Changes of Nuclear Factor Kappa-B Pathway Activity in Hippocampus After Acute Carbon Monoxide Poisoning and Its Role in Nerve Cell Injury.

Acute carbon monoxide poisoning (ACOP) causes tissue hypoxia and damage mainly by binding to hemoglobin (Hb). This article aimed to explore the changes in the activity of nuclear factor kappa-B (NF-κB) pathway in the hippocampus after ACOP and its role in nerve cell damage. This article used 30 Sprague-Dawley (SD) rats as the research object, which were randomly divided into two groups, ACOP group and controls. The model of carbon monoxide (CO) poisoning was established, and then the activity of NF-κB pathway in the hippocampus of the two groups of rats was detected, and the statistical analysis was performed. Compared with the controls, the activity of NF-κB pathway in the hippocampus of the ACOP group was significantly increased (P < 0.05). The degree of neuronal damage in the ACOP group was also significantly increased. ACOP increases the activity of the NF-κB pathway in the hippocampus and may cause neuronal damage through this pathway. This provides new ideas and methods for the treatment of ACOP, and also provides new evidence for the role of NF-κB pathway in neuronal injury.

The Accuracy of Point-of-Care Ultrasound in the Detection of Gallbladder Disease: A Meta-analysis.

RATIONALE AND OBJECTIVES: The aim of this meta-analysis was to systematically assess the diagnostic value of point of care ultrasound (POCUS) in the detection of gallbladder diseases. MATERIALS AND METHODS: Pubmed, Web of Science, Embase, and the Cochrane Library were searched for studies up to May 22, 2023. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio, diagnostic odds ratio, area under the curve of summary receiver operating characteristic were calculated using the bivariate model. Subgroup analysis based on cholecystitis and cholelithiasis was conducted. RESULTS: A total of seven studies with 1464 participants were identified in this meta-analysis. The pooled sensitivity of POCUS for the detection of gallbladder disease was 0.86 (95% CI: 0.75, 0.93) and the pooled specificity was 0.92 (95% CI: 0.87, 0.96). The pooled sensitivity and specificity of POCUS for the detection of acute cholecystitis were 0.73 (95% CI: 0.55, 0.86) and 0.93 (95% CI: 0.82, 0.98). The pooled sensitivity and specificity of POCUS for the detection of gallstones were 0.94 (95% CI: 0.91, 0.96) and 0.93 (95% CI: 0.91, 0.95). CONCLUSION: POCUS was a favorable modality for the detection of patients suspected of gallbladder disease, especially for cholelithiasis. Physicians are advised to use POCUS in clinical practice as a non-invasive test to detect gallbladder disease.

Dietary intakes of total, nonheme, and heme iron and hypertension risk: a longitudinal study from the China Health and Nutrition Survey.

AIMS: Evidence is limited regarding the long-term impact of dietary iron intake on the development of hypertension. We investigated the association between dietary intakes of total, nonheme, and heme iron and hypertension risk in a large prospective cohort of Chinese populations over 26 years. METHODS: A total of 16,122 adults (7810 men and 8312 women) who participated in the China Health and Nutrition Survey (1989-2015) were included. Dietary intake was repeatedly assessed by combining three consecutive 24­h individual dietary recalls with household food inventory weighing at each survey round. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, diagnosis by physicians, or current use of anti-hypertensive drugs. RESULTS: During a median follow­up of 11.1 years, 2863 men and 2532 women developed hypertension. After adjustment for non-dietary and dietary factors, a lower risk of hypertension was found in men and women with higher intakes of total, nonheme, or heme iron. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest vs. lowest quartiles were 0.76 (0.67, 0.87) in men and 0.85 (0.74, 0.97) in women for total iron intake, 0.77 (0.67, 0.87) in men and 0.85 (0.74, 0.98) in women for nonheme iron intake, and 0.73 (0.62, 0.87) in men and 0.69 (0.58, 0.82) in women for heme iron intake. Dose-response analyses further revealed a U-shaped association of total and nonheme iron intake and an L-shaped association of heme iron intake with hypertension risk in both men and women (all P for non-linearity < 0.001). CONCLUSIONS: Our findings emphasize the importance of maintaining moderate iron intake in the prevention of hypertension. Both insufficient and excess intake of iron might increase the risk of hypertension.

