise ratio will be progressively built up to resolve fine structures and to improve image quality. The proposed method not only adds practicability to single-pixel imaging, but also generates a new, to the best of our knowledge, insight in data redundancy reduction and information capacity improvement for other computational imaging schemes.

The Effects of Simultaneous Aerobic Exercise and Video Game Training on Executive Functions and Brain Connectivity in Older Adults.

OBJECTIVE: The study was designed to examine the effects of simultaneous combination of aerobic exercise and video game training on executive functions (EFs) and brain functional connectivity in older adults. DESIGN: A four-armed, quasi-experimental study. SETTING AND PARTICIPANTS: Community-dwelling adults aged 55 years and older. METHODS: A total of 97 older adults were divided into one of four groups: aerobic exercise (AE), video game (VG), combined intervention (CI), and passive control (PC). Participants in intervention groups received 32 sessions of training over a 4-month period at a frequency of twice a week. EFs was evaluated using a composite score derived from a battery of neuropsychological tests. The Montreal Cognitive Assessment (MoCA) was employed to evaluate overall cognitive function, while the 6-Minute Walking Test (6MWT) was utilized to gauge physical function. Additionally, the functional connectivity (FC) of the frontal-parietal networks (FPN) was examined as a neural indicator of cognitive processing and connectivity changes. RESULTS: In terms of EFs, both VG and CI groups demonstrated improvement following the intervention. This improvement was particularly pronounced in the CI group, with a large effect size (Hedge's g = 0.83), while the VG group showed a medium effect size (Hedge's g = 0.56). A significant increase in MoCA scores was also observed in both the VG and CI groups, whereas a significant increase in 6MWT scores was observed in the AE and CI groups. Although there were no group-level changes observed in FC of the FPN, we found that changes in FC was behaviorally relevant as increased FC was associated with greater improvement in EFs. CONCLUSION: The study offers preliminary evidence that both video game training and combined intervention could enhance EFs in older adults. Simultaneous combined intervention may hold greater potential for facilitating EFs gains. The initial evidence for correlated changes in brain connectivity and EFs provides new insights into understanding the neural basis underlying the training gains.

The flower of Abelmoschus manihot (L.) medik exerts antioxidant effects by regulating the Nrf2 signalling pathway in scald injury.

Scald is a common skin injury in daily life. It is well known that skin burns are associated with inflammation and oxidative stress. In our previous study, we found that Abelmoschus manihot (L.) medik had excellent therapeutic effects on scald-induced inflammation, but its effect on scald-induced oxidative stress was not reported. In this study, a deep second-degree scald model in mice was established, and the wound healing rate, healing time, malondialdehyde (MDA) and total superoxide dismutase (T-SOD) levels, and nuclear factor erythroid 2-related Factor 2 (Nrf2) expression in wound tissue were measured to evaluate the scald wound healing performance of extraction from A. manihot (L.) medik (EAM). Scalding activity in mice was examined in vivo by hot water-induced finger swelling. The treatment scald activities were also examined in vivo by subjecting mice to thermal water-induced digit swelling. Additionally, the antioxidant effect of EAM on fibroblasts was also used to determine the mechanism in vitro. The results showed that EAM not only decreased the wound healing time but also effectively regulated the levels of oxidising, MDA and T-SOD in wound tissue. Concurrently, EAM suppressed digit swelling and hyperalgesia. Furthermore, EAM had a significant protective effect on NIH-3T3 cells after H2 O2 injury by regulating the Nrf2 signalling pathway against oxidative injury. Therefore, EAM is a promising drug for the treatment of scald-induced inflammation.

Association between liver fibrosis and stroke recurrence in young patients with ischemic stroke.

