[Relationship between the percentage of energy intake from macronutrients and obesity among adult residents in 15 provinces of China in 1991-2018].

OBJECTIVE: To explore the relationship between the percentage of energy intake from macronutrients and obesity in Chinese adult residents, and analyze the cut-off values of macronutrients for predicting obesity. METHODS: Data was collected in China Health and Nutrition Survey(CHNS)in 1991-2018. Adults who participated in at least two waves of the surveys and were not obese at baseline were selected as the study subjects. Obesity was defined as body mass index(BMI)≥28.0 kg/m~2. Generalized estimating equation was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and obesity, and receiver operating characteristic curve(ROC) was used to analyze the cut-off values of percentage of energy intake from macronutrients to predict obesity. RESULTS: The percentage of energy intake from protein and fat of adult residents in 15 provinces(autonomous regions and municipalities) in China showed an increasing trend(P<0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend(P<0.01) between 1991 and 2018. After adjusting for covariates, the group of percentage of energy intake from fat in 20%～30%(ß=0.05, 95%CI 0.01-0.08)and ≥30%(ß=0.15, 95%CI 0.11-0.18)were positively correlated with BMI compared with the group of percentage of energy intake from fat <20%, and the risk of obesity in 20%-30% and ≥ 30% was increased by 17%(OR=1.17, 95%CI 1.04-1.31)and 6%(OR=1.06, 95%CI 1.24-1.56), respectively. Compared with the group of the percentage of energy intake from carbohydrate < 50%, the group of 50% to 65%(ß=-0.08, 95% CI-0.11--0.05) and ≥ 65%(ß=-0.17, 95%CI-0.20--0.13) was negatively correlated with BMI, and the percentage of energy intake from carbohydrate ≥ 65% reduced the risk of obesity(OR=0.71, 95%CI 0.63-0.80). CONCLUSION: Carbohydrate intake was inversely correlated with the risk of obesity, and fat intake was positively correlated with the risk of obesity. Moderate intake of carbohydrates and reduced fat intake can prevent obesity.

Diet Mediate the Impact of Host Habitat on Gut Microbiome and Influence Clinical Indexes by Modulating Gut Microbes and Serum Metabolites.

The impact of external factors on the human gut microbiota and how gut microbes contribute to human health is an intriguing question. Here, the gut microbiome of 3,224 individuals (496 with serum metabolome) with 109 variables is studied. Multiple analyses reveal that geographic factors explain the greatest variance of the gut microbiome and the similarity of individuals' gut microbiome is negatively correlated with their geographic distance. Main food components are the most important factors that mediate the impact of host habitats on the gut microbiome. Diet and gut microbes collaboratively contribute to the variation of serum metabolites, and correlate to the increase or decrease of certain clinical indexes. Specifically, systolic blood pressure is lowered by vegetable oil through increasing the abundance of Blautia and reducing the serum level of 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1), but it is reduced by fruit intake through increasing the serum level of Blautia improved threonate. Besides, aging-related clinical indexes are also closely correlated with the variation of gut microbes and serum metabolites. In this study, the linkages of geographic locations, diet, the gut microbiome, serum metabolites, and physiological indexes in a Chinese population are characterized. It is proved again that gut microbes and their metabolites are important media for external factors to affect human health.

Longitudinal Relationship between the Percentage of Energy Intake from Macronutrients and Overweight/Obesity among Chinese Adults from 1991 to 2018.

To investigate the prospective relationship between macronutrient intake and overweight/obesity, data were collected in the China Health and Nutrition Survey (CHNS) from 1991 to 2018. Adults who participated in at least two waves of the survey and were not obese at baseline were selected as the study subjects. A total of 14,531 subjects were finally included with complete data. Overweight/obesity was defined as a body mass index (BMI) ≥ 24.0 kg/m2. The generalized estimating equation (GEE) was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and overweight/obesity. The percentages of energy intake from protein and fat showed an increasing trend (p < 0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend (p < 0.01) among Chinese adults between 1991 and 2018. Adjusting for covariates, the energy intake from fat was positively correlated with BMI, while the energy intake from carbohydrates was negatively correlated with BMI. The percentage of energy intake from non-high-quality protein and polyunsaturated fatty acids (PUFA) were positively correlated with overweight/obesity. In contrast, monounsaturated fatty acids (MUFA) and high-quality carbohydrates were negatively correlated with overweight/obesity. In short, fat, non-high-quality protein, saturated fatty acids (SFA), and PUFA were positively correlated with the risk of obesity, whereas higher carbohydrate, MUFA, and high-quality carbohydrate intake were associated with a lower risk of obesity. Obesity can be effectively prevented by appropriately adjusting the proportion of intake from the three major macronutrients.

