Serine synthesis controls mitochondrial biogenesis in macrophages.

Mitochondrial dysfunction is the pivotal driving factor of multiple inflammatory diseases, and targeting mitochondrial biogenesis represents an efficacious approach to ameliorate such dysfunction in inflammatory diseases. Here, we demonstrated that phosphoglycerate dehydrogenase (PHGDH) deficiency promotes mitochondrial biogenesis in inflammatory macrophages. Mechanistically, PHGDH deficiency boosts mitochondrial reactive oxygen species (mtROS) by suppressing cytoplasmic glutathione synthesis. mtROS provokes hypoxia-inducible factor-1α signaling to direct nuclear specificity protein 1 and nuclear respiratory factor 1 transcription. Moreover, myeloid Phgdh deficiency reverses diet-induced obesity. Collectively, this study reveals that a mechanism involving de novo serine synthesis orchestrates mitochondrial biogenesis via mitochondrial-to-nuclear communication, and provides a potential therapeutic target for tackling inflammatory diseases and mitochondria-mediated diseases.

[Multi-index evaluation of different parts of Amomum villosum].

To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.

Bacterial cellulose/multi-walled carbon nanotube composite films for moist-electric energy harvesting.

Generation of renewable and clean electricity energy from ubiquitous moisture for the power supply of portable electronic devices has become one of the most promising energy collection methods. However, the modest electrical output and transient power supply characteristics of existing moist-electric generator (MEG) severely limit its commercial application, leading to an urgent demand of developing a MEG with high electrical output and continuous power generation capacity. In this work, it is demonstrated that a flexible bacterial cellulose (BC)/Multi-walled carbon nanotube (MWCNT) double-layer (BM-dl) film prepared by vacuum filtration can maintain the moisture concentration difference in the film MEG. Unlike previous studies on cellulose based MEG, BM-dl film has a heterogeneous structure, resulting in a maximum output power density of 0.163 µW/cm2, an extreme voltage of 0.84 V, and current of 2.21 µA at RH = 90 %. BM-dl MEG can generate a voltage of 0.55 V continuously for 45 h in a natural environment (RH = 63-77 %, T = 26-27 °C), which is in a leading level among existing reported cellulose-based MEGs. In summary, this study provides new ideas for innovative design of MEG, which is highly competitive in terms of energy supply for the Internet of Things and wearable devices.

Bonus-based mercenary punishment promotes cooperation in public goods games.

Various regions often adopt punish strategies to solve traffic congestion problems. Punishing defectors is an effective strategy to solve the first-order free-rider problem in a public goods game. But this behavior is costly because the punisher is often also involved in the original joint venture and therefore vulnerable, which jeopardizes the effectiveness of this incentive. As an option, we could hire special players whose sole duty would be to monitor the population and punish defectors. The fines collected by various regions will also be used to subsidize the construction of public transportation. Thereby, we derive inspiration, and propose an improved public goods game model based on bonus and mercenary punishment. Research has shown that after cooperator gives the punisher an appropriate bonus, cooperators can strengthen the punisher, thereby weakening the defector's advantage and indirectly promoting cooperation by stabilizing the punisher's position in the system. In addition, the mechanism of reusing the fines collected from defectors and then subsidize to other players in the system can directly promote the emergence of cooperation.

Serine synthesis sustains macrophage IL-1ß production via NAD+-dependent protein acetylation.