BACKGROUND AND AIM: Stroke incidence rates are rising among young adults. Liver fibrosis has recently been recognized as a risk factor for cardiovascular events and stroke in the general population. It remains unclear whether liver fibrosis influences the prognosis of stroke. We aimed to evaluate the association between liver fibrosis and stroke recurrence in young stroke patients. METHODS AND RESULTS: Young adults with first-ever ischemic stroke were enrolled from a prospective stroke registry and were followed up for stroke recurrence. Liver fibrosis was evaluated by Fibrosis-4 (FIB-4) score and was stratified into three categories. Cox regression analysis was performed to assess the relationship between liver fibrosis and stroke recurrence. Over a median follow-up of 3.1 (1.7-4.6) years, 72 (11.6%) recurrent strokes occurred among 621 patients. According to the FIB-4 score, 73 (11.7%) patients had indeterminate fibrosis, while 11 (1.8%) had advanced fibrosis. Univariate Cox analysis revealed that patients with a high FIB-4 score were more likely to experience stroke recurrence than those with a low FIB-4 score (hazard ratio 3.748, 95% confidence interval 1.359-10.332, P = 0.011). After adjusting for potential confounders in the multivariate analysis, FIB-4 score remained an independent risk factor. CONCLUSIONS: Young stroke patients with advanced liver fibrosis were at a greater risk of stroke recurrence. Evaluating liver fibrosis may provide valuable information for stroke risk stratification, and the FIB-4 score could serve as a useful tool.

Low-frequency band noise generated by industrial recirculating aquaculture systems exhibits a greater impact on Micropterus salmoidess.

The effect of underwater noise environment generated by equipment in industrial recirculating aquaculture systems (RAS) on fish is evident. However, different equipment generate noise in various frequency ranges. Understanding the effects of different frequency ranges noise on cultured species is important for optimizing the underwater acoustic environment in RAS. Given this, the effects of underwater noise across various frequency bands in RAS on the growth, physiology, and collective behavior of juvenile largemouth bass (Micropterus salmoides) were comprehensively evaluated here. In this study, three control groups were established: low-frequency noise group (80-1000 Hz, 117 dB re 1µPa RMS), high-frequency noise group (1-19 kHz, 117 dB re 1µPa RMS), and ambient group. During a 30-day experiment, it was found that: 1) industrial RAS noise with different frequency bands all had a certain inhibitory effect on the growth of fish, which the weight gain rate and product of length and depth of caudal peduncle in the ambient group were significantly higher than those of the two noise groups, with the low-frequency noise group showing significantly lower values than the high-frequency noise group; 2) industrial RAS noise had a certain degree of adverse effect on the digestive ability of fish, with the low-frequency noise group being more affected; 3) industrial RAS noise affected the collective feeding behavior of fish, with the collective feeding signal propagation efficiency and feeding intensity of the noise groups being significantly lower than those of the ambient group, and the high-frequency noise group performing better than the low-frequency noise group as a whole therein. From the above, the underwater noise across different frequency bands generated by equipment operation in industrial RAS both had an impact on juvenile largemouth bass, with the low-frequency noise group being more severely affected.

Modal Parameter Recursive Estimation of Concrete Arch Dams under Seismic Loading Using an Adaptive Recursive Subspace Method.

Modal parameter estimation is crucial in vibration-based damage detection and deserves increased attention and investigation. Concrete arch dams are prone to damage during severe seismic events, leading to alterations in their structural dynamic characteristics and modal parameters, which exhibit specific time-varying properties. This highlights the significance of investigating the evolution of their modal parameters and ensuring their accurate identification. To effectively accomplish the recursive estimation of modal parameters for arch dams, an adaptive recursive subspace (ARS) method with variable forgetting factors was proposed in this study. In the ARS method, the variable forgetting factors were adaptively updated by assessing the change rate of the spatial Euclidean distance of adjacent modal frequency identification values. A numerical simulation of a concrete arch dam under seismic loading was conducted by using ABAQUS software, in which a concrete damaged plasticity (CDP) model was used to simulate the dam body's constitutive relation, allowing for the assessment of damage development under seismic loading. Utilizing the dynamic responses obtained from the numerical simulation, the ARS method was implemented for the modal parameter recursive estimation of the arch dam. The identification results revealed a decreasing trend in the frequencies of the four initial modes of the arch dam: from an undamaged state characterized by frequencies of 0.910, 1.166, 1.871, and 2.161 Hz to values of 0.895, 1.134, 1.842, and 2.134 Hz, respectively. Concurrently, increases in the damping ratios of these modes were observed, transitioning from 4.44%, 4.28%, 5.42%, and 5.56% to 4.98%, 4.91%, 6.61%, and 6.85%%, respectively. The correlation of the identification results with damage progression validated the effectiveness of the ARS method. This study's outcomes have substantial theoretical and practical importance, facilitating the immediate comprehension of the dynamic characteristics and operational states of concrete arch dam structures.