Reduction characteristic of chlorobenzene by a newly isolated Paenarthrobacter ureafaciens LY from a pharmaceutical wastewater treatment plant.

A highly efficient chlorobenzene-degrading strain was isolated from the sludge of a sewage treatment plant associated with a pharmaceutical company. The strain exhibited a similarity of over 99.9% with multiple strains of Paenarthrobacter ureafaciens. Therefore, the strain was suggested to be P. ureafaciens LY. This novel strain exhibited a broad spectrum of pollutant degradation capabilities, effectively degrading chlorobenzene and other organic pollutants, such as 1, 2, 4-trichlorobenzene, phenol, and xylene. Moreover, P. ureafaciens LY co-metabolized mixtures of chlorobenzene with 1, 2, 4-trichlorobenzene or phenol. Evaluation of its degradation efficiency showed that it achieved an impressive degradation rate of 94.78% for chlorobenzene within 8 h. The Haldane-Andrews model was used to describe the growth of P. ureafaciens LY under specific pollutants and its concentrations, revealing a maximum specific growth rate (µmax ) of 0.33 h-1 . The isolation and characterization of P. ureafaciens LY, along with its ability to degrade chlorobenzene, provides valuable insights for the development of efficient and eco-friendly approaches to mitigate chlorobenzene contamination. Additionally, investigation of the degradation performance of the strain in the presence of other pollutants offers important information for understanding the complexities of co-metabolism in mixed-pollutant environments.

Efficient pulmonary fibrosis therapy via regulating macrophage polarization using respirable cryptotanshinone-loaded liposomal microparticles.

Lung inflammation and fibrogenesis are the two main characteristics during the development of pulmonary fibrosis (PF), which are particularly associated with pulmonary macrophages. In this context, whether cryptotanshinone (CTS) could alleviate PF through regulating macrophage polarization were preliminarily demonstrated in vitro. Then the time course of PF and its relationship with macrophage polarization was determined in BLM-induced mice based on cytokine levels in bronchoalveolar lavage fluid (BALF), lung histopathology, flow cytometric analysis, mRNA and protein expression. CTS was loaded into macrophage-targeted and responsively released mannose-modified liposomes (Man-lipo), and the liposomes were then embedded into mannitol microparticles (M-MPs) using spray drying to achieve efficient pulmonary delivery. Afterwards, how CTS regulates macrophage polarization in vivo during different time courses of PF was probed. Furthermore, the molecular mechanisms of CTS against PF by regulating macrophage polarization were elucidated in vivo and in vitro. The full-course therapy group could achieve comparable therapeutic effects compared with the positive control drug PFD group. CTS can alleviate PF through regulating macrophage polarization, mainly by inhibiting NLRP3/TGF-ß1 pathway during the inflammation course and modulating MMP-9/TIMP-1 balance during the fibrosis development course, providing new insights into chronic PF treatment.

Sorting nexin 3 exacerbates doxorubicin-induced cardiomyopathy via regulation of TFRC-dependent ferroptosis.

The clinical utilization of doxorubicin (Dox) in various malignancies is restrained by its major adverse effect: irreversible cardiomyopathy. Extensive studies have been done to explore the prevention of Dox cardiomyopathy. Currently, ferroptosis has been shown to participate in the incidence and development of Dox cardiomyopathy. Sorting Nexin 3 (SNX3), the retromer-associated cargo binding protein with important physiological functions, was identified as a potent therapeutic target for cardiac hypertrophy in our previous study. However, few study has shown whether SNX3 plays a critical role in Dox-induced cardiomyopathy. In this study, a decreased level of SNX3 in Dox-induced cardiomyopathy was observed. Cardiac-specific Snx3 knockout (Snx3-cKO) significantly alleviated cardiomyopathy by downregulating Dox-induced ferroptosis significantly. SNX3 was further demonstrated to exacerbate Dox-induced cardiomyopathy via induction of ferroptosis in vivo and in vitro, and cardiac-specific Snx3 transgenic (Snx3-cTg) mice were more susceptible to Dox-induced ferroptosis and cardiomyopathy. Mechanistically, SNX3 facilitated the recycling of transferrin 1 receptor (TFRC) via direct interaction, disrupting iron homeostasis, increasing the accumulation of iron, triggering ferroptosis, and eventually exacerbating Dox-induced cardiomyopathy. Overall, these findings established a direct SNX3-TFRC-ferroptosis positive regulatory axis in Dox-induced cardiomyopathy and suggested that targeting SNX3 provided a new effective therapeutic strategy for Dox-induced cardiomyopathy through TFRC-dependent ferroptosis.

