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Soft robotic manipulators have promising features for performing non-destructive underwater tasks. Nevertheless, soft robotic systems are sensitive to the inherent nonlinearity of soft materials, the underwater flow current disturbance, payload, etc. In this paper, we propose a prediction model-based guided reinforcement learning adaptive controller (GRLMAC) for a soft manipulator to perform spatial underwater grasping tasks. In the GRLMAC, a feed-forward prediction model (FPM) is established for describing the length/pressure hysteresis of a chamber in the soft manipulator. Then, the online adjustment for FPM is achieved by reinforcement learning. Introducing the human experience into the reinforcement learning method, we can choose an appropriate adjustment action for the FPM from the action space without the offline training phase, allowing online adjusting the inflation pressure. To demonstrate the effectiveness of the controller, we tested the soft manipulator in the pumped flow current and different gripping loads. The results show that GRLMAC acquires promising accuracy, robustness, and adaptivity. We envision that the soft manipulator with online learning would endow future underwater robotic manipulation under natural turbulent conditions.

Background Mechanistic insights of glucagon‐like peptide‐1 receptor agonists remain incompletely identified, despite the efficacy in heart failure observed in clinical trials. Here, we evaluated the effects of dulaglutide on heart complications and illuminated its underlying mechanism. Methods and Results We used mice with high‐fat diet (HFD)/streptozotocin‐induced type 2 diabetes to investigate the effects of dulaglutide upon diabetic cardiac dysfunction. After the onset of diabetes, control and diabetic mice were injected subcutaneously with either dulaglutide (type 2 diabetes‐dulaglutide and control‐dulaglutide groups) or vehicle (type 2 diabetes‐vehicle and control‐vehicle groups) for 8 weeks. Subsequently, heart characteristics, cardiometabolic profile and mitochondrial morphology and function were evaluated. Also, we analyzed the effects of dulaglutide on neonatal rat ventricular myocytes treated with high glucose plus palmitic acid. In addition, wild type and AMP‐activated protein kinase α2 mutant mice were used to evaluate the underlying mechanism. In type 2 diabetes mouse model, dulaglutide ameliorated insulin resistance, improved glucose tolerance, reduced hyperlipidemia, and promoted fatty acid use in the myocardium. Dulaglutide treatment functionally attenuated cardiac remodeling and dysfunction and promoted metabolic reprogramming in diabetic mice. Furthermore, dulaglutide improved mitochondria fragmentation in myocytes, and simultaneously reinstated mitochondrial morphology and function in diabetic hearts. We also found that dulaglutide preserved AMP‐activated protein kinase α2‐dependent mitochondrial homeostasis, and the protective effects of dulaglutide on diabetic heart was almost abated by AMP‐activated protein kinase α2 knockout. Conclusions Dulaglutide prevents diabetic heart failure and favorably affects myocardial metabolic remodeling by impeding mitochondria fragmentation, and we suggest a potential strategy to develop a long‐term activation of glucagon‐like peptide‐1 receptor–based therapy to treat diabetes associated cardiovascular complications.

NK cells are known for their potent ability to kill stressed cells, whereas host cells infected with intracellular bacteria may also be benefit from the selective killing function of NK cells and survive. The mechanism of how NK cells protect host cells infected with intracellular bacteria is still unclear. Here, we discovered that decidual NK cells can not only eliminate intracellular bacteria which infected trophoblasts, but can also synthesize more lipids and transport lipids to trophoblasts to avoid their apoptosis. Mechanically, NK cells synthesize more lipids accompanied by increasing expression of apolipoprotein APOD. Lipids in NK cells can be delivered to trophoblast cells through APOD, maintaining adequate lipid droplet content and lipid metabolism homeostasis in trophoblasts. Blocking the APOD receptor LRP1 abolished lipid transport from NK cells to trophoblasts, and the reduction of lipid droplets caused by bacterial infection in trophoblast cells could not be restored, culminating in cell apoptosis. Our study provides new evidence for the immune surveillance and protective effect of NK cells on embryos during early pregnancy. This article is protected by copyright. All rights reserved.

Mitochondrial dysfunction in heart triggers an integrated stress response (ISR) through phosphorylation of eIF2α and subsequent ATF4 activation. DAP3 Binding Cell Death Enhancer 1 (DELE1) is a mitochondrial protein recently found to be critical for mediating mitochondrial stress-triggered ISR (MSR)-induced eIF2α-ATF4 pathway activation. However, the specific role of DELE1 in heart at baseline or in response to mitochondrial stress remains largely unknown. In this study, we report that DELE1 is dispensable for cardiac development and function under baseline conditions. Conversely, DELE1 is essential for mediating an adaptive response to mitochondrial dysfunction-triggered stress in the heart, playing a protective role in mitochondrial cardiomyopathy.