Serine metabolism is involved in the fate decisions of immune cells; however, whether and how de novo serine synthesis shapes innate immune cell function remain unknown. Here, we first demonstrated that inflammatory macrophages have high expression of phosphoglycerate dehydrogenase (PHGDH, the rate-limiting enzyme of de novo serine synthesis) via nuclear factor κB signaling. Notably, the pharmacological inhibition or genetic modulation of PHGDH limits macrophage interleukin (IL)-1ß production through NAD+ accumulation and subsequent NAD+-dependent SIRT1 and SIRT3 expression and activity. Mechanistically, PHGDH not only sustains IL-1ß expression through H3K9/27 acetylation-mediated transcriptional activation of Toll-like receptor 4 but also supports IL-1ß maturation via NLRP3-K21/22/24/ASC-K21/22/24 acetylation-mediated activation of the NLRP3 inflammasome. Moreover, mice with myeloid-specific depletion of Phgdh show alleviated inflammatory responses in lipopolysaccharide-induced systemic inflammation. This study reveals a network by which a metabolic enzyme, involved in de novo serine synthesis, mediates post-translational modifications and epigenetic regulation to orchestrate IL-1ß production, providing a potential inflammatory disease target.

FGF3 Directs the Pathfinding of Prethalamic GABAergic Axons.

The thalamus plays a crucial role in ensuring the faithful transfer of sensory information, except olfactory signals, to corresponding cortical areas. However, thalamic function is not simply restricted to relaying information to and from the cerebral cortex. The ability to modulate the flow of sensory information is supported by a second abundant neuronal type in the prethalamus, the inhibitory gamma-aminobutyric acid (GABAergic) neurons, which project inhibitory GABAergic axons to dorsal thalamic glutamatergic neurons. Interestingly, during the trajectory of pioneer prethalamic axons, morphogen fibroblast growth factor (FGF)-3 is expressed in the ventral chick hypothalamus. Using in vitro analyses in chick explants, we identify a chemorepellent effect of FGF3 on nearby prethalamic GABAergic axons. Furthermore, inhibition of FGF3 guidance functions indicates that FGF3 signaling is necessary to navigate prethalamic axons correctly. Gene expression analyses and loss of function studies demonstrate that FGF3 mediates prethalamic axonal guidance through the downstream pathway of the FGF receptor (FGFR)-1. Together, these results suggest that FGF3 expressed in the hypothalamus functions as a chemorepellent molecule to direct the pathway selection of neighboring GABAergic axons.

Dietary trace mineral pattern influences gut microbiota and intestinal health of broilers.

Dietary trace minerals can impact gut flora, which can further affect intestinal health. However, the dietary balance pattern of trace minerals for the intestinal health of broilers needs to be explored. The present study was conducted to investigate the effect of the dietary pattern of Cu, Fe, Mn, Zn, and Se on the intestinal morphology, microbiota, short-chain fatty acid concentrations, antioxidant status, and the expression of tight junction proteins in broilers. A total of 240 1-d-old Arbor Acres male broilers were randomly assigned to one of five treatments with six replicate cages of eight birds per cage for each treatment. The birds were fed the corn-soybean meal basal diet supplemented with five combination patterns of trace minerals for 42 d. The dietary treatments were as follows: the inorganic sources were added to the diet based on the recommendations of the current National Research Council (NRC, T1) and Ministry of Agriculture of P.R. China (MAP) (T2) for broiler chicks, respectively; the inorganic sources were added to the diet at the levels based on our previous results of inorganic trace mineral requirements for broilers (T3); the organic sources were added to the diet at the levels considering the bioavailabilities of organic trace minerals for broilers described in our previous studies (T4); and the organic sources were added to the diet based on the recommendations of the current MAP for broiler chicks (T5). The results showed that broilers from T1 had lower (P < 0.05) crypt depth (CD), and a higher (P < 0.05) villus height: CD in duodenum on day 21 and lower CD (P < 0.05) in jejunum on day 42 than those from T3 and T4. Broilers from T1, T3, and T5 had a higher (P < 0.05) Shannon index in cecum on day 21 than those from T4. Broilers from T1 had a higher (P < 0.05) abundance of Lactobacillus in ileum on day 21 than those from T2 and T3. Broilers from T1, T2, and T5 had a higher (P < 0.05) valeric acid concentrations in cecum on day 42 than those from T3 and T4. In addition, Birds from T2 had higher (P < 0.05) Claudin-1 mRNA levels in jejunum on day 42 than those from T3 and T4. And birds from T3, T4, and T5 had a higher (P < 0.05) Occludin protein expression levels in duodenum on day 42 than those from T2. These results indicate that dietary pattern of Cu, Fe, Mn, Zn, and Se influenced gut flora and intestinal health of broilers, and the appropriate pattern of Cu, Fe, Mn, Zn, and Se in the diet for intestinal health of broilers would be Cu 12 mg, Fe 229 mg, Mn 81 mg, Zn 78 mg, and Se 0.24 mg/kg (1 to 21 d of age), and Cu 11 mg, Fe 193 mg, Mn 80 mg, Zn 73 mg, and Se 0.22 mg/kg (22 to 42 d of age), when the trace minerals as inorganic sources were added to diets according to the recommendations of the current NRC.