Early-life exposure to the Great Chinese Famine and gut microbiome disruption across adulthood for type 2 diabetes: three population-based cohort studies.

BACKGROUND: The early life stage is critical for the gut microbiota establishment and development. We aimed to investigate the lifelong impact of famine exposure during early life on the adult gut microbial ecosystem and examine the association of famine-induced disturbance in gut microbiota with type 2 diabetes. METHODS: We profiled the gut microbial composition among 11,513 adults (18-97 years) from three independent cohorts and examined the association of famine exposure during early life with alterations of adult gut microbial diversity and composition. We performed co-abundance network analyses to identify keystone taxa in the three cohorts and constructed an index with the shared keystone taxa across the three cohorts. Among each cohort, we used linear regression to examine the association of famine exposure during early life with the keystone taxa index and assessed the correlation between the keystone taxa index and type 2 diabetes using logistic regression adjusted for potential confounders. We combined the effect estimates from the three cohorts using random-effects meta-analysis. RESULTS: Compared with the no-exposed control group (born during 1962-1964), participants who were exposed to the famine during the first 1000 days of life (born in 1959) had consistently lower gut microbial alpha diversity and alterations in the gut microbial community during adulthood across the three cohorts. Compared with the no-exposed control group, participants who were exposed to famine during the first 1000 days of life were associated with consistently lower levels of keystone taxa index in the three cohorts (pooled beta - 0.29, 95% CI - 0.43, - 0.15). Per 1-standard deviation increment in the keystone taxa index was associated with a 13% lower risk of type 2 diabetes (pooled odds ratio 0.87, 95% CI 0.80, 0.93), with consistent results across three individual cohorts. CONCLUSIONS: These findings reveal a potential role of the gut microbiota in the developmental origins of health and disease (DOHaD) hypothesis, deepening our understanding about the etiology of type 2 diabetes.

Setting sodium targets for pre-packaged foods in China - an exploratory study.

Introduction: Setting sodium targets for pre-packaged food has been a priority strategy for reducing population sodium intake. This study aims to explore the attitudes and considerations of researchers and key stakeholders toward implementing such policy in China. Methods: An exploratory study comprising a survey and a focus group discussion was conducted among 27 purposively selected participants including 12 researchers, 5 consumers, 4 administrators, 3 industry association representatives and 3 food producers. The survey/discussion covered the key questions considered when developing/promoting sodium targets. Free-text responses were manually classified and summarized using thematic analysis. Results: Two-thirds of the participants supported target-setting policy. Researchers and administrators were most supportive, and food producers and associations were least supportive. Adapted WHO food categorization framework was well accepted to underpin target-setting to ensure international comparability and applicability for Chinese products. Maximum values were the most agreed target type. The WHO benchmarks were thought to be too ambitious to be feasible given the current food supply in China but can be regarded as long-term goals. Initially, a reduction of sodium content by 20% was mostly accepted to guide the development of maximum targets. Other recommendations included implementing a comprehensive strategy, strengthening research, engaging social resources, establishing a systematic monitoring/incentive system, maintaining a fair competitive environment, and developing a supportive information system. Target-setting policy was acceptable by most stakeholders and should be implemented alongside strategies to reduce discretionary salt use. Discussion: Our findings provide detailed guidance for the Chinese government when developing a target-setting strategy. The methods and results of this study also provide meaningful references for other countries to set sodium targets for pre-packaged foods and implement other salt reduction strategies simultaneously.

[Designing effective front-of-package warning labels for prepackaged food in China:based on Delphi method].