Deep learning-assisted identification and quantification of aneurysmal subarachnoid hemorrhage in non-contrast CT scans: Development and external validation of Hybrid 2D/3D UNet.

Accurate stroke assessment and consequent favorable clinical outcomes rely on the early identification and quantification of aneurysmal subarachnoid hemorrhage (aSAH) in non-contrast computed tomography (NCCT) images. However, hemorrhagic lesions can be complex and difficult to distinguish manually. To solve these problems, here we propose a novel Hybrid 2D/3D UNet deep-learning framework for automatic aSAH identification and quantification in NCCT images. We evaluated 1824 consecutive patients admitted with aSAH to four hospitals in China between June 2018 and May 2022. Accuracy and precision, Dice scores and intersection over union (IoU), and interclass correlation coefficients (ICC) were calculated to assess model performance, segmentation performance, and correlations between automatic and manual segmentation, respectively. A total of 1355 patients with aSAH were enrolled: 931, 101, 179, and 144 in four datasets, of whom 326 were scanned with Siemens, 640 with Philips, and 389 with GE Medical Systems scanners. Our proposed deep-learning method accurately identified (accuracies 0.993-0.999) and segmented (Dice scores 0.550-0.897) hemorrhage in both the internal and external datasets, even combinations of hemorrhage subtypes. We further developed a convenient AI-assisted platform based on our algorithm to assist clinical workflows, whose performance was comparable to manual measurements by experienced neurosurgeons (ICCs 0.815-0.957) but with greater efficiency and reduced cost. While this tool has not yet been prospectively tested in clinical practice, our innovative hybrid network algorithm and platform can accurately identify and quantify aSAH, paving the way for fast and cheap NCCT interpretation and a reliable AI-based approach to expedite clinical decision-making for aSAH patients.

White matter changes in young and middle-aged males with chronic prostatitis/chronic pelvic pain syndrome: Tract-based spatial statistics analysis.

The supraspinal mechanism plays a key role in developing and maintaining chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, it is not clear how white matter changes in young and middle-aged males with CP/CPPS. In this cross-sectional study, 23 CP/CPPS patients and 22 healthy controls (HCs) were recruited. Tract-based spatial statistics was applied to investigate the differences in diffusion tensor imaging metrics, including fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD) and axial diffusion (AD), between CP/CPPS patients and HCs. The study also examined the association between white matter alterations and clinical variables in patients using correlation analysis. Compared with HCs, patients showed decreased FA, MD, RD and AD in the body and genu of the corpus callosum and right anterior corona radiata. In addition, they showed increased FA along with decreased MD, RD and AD in the left posterior limb of the internal capsule (PLIC-L), left external capsule and left cerebral peduncle. The FA of PLIC-L was negatively correlated with disease duration (r = -.54, corrected p = .017), while MD and RD were positively correlated (r = .45, corrected p = .042; r = .57, corrected p = .017). These results suggest that CP/CPPS is associated with extensive changes in white matter tracts, which are involved in pain processing. In particular, the FA, MD and RD values in the PLIC-L were correlated with the disease duration, indicating that the long-term course of CP/CPPS may have effects on the white matter microstructure of the pain perception pathways.

Reversal of neurovascular decoupling and cognitive impairment in patients with end-stage renal disease during a hemodialysis session: Evidence from a comprehensive fMRI analysis.

