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A novel method to prepare fluorescent polymeric aggregates via Eu 3+ -induced self-assembly is described in this research contribution. The amphiphilic polymeric ligand, polystyrene-block-poly(N-vinylpyrrolidone) (PS-b-PNVP) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Eu 3+ ions that function as coordination crosslinking agents were added to the reactive solution to induce self-assembly within the PNVP block. Eu 3+ ions preferentially coordinate to PNVP segments, yielding coordinatively cross-linked networks with reduced solubility in the solvent. Polystyrene segments retain their solubility in solution due to the amphiphilic character of the block copolymer. Mechanisms for self-assembly and reversible network formation are discussed. Due to the unique optical properties of Eu 3+ ions, in-depth analysis of fluorescent data was performed. These aggregates were drip-coated onto the surface of silicon wafers, with subsequent investigation of polymer morphology near the interface with silicon. This represents the initial step in the development of opto-electronic and photovoltaic applications for these self-assembled fluorescent polymeric aggregates. [ABSTRACT FROM AUTHOR]

Exorbitant substrates for Schizochytrium culture result in the high cost of docosahexaenoic acid (DHA) production. In order to develop a feasible approach that is expected to reduce DHA production cost, Schizochytrium sp. S31 cultivation with a mixture of saline wastewater (SWW) and tofu whey wastewater (TWW) was investigated in this study. Using glucose as the carbon source, the maximum biomass and DHA yield in cultures using mixed wastewater containing 5% SWW reached 19.08 and 2.66 g/L, respectively, which were 2.29 and 2.66 times higher than those of cultures using control medium. Moreover, a good wastewater treatment performance was achieved as approximately 60% of the COD, TN, and TP were reduced in the cultures using mixed wastewater with a SWW ratio of 5%. The mixed wastewater presented better performance on DHA production than control medium using all tested carbon sources including glucose, fructose, and pure and crude glycerol. The components of control medium can be completely replaced by the mixed wastewater and crude glycerol. It is expected to effectively decrease the medium cost for DHA production and reduce the environmental risk of food processing wastewater. [Display omitted] • The mixed wastewater greatly enhanced the growth of Schizochytrium sp. S31. • The DHA yield was increased by 2.66 times using mixed wastewater added glucose. • About 60% of COD, TN, and TP were reduced from the mixed wastewater. • The medium components can be completely replaced by wastewater and crude glycerol. [ABSTRACT FROM AUTHOR]

Cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD) and dampens antiviral response, which increases viral infections and leads to COPD acute exacerbation (AECOPD). Adenovirus, a nonenveloped DNA virus, is linked with AECOPD, whose DNAs trigger innate immune response via interacting with pattern recognition receptors (PRRs). Stimulator of interferon genes (STING), as a cytosolic DNA sensor, participates in adenovirus-induced interferon β (IFNβ)-dependent antiviral response. STING is involved in various pulmonary diseases, but role of STING in pathogenesis of AECOPD is not well documented. In the present study, we explored relationship between STING and AECOPD induced by recombinant adenovirus vectors (rAdVs) and CS in wild type (WT) and STING-/- mice; and also characterized the inhibition of STING- IFNβ pathway in pulmonary epithelium exposed to cigarette smoke extract (CSE). We found that CS or CSE exposure alone dramatically inhibited STING expression, but not significantly effected IFNβ production. Moreover, CS or CSE-exposed significantly suppressed activation of STING-IFNβ pathway induced by rAdVs and suppressed clearance of rAdVs DNA. Inflammation, fibrosis and emphysema of lung tissues were exaggerated when treated with CS plus rAdVs, which further deteriorate in absences of STING. In A549 cells with knockdown of STING, we also observed enhancing apoptosis related to emphysema, especially CSE and adenovirus vectors in combination. Therefore, STING may play a protective role in preventing the progress of COPD. • CS damped STING-IFNβ pathway activated by rAdVs in vitro and vivo. • CS alleviated rAdVs DNA clearance in lung which partially depended on suppression of STING. • STING played a protective role in the pathophysiology of AECOPD model induced by CS plus rAdVs. [ABSTRACT FROM AUTHOR]