OBJECTIVE: To design front-of-package warning labels for prepackaged food adapted to the Chinese context. METHODS: Delphi method was used to evaluate the first graft of indicatorsof the front-of-package warning labels. The front-of-package warning labels suitable for China's national conditions was selected according to the direct scoring method. RESULTS: 4 sets of front-of-package warning labels for prepackaged food were selected after two rounds of Delphi expert method. CONCLUSION: The final draft of the front-of-package warning labels for prepackaged food is in line with expectations.

[Evaluation of the front-of-package warning labels of prepackaged food in China based on focus group discussion].

OBJECTIVE: To understand the public's perceptions and preferences on the designed front-of-package warning labels of prepackaged food, and to evaluate and identify the effective warning label. METHODS: A total of 116 participants were recruited from six provinces(autonomous regions/municipalities) in China. Focus group discussions were conducted with four types of warning labels on prepackaged food. And the score of attitude on different warning labels were compared. RESULTS: There was no difference in the total score of the four warning labels. Total score of black shield label was higher in citizen participants and college education level participants than in their respective counterparts(P<0.05). Parents or primary caregiver of children under 16 years old gave higher scores to each labels than their respective counterparts(P<0.05). The black shield label was most likely to attract the attention of the respondents, most likely to influence the decision on eating and drinking, and most likely to have an unhealthy warning effect. The yellow hexagonal label was least likely to attract the attention of the respondents, least likely to affect the decision to eat and drink food, and least likely to have an unhealthy warning effect. CONCLUSION: Black shield warning label is the most effective.

Generational Differences in Food Consumption among Chinese Adults of Different Ages.

Limited knowledge currently exists regarding the dynamics of generational shifts in food consumption among adult residents in China. This study aimed to investigate the generational differences in dietary status among different generations of Chinese adult residents aged 20 years and older. Survey participants from four waves (1991, 2000, 2009, and 2018) of the China Health and Nutrition Survey (CHNS) cohort were included in the study (N = 40,704), providing three-day 24 h dietary data. Participants were categorized into six age groups (20-29, 30-39, 40-49, 50-59, 60-69, and ≥70 years old), each corresponding to specific generations (Gen 10, 20, 30, 40, 50, 60, 70, 80, and 90) based on their age at the time of the survey. This study examined generational differences in the intake of cereals, animal-based foods, vegetables, fruits, dairy, energy, and the contribution of macronutrients to energy using chi-square tests and Kruskal-Wallis tests. All analyses were stratified by gender. Our findings revealed that younger generations exhibited lower daily intake of cereals, vegetables, energy, and contribution of carbohydrates to energy, compared to their older counterparts, regardless of gender. Conversely, regardless of male or female, younger generations showed higher daily consumption of animal-based foods, average fruit and dairy intake, fruit and dairy consumption rates, as well as contributions of protein and fat to energy, compared to older generations. The magnitude of generational differences in food consumption varied by age and gender. In addition, cereal and vegetable intake, energy intake, and contribution of carbohydrates to energy declined with age across all generations, while average dairy intake, fruit and dairy consumption rates, and the contribution of fat to energy tended to increase, regardless of gender. In conclusion, generational differences in food consumption were evident among different generations of Chinese adult residents, characterized by an increase in animal-based food intake and the contribution of fat to energy among generations. Attention should be directed towards addressing the eating behavior of younger generations.

[Expert knowledge-based strategies for ventilator parameter setting and stepless adaptive adjustment].

The setting and adjustment of ventilator parameters need to rely on a large amount of clinical data and rich experience. This paper explored the problem of difficult decision-making of ventilator parameters due to the time-varying and sudden changes of clinical patient's state, and proposed an expert knowledge-based strategies for ventilator parameter setting and stepless adaptive adjustment based on fuzzy control rule and neural network. Based on the method and the real-time physiological state of clinical patients, we generated a mechanical ventilation decision-making solution set with continuity and smoothness, and automatically provided explicit parameter adjustment suggestions to medical personnel. This method can solve the problems of low control precision and poor dynamic quality of the ventilator's stepwise adjustment, handle multi-input control decision problems more rationally, and improve ventilation comfort for patients.

Temporal Trends in Cardiovascular Health Status Among Chinese School-Aged Children From 1989 to 2018: Multiwave Cross-Sectional Analysis.