Long-term dietary iron intake and risk of non-fatal cardiovascular diseases in the China Health and Nutrition Survey.

AIMS: We aimed to investigate the association of long-term dietary iron intake with the risk of non-fatal cardiovascular diseases (CVDs), myocardial infarction (MI), and stroke in Chinese populations with predominantly plant-based diets by sex. METHODS AND RESULTS: A total of 17 107 participants (8569 men and 8538 women) aged 18-80 years in the China Health and Nutrition Survey (CHNS) 1989-2015 were included. Dietary intake was assessed repeatedly by three consecutive 24-h dietary recalls. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 11.1 years, the adjusted HRs (95% CIs) for non-fatal CVDs risk across quintiles of total iron intake in men were 1.00, 0.65 (0.46-0.93), 0.54 (0.37-0.78), 0.66 (0.46-0.94), 0.69 (0.47-1.03), but no significant association in women. Similar associations were found for stroke risk, but not for MI risk. The dose-response curves for the association of total iron and non-heme iron intake with the risk of non-fatal CVDs and stroke followed a reverse J-shape only in men and similar reverse J-shaped association of heme iron intake with non-fatal CVDs and stroke risk in both men and women (P-non-linearity <0.05). CONCLUSION: Moderate dietary iron intake may protect against non-fatal CVDs and stroke, especially in Chinese men consuming plant-based diets. Both quantity and quality of dietary iron intake should be considered in the prevention of non-fatal CVDs due to differences in dietary patterns among diverse populations.

This prospective cohort study, using data from 8569 men and 8538 women who participated in the China Health and Nutrition Survey (CHNS) 1989­2015, suggests that moderate intake of dietary iron may protect against non-fatal cardiovascular diseases (CVDs) and stroke, especially in men consuming predominantly plant-based diets. Key findings In men, the association of dietary intake of total iron, heme iron, and non-heme iron with the risk of non-fatal CVDs and stroke followed a reverse J-shape, with the lowest risk at ∼26 mg/d of total iron intake, ∼2 mg/d of heme iron intake, and ∼24 mg/d of non-heme iron intake. In women, a J-shaped association between dietary heme iron intake and the risk of non-fatal CVDs and stroke were observed, with the lowest risk at ∼1.8 mg/d of heme iron intake; while higher dietary intakes of total iron and non-heme iron tended to be associated with a lower risk of non-fatal stroke.

Differential Effects of Astrocyte Manipulations on Learned Motor Behavior and Neuronal Ensembles in the Motor Cortex.

Although motor cortex is crucial for learning precise and reliable movements, whether and how astrocytes contribute to its plasticity and function during motor learning is unknown. Here, we report that astrocyte-specific manipulations in primary motor cortex (M1) during a lever push task alter motor learning and execution, as well as the underlying neuronal population coding. Mice that express decreased levels of the astrocyte glutamate transporter 1 (GLT1) show impaired and variable movement trajectories, whereas mice with increased astrocyte Gq signaling show decreased performance rates, delayed response times, and impaired trajectories. In both groups, which include male and female mice, M1 neurons have altered interneuronal correlations and impaired population representations of task parameters, including response time and movement trajectories. RNA sequencing further supports a role for M1 astrocytes in motor learning and shows changes in astrocytic expression of glutamate transporter genes, GABA transporter genes, and extracellular matrix protein genes in mice that have acquired this learned behavior. Thus, astrocytes coordinate M1 neuronal activity during motor learning, and our results suggest that this contributes to learned movement execution and dexterity through mechanisms that include regulation of neurotransmitter transport and calcium signaling.SIGNIFICANCE STATEMENT We demonstrate for the first time that in the M1 of mice, astrocyte function is critical for coordinating neuronal population activity during motor learning. We demonstrate that knockdown of astrocyte glutamate transporter GLT1 affects specific components of learning, such as smooth trajectory formation. Altering astrocyte calcium signaling by activation of Gq-DREADD upregulates GLT1 and affects other components of learning, such as response rates and reaction times as well as trajectory smoothness. In both manipulations, neuronal activity in motor cortex is dysregulated, but in different ways. Thus, astrocytes have a crucial role in motor learning via their influence on motor cortex neurons, and they do so by mechanisms that include regulation of glutamate transport and calcium signals.

