Functional near-infrared spectroscopy evidence of cognitive-motor interference in different dual tasks.

Dual tasks (DTs) combining walking with a cognitive task can cause various levels of cognitive-motor interference, depending on which brain resources are recruited in each case. However, the brain activation and functional connectivity underlying cognitive-motor interferences remain to be elucidated. Therefore, this study investigated the neural correlation during different DT conditions in 40 healthy young adults (mean age: 27.53 years, 28 women). The DTs included walking during subtraction or N-Back tasks. Cognitive-motor interference was calculated, and brain activation and functional connectivity were analysed. Portable functional near-infrared spectroscopy was utilized to monitor haemodynamics in the prefrontal cortex (PFC), motor cortex and parietal cortex during each task. Walking interference (decrease in walking speed during DT) was greater than cognitive interference (decrease in cognitive performance during DT), regardless of the type of task. Brain activation in the bilateral PFC and parietal cortex was greater for walking during subtraction than for standing subtraction. Furthermore, brain activation was higher in the bilateral motor and parietal and PFCs for walking during subtraction than for walking alone, but only increased in the PFC for walking during N-Back. Coherence between the bilateral lateral PFC and between the left lateral PFC and left motor cortex was significantly greater for walking during 2-Back than for walking. The PFC, a critical brain region for organizing cognitive and motor functions, played a crucial role in integrating information coming from multiple brain networks required for completing DTs. Therefore, the PFC could be a potential target for the modulation and improvement of cognitive-motor functions during neurorehabilitation.

Transcriptional profiling of mucus production in rhesus macaque endocervical cells under hormonal regulation.

OBJECTIVE: Endocervical mucus production is a key regulator of fertility throughout the menstrual cycle. With cycle-dependent variability in mucus quality and quantity, cervical mucus can either facilitate or block sperm ascension into the upper female reproductive tract. This study seeks to identify genes involved in the hormonal regulation of mucus production, modification, and regulation through profiling the transcriptome of endocervical cells from the non-human primate, the rhesus macaque (Macaca mulatta). INTERVENTION: We treated differentiated primary endocervical cultures with estradiol (E2) and progesterone (P4) to mimic peri-ovulatory and luteal-phase hormonal changes. Using RNA-sequencing, we identified differential expression of gene pathways and mucus producing and modifying genes in cells treated with E2 compared to hormone-free conditions and E2 compared to E2-primed cells treated with P4. MAIN OUTCOME MEASURES: We pursued differential gene expression analysis on RNA-sequenced cells. Sequence validation was done using qPCR. RESULTS: Our study identified 158 genes that show significant differential expression in E2-only conditions compared to hormone-free control, and 250 genes that show significant differential expression in P4-treated conditions compared to E2-only conditions. From this list, we found hormone-induced changes in transcriptional profiles for genes across several classes of mucus production, including ion channels and enzymes involved in post-translational mucin modification that have not previously been described as hormonally regulated. CONCLUSION: Our study is the first to use an in vitro culture system to create an epithelial-cell specific transcriptome of the endocervix. As a result, our study identifies new genes and pathways altered by sex-steroids in cervical mucus production.

Abdominal Diffusion-Weighted MRI With Simultaneous Multi-Slice Acquisition: Agreement and Reproducibility of Apparent Diffusion Coefficients Measurements.