Information is still scarce regarding the effect of dietary trace mineral patterns on the intestinal health of broilers. The results indicated that dietary trace mineral pattern influenced intestinal health of broilers, and the appropriate pattern of trace minerals in the diet for intestinal health of broilers would be Cu 12 mg, Fe 229 mg, Mn 81 mg, Zn 78 mg, and Se 0.24 mg/kg (1 to 21 d of age), and Cu 11 mg, Fe 193 mg, Mn 80 mg, Zn 73 mg, and Se 0.22 mg/kg (22 to 42 d of age), when the trace minerals as inorganic sources were added to diets according to the recommendations of the current National Research Council. Our results provided scientific experimental bases for improving intestinal health of broilers by nutritional strategy.

GABA signaling enforces intestinal germinal center B cell differentiation.

Recent compelling results indicate possible links between neurotransmitters, intestinal mucosal IgA+ B cell responses, and immunoglobulin A nephropathy (IgAN) pathogenesis. Here, we demonstrated that γ-amino butyric acid (GABA) transporter-2 (GAT-2) deficiency induces intestinal germinal center (GC) B cell differentiation and worsens the symptoms of IgAN in a mouse model. Mechanistically, GAT-2 deficiency enhances GC B cell differentiation through activation of GABA-mammalian target of rapamycin complex 1 (mTORC1) signaling. In addition, IgAN patients have lower GAT-2 expression but higher activation of mTORC1 in blood B cells, and both are correlated with kidney function in IgAN patients. Collectively, this study describes GABA signaling-mediated intestinal mucosal immunity as a previously unstudied pathogenesis mechanism of IgAN and challenges the current paradigms of IgAN.

Prenatal Symptom Cluster of Psychopathology and Associations With Mindfulness and Rumination: A Network Analysis.

ABSTRACT: The present study aimed to examine the interrelationships of prenatal psychopathology (specifically symptom cluster), dispositional mindfulness, and rumination using network analysis. Network analysis estimates the links between symptoms and can evaluate the presence and strength of the links. A total of 1122 pregnant women were recruited from a tertiary hospital in China. Psychopathology symptoms (including anxiety, depression, stress, fatigue, sleep, fear of childbirth [FOC], and memory problems) were assessed and used along with mindfulness and rumination to construct networks of association using R. Results illustrated five communities within the network. Anxiety resulted in the highest strength of centrality followed by two symptoms: FOC and retrospective memory. Paths showed that mindfulness was directly connected to depression, prospective memory, retrospective memory, and lack of positive anticipation in FOC, whereas mindfulness was connected indirectly through rumination to anxiety, fatigue, stress, and sleep problems. The findings reinforce that anxiety is a key symptom of prenatal psychopathology and requires priority consideration. The direct associations between mindfulness and prenatal psychopathology symptoms provide potential targets for future mindfulness-based interventions, and mindfulness reducing rumination thus in turn decrease anxiety, suggesting potential mediating mechanism of mindfulness.

Associations of physical activity, sedentary behavior and sleep duration with anxiety symptoms during pregnancy: An isotemporal substitution model.