Background Renal interstitial fibrosis (RIF) is a common pathway to end-stage renal disease regardless of the initial etiology. Currently, the molecular mechanisms for RIF remains not fully elucidated. Nuclear receptor subfamily 4 group A member 1(Nr4a1), a member of the NR4A subfamily of nuclear receptors, is a ligand-activated transcription factor. The role of Nr4a1 in RIF remains largely unknown. Methods In this study, we determined the role and action mechanism of Nr4a1 in RIF. We used unilateral ureteral obstruction (UUO) mice and transforming growth factor (TGF)-β1-treated human renal proximal tubular epithelial cells (HK-2 cells) as in vivo and in vitro models of RIF. A specific Nr4a1 agonist Cytosporone B (Csn-B) was applied to activate Nr4a1 both in vivo and in vitro, and Nr4a1 small interfering RNA was applied in vitro. Renal pathological changes were evaluated by hematoxylin and eosin and Masson staining, and the expression of fibrotic proteins including fibronectin (Fn) and collagen-I (Col-I), and phosphorylated p38 MAPK was measure by immunohistochemical staining and western blot analysis. Results The results showed that Nr4a1 was upregulated in UUO mouse kidneys, and was positively correlated with the degree of interstitial kidney injury and the levels of fibrotic proteins. Csn-B treatment aggravated UUO-induced renal interstitial fibrosis, and induced p38 MAPK phosphorylation. In vitro, TGF-β induced Nr4a1 expression, and Nr4a1 downregulation prevented TGF-β1-induced expression of Fn and Col-I and the activation of p38 MAPK. Csn-B induced fibrotic proteins expression and p38 MAPK phosphorylation, and moreover Csn-B induced fibrotic proteins expression was abrogated by treatment with p38 MAPK inhibitor SB203580. We provided further evidence that Csn-B treatment promoted cytoplasmic accumulation of Nr4a1. Conclusion The findings in the present study indicate that Nr4a1 promotes renal fibrosis potentially through activating p38 MAPK kinase.

BackgroundIt is difficult to conduct the precise diagnosis of post-stroke depression (PSD) in clinical practice due to the complex psychopathology of depressive disorder. Several studies showed that gas chromatography–mass spectrometry (GC-MS)-identified urinary metabolite biomarkers could significantly discriminate PSD from stroke survivors.MethodsA systematic review was performed for the keywords of “urinary metabolite” and “PSD” using Medline, Cochrane Library, Embase, Web of Science, PsycINFO, Wanfang, CNKI, CBM, and VIP database from inception to 31 March 2022.ResultsFour related studies were included in the review. Differential urinary metabolites including lactic acid, palmitic acid, azelaic acid, and tyrosine were identified in all the included studies. As a significant deviation in the metabolite biomarker panel, glyceric acid, azelaic acid, phenylalanine, palmitic acid, pseudouridine, and tyrosine were found in at least 2 included studies, which indicated good potential for the differentiation of PSD.ConclusionThe systematic review provided evidence that differential urinary metabolites analyzed by the GC-MS-based approach might be used as a biomarker for the diagnosis and prognosis of PSD.

Significant evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the Taq1A polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the Ankyrin repeat and kinase domain containing 1 kinase (ANKK1) near the dopamine D2 dopamine receptor (DR2) gene. Depending on race it affects 30 to 80% of the population and its homozygous expression of the A1 allele correlates with a 30 to 40% reduction of striatal DR2, a typical feature of addiction, over-eating and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior is unknown. Here we used transgenic and viral-mediated strategies to reveal the role of ANKK1 in the regulation of activity and functions of the striatum. We found that Ankk1 is preferentially enriched in striatal DR2 expressing neurons and that Ankk1 loss-of-function in dorsal and ventral striatum leads to alteration in learning, impulsive, and flexible behaviors resembling the endophenotypes described in A1 carriers. We also observed an unsuspected role of ANKK1 in striatal DR2-expressing neurons in the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with versus without the A1 allele. Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for ANKK1 in the regulation of body metabolism.