Predictive Value of FNA-Tg and TgAb in Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma.

Objectives: To analyze whether thyroglobulin (Tg) and anti-Tg antibody (TgAb) detection in fine-needle aspiration (FNA) of cervical lymph node (LN; LN-FNA-Tg and LN-FNA-TgAb) can predict LN metastasis and obtain the best cutoff value. Methods: The patients admitted to our hospital from January 2020 to March 2021 were prospectively enrolled. The LNs were sampled by FNA. All patients underwent thyroid surgery and neck dissection. LN-FNA-Tg, LN-FNA-TgAb, and blood Tg and TgAb were measured. The receiver operating characteristic curve analysis was used to determine the best cutoff points for positive LN. Results: There were 29 participants in the LN metastasis group and 42 in the nonmetastasis group. Compared with the nonmetastasis group, the participants in the metastasis group had higher LN-FNA-Tg (median: 1897 vs 7.74 ng/mL, P < .001), higher LN-FNA-TgAb (median: 15.65 vs 8.21 IU/mL, P < .001), and higher serum Tg (median: 25.4 vs 18.81 ng/mL); there were no differences in serum TgAb (median: 26.6 vs 28.6 IU/mL, P = .477). The best accuracy (87.5%) was observed with LN-FNA-Tg of >227.1 ng/mL, resulting in an area under the curve of 0.927, 84.5% sensitivity, and 89.5% specificity. LN-FNA-TgAb >10.85 IS/mL had an accuracy of 79.6%, sensitivity 64.8%, and specificity 89.5%. Serum Tg and TgAb had the lowest accuracy, with 64.2% and 57.4%, respectively, sensitivity of 53.5% and 67.6%, and specificity of 71.4% and 50.5%. Similar results were observed in first-operation participants and postoperative participants. Conclusions: LN-FNA-Tg has high accuracy, sensitivity, and specificity for detecting cervical LN in patients with papillary thyroid cancer.

Dietary Total Vitamin A, ß-carotene, and Retinol Intake and the Risk of Diabetes in Chinese Adults with Plant-based Diets.

PURPOSE: Epidemiologic evidence regarding the role of dietary vitamin A in the development of diabetes is limited and inconsistent. This study was to explore the association between vitamin A intake and diabetes risk in Chinese adults. METHODS: A prospective cohort study was conducted among 17 111 adults (8537 men and 8577 women) who participated in the China Health and Nutrition Survey between 1989 and 2015. Dietary intakes were assessed by 3 consecutive 24-hour dietary recalls combined with a household food inventory. Diabetes was determined by self-reported diagnosis, diabetes medication use, or additional criterion in 2009 of fasting blood glucose or hemoglobin A1c. We analyzed the association of vitamin A intake (total, ß-carotene, retinol) with diabetes risk using Cox proportional hazards models. RESULTS: A total of 519 men and 531 women developed diabetes during a median of 11 years of follow-up. Higher dietary total vitamin A intakes were associated with a lower risk of diabetes in both men (quintile 5 [Q5] vs Q1: hazard ratio [HR] = 0.69, 95% CI, 0.49-0.97, P-trend = 0.079) and women (Q5 vs Q1: HR = 0.63; 95% CI, 0.45-0.89; P-trend = 0.039). An inverse relation with diabetes risk was observed for dietary intakes of ß-carotene (Q5 vs Q1: HR = 0.71; 95% CI, 0.52-0.97) and retinol (Q5 vs Q1: HR = 0.58; 95% CI, 0.39-0.85) among men, but not women. Dose-response analyses showed the association of dietary intakes of total vitamin A, ß-carotene, and retinol with diabetes risk in men was L-shaped (P-nonlinearity = 0.043), reverse J-shaped (P-nonlinearity = 0.001), and linear, respectively. CONCLUSION: Our findings suggest that adequate intake of vitamin A may help protecting against diabetes, especially for men.