BACKGROUND: Studies have evidenced the close relationships between movement behavior [physical activity (PA), sedentary behavior (SB), and sleep duration)] and anxiety. Capturing 24 h of these maternal movement behaviors during pregnancy is necessary to understand their relationships. METHODS: In a cross-sectional study design, a total of 946 prenatal women filled Pregnancy Physical Activity Questionnaire-Chinese version, Pregnancy-Related Anxiety Questionnaire, and 7-item Generalised Anxiety Disorders scale between May 2020 and April 2021. An Isotemporal Substitution Model was used to estimate the per-hour effects of replacing one behavior. RESULTS: Replacing moderate-to-vigorous PA(MVPA), light PA (LPA), or SB with sleep could reduce both general and pregnancy-specific anxiety (LPA, B = -0.61∼-0.37, P ≤ 0.01; MVPA, B = -0.35, P = 0.03; SB, B = -0.45∼-0.34, P ≤ 0.01). Replacing SB with MVPA could reduce pregnancy-specific anxiety in the group without adequate sleep duration (SB, B = -0.62,95%CI = -1.13∼-0.17). As for the types of PA, replacing household, occupational or inactivity PA with transportation PA or sleep duration reduced general anxiety (household PA: B = -0.51, 95%CI = -0.73∼-0.29, P < 0.001; occupational PA: B = -0.48, 95%CI = -0.69∼-0.27, P < 0.001; inactivity: B = -0.45, 95%CI = -0.68∼-0.24, P < 0.001). Replacing household PA, occupational PA, or inactivity with transport PA was associated with improved general anxiety (household: B = -0.33, 95%CI = -0.64∼-0.03, P = 0.29; occupational PA: B = -0.31, 95%CI = -0.62∼-0.003, P = 0.35; inactivity: B = -0.28, 95%CI = -0.56∼-0.01, P = 0.33). LIMITATIONS: A cross-sectional study design and self-reported measurement limits the reliability of study. CONCLUSION: Longer time spent in sleep and MVPA may mitigate the negative effects of SB on anxiety.

A Particle Swarm Algorithm Based on a Multi-Stage Search Strategy.

Particle swarm optimization (PSO) has the disadvantages of easily getting trapped in local optima and a low search accuracy. Scores of approaches have been used to improve the diversity, search accuracy, and results of PSO, but the balance between exploration and exploitation remains sub-optimal. Many scholars have divided the population into multiple sub-populations with the aim of managing it in space. In this paper, a multi-stage search strategy that is dominated by mutual repulsion among particles and supplemented by attraction was proposed to control the traits of the population. From the angle of iteration time, the algorithm was able to adequately enhance the entropy of the population under the premise of satisfying the convergence, creating a more balanced search process. The study acquired satisfactory results from the CEC2017 test function by improving the standard PSO and improved PSO.

Trust-based partner switching among partitioned regions promotes cooperation in public goods game.

In this paper, the coevolution mechanism of trust-based partner switching among partitioned regions on an adaptive network is studied. We investigate a low-information approach to building trust and cooperation in public goods games. Unlike reputation, trust scores are only given to players by those with whom they have a relationship in the game, depending on the game they play together. A player's trust score for a certain neighbor is given and known by that player only. Players can adjust their connections to neighbors with low trust scores by switching their partners to other players. When switching partners, players divide other nodes in the network into three regions: immediate neighbors as the known region, indirectly connected second-order neighbors as the intermediate region, and other nodes as the unknown region. Such choices and compartmentalization often occur in global and regional economies. Our results show that preference for switching to partners in the intermediate region is not conducive to spreading cooperation, while random selection has the disadvantage of protecting the cooperator. However, selecting new partners in the remaining two regions based on the average trust score of the known region performs well in both protecting partners and finding potential cooperators. Meanwhile, by analyzing the parameters, we find that the influence of vigilance increasing against unsatisfactory behavior on evolution direction depends on the level of cooperation reward.

A Diversity Model Based on Dimension Entropy and Its Application to Swarm Intelligence Algorithm.