Neurovascular (NV) decoupling is a potential neuropathologic mechanism of cognitive impairment in patients with end-stage renal disease (ESRD). Hemodialysis improves cognitive impairment at 24 h post-dialysis, which suggests a potential neuroprotective effect of hemodialysis treatment on the brain. We investigated the effects of hemodialysis treatment on the reversal of NV decoupling associated with cognitive improvement. A total of 39 patients with ESRD and 39 healthy controls were enrolled. All patients were imaged twice during a dialysis session: before hemodialysis (T1pre-dialysis ) and at 24 h after dialysis (T2post-dialysis ). The healthy controls were imaged once. NV coupling was characterized based on correlation coefficients between four types of blood oxygen level-dependent signals and cerebral blood flow (CBF). A battery of neuropsychological and blood tests was performed before the imaging. Patients with ESRD showed improvements in memory and executive function at T2post-dialysis compared with that at T1pre-dialysis . At both T1pre-dialysis and T2post-dialysis , patients with ESRD had lower amplitude of low-frequency fluctuation (ALFF)-CBF coupling than healthy controls. Additionally, patients with ESRD had higher ALFF-CBF coupling at T2post-dialysis than at T1pre-dialysis . Higher memory scores, higher hemoglobin level, lower total plasma homocysteine level, lower systolic blood pressure variance, and lower ultrafiltration volume were associated with higher ALFF-CBF coupling in patients with ESRD after a hemodialysis session. These findings indicate that partial correction of anemia and hyperhomocysteinemia, stable systolic blood pressure, and fluid restriction may be closely linked to the reversal of NV decoupling and improvement in cognition in patients with ESRD.

Improved Mood Boosts Memory Training Gains in Older Adults With Subjective Memory Complaints via Enhanced Amygdala-hippocampal Connectivity.

OBJECTIVE: Older adults with subjective memory complaints (SMC) have a higher risk of dementia and commonly demonstrate symptoms of anxiety. This study examined the neural correlates of group counseling (GC)-boosted memory training (MT) gains. DESIGN: This study was an active, controlled, randomized trial. SETTING: Neighborhoods near the Institute of Psychology of the Chinese Academy of Sciences (CAS). PARTICIPANTS: Community-dwelling older adults, aged 60 or above with a minimum of 6 years of education, were recruited through advertisements and flyers posted at community service stations. MEASUREMENTS: The amplitude of low-frequency fluctuations and resting-state functional connectivity (rs-FC) analyses were used to examine the neural correlates associated with MT gains enhanced by improved mood in older adults with SMC. Participants were randomly assigned to the combined intervention (CI) or GC group. The CI group received 3 weeks of GC followed by 4 weeks of MT, and the GC group received GC and health lectures. Cognitive function and emotions were assessed before GC (T1), after GC (T2), and after MT (T3). Both groups underwent resting-state functional magnetic resonance imaging scanning at T2 and T3. RESULTS: Alleviated anxiety was positively correlated with rs-FC between the amygdala and left hippocampus and negatively correlated with rs-FC between the amygdala and right hippocampus. MT improvement was negatively correlated with rs-FC between the amygdala and right hippocampus in the CI group; the correlation was not significant after controlling for emotional changes. CONCLUSIONS: Amygdala-hippocampal connectivity may be associated with improved mood-enhanced MT gains in individuals with SMC.

Cognitive Benefit of a Multidomain Intervention for Older Adults at Risk of Cognitive Decline: A Cluster-Randomized Controlled Trial.