Association between Protein Intake and the Risk of Hypertension among Chinese Men and Women: A Longitudinal Study.

This study aimed to examine the relationship between hypertension risk and protein intake in Chinese individuals. Our analysis included 7007 men and 7752 women from 9 China Health and Nutrition Survey waves (1991−2015). The main outcome was incident hypertension. Dietary intake was recorded using a combination of 3 consecutive 24-h recalls and a household food inventory survey. Energy-adjusted cumulative average intakes were analyzed, and Cox proportional hazards regression models were built. After 143,035 person-years of follow-up, 2586 and 2376 new male and female hypertension cases were identified, respectively. In multivariate-adjusted models with dietary protein intakes included as categorical variables, higher animal protein intake was associated with lower hypertension risk in women (p-trend = 0.01), whereas non-significant in men. Plant protein intake showed a significant positive correlation with hypertension risk, while non-significant for total protein. On a continuous scale, restricted cubic spline curves visually revealed L-, J-, and U-shaped associations between hypertension risk and animal-, plant-, and total-protein intakes, respectively, in both sexes (all p-nonlinearity < 0.0001). Our results suggest a beneficial association between intakes of animal, plant, and total proteins and hypertension risk at lower intake levels, and excessive intake of plant or total protein may increase the hypertension risk in the Chinese population.

Evaluation of testicular spermatogenic function by ultrasound elastography in patients with varicocele-associated infertility.

OBJECTIVE: To investigate the application of ultrasound elastography and color Doppler ultrasound in the evaluation of testicular spermatogenic function in patients with varicocele (VC) associated infertility. METHODS: A total of 196 patients with VC-associated infertility treated in our hospital from January 2018 to January 2020 were included as the research subjects (VC group), and were classified into VC I group (66 cases), VC II group (60 cases), and VC III group (70 cases) according to the diameter of spermatic vein and the degree of reflux under ultrasound. 50 age-matched healthy subjects were included as the control group. Color ultrasound, ultrasound elastography and semen examination were performed on all patients. RESULTS: Compared with control group, a lower left testicular volume in VC group and a lower right testicular volume in VC III group were observed, and the left testicular volume was inversely proportional to VC grade (all P<0.05). Statistically significant differences in sperm viability, sperm density, peak systolic velocity (PSV), and MEAN values were determined among the 4 groups by one-way ANOVA, and between two groups by the independent-samples t test (all P<0.05). Pearson correlation analysis revealed that sperm viability and sperm density had no correlation with PSV, resistive index (RI) and pulsatility index (PI) of the left testicular artery in VC group, but were negatively correlated with the MEAN values of the testis. CONCLUSION: Ultrasound elastography can predict the semen quality in patients with VC-associated infertility. CLINICAL TRIAL REGISTRATION: This study was registered with the registration No. ChiCTR2010189 (URL: http://www.chictr.org.cn/showproj.aspx?proj=2018XE057-3).

Dietary Nonheme, Heme, and Total Iron Intake and the Risk of Diabetes in Adults: Results From the China Health and Nutrition Survey.