BACKGROUND: Simultaneous multi-slice diffusion-weighted imaging (SMS-DWI) can shorten acquisition time in abdominal imaging. PURPOSE: To investigate the agreement and reproducibility of apparent diffusion coefficient (ADC) from abdominal SMS-DWI acquired with different vendors and different breathing schemes. STUDY TYPE: Prospective. SUBJECTS: Twenty volunteers and 10 patients. FIELD STRENGTH/SEQUENCE: 3.0 T, SMS-DWI with a diffusion-weighted echo-planar imaging sequence. ASSESSMENT: SMS-DWI was acquired using breath-hold and free-breathing techniques in scanners from two vendors, yielding four scans in each participant. Average ADC values were measured in the liver, pancreas, spleen, and both kidneys. Non-normalized ADC and ADCs normalized to the spleen were compared between vendors and breathing schemes. STATISTICAL TESTS: Paired t-test or Wilcoxon signed rank test; intraclass correlation coefficient (ICC); Bland-Altman method; coefficient of variation (CV) analysis; significance level: P < 0.05. RESULTS: Non-normalized ADCs from the four SMS-DWI scans did not differ significantly in the spleen (P = 0.262, 0.330, 0.166, 0.122), right kidney (P = 0.167, 0.538, 0.957, 0.086), and left kidney (P = 0.182, 0.281, 0.504, 0.405), but there were significant differences in the liver and pancreas. For normalized ADCs, there were no significant differences in the liver (P = 0.315, 0.915, 0.198, 0.799), spleen (P = 0.815, 0.689, 0.347, 0.423), pancreas (P = 0.165, 0.336, 0.304, 0.584), right kidney (P = 0.165, 0.336, 0.304, 0.584), and left kidney (P = 0.496, 0.304, 0.443, 0.371). Inter-reader agreements of non-normalized ADCs were good to excellent (ICCs ranged from 0.861 to 0.983), and agreement and reproducibility were good to excellent depending on anatomic location (CVs ranged from 3.55% to 13.98%). Overall CVs for abdominal ADCs from the four scans were 6.25%, 7.62%, 7.08, and 7.60%. DATA CONCLUSION: The normalized ADCs from abdominal SMS-DWI may be comparable between different vendors and breathing schemes, showing good agreement and reproducibility. ADC changes above approximately 8% may potentially be considered as a reliable quantitative biomarker to assess disease or treatment-related changes. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Efficacy of non-invasive brain stimulation for post-stroke dysphagia: a meta-analysis.

BACKGROUND: Given the potential harms of dysphagia after stroke, we noticed the possibility of non-invasive brain stimulation treatments in the management process. METHODS: The meta-analysis search for articles published before May 2023 in databases. We used STATA 12.0 software to compute the standard mean difference (SMD) and 95% confidence intervals (CI). RESULTS: The study showed a greater improvement in swallowing function in post-stroke dysphagia given transcranial direct current stimulation (tDCS) immediately after treatment, compared to those given sham tDCS (SMD = 2.99, 95% CI = 1.86-4.11). The study showed a greater improvement in swallowing function in post-stroke dysphagia given tDCS some days after treatment, compared to those given sham tDCS (SMD = 2.01, 95% CI = 0.87-3.16). The study showed a greater improvement in swallowing function in post-stroke dysphagia given repetitive transcranial magnetic stimulation (rTMS) immediately after treatment, compared to those given sham rTMS (SMD = 4.17, 95% CI = 3.11-5.23). The study showed a greater improvement in swallowing function in post-stroke dysphagia given rTMS some days after treatment, compared to those given sham rTMS (SMD = 1.77, 95% CI = 0.94-2.60). CONCLUSIONS: In conclusion, our study showed the beneficial effects of non-invasive brain stimulation on difficulty swallowing for stroke patients and speculated about the potential application of non-invasive brain stimulation on post-stroke dysphagia improvement.

Intravoxel incoherent motion diffusion weighted imaging for preoperative evaluation of liver regeneration after hepatectomy in hepatocellular carcinoma.