OBJECTIVE: We sought to assess cognitive benefits of a community-based multidomain intervention for improving cognition among older adults at risk of cognitive decline (COMBAT). DESIGN: A two-armed cluster-randomized controlled trial. SETTING AND PARTICIPANTS: Community-dwelling older adults aged 60 years or older and were at risk of cognitive decline (n = 209). INTERVENTION: In this 9-month intervention study, 10 community hospitals in Beijing, China, were randomized (1:1) to receive either a multidomain intervention of meditation, cognitive training, exercise, and nutrition counseling or usual care. The intervention was delivered with weekly 1-hour group training sessions and weekly home homework. MEASUREMENTS: Primary outcome was change in cognition as measured by a composite Z score of seven cognitive tests. Secondary outcomes included subjective cognitive abilities, positive and negative affective experiences, physical activity, and dietary habits. Assessments were administered at baseline, end of the intervention, and 1 year after completing the intervention (1-year follow-up). RESULTS: Immediately after the intervention, the intervention group showed significant enhancement in cognitive performance (p = 0.026). The between-group difference in the Z score of change of cognition was 0.20 (95% CI: 0.053, 0.35), with a Hedges' g of 0.40 (95% CI: 0.29, 0.50). However, this cognitive benefit was not significant at 1-year follow-up. CONCLUSION: This multidomain intervention was effective to improve cognition for at-risk individuals. Long-term effects on cognitive function and individual differences in response to the intervention deserve further investigation.

Haemoglobin A1c variability is independently associated with carotid intima media thickness and plaque in type 2 diabetes: a retrospective, cross-sectional study.

Haemoglobin A1c (HbA1c) variability, a metric reflecting long-term glycaemic fluctuation, is associated with macrovascular events in type 2 diabetes. We aimed to investigate the impacts of HbA1c variability on preclinical atherosclerosis in patients without prior cardiovascular disease. We conducted a cross-sectional study on 564 participants with diabetes who underwent general health checkups from 2016-2022. At least three HbA1c measurements were conducted for each patient. Carotid intima-media thickness (CIMT) and plaque were evaluated by B-mode ultrasonography on bilateral carotid common arteries. The standard deviation (SD) and coefficient of variance (CV) of HbA1c were calculated. We found that each doubling in CV-HbA1c and SD-HbA1c was associated with a significant increment in CIMT. The effects were more pronounced in the groups with higher mean-HbA1c (mean-HbA1c ≥6.5%). The odds ratio (95% confidence interval) for the carotid plaque was 2.68 (1.57, 4.56) and 2.88 (1.16, 5.13) in the third tertile of CV-HbA1c and SD-HbA1c respectively after fully adjusting for all the conventional risk factors in the multivariable logistic regression analysis. High mean-HbA1c plus the third tertile of HbA1c variability sharply increased the prevalence of carotid plaques. In conclusion, HbA1c variability was independently associated with CIMT and plaques in populations with diabetes. CV-HbA1c and SD-HbA1c had more effects on subclinical atherosclerosis in patients with poorly-controlled blood glucose levels.

The effects of loneliness, social isolation, and associated gender differences on the risk of developing cognitive impairment for Chinese oldest old.

OBJECTIVES: To investigate whether loneliness and social isolation could independently predict subsequent risk of cognitive impairment in Chinese oldest old, and to examine possible gender differences. METHODS: The sample included 2,732 older adults aged 80 years and above with intact cognitive function from the Chinese Longitudinal Healthy Longevity Survey 2002-2018 waves, with an average follow-up of 4.24 years. Loneliness was measured by a single-item question about how often the participant felt lonely. Social isolation was defined by marital status, frequent visits by family members, and social activity engagement. Cognitive impairment was defined based on Mini-Mental State Examination scores. RESULTS: Cox regression showed that social isolation independently predicted a higher risk of developing cognitive impairment at follow-up (HR = 1.14, 95% CI [1.03, 1.27], p = 0.014). Importantly, although there was no main effect of loneliness, a significant interaction between gender and loneliness (p = 0.013) suggested that increased loneliness was associated with a higher risk of developing cognitive impairment for men but not for women. CONCLUSION: To prevent cognitive impairment and promote healthy longevity, socially isolated adults in their oldest old age should receive more attention, and men who often feel lonely should be offered with more emotional support.

Relations between social withdrawal subtypes and socio-emotional adjustment among Chinese children and early adolescents.