OBJECTIVE: Excessive iron intake has been linked to diabetes risk. However, the evidence is inconsistent. This study examined the association between dietary heme and nonheme iron intake and diabetes risk in the Chinese population. RESEARCH DESIGN AND METHODS: We included 17,026 adults (8,346 men and 8,680 women) who were part of the China Health and Nutrition Survey (1991-2015) prospective cohort. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. Diabetes cases were identified through a questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A total of 547 men and 577 women developed diabetes during 202,138 person-years of follow-up. For men, the adjusted HRs (95% CIs) for quintiles of nonheme iron intake were 1.00, 0.77 (0.58-1.02), 0.72 (0.54-0.97), 0.63 (0.46-0.85), and 0.87 (0.64-1.19) (P-nonlinearity = 0.0015). The corresponding HRs (95% CIs) for women were 1.00, 0.63 (0.48-0.84), 0.57 (0.43-0.76), 0.58 (0.43-0.77), and 0.67 (0.49-0.91) (P-nonlinearity < 0.0001). The dose-response curves for the association between nonheme iron and total iron intake and diabetes followed a reverse J shape in men and an L shape in women. No significant associations were observed between heme iron intake and diabetes risk. CONCLUSIONS: Total iron and nonheme iron intake was associated with diabetes risk, following a reverse J-shaped curve in men and an L-shaped curve in women. Sufficient intake of nonheme or total iron might be protective against diabetes, while excessive iron intake might increase the risk of diabetes among men.

Pharmacological enhancement of KCC2 gene expression exerts therapeutic effects on human Rett syndrome neurons and Mecp2 mutant mice.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl CpG binding protein 2 (MECP2) gene. There are currently no approved treatments for RTT. The expression of K+/Cl- cotransporter 2 (KCC2), a neuron-specific protein, has been found to be reduced in human RTT neurons and in RTT mouse models, suggesting that KCC2 might play a role in the pathophysiology of RTT. To develop neuron-based high-throughput screening (HTS) assays to identify chemical compounds that enhance the expression of the KCC2 gene, we report the generation of a robust high-throughput drug screening platform that allows for the rapid assessment of KCC2 gene expression in genome-edited human reporter neurons. From an unbiased screen of more than 900 small-molecule chemicals, we have identified a group of compounds that enhance KCC2 expression termed KCC2 expression-enhancing compounds (KEECs). The identified KEECs include U.S. Food and Drug Administration-approved drugs that are inhibitors of the fms-like tyrosine kinase 3 (FLT3) or glycogen synthase kinase 3ß (GSK3ß) pathways and activators of the sirtuin 1 (SIRT1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) pathways. Treatment with hit compounds increased KCC2 expression in human wild-type (WT) and isogenic MECP2 mutant RTT neurons, and rescued electrophysiological and morphological abnormalities of RTT neurons. Injection of KEEC KW-2449 or piperine in Mecp2 mutant mice ameliorated disease-associated respiratory and locomotion phenotypes. The small-molecule compounds described in our study may have therapeutic effects not only in RTT but also in other neurological disorders involving dysregulation of KCC2.

Extract of Cycas revoluta Thunb. enhances the inhibitory effect of 5-fluorouracil on gastric cancer cells through the AKT-mTOR pathway.