BACKGROUND: Despite the release of updated metrics for Life's Essential 8 (LE8), key indicators for assessing cardiovascular health (CVH) status, there is currently no report on their distribution among Chinese children. OBJECTIVE: This study aimed to assess the nationwide distribution of CVH in Chinese school-aged children using LE8 scores and analyze temporal changes in these scores over time. METHODS: Participants aged 7 to 19 years from 11 waves (between 1989 and 2018) of the China Health and Nutrition Survey were included in this study. LE8 components were grouped into 2 domains of health behaviors (diet, physical activity, nicotine exposure, sleep) and health factors (BMI, blood lipids, blood glucose, blood pressure). Scores of overall CVH and each LE8 metric were calculated individually. Temporal changes were assessed with joint point regression models by rural and urban living residence. The causal relationships between health behaviors and health factors that changed the most over time were built with cross-lagged panel models. RESULTS: A total of 21,921 participants, 52.6% (n=11,537) of whom were male, who had data for at least 4 CVH components were included in the analysis. The mean age was 13 (SD 3.6) years. The overall CVH score remained stable in most regions, with the lowest found in Shandong from East China, which had a mean between 67 (SD 10.9) and 67.2 (SD 12.4). In contrast, the highest score was found in Guizhou from Southwest China, with a mean between 71.4 (SD 10.8) and 74.3 (SD 10.3). In rural areas, the diet score decreased significantly from 1997 onward with a speed of 0.18 (95% CI: 0.15-0.21; P<.001) per year, and the BMI score decreased significantly from 2005 onward with a speed of 0.56 (95% CI 0.44-0.68; P<.001) per year. In urban areas, the diet score decreased from 1994 onward with a speed of 0.03 (95% CI: 0.001-0.07; P=.04) per year, and the BMI score decreased from 2002 onward with a speed of 0.63 (95% CI 0.47-0.79; P<.001) per year. The sleep score dropped constantly in both urban and rural areas, with a speed of 0.69 (95% CI 0.58-0.80; P<.001) and 0.69 (95% CI: 0.52-0.86; P<.001) per year, respectively. A decline in the diet score led to a decline in the BMI score with a coefficient of 0.190 (95% CI 0.030-0.351; P=.02), while a decline in the BMI score led to a decline in sleep health with a coefficient of 0.089 (95% CI 0.010-0.168; P=.03). CONCLUSIONS: Chinese school-aged children and adolescents were generally of moderate CVH status, but mutual influences existed between CVH metrics. Dietary interventions should be prioritized for promoting overall CVH in the future.

Carboxymethyl Cellulose/Polyacrylamide/Fe3O4 Magnetic Ion Imprinting Biosorbent for Removal and Recovery of La3.

To use resources rationally, the recovery and recycling of rare earth (RE) from industrial sewage have attracted a lot of attention. Herein, a polymer adsorbent CMC/PAM/Fe3O4 (CPF) was synthesized from renewable carboxymethyl cellulose (CMC), polyacrylamide (PAM), and Fe3O4 by the template of La3+ using ion imprinting technology. The CPF was characterized with X-ray diffraction (XRD), IR, X-ray photoelectron spectroscopy (XPS), and scanning electron microscope (SEM), and results show that PAM and CMC can crosslink with each other and form copolymers with Fe3O4 particles dispersing in it. The adsorption properties for the template ions La3+ were fully studied. It is found that CPF exhibited good adsorption performance with an adsorption capacity of 34.6 mg·g-1. Cycling experiments show that CPF still has high efficiency even after 5 cycles. Meanwhile, the desorption rate can reach more than 98%. The low wastage and high adsorption/desorption efficiency would enable CPF to be a good candidate adsorbent for removal/recovery of La3+ from industrial sewage.

Sodium content targets for pre-packaged foods, China: a quantitative study and proposal.