The swarm intelligence algorithm has become an important method to solve optimization problems because of its excellent self-organization, self-adaptation, and self-learning characteristics. However, when a traditional swarm intelligence algorithm faces high and complex multi-peak problems, population diversity is quickly lost, which leads to the premature convergence of the algorithm. In order to solve this problem, dimension entropy is proposed as a measure of population diversity, and a diversity control mechanism is proposed to guide the updating of the swarm intelligence algorithm. It maintains the diversity of the algorithm in the early stage and ensures the convergence of the algorithm in the later stage. Experimental results show that the performance of the improved algorithm is better than that of the original algorithm.

Effectiveness of Smartphone-Based Mindfulness Training on Maternal Perinatal Depression: Randomized Controlled Trial.

BACKGROUND: Despite potential for benefit, mindfulness remains an emergent area in perinatal mental health care, and evidence of smartphone-based mindfulness training for perinatal depression is especially limited. OBJECTIVE: The objective of this study was to evaluate the effectiveness of a smartphone-based mindfulness training intervention during pregnancy on perinatal depression and other mental health problems with a randomized controlled design. METHODS: Pregnant adult women who were potentially at risk of perinatal depression were recruited from an obstetrics clinic and randomized to a self-guided 8-week smartphone-based mindfulness training during pregnancy group or attention control group. Mental health indicators were surveyed over five time points through the postpartum period by online self-assessment. The assessor who collected the follow-up data was blind to the assignment. The primary outcome was depression as measured by symptoms, and secondary outcomes were anxiety, stress, affect, sleep, fatigue, memory, and fear. RESULTS: A total of 168 participants were randomly allocated to the mindfulness training (n=84) or attention control (n=84) group. The overall dropout rate was 34.5%, and 52.4% of the participants completed the intervention. Mindfulness training participants reported significant improvement of depression (group × time interaction χ24=16.2, P=.003) and secondary outcomes (χ24=13.1, P=.01 for anxiety; χ24=8.4, P=.04 for positive affect) compared to attention control group participants. Medium between-group effect sizes were found on depression and positive affect at postintervention, and on anxiety in late pregnancy (Cohen d=0.47, -0.49, and 0.46, respectively). Mindfulness training participants reported a decreased risk of positive depressive symptom (Edinburgh Postnatal Depression Scale [EPDS] score>9) compared to attention control participants postintervention (odds ratio [OR] 0.391, 95% CI 0.164-0.930) and significantly higher depression symptom remission with different EPDS reduction scores from preintervention to postintervention (OR 3.471-27.986). Parity did not show a significant moderating effect; however, for nulliparous women, mindfulness training participants had significantly improved depression symptoms compared to nulliparous attention control group participants (group × time interaction χ24=18.1, P=.001). CONCLUSIONS: Smartphone-based mindfulness training is an effective intervention in improving maternal perinatal depression for those who are potentially at risk of perinatal depression in early pregnancy. Nulliparous women are a promising subgroup who may benefit more from mindfulness training. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900028521; http://www.chictr.org.cn/showproj.aspx?proj=33474.

Co-Evolution of Complex Network Public Goods Game under the Edges Rules.

The reconnection of broken edges is an effective way to avoid drawback for the commons in past studies. Inspired by this, we proposed a public goods game model under the edges rules, where we evaluate the weight of edges by their nodes' payoff. The results proved that the game obtains a larger range of cooperation with a small gain factor by this proposed model by consulting Monte Carlo simulations (MCS) and real experiments. Furthermore, as the following the course of game and discussing the reason of cooperation, in the research, we found that the distribution entropy of the excess average degree is able to embody and predict the presence of cooperation.

Suicidal ideation among nurses: Unique and cumulative effects of different subtypes of sleep problems.