BACKGROUND: Gastric cancer is one of the most common and deadly malignancies worldwide. Despite recent medical progress, the 5-year survival rate of gastric cancer is still unsatisfactory. 5-fluorouracil (5-Fu) is one of the first-line antineoplastic treatments for gastric cancer, as it can effectively induce cancer cell apoptosis. However, the effect of 5-Fu is limited due to drug resistance of the malignant tumor. Previous studies have reported that Sotetsuflavone from Cycas revoluta Thunb. can markedly suppress lung cancer cell proliferation by apoptosis, though its effect on gastric cancer remains unknown. AIM: To investigate the inhibitory effect of Cycas revoluta Thunb. and to determine whether it can overcome gastric cancer cell drug resistance to 5-Fu. METHODS: Cell viability was examined to determine whether the natural extract of Cycas revoluta Thunb. induced gastric cancer cell death. The half-maximal effective concentration and the half-maximal lethal concentration were calculatede. Wound-healing and transwell assays were performed to examine gastric cancer cell motility. Clonogenic assays were performed to investigate the synergistic effects of Cycas revoluta Thunb. with 5-Fu, and apoptotic bodies were detected by Hoechst staining. Western blotting was performed to examine the expression of related proteins and to investigate the molecular mechanism of Cycas revoluta Thunb.-induced cancer cell apoptosis. The expressions of proteins, including mammalian target of rapamycin (mTOR) and p-AKT, were detected in different combinations of treatments for 48 h, then analyzed by ECL detection. RESULTS: Gastric cancer cells were more sensitive to the natural extract of Cycas revoluta Thunb. compared to normal gastric epithelial cells, and the extract effectively inhibited gastric cancer cell migration and invasion. The extract improved the anti-cancer effect of 5-Fu by enhancing the chemosensitization of gastric cancer cells. Extract plus 5-Fu further reduced the expression of the drug-resistance-related proteins p-AKT and mTOR after 48 h compared to 5-Fu alone. Compared to 5-Fu treatment alone, mTOR and p-AKT expression was significantly reduced by about 50% and 75%, respectively. We also found that the natural extract of Cycas revoluta Thunb. further increased 5-Fu-induced gastric cancer cell apoptosis. Expression of apoptosis-related protein X-linked inhibitor of apoptosis protein and apoptosis inducing factor were significantly reduced and increased, respectively, in the 5-Fu-resistant gastric cancer line SGC-7901/R treated with extract plus 5-Fu, while the expression of survivin did not change. CONCLUSION: The natural extract of Cycas revoluta Thunb. effectively inhibited gastric cancer cell growth and enhanced the anti-cancer effect of 5-Fu through the AKT-mTOR pathway.

Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder.

With the recent 50th anniversary of the first publication on Rett syndrome, and the almost 20 years since the first report on the link between Rett syndrome and MECP2 mutations, it is important to reflect on the tremendous advances in our understanding and their implications for the diagnosis and treatment of this neurodevelopmental disorder. Rett syndrome features an interesting challenge for biologists and clinicians, as the disorder lies at the intersection of molecular mechanisms of epigenetic regulation and neurophysiological alterations in synapses and circuits that together contribute to severe pathophysiological endophenotypes. Genetic, clinical, and neurobiological evidences support the notion that Rett syndrome is primarily a synaptic disorder, and a disease model for both intellectual disability and autism spectrum disorder. This review examines major developments in both recent neurobiological and preclinical findings of Rett syndrome, and to what extent they are beginning to impact our understanding and management of the disorder. It also discusses potential applications of knowledge on synaptic plasticity abnormalities in Rett syndrome to its diagnosis and treatment.

Cortical projections to the two retinotopic maps of primate pulvinar are distinct.

Comprised of at least five distinct nuclei, the pulvinar complex of primates includes two large visually driven nuclei; one in the dorsal (lateral) pulvinar and one in the ventral (inferior) pulvinar, that contain similar retinotopic representations of the contralateral visual hemifield. Both nuclei also appear to have similar connections with areas of visual cortex. Here we determined the cortical connections of these two nuclei in galagos, members of the stepsirrhine primate radiation, to see if the nuclei differed in ways that could support differences in function. Injections of different retrograde tracers in each nucleus produced similar patterns of labeled neurons, predominately in layer 6 of V1, V2, V3, MT, regions of temporal cortex, and other visual areas. More complete labeling of neurons with a modified rabies virus identified these neurons as pyramidal cells with apical dendrites extending into superficial cortical layers. Importantly, the distributions of cortical neurons projecting to each of the two nuclei were highly overlapping, but formed separate populations. Sparse populations of double-labeled neurons were found in both V1 and V2 but were very low in number (<0.1%). Finally, the labeled cortical neurons were predominately in layer 6, and layer 5 neurons were labeled only in extrastriate areas. Terminations of pulvinar projections to area 17 was largely in superficial cortical layers, especially layer 1.

Association of Habitually Low Intake of Dietary Calcium with Blood Pressure and Hypertension in a Population with Predominantly Plant-Based Diets.