OBJECTIVES: To explore whether intravoxel incoherent motion (IVIM) parameters could evaluate liver regeneration preoperatively. METHODS: A total of 175 HCC patients were initially recruited. The apparent diffusion coefficient, true diffusion coefficient (D), pseudodiffusion coefficient (D*), pseudodiffusion fraction (f), diffusion distribution coefficient, and diffusion heterogeneity index (Alpha) were measured by two independent radiologists. Spearman's correlation test was used to assess correlations between IVIM parameters and the regeneration index (RI), calculated as 100% × (the volume of the postoperative remnant liver - the volume of the preoperative remnant liver) / the volume of the preoperative remnant liver. Multivariate linear regression analyses were used to identify the factors for RI. RESULTS: Finally, 54 HCC patients (45 men and 9 women, mean age 51.26 ± 10.41 years) were retrospectively analyzed. The intraclass correlation coefficient ranged from 0.842 to 0.918. In all patients, fibrosis stage was reclassified as F0-1 (n = 10), F2-3 (n = 26), and F4 (n = 18) using the METAVIR system. Spearman correlation test showed D* (r = 0.303, p = 0.026) was associated with RI; however, multivariate analysis showed that only D value was a significant predictor (p < 0.05) of RI. D and D*showed moderate correlations with fibrosis stage (r = -0.361, p = 0.007; r = -0.457, p = 0.001). Fibrosis stage showed a negative correlation with RI (r = -0.263, p = 0.015). In the 29 patients who underwent minor hepatectomy, only the D value showed a positive association (p < 0.05) with RI, and a negative correlation with fibrosis stage (r = -0.360, p = 0.018). However, in the 25 patients who underwent major hepatectomy, no IVIM parameters were associated with RI (p > 0.05). CONCLUSIONS: The D and D* values, especially the D value, may be reliable preoperative predictors of liver regeneration. KEY POINTS: • The D and D* values, especially the D value, derived from IVIM diffusion-weighted imaging may be useful markers for the preoperative prediction of liver regeneration in patients with HCC. • The D and D* values derived from IVIM diffusion-weighted imaging show significant negative correlations with fibrosis, an important predictor of liver regeneration. • No IVIM parameters were associated with liver regeneration in patients who underwent major hepatectomy, but the D value was a significant predictor of liver regeneration in patients who underwent minor hepatectomy.

Characteristics and prognostic implications of peripheral blood lymphocyte subsets in patients with anti-MDA5 antibody positive dermatomyositis-interstitial lung disease.

OBJECTIVES: To examine the characteristics of blood lymphocyte subsets in dermatomyositis-interstitial lung disease (DM-ILD) inflicted patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5), as well as its prognosis value in this set of patients. METHODS: Data were retrospectively collected from 253 DM-ILD patients from three hospitals in China between January 2016 to January 2021. Patients were grouped into anti-MDA5 antibody positive group (MDA5+ DM-ILD) and anti-MDA5 antibody negative group (MDA5- DM-ILD) based on myositis-specific autoantibody test results. Demographic characteristics, lymphocyte subsets patterns and other clinical features were compared between the two groups. The association of lymphocyte subsets with 180-day mortality was investigated using survival analysis in MDA5+ DM-ILD. RESULTS: Out of 253 eligible patients with DM-ILD, 59 patients were anti-MDA5+ and 194 were anti-MDA5-. Peripheral blood lymphocyte count, CD3+ count, percentage of CD3+, CD3+CD4+ count, and CD3+CD8+ count was lower in MDA5+ DM-ILD than in MDA5- DM-ILD- (all P < 0.001) as well as CD3-CD19+ count (P = 0.04). In MDA5+ DM-ILD, CD3+CD8+ count ≤ 49.22 cell/µL (HR = 3.81, 95%CI [1.20,12.14]) and CD3-CD19+ count ≤ 137.64 cell/µL (HR = 3.43, 95%CI [1.15,10.24]) were independent predictors of mortality. CD3+CD8+ count ≤ 31.38 cell/µL was associated with a higher mortality risk in all DM-ILD patients (HR = 8.6, 95%CI [2.12,31.44]) after adjusting for anti-MDA5 and other clinical characteristics. CONCLUSION: Significant lymphocytes decrease was observed in MDA5+ DM-ILD patients. CD3+CD8+ cell count was associated with worse prognosis in both MDA5+ DM-ILD and all DM-ILD patients.

The association between vision impairment and cognitive outcomes in older adults: a systematic review and meta-analysis.