Cardiac myocytes require large amounts of energy generated by mitochondria to sustain contraction, and there is a strong link between mitochondrial dysfunction and heart disease. Defective mitochondria are less efficient at generating ATP, produce excessive reactive oxygen species, and release pro-apoptotic proteins, all of which can lead to loss of cardiac myocytes and reduced ability to sustain contractile function. Therefore, mitochondrial quality control is critical in preventing mitochondria from causing harm to the cell. Selective autophagy of the mitochondria (mitophagy) is the primary mechanism responsible for eliminating dysfunctional mitochondria. Despite intense research focus on mitophagy over the past decade, little is still known about early events in the pathway, and the signals that orchestrate the selective recruitment of the autophagic machinery to dysfunctional mitochondria are unclear. It is known that autophagosome formation requires Atg9, which is embedded in small Golgi-derived vesicles. To date, most data on Atg9 are from yeast and our knowledge of mammalian Atg9a and Atg9b functions in cells and tissues are still limited. Here, we found that Atg9a and Atg9b are expressed in the heart and that both proteins are increased in the infarct border zone after ligation of the LAD. We also discovered that Atg9a and Atg9b are present on distinct vesicles in myocytes. Atg9b-positive vesicles are localized throughout the cytosol, whereas Atg9a-positive vesicles are associated with the mitochondria even under basal conditions. This suggests that they might have distinct functions and that Atg9a may play a more selective role at the mitochondria. Interestingly, Atg9a, but not Atg9b, is degraded by the proteasome upon activation of mitophagy, a potential indication that this may be a mechanism to prevent excessive mitophagy. Overall, our findings suggest that Atg9a and Atg9b play distinct roles in autophagy and mitophagy and that the mitochondrial localization of Atg9a allows it to initiate autophagosome formation more efficiently during mitophagy.

Temperature and humidity independent control (THIC) air-conditioning system is a promising technology. In this work, a novel temperature and humidity independent control (THIC) system is proposed, namely VMD-ACERS, which integrates vacuum membrane-based dehumidification and air carrying energy radiant air-conditioning system. This work establishes a novel coefficient of performance (COP) model of VMD-ACERS. The main parameters affecting the COP of conventional fan coil unit cooling system (FCUCS) and VMD-ACERS are investigated. The performance of FCUCS and VMD-ACERS are compared, and the energy-saving potential of VMD-ACERS is proved. Results indicate that, for FCUCS, the importance ranking of parameters is basically stable. However, for VMD-ACERS, the importance ranking will be affected by FCU and refrigerant. The most important parameters of VMD-ACERS are condensation temperature and permeate side pressure. On the contrary, superheating, subcooling are relatively less important parameters. For VMD-ACERS, it is not necessary to pursue the membrane with very high selectivity, because the selectivity of membrane would also be a less important parameter when it reaches 500. The COP of VMD-ACERS is higher than that of FCUCS when the permeate side pressure is higher than 8 kPa. The VMD-ACERS solves two technical problems about power-saving and thermal comfort of conventional THIC, and can extend the application of THIC air-conditioning system.

Background One of the increasingly accepted methods to evaluate the privacy of synthetic data is by measuring the risk of membership disclosure. This is a measure of the F1 accuracy that an adversary would correctly ascertain that a target individual from the same population as the real data is in the dataset used to train the generative model, and is commonly estimated using a data partitioning methodology with a 0.5 partitioning parameter. Objective Validate the membership disclosure F1 score, evaluate and improve the parametrization of the partitioning method, and provide a benchmark for its interpretation. Materials and methods We performed a simulated membership disclosure attack on 4 population datasets: an Ontario COVID-19 dataset, a state hospital discharge dataset, a national health survey, and an international COVID-19 behavioral survey. Two generative methods were evaluated: sequential synthesis and a generative adversarial network. A theoretical analysis and a simulation were used to determine the correct partitioning parameter that would give the same F1 score as a ground truth simulated membership disclosure attack. Results The default 0.5 parameter can give quite inaccurate membership disclosure values. The proportion of records from the training dataset in the attack dataset must be equal to the sampling fraction of the real dataset from the population. The approach is demonstrated on 7 clinical trial datasets. Conclusions Our proposed parameterization, as well as interpretation and generative model training guidance provide a theoretically and empirically grounded basis for evaluating and managing membership disclosure risk for synthetic data.

The impact of natural disasters on rural areas has recently increased, the question of how to effectively improve the livelihood resilience of rural residents has therefore become an essential issue. In this context, a livelihood resilience evaluation index system for rural residents was constructed in four dimensions: livelihood quality, livelihood promotion, livelihood provision, and disaster stress. A structural dynamics model was used to analyze the changing characteristics of the livelihood resilience of rural residents in China between the years 1980 and 2020, and a livelihood resilience trend from 2021 to 2030 was predicted based on the ARIMA model. The main factors influencing livelihood resilience were explored using ridge regression analysis. The results show that: (1) livelihood resilience of rural residents in China fluctuated significantly between 1980 and 2020, tending generally to increase; (2) livelihood resilience is positively correlated with livelihood quality, livelihood promotion, and livelihood provision, while it is negatively correlated with disaster stress; (3) livelihood quality, livelihood promotion, and livelihood supply will still increase between the years 2021 and 2030, while the increase of livelihood resilience will tend to slow down; and (4) six variables have a significant positive impact on livelihood resilience, and provide a basis for the subsequent enhancement of livelihood resilience.

The performance and stability of mesophilic codigestion of waste activated sludge (WAS) and food waste (FW) were compared in two parallel, continuously stirred tank reactors using high- and low-magnitude loading increments for the loading regimes. The results indicated that a high methane (CH