Objective: To determine the contribution of pre-packaged foods to population sodium intake in China, and to propose sodium content targets for food subcategories used for the World Health Organization's (WHO's) global sodium benchmarks. Methods: The impact of four different approaches to reducing the sodium content of pre-packaged foods on population sodium intake was estimated using data from national databases covering the nutrient content and ingredients of 51 803 food products and food consumption by 15 670 Chinese adults. We recategorized food products using a food categorization framework developed for WHO's global sodium benchmarks and adapted for China-specific foods. Findings: Pre-packaged foods, including condiments, contributed 1302.5 mg/day of sodium intake per adult in 2021, accounting for 30.1% of population sodium intake in China. Setting maximum sodium content levels using a 90th-percentile target would reduce sodium intake from pre-packaged foods by 96.2 mg/day, corresponding to a 1.9% reduction in population intake. Using the 75th-percentile, a fixed 20% reduction and WHO benchmark targets would further reduce intake by 262.0 mg/day (5.2% population intake), 302.8 mg/day (6.0% population intake) and 701.2 mg/day per person (13.9% population intake), respectively. Maximum sodium content levels based on revised 20% reduction targets were proposed because they should result in substantial and acceptable reductions in sodium content for most food subcategories: overall sodium intake would decline by 305.0 mg/day per person, and population intake by 6.1%. Conclusion: This study provides the scientific rationale for government policy on setting targets for food sodium content in China. Simultaneous action on discretionary salt use should also be taken.

[Trajectories of body mass index and risk of hypertension and blood pressure among Chinese adults].

OBJECTIVE: To explore the relationship between trajectories of body mass index(BMI) and the risk of hypertension and blood pressure among Chinese adults. METHODS: The current study was based on data from 10 waves of the China Health and Nutrition Survey from 1991 to 2018. A multistage stratified random sample was used in this study.11885 adults whose BMI had been measured at least three times were included in the study. Group-based trajectory modeling(GBTM) was used to identify the BMI trajectories in different genders, Cox regression model was used to analyze the association between BMI trajectories and the risk of incident hypertension. Generalized linear model was used to analyze the association between BMI trajectories and the blood pressure level. RESULTS: Three distinct BMI trajectories were determined for both genders: normal-stable group, normal-overweight group, obesity-stable group. The numbers of each group among males were 3595(63.23%), 1412(24.83%) and 679(11.94%), and the numbers of each group among females were 4566(73.66%), 1214(19.58%) and 419(6.76%). Taking the normal-stable group as a reference, after adjusting for confounding factors, the normal-overweight group, obesity-stable group had 1.14(1.03-1.25), P=0.01 and 1.42(1.24-1.63), P<0.01 increased risk(HR(95% CI)) of developing hypertension in male. The normal-overweight group, obesity-stable group had 1.29(1.13-1.46), P<0.01 and 1.58(1.23-2.03), P<0.01 increased risk of developing hypertension in female. Taking the normal-stable group as a reference, after adjusting for confounding factors, the systolic blood pressure[ß(95% CI)] in the male normal-overweight group and obesity-stable group increased by 3.01(1.88-4.14)mmHg, P<0.01 and 5.44(3.85-7.03)mmHg, P<0.01 respectively. The diastolic blood-pressure level was increased by 2.20(1.48-2.91)mmHg, P<0.01 and 4.04(3.04-5.04)mmHg, P<0.01 respectively. The systolic blood pressure in the female normal-overweight group and obesity-stable group were increased by 3.65(2.44-4.85)mmHg, P<0.01 and 2.96(0.97-4.94)mmHg, P<0.01 respectively. The diastolic blood pressure level was increased by 3.11(2.38-3.86)mmHg, P<0.01 and 1.25(0.03-2.47)mmHg, P=0.05 respectively. CONCLUSION: Both the trajectory of BMI increasing with age and the trajectory of maintaining a high BMI level increased the risk of hypertension, and blood pressure also increased significantly compared with those who maintained normal BMI.

Corrigendum: Essential role of microglia in the fast antidepressant action of ketamine and hypidone hydrochloride (YL-0919).

[This corrects the article DOI: 10.3389/fphar.2023.1122541.].

Essential role of microglia in the fast antidepressant action of ketamine and hypidone hydrochloride (YL-0919).