Studies have found that flipped classroom teaching (FT) improves learning compared to lecture-based teaching (LT). However, whether the structured teacher-student interaction-the key feature of FT-plays an essential role in enhancing learning remains unclear, as do its neural underpinnings. Here, we compared three teaching conditions: FT with a video lecture and structured interaction, LT with a face-to-face lecture and spontaneous interaction, and control teaching (CT) with a video lecture and spontaneous interaction. The fNIRS-based hyperscanning technique was used to assess the interbrain synchrony (IBS) from teacher-student dyads. Results showed that the learning was significantly improved in FT than in LT and CT, and FT significantly increased teacher-student IBS in left DLPFC. Moreover, the IBS and learning improvements were positively correlated. Therefore, these findings indicate that the structured teacher-student interaction is crucial for enhancing learning in FT, and IBS serves as its neural foundation., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The objective of this study is to explore the correlation of metal levels with assisted reproductive technology (ART) outcomes in polycystic ovary syndrome (PCOS) patients. The individuals were recruited who met the research criteria, only tubal factor or male infertility served as the control group (n = 40) and patient group was PCOS patients (n = 35). Individuals (n = 75) were divided into PCOS group (n = 35) and control group (n = 40). The normal body mass index (BMI) group (control) includes women with BMI < 25 kg/m 2 in PCOS group (n = 24) and control group (n = 33), and BMI ≥ 25 kg/m 2 in PCOS group (n = 11) and control group (n = 7). We performed an analysis of insulin resistance (IR) (n = 15) group and without insulin resistance (NIR) group (n = 20) in PCOS patient and control patients. Comparing difference demographic data, ART outcomes and the metal levels in every group respectively, the correlation of metal levels and ART outcomes in control participants and PCOS patients were analyzed by the Spearman correlation analysis, and multiple linear regression model was used to examine the association between the concentration of 19 metals and ART outcomes in PCOS group and control group. Plasma manganese (Mn), titanium (Ti), sodium (Na), magnesium (Mg), copper (Cu), calcium (Ca)/Mg ratio, and Cu/zinc (Zn) ratio levels in PCOS patients were higher than that in control, while Zn and Ca levels were lower in PCOS patients than that in control. The Mg levels had a positive connection with the number of eggs recovered, and the iron (Fe) levels were positively associated with the number of transplanted embryos in PCOS-IR. In PCOS-NIR, Mn levels positively correlated with the number of follicles and the number of good embryos. Silver (Ag) levels were negatively correlated with the number of follicles, and aluminum (Al) levels were negatively related with the normal fertilization and the number of good embryos. The Spearman analysis in PCOS-BMI ≥ 25 group exhibited that nickel (Ni) levels were negatively associated with the number of follicles. The plasma metal levels seem to affect the clinical manifestations and in vitro fertilization outcomes in assisted reproduction., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study used the Actor-Partner Interdependence Model to examine how parents' adult attachment influences their their own and the partners' co-parenting and parent-child relationships. Participants were from a cross-sectional sample of 1313 Chinese heterosexual married couples (fathers' M age = 39.74, SD = 5.61; mothers' M age = 37.55, SD = 5.04) whose biological children were pupils (M age = 10.25, SD = 2.35). Results revealed that: (a) Couple members' actor effects from adult attachment avoidance to positive and negative co-parenting and parent-child closeness and conflict were found both significant; (b) The actor effects from adult attachment anxiety to negative co-parenting and parent-child conflict were found significant, whereas only partner effect from attachment avoidance to positive co-parenting and from attachment anxiety to parent-child conflict were significant. The results highlight the negative effects of parents' attachment avoidance and anxiety