OBJECTIVES: To provide a quantitative synthesis of studies on the relationship between vision impairment (VI) and cognitive outcomes in older adults. METHOD: A systematic search was undertaken of relevant databases for original articles published before April 2020. Random effect models were used to obtain pooled estimates of the associations between VI and cognitive outcomes (cognitive impairment and dementia) with subgroup analyses of VI measures, cross-sectional associations of VI with cognitive impairment, and longitudinal associations of baseline VI with incident cognitive impairment and dementia. Potential sources of heterogeneity were explored by meta-regression. Publication bias was evaluated with Egger's test. RESULTS: Sixteen studies including 76,373 participants were included in this meta-analysis, with five cross-sectional studies and eleven longitudinal studies. There was a significantly increased risk of cognitive outcomes with VI identified by subjective measures (odds ratio (OR)=1.63; 95% confidence interval (CI): 1.26-1.99) and objective measures (OR = 1.59; 95% CI: 1.40-1.78). The odds of baseline cognitive impairment were 137% higher in older adults with VI compared with those without VI (OR = 2.37, 95% CI: 1.84-3.03) at baseline. Compared with older adults without VI at baseline, those with baseline VI had a higher relative risk (RR) of incident cognitive impairment (RR = 1.41; 95% CI: 1.31-1.51) and dementia (RR = 1.44, 95% CI: 1.19-1.75). CONCLUSIONS: VI was associated with increased risks of cognitive impairment and dementia across cross-sectional and longitudinal studies. Additional research and randomized clinical trials are warranted to examine the implications of treatment for VI, such as wearing glasses and cataract surgery, to avoid cognitive impairment and dementia.

Comparison of a preoperative MR-based recurrence risk score versus the postoperative score and four clinical staging systems in hepatocellular carcinoma: a retrospective cohort study.

OBJECTIVES: To establish a risk score integrating preoperative gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) and clinical parameters to predict recurrence after hepatectomy for patients with hepatocellular carcinoma (HCC) and to compare its performance with that of a postoperative score and four clinical staging systems. METHODS: Consecutive patients with surgically confirmed HCC who underwent preoperative EOB-MRI between July 2015 and November 2020 were retrospectively included. Two recurrence risk scores, one incorporating only preoperative variables and the other incorporating all preoperative and postoperative variables, were constructed via Cox regression models. RESULTS: A total of 214 patients (derivation set, n = 150; test set, n = 64) were included. Six preoperative variables, namely tumor number, infiltrative appearance, corona enhancement, alpha-fetoprotein (AFP) level, aspartate aminotransferase (AST) level, and sex, were independently associated with recurrence. After adding postoperative features, microvascular invasion and tumor differentiation were additional significant variables in lieu of corona enhancement and AFP level. Using the above variables, the preoperative score achieved a C-index of 0.741 on the test set, which was comparable with that of the postoperative score (0.729; p = 0.235). The preoperative score yielded a larger time-dependent area under the receiver operating characteristic curve at 1 year (0.844) than three existing systems (0.734-0.742; p < 0.05 for all). Furthermore, the preoperative score stratified patients into two prognostically distinct risk strata with low and high risks of recurrence (p < 0.001). CONCLUSION: The preoperative score integrating EOB-MRI features, AFP and AST levels, and sex improves recurrence risk estimation in HCC. KEY POINTS: • The preoperative risk score incorporating three EOB-MRI findings, AFP and AST levels, and sex achieved comparable performance with that of the postoperative score for predicting recurrence after hepatectomy in patients with HCC. • Two risk strata with low and high risks of recurrence were obtained based on the preoperative score. • The preoperative score may help tailor pretreatment decision-making and facilitate candidate selection for adjuvant clinical trials.

Effect of aerobic exercise on cardiotoxic outcomes in women with breast cancer undergoing anthracycline or trastuzumab treatment: a systematic review and meta-analysis.

PURPOSE: We aimed to assess the impact of aerobic exercise (AE) on parameters related to cardiotoxicity in breast cancer (BC) patients receiving anthracycline or trastuzumab. METHODS: We performed a systematic review and meta-analysis of comparative studies on AE via the screening of standard databases from their inception to January 18, 2022. The risk of bias was assessed qualitatively using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data were analyzed quantitatively using fixed effects meta-analysis and subgroup analysis in RevMan software. Notable outcomes included imaging outcomes of cardiotoxicity, cardiorespiratory fitness, and cardiac biomarkers. RESULTS: A meta-analysis of the pooled evidence obtained from seven studies revealed that AE significantly increased peak oxygen consumption (VO2 peak) and E/A values, compared to the values observed during usual care. Moreover, AE was safe and feasible, and was associated with a lower risk of adverse effects, a higher participation rate, and better results, when combined with resistance exercise. CONCLUSION: In BC patients receiving anthracyclines or trastuzumab, the effects of AE on the levels of cardiotoxicity were mixed; the diastolic functions and VO2 peak values were improved, biomarkers were not affected, and the overall improvements in the levels of cardiotoxicity were promising, despite the use of different exercise parameters.