Introduction: Intracerebral microglia play a vital role in mediating central immune response, neuronal repair and synaptic pruning, but its precise role and mechanism in fast action of antidepressants have remained unknown. In this study, we identified that the microglia contributed to the rapid action of antidepressants ketamine and YL-0919. Methods: The depletion of microglia was achieved with the diet containing the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in mice. The tail suspension test (TST), forced swimming test (FST) and novelty suppressed feeding test (NSFT) were employed to evaluate the rapid acting antidepressant behavior of ketamine and YL-0919 in the microglia depletion model. The number of microglia in the prefrontal cortex (PFC) was assayed by the immunofluorescence staining. The expressions of synaptic proteins (synapsin-1, PSD-95, GluA1) and brain-derived neurotrophic factor (BDNF) in the PFC were tested by Western blot. Results: The immobility duration in FST and the latency to feed in NSFT were shortened 24 h after an intraperitoneal (i.p.) injection of ketamine (10 mg/kg). The microglial depletion of PLX3397 blocked the rapid antidepressant-like effect of ketamine in mice. In addition, the immobility time in TST and FST as well as latency to feed in NSFT were reduced 24 h after the intragastric (i.g.) administration of YL-0919 (2.5 mg/kg), and the rapid antidepressant effect of YL-0919 was also blocked by the microglial depletion using PLX5622. About 92% of microglia in the prefrontal cortex was depleted in PLX5622 diet-fed mice, while both ketamine and YL-0919 promoted proliferation on the remaining microglia. YL-0919 significantly increased the protein expressions of synapsin-1, PSD-95, GluA1 and BDNF in the PFC, all of which could be blocked by PLX5622. Conclusion: These results suggested the microglia underlying the rapid antidepressant-like effect of ketamine and YL-0919, and microglia would likely constitute in the rapid enhancing impact of synaptic plasticity in the prefrontal cortex by YL-0919.

Longitudinal study of dietary patterns and hypertension in adults: China Health and Nutrition Survey 1991-2018.

China is undergoing the nutrition transition that may explain partly the high prevalence of hypertension. We aimed to investigate the longitudinal association between dietary patterns and hypertension in Chinese adults over 28 years of follow-up. We used data collected in the China Health and Nutrition Survey from 1991 to 2018. Adults aged 18 years and above (n = 15,929) were included in the analysis, for whom questionnaires and anthropometric data were collected during at least two waves. Factor analysis was conducted to derive food patterns based on 18 foods or food groups. We constructed three-level mixed-effect linear regression models to estimate systolic blood pressure (SBP) and diastolic blood pressure (DBP) in relation to quartiles of dietary pattern score and performed three-level mixed-effect logistic regression models to assess the risk of hypertension. Participants in the top quartile of the modern pattern had a decrease in SBP (ß = - 0.51; 95% CI -0.86, -0.16; P < 0.01) when adjusted for all potential confounders, whereas participants in the top quartile of the meat pattern had an increase in DBP (ß = 0.31; 95% CI 0.08, 0.53; P < 0.01). Participants in the highest quartile of the meat pattern were more likely to have hypertension (OR = 1.14; 95% CI 1.03, 1.24; P < 0.01). Adherence to the modern pattern characterized by high intake of fruits and dairy products was inversely associated with SBP, whereas the meat pattern was positively associated with DBP and the risk of hypertension. These findings may well have important public health implications.

JMJD6 protects against isoproterenol-induced cardiac hypertrophy via inhibition of NF-κB activation by demethylating R149 of the p65 subunit.

Histone modification plays an important role in pathological cardiac hypertrophy and heart failure. In this study we investigated the role of a histone arginine demethylase, Jumonji C domain-containing protein 6 (JMJD6) in pathological cardiac hypertrophy. Cardiac hypertrophy was induced in rats by subcutaneous injection of isoproterenol (ISO, 1.2 mg·kg-1·d-1) for a week. At the end of the experiment, the rats underwent echocardiography, followed by euthanasia and heart collection. We found that JMJD6 levels were compensatorily increased in ISO-induced hypertrophic cardiac tissues, but reduced in patients with heart failure with reduced ejection fraction (HFrEF). Furthermore, we demonstrated that JMJD6 overexpression significantly attenuated ISO-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) evidenced by the decreased cardiomyocyte surface area and hypertrophic genes expression. Cardiac-specific JMJD6 overexpression in rats protected the hearts against ISO-induced cardiac hypertrophy and fibrosis, and rescued cardiac function. Conversely, depletion of JMJD6 by single-guide RNA (sgRNA) exacerbated ISO-induced hypertrophic responses in NRCMs. We revealed that JMJD6 interacted with NF-κB p65 in cytoplasm and reduced nuclear levels of p65 under hypertrophic stimulation in vivo and in vitro. Mechanistically, JMJD6 bound to p65 and demethylated p65 at the R149 residue to inhibit the nuclear translocation of p65, thus inactivating NF-κB signaling and protecting against pathological cardiac hypertrophy. In addition, we found that JMJD6 demethylated histone H3R8, which might be a new histone substrate of JMJD6. These results suggest that JMJD6 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.