BACKGROUND: Nurses have high rates of sleep problems, and higher risk of suicide than the general population. However, there is no empirical evidence showing the extent to which sleep problems among nurses are related to suicidal ideation. METHODS: Multistage stratified cluster sampling was performed to recruit nurses from tertiary hospitals in Shandong, China. Item 9 of the Patient Health Questionnaire-9 was used to assess suicidal ideation. The Pittsburgh Sleep Quality Index was used to assess different subtypes of sleep problems. RESULTS: Overall prevalence of suicidal ideation among the sample was 10.8%. Nurses with sleep problems were at high risk for suicidal ideation (bOR = 1.79, 95% CI = 1.20-2.65). Among different sleep problem subtypes, only "cannot breathe comfortably" was independently related to suicidal ideation. Different subtypes of sleep problems had cumulative effects on suicidal ideation: the more subtypes of sleep problems nurses experienced, the higher the likelihood of suicidal ideation. LIMITATIONS: The cross-sectional study design prevents inferring causation, and the use of self-report measures may lead to recall bias. Other physical/mental conditions, besides depression, were not assessed. Statistical power may have been insufficient due to the small sub-sample who reported suicidal ideation. Also, the generalizability of the results is limited, as the sample only comprised nurses in tertiary hospitals. CONCLUSIONS: Nurses experiencing sleep problems were associated with increased likelihood of suicidal ideation. It may be beneficial to incorporate sleep problems into routine screening and intervention for suicide prevention in clinical practice.

Suicide ideation among pregnant women: The role of different experiences of childhood abuse.

BACKGROUND: Childhood abuse has a negative effect on mental health during pregnancy; however, the association between childhood abuse and suicide ideation has received relatively little attention. METHOD: Women at 28 weeks or more into their pregnancy were recruited from a prenatal clinic in Shandong province, China. Suicide ideation was measured using item 9 of the Patient Health Questionnaire-9. Childhood abuse was measured using childhood abuse subscales of the Childhood Trauma Questionnaire. RESULTS: Women with any experience of childhood abuse had high risk of suicide ideation (OR = 2.44, 95%CI: 1.31-4.55). The association of continuous childhood abuse scores with suicide ideation was consistent with the finding using dichotomous childhood abuse (OR = 1.07, 95%CI: 1.02-1.12). After adjustment for depression, pregnant women with only physical abuse experience had high risk of suicide ideation (OR = 3.63, 95%CI: 1.32-10.03). Pregnant women with both childhood abuse and depression had increased risk of suicide ideation compared to those with neither risk factor (OR = 17.78, 95%CI 7.20-43.92). LIMITATIONS: Using a self-report measure to assess childhood abuse is susceptible to recall bias. Using a single item to measure suicide ideation and assessing only suicide ideation were limitations of the study. CONCLUSIONS: Pregnant women who experienced childhood abuse, especially physical abuse, had a high risk of suicide ideation during pregnancy. Screening for both childhood abuse and antenatal depression may be an effective way to identify high-risk groups with suicide ideation.

In silico prediction of mitochondrial toxicity by using GA-CG-SVM approach.

Drug-induced mitochondrial toxicity has become one of the key reasons for which some drugs fail to enter market or are withdrawn from market. Thus early identification of new chemical entities that injure mitochondrial function grows to be very necessary to produce safer drugs and directly reduce attrition rate in later stages of drug development. In this study, support vector machine (SVM) method combined with genetic algorithm (GA) for feature selection and conjugate gradient method (CG) for parameter optimization (GA-CG-SVM), has been employed to develop prediction model of mitochondrial toxicity. We firstly collected 288 compounds, including 171 MT+ and 117 MT-, from different literature resources. Then these compounds were randomly separated into a training set (253 compounds) and a test set (35 compounds). The overall prediction accuracy for the training set by means of 5-fold cross-validation is 84.59%. Further, the SVM model was evaluated by using the independent test set. The overall prediction accuracy for the test set is 77.14%. These clearly indicate that the mitochondrial toxicity is predictable. Meanwhile impacts of the feature selection and SVM parameter optimization on the quality of SVM model were also examined and discussed. The results implicate the potential of the proposed GA-CG-SVM in facilitating the prediction of mitochondrial toxicity.