Downstream processing of virus-like particles with aqueous two-phase systems: Applications and challenges.

The advancement of recombinant virus-like particle-based vaccines has attracted global attention owing to substantially safety and high efficacy in provoking a protective immunity against various chronic and infectious diseases in humans and animals. A robust, low-cost, and scalability separation and purification technology is of utmost importance in the downstream processing of recombinant virus-like particles to produce affordable and safe vaccines. Being a relatively simple, environmentally friendly, and efficient biomolecules recovery approach, aqueous two-phase systems have received great attention from researchers worldwide. This review aims to highlight the challenges and outlook in addition to the current applications of aqueous two-phase systems in downstream processing of virus-like particles. The efforts will confidently reinforce scholars' knowledge and fill in the valuable research gap in the aspect of concerning recombinant virus-like particle-based vaccines development, particularly related to the virus-like particles downstream production processes.

An autophagy-related lncRNA prognostic risk model for thyroid cancer.

PURPOSE: Thyroid cancer (TC) is the most common malignancy of the endocrine system and its incidence is gradually rising. Research has demonstrated a close link between autophagy and thyroid cancer. We constructed a prognostic model of autophagy-related long non-coding RNA (lncRNA) in thyroid cancer and explored its prognostic value. METHODS: The data used in this study were all obtained from The Cancer Genome Atlas (TCGA) database and the Human Autophagy Database (HADb). We construct a co-expression network by autophagy-related genes and lncRNA to obtain autophagy-related lncRNAs. After univariate Cox regression analysis and multivariate Cox regression analysis, autophagy-related lncRNAs significantly associated with prognosis were identified. Based on the risk score of lncRNA, thyroid cancer patients are divided into high-risk group and low-risk group. RESULTS: A total of 14,142 lncRNAs and 212 autophagy-related genes (ATGs) were obtained from the TCGA database and the HADb, respectively. We performed lncRNA-ATGs correlation analysis and finally obtained 1,166 autophagy-associated lncRNAs. Subsequently, we conducted univariate Cox regression analysis and multivariate Cox regression analysis, nine autophagy-related lncRNAs (AC092279.1, AC096677.1, DOCK9-DT, LINC02454, AL136366.1, AC008063.1, AC004918.3, LINC02471 and AL162231.2) significantly associated with prognosis were identified. Based on these autophagy-related lncRNAs, a risk model was constructed. The area under the curve (AUC) of the risk score was 0.905, proving that the accuracy of risk signature was superior. In addition, multiple regression analysis showed that risk score was a significant independent prognostic risk factor for thyroid cancer. CONCLUSION: In this study, nine autophagy-related lncRNAs in thyroid cancer were established to predict the prognosis of thyroid cancer patients.

Hepatic Steatosis Has No Effect in Diagnosis Accuracy of LI-RADS v2018 Categorization of Hepatocellular Carcinoma in MR Imaging.

BACKGROUND: In clinical practice, hepatocellular carcinoma (HCC) is widely diagnosed by using MRI, however, whether the imaging features are affected by hepatic steatosis (HS) is still unknown. PURPOSE: To investigate and compare the differences in HCC related imaging features between with- and without-HS groups, and to further determine whether HS affects the diagnosis accuracy of Liver Imaging Reporting and Data System (LI-RADS) v2018 of HCC in MRI. STUDY TYPE: Prospective. SUBJECTS: One hundred and seventy-one patients (mean age, 52 ± 11 years; range, 26-83 years) including 137 men and 34 women. FIELD STRENGTH/SEQUENCE: 3.0 T, gradient echo (GRE). ASSESSMENT: Subjects were classified as HS and non-HS groups according to MRI-proton density fat-fraction (PDFF). HS was defined as MRI-PDFF >5.6%. Three radiologists accessed HCC features and assigned LI-RADS categories in MRI independently based on LI-RADS v2018. Frequencies of HCC major features and LR categorization assignment between the two groups as well as interobserver agreement between the two radiologists were assessed. STATISTICAL TESTS: Unpaired t-test, Chi-square test, Fisher's exact test, kappa statistic, intraclass correlation coefficient (ICC). A two-sided P value <0.05 was considered as statistically significant. RESULTS: Major features including arterial hyperenhancement (APHE), enhancing "capsule" and nonperipheral "washout" observed between HS and non-HS groups were not significantly different (78.95% vs.78.62%, P = 0.866; 57.89% vs.52.98%, P = 0.483; and 75% vs.81.46%, P = 0.257, respectively), and the assessment of observation size showed a borderline difference (P = 0.059). No significant difference in LR-5 assignment between the two groups (69.74% vs. 72.85% for reader 1, P = 0.641; 71.05% vs. 72.19% for reader 2, P = 0.877). Interobserver agreement between the two radiologists showed almost perfect in LR-5 assignment (κ = 0.869) and size observation (ICC = 0.997). DATA CONCLUSION: The diagnosis of HCC based on LI-RADS v2018 in MRI is of comparable performance regardless of HS, in which there is no significant difference in either the major imaging features or LR categorization. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2.