This study aimed to assess the association of habitually low dietary calcium intake with blood pressure or hypertensive risk using data from the China Health and Nutrition Survey (CHNS) in 2009. We included 6298 participants (2890 men and 3408 women) aged 18 years or older in this analysis. Food intakes were measured by 3-day 24-h individual recalls combined with a weighing and measuring of household food inventory. The participants were divided into normotensive, pre-hypertensive and hypertensive groups according to their mean blood pressure of three repeated measurements. Six intake levels were decided by percentiles of gender-specific dietary calcium intakes (P0⁻10, P10⁻30, P30⁻50, P50⁻70, P70⁻90, and P90⁻100). Average dietary calcium intakes were 405 mg/day for men and 370 mg/day for women, 80% and 84% of which were derived from plant-based food in men and women, respectively. Multiple linear regression analyses showed that dietary calcium intakes were not related with blood pressure in both genders (all P > 0.05). Logistic regression analyses showed a lower risk of pre-hypertension with higher dietary calcium intakes in women (all Pfor trend < 0.001), but not in men; no association between dietary calcium intake and hypertensive risk was found in both genders (all Pfor trend > 0.05). This study suggests that there are no conclusive associations of habitually low dietary calcium intake with blood pressure or hypertensive risk in Chinese individuals consuming predominantly plant-based diets.

Major Vault Protein, a Candidate Gene in 16p11.2 Microdeletion Syndrome, Is Required for the Homeostatic Regulation of Visual Cortical Plasticity.

Microdeletion of a region in chromosome 16p11.2 increases susceptibility to autism. Although this region contains exons of 29 genes, disrupting only a small segment of the region, which spans five genes, is sufficient to cause autistic traits. One candidate gene in this critical segment is MVP, which encodes for the major vault protein (MVP) that has been implicated in regulation of cellular transport mechanisms. MVP expression levels in MVP+/- mice closely phenocopy those of 16p11.2 mutant mice, suggesting that MVP+/- mice may serve as a model of MVP function in 16p11.2 microdeletion. Here we show that MVP regulates the homeostatic component of ocular dominance (OD) plasticity in primary visual cortex. MVP+/- mice of both sexes show impairment in strengthening of open-eye responses after several days of monocular deprivation (MD), whereas closed-eye responses are weakened as normal, resulting in reduced overall OD plasticity. The frequency of miniature EPSCs (mEPSCs) in pyramidal neurons is decreased in MVP+/- mice after extended MD, suggesting a reduction of functional synapses. Correspondingly, upregulation of surface GluA1 AMPA receptors is reduced in MVP+/- mice after extended MD, and is accompanied by altered expression of STAT1 and phosphorylated ERK, which have been previously implicated in OD plasticity. Normalization of STAT1 levels by introducing STAT1 shRNA rescues surface GluA1 and open-eye responses, implicating STAT1 as a downstream effector of MVP. These findings demonstrate a specific role for MVP as a key molecule influencing the homeostatic component of activity-dependent synaptic plasticity, and potentially the corresponding phenotypes of 16p11.2 microdeletion syndrome.SIGNIFICANCE STATEMENT Major vault protein (MVP), a candidate gene in 16p11.2 microdeletion syndrome, has been implicated in the regulation of several cellular processes including transport mechanisms and scaffold signaling. However, its role in brain function and plasticity remains unknown. In this study, we identified MVP as an important regulator of the homeostatic component of experience-dependent plasticity, via regulation of STAT1 and ERK signaling. This study helps reveal a new mechanism for an autism-related gene in brain function, and suggests a broader role for neuro-immune interactions in circuit level plasticity. Importantly, our findings might explain specific components of the pathophysiology of 16p11.2 microdeletion syndrome.

Low Habitual Dietary Calcium and Linear Growth from Adolescence to Young Adulthood: results from the China Health and Nutrition Survey.