The aim of the present study was to compare the relations between subtypes of social withdrawal and socio-emotional adjustment in Chinese children and early adolescents. Participants included 571 children (Mage  = 9.62 years) and 345 adolescents Mage  = 12.12 years) in mainland China. Social withdrawal subtypes (i.e., shyness, unsociability, social avoidance) and indices of socio-emotional adjustment were assessed via self-reports, peer nominations, and teacher ratings. Shyness tended to be more strongly associated with emotional maladjustment in early adolescence, whereas unsociability was more strongly associated with socio-emotional difficulties in childhood. For social avoidance, associations with indices of negative adjustment (i.e., social anxiety, emotional symptoms, peer problems) were stronger in childhood, however, associations with indices of positive adjustment (i.e., life satisfaction, well-being) were stronger in early adolescence.

Enhancing visual perceptual learning using transcranial electrical stimulation: Transcranial alternating current stimulation outperforms both transcranial direct current and random noise stimulation.

Diverse strategies can be employed to enhance visual skills, including visual perceptual learning (VPL) and transcranial electrical stimulation (tES). Combining VPL and tES is a popular method that holds promise for producing significant improvements in visual acuity within a short time frame. However, there is still a lack of comprehensive evaluation regarding the effects of combining different types of tES and VPL on enhancing visual function, especially with a larger sample size. In the present study, we recruited four groups of subjects (26 subjects each) to learn an orientation discrimination task with five daily training sessions. During training, the occipital region of each subject was stimulated by one type of tES-anodal transcranial direct current stimulation (tDCS), alternating current stimulation (tACS) at 10 Hz, high-frequency random noise stimulation (tRNS), and sham tACS-while the subject performed the training task. We found that, compared with the sham stimulation, both the high-frequency tRNS and the 10-Hz tACS facilitated VPL efficiently in terms of learning rate and performance improvement, but there was little modulatory effect in the anodal tDCS condition. Remarkably, the 10-Hz tACS condition exhibited superior modulatory effects compared with the tRNS condition, demonstrating the strongest modulation among the most commonly used tES types for further enhancing vision when combined with VPL. Our results suggest that alpha oscillations play a vital role in VPL. Our study provides a practical guide for vision rehabilitation.

Deciphering the photoactive species-directed antibacterial mechanism of bismuth oxychloride with modulated nanoscale thickness.

As an environmentally benign disinfection strategy, photocatalytic bacterial inactivation using nanoparticles involves photogenerated reactive species that cause cellular oxidative stress. Rationalising the structural performance of photocatalysts for the practical uses such as wastewater treatment has attracted significant attention; however, the contribution of reactive species to their photocatalytic antibacterial activities at the molecular and transcriptomic levels remains unclear. In this study, nontoxic bismuth oxychloride (BiOCl) photocatalysts with different nanoscale thicknesses, including nanosheets (Ns, ∼5.4 nm), nanoplates (Np, ∼1.8 nm), and ultra-nanosheets (Uns, ∼1.1 nm), were synthesised under hydrothermal conditions. Among the three samples, BiOCl Uns exhibited the most effective photocatalytic degradation efficiency with the calculated apparent rate constant of 0.0294 min-1, ∼4 times faster than that of Ns, whereas BiOCl Ns possessed the most pronounced bactericidal effect (5.4 log inactivation). Such findings indicate the distinct role of the photoactive species responsible for photocatalytic bacterial inactivation. Moreover, transcriptome analysis of Escherichia coli after photocatalytic treatment revealed that the underlying photocatalytic antibacterial mechanism at the genetic expression level involves cellular component biosynthesis, energy metabolism, and material transportation. Notably, the differences between BiOCl Ns and BiOCl Uns were significantly enriched in purine metabolism. Therefore, the cost-effective preparation of BiOCl nanosheets with nanoscale thickness-modulated photocatalytic antibacterial activity has remarkable potential for sustainable environmental and biomedical applications.