Process development and optimization of continuous capture with three-column periodic counter-current chromatography.

Continuous capture with affinity chromatography is one of the most important units for continuous manufacturing of monoclonal antibody (mAb). Due to the complexity of three-column periodic counter-current chromatography (3C-PCC), three approaches (experimental, model-based, and simplified approaches) were studied for process development and optimization. The effects of residence time for interconnected load (RT C ), breakthrough percentage of the first column for interconnected load (s) and feed protein concentration (c 0 ) on productivity and capacity utilization were focused. The model-based approach was found superior to the experimental approach in process optimization and evaluation. Two phases of productivity were observed and the optimal RT C for the maximum productivity was located at the boundary of the two phases. The comprehensive effects of the operating parameters (RT C , s, and c 0 ) were evaluated by the model-based approach, and the operation space was predicted. The best performance of 34.5 g/L/h productivity and 97.6% capacity utilization were attained for MabSelect SuRe LX resin under 5 g/L concentration at RT C = 2.8 min and s = 87.5%. Moreover, a simplified approach was suggested to obtain the optimal RT C for the maximum productivity. The results demonstrated that model-assisted tools are useful to determine the optimum conditions for 3C-PCC continuous capture with high productivity and capacity utilization.

Self-reported vision impairment, vision correction, and depressive symptoms among middle-aged and older Chinese: Findings from the China health and retirement longitudinal study.

OBJECTIVE: To investigate associations between vision impairment (VI), vision correction (VC) and depressive symptoms among middle-aged and older Chinese. METHODS: 22 203 participants aged ≥45 years from China Health and Retirement Longitudinal Study 2011 to 2015 were divided into four self-reported VI categories: no VI, distance VI (DVI) only, near VI (NVI) only, and both distance and near VI (DNVI); and four self-reported VI/VC subgroups: VI(+)/VC(-), VI(+)/VC(+), VI(-)/VC(-) and VI(-)/VC(+). Depressive symptoms were evaluated by 10-item Center for Epidemiological Studies Depression Scale (CESD-10). RESULTS: Compared with no VI, DVI only (OR = 2.12, 95% CI: 1.95, 2.31), NVI only (OR = 1.51, 95% CI: 1.39, 1.63) and DNVI (OR = 2.75, 95% CI: 2.47, 3.07) were associated with higher odds of depressive symptoms. Compared with VI(+)/VC(-), VI(+)/VC(+) (OR = 0.91, 95% CI: 0.83, 0.98), VI (-)/VC(-) (OR = 0.50, 95% CI: 0.48, 0.53) and VI(-)/VC(+) (OR = 0.49, 95% CI: 0.47, 0.54) were associated with lower odds of depressive symptoms. Compared with no VI at baseline, baseline DNVI was significantly associated with higher odds of depressive symptoms after two (OR = 1.48, 95% CI: 1.16, 1.88) and four (OR = 1.32, 95% CI: 1.04, 1.68) years. Baseline depressive symptoms were significantly associated with higher odds of VI after two (OR = 1.53, 95% CI: 1.34, 1.74) and four (OR = 1.54, 95% CI: 1.34, 1.76) years. CONCLUSION: Adults with DNVI were more likely to report depressive symptoms in the future and those with depressive symptoms were more likely to report VI in the future. VC might be a protective factor for preventing depressive symptoms among adults with VI.