Evidences from clinical trials and meta-analyses of calcium supplementation in linear growth have given conflicting results, and few longitudinal studies have investigated the long-term associations between dietary calcium and linear growth, especially in the population with low-calcium plant-based diets. We investigated the prospective associations of low habitual dietary calcium with adult height and height-for-age z-score (HAZ) from adolescence to adulthood among 2019 adolescents from the China Health and Nutrition Survey (CHNS). The average dietary calcium intakes were 426(standard deviation: 158) mg/d in boys and 355(134) mg/d in girls during adolescence. During a median follow-up of 7.0 (interquartile range: 5.9-9.0) years, boys reached an average of 169.0(6.7) cm and girls reached 158.4(5.8) cm in adulthood. After adjusting for other potential confounders, non-linear regression found that boys with dietary calcium intakes below 327 mg/d had shorter adult stature, and those taking over 566 mg/d had faster height growth whether adjusting for physical exercises level or not. No significant associations were found in girls. Our study suggests that in boys with plant-based diets, higher dietary calcium intake during adolescence is associated with faster height growth, but not with adult height; calcium intake below 300 mg/d may result in shorter adult stature.

Trends in dietary fat and fatty acid intakes and related food sources among Chinese adults: a longitudinal study from the China Health and Nutrition Survey (1997-2011).

OBJECTIVE: Few studies have evaluated the intake trends of fatty acids in China. The present study aimed to describe the profile of longitudinal dietary fat and fatty acid intakes and their related food sources in Chinese adults. DESIGN: A longitudinal study using data from the China Health and Nutrition Survey (1997-2011) was conducted. Dietary intake was estimated using 24 h recalls combined with a food inventory for three consecutive days. Linear mixed models were used to calculate the adjusted mean intake values. SETTING: Urban and rural communities in nine provinces (autonomous regions), China. SUBJECTS: Adults (n 19 475; 9420 men and 10 055 women). RESULTS: Fat intake among men in 1997 was 73·4 g/d (28·1 % of total energy (%TE)), while in 2011 it increased to 86·3 g/d (33·2 %TE). Similarly, for women, this intake increased from 62·7 g/d (28·4 %TE) in 1997 to 74·1 g/d (33·7 %TE) in 2011. Energy intake from SFA grew from 6·8 to 7·6 %TE for both sexes. PUFA intake increased from 18·4 to 22·5 g/d for men and from 15·7 to 19·7 g/d for women, and was above 6 %TE in all survey periods. Intakes of 18:2 and 18:3 fatty acids showed significant upward trends in both sexes. Participants consumed less animal fats and more vegetable oils, with more PUFA intake and less energy from SFA. EPA and DHA intakes fluctuated around 20 mg/d. CONCLUSIONS: Fatty acid intakes and profile in Chinese adults are different from those reported in other countries.

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome.

Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging. Targeted recordings reveal that parvalbumin-expressing (PV+) interneurons in mutant mice have reduced responses. PV-specific MeCP2 deletion alone recapitulates effects of global MeCP2 deletion on cortical circuits, including reduced pyramidal neuron responses and reduced response reliability and selectivity. Furthermore, MeCP2 mutant mice show reduced expression of the cation-chloride cotransporter KCC2 (K+/Cl- exporter) and a reduced KCC2/NKCC1 (Na+/K+/Cl- importer) ratio. Perforated patch recordings demonstrate that the reversal potential for GABA is more depolarized in mutant mice, but is restored by application of the NKCC1 inhibitor bumetanide. Treatment with recombinant human insulin-like growth factor-1 restores responses of PV+ and pyramidal neurons and increases KCC2 expression to normalize the KCC2/NKCC1 ratio. Thus, loss of MeCP2 in the brain alters both excitation and inhibition in brain circuits via multiple mechanisms. Loss of MeCP2 from a specific interneuron subtype contributes crucially to the cell-specific and circuit-wide deficits of RTT. The joint restoration of inhibition and excitation in cortical circuits is pivotal for functionally correcting the disorder.