Vision impairment, vision correction, and cognitive decline among middle-aged and older Chinese: results from the China health and retirement longitudinal study.

OBJECTIVES: To investigate the associations between vision impairment (VI), vision correction (VC), and cognitive function. METHOD: We included 20,677 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (2011-2015). Participants were grouped into no VI, distance VI (DVI) only, near VI (NVI) only, or both distance and near VI (DNVI), and VI(+)/VC(-), VI(+)/VC(+), VI(-)/VC(-), or VI(-)/VC(+) further at baseline. Cognitive function at baseline and subsequently every two years was applied as a dependent variable in a generalized estimating equation model. RESULTS: DVI only, NVI only, and DNVI had significantly worse cognitive function over time than no VI (all p < .05). DNVI had significantly worse cognitive function over time than DVI only and NVI only (all p < .001). VI(+)/VC(+), VI(-)/VC(-), and VI(-)/VC(+) had significantly better cognitive function over time than VI(+)/VC(-) (all p < .05). VI(-)/VC(+) had significantly better cognitive function over time than VI(+)/VC(+) and VI(-)/VC(-) (all p < .05). CONCLUSION: Cognitive function was worse in middle-aged and older Chinese with VI, especially in those with DNVI. VC was associated with better cognitive function over time regardless of the status of vision.

Diagnostic application of cyclin D1 fluorescent in situ hybridization for histologically undetermined early lesions of acral melanoma in situ: A case series.

Histologically undetermined early acral melanoma in situ (HUAMIS) is rare but a diagnostic challenge, being clinically and dermoscopically MIS (late onset, a large size (>7 mm), parallel ridges pattern) but microscopically without recognizable cytological atypia. Cyclin D1 (CCND1) gene amplification is a genetic aberration occurring in the early radial growth phase of AMs and could thus help determine malignancy for this disease. We determine the value of CCND1 amplification by FISH as a diagnostic marker for HUAMIS. CCND1 amplification was examined in paraffin-embedded skin biopsies and excisions using a dual-probes fluorescence in situ hybridization (FISH) (11q13 and CEP11). One FISH-negative case 6 was additionally examined by Mypath Melanoma (qRT-PCR). Seventeen cases (12 dysplastic nevi, 3 AMIS, and 2 invasive AM) were served as negative controls for FISH. All six patients (4 females and 2 males) were Hispanic. Pigment lesions were on the left plantar foot (4), right third finger palm (1), and right thumb subungual (1). All cases showed similar clinical and dermoscopical characteristics, including late onset (50 to 74 years old), long duration (from 2 to 15 years), large-sized pigments (from 16 to 40 mm), and a parallel ridge pattern. Junctional melanocytes with no or minimal atypia from five cases showed CCND1 amplifications. Four of 5 cases were received 1st or/and 2nd wide excisions, which demonstrated foci of histologically overt MIS. One FISH-negative case 6 demonstrated "likely malignancy" scores (>2) by Mypath Melanoma (qRT-PCR). None of negative controls showed the amplification. We propose here a simple CCND1 FISH is a practical diagnostic test to determine the malignancy of the very early progression phase of AM preceding histopathologically defined MIS. Cases presented here could be an indolent subtype of AMIS characterized by carrying a long latent radial growth phase without vertical growth, mimicking lentigo maligna.

Anti-depression effects of ketogenic diet are mediated via the restoration of microglial activation and neuronal excitability in the lateral habenula.

Depression is a severe neuropsychiatric disorder, of which the underlying pathological mechanisms remain unclear. The ketogenic diet (KD) has been reported to exhibit preventative effects on depressive-like behaviors in rodents. However, the therapeutic effects of KD on depressive-like behaviors have not been illustrated thus far. Here, we found that KD treatment dramatically ameliorated depressive-like behaviors in both repeated social defeat stress (R-SDS) and lipopolysaccharide (LPS) models, indicating the potential therapeutic effects of KD on depression. Our electrophysiological studies further showed that neuronal excitability was increased in the lateral habenula (LHb) of mice exposed to R-SDS or LPS, which can be reversed in the presence of KD treatment. Moreover, R-SDS and LPS were also found to induce robust microglial inflammatory activation in the LHb. Importantly, these phenotypes were rescued in mice fed with KD. In addition, we found that the protein level of innate immune receptor Trem2 in the LHb was significantly decreased in depression models. Specific knockdown of Trem2 in LHb microglia induced depressive-like behaviors, increased neuronal excitability as well as robust microglial inflammatory activation. Altogether, we demonstrated the therapeutic effects of KD on depressive-like behaviors, which are probably mediated via the restoration of microglial inflammatory activation and neuronal excitability. Besides, we also proposed an unrecognized function of Trem2 in the LHb for depression. Our study sheds light on the pathogenesis of depression and thereby offers a potential therapeutic intervention.

A novel dextran-grafted tetrapeptide resin for antibody purification.

Short peptide biomimetic affinity chromatography as a novel antibody separation chromatography is a potential alternative to protein A chromatography. However, if directly attaching ligand to matrix, the adsorption capacity and mass transfer rate would be affected by pore blockage and steric effect. Grafting resin is an effective method to solve this problem by using polymer as a bridge between matrix and ligand. In this work, a novel resin was prepared by grafting a tetrapeptide to the dextran-grafted matrix. Then, the adsorption properties for human immunoglobin G and BSA were determined. The results showed the saturation adsorption capacity could reach to 133 mg/g resin at pH 8.9 with a significantly low dissociation constant (0.03 mg/mL). The influence of flow rates to dynamic binding capacity of this resin was less than that of the non-grafted resin. The separation performance of the resin showed monoclonal antibody could be well isolated from the Chinese hamster ovary culture supernatant at pH 9.0 with the purity of 93.0% and yield of 84.7% by one step. Overall, this resin could achieve higher binding capacity by the possible of gaining higher ligand density, indicating its potential significance for separation in larger scale systems.

Rational design of specific ligands for human serum albumin separation and applications.

Human serum albumin is widely used in clinical practice, and the development of new ligands with high affinity is beneficial to improve its separation efficiency. The Site II of human serum albumin is an active binding site of various molecules such as l-tryptophan, which was studied with molecular simulation to obtain insights for the design of new ligands. The results showed that the carboxyl and indolyl groups of l-tryptophan were critical for the binding on Site II. Seven ligands containing carboxyl groups and indolyl groups were designed, and molecular simulation showed that indole-3-pentanoic acid was the best ligand. A new ligand combined indole-3-acetic acid and cysteine was designed for easier resin preparation, and molecular simulation also indicated that the new ligand bound strongly to Site II. Resins with the new ligand designed was prepared and static adsorption experiments indicated that the new resin had high adsorption capacity of human serum albumin and strong salt tolerance. Finally, recombinant human serum albumin was separated from yeast broth with high purity of 90.4% and recovery of 94.2%, which indicated that the new resin had good adsorption selectivity and strong potential for applications.

Ti3 C2 : An Ideal Co-catalyst?

How 2D Ti3 C2 enhances photocatalytic efficiency remains unclear. Now, it is shown that it is graphene quantum dots (GQDs) derived from Ti3 C2 , rather than 2D Ti3 C2 itself, that play the role of co-catalyst for La2 Ti2 O7 /Ti3 C2 (LTC) composites during the photocatalytic reaction. After modification of Ti3 C2 derivatives, the photocatalytic efficiency of La2 Ti2 O7 is enhanced 16 times over pure La2 Ti2 O7 . Solid-state NMR, Raman, and HRTEM results confirm the existence of GQDs in Ti3 C2 and LTC composites. The GQDs are formed during the chemical change from Ti3 AlC2 to Ti3 C2 via HF etching, as Ti atoms are removed and unsaturated carbon bonds are left, which react with each other to form sp2 π-conjugation GQDs. 2D Ti3 C2 is completely oxidized to COx modified TiOx species, causing Ti3 C2 to lose its electrical conductivity and the role as co-catalyst. GQDs largely suppress the photogenerated charge recombination of La2 Ti2 O7 , as revealed by the photoluminescence (PL) and transient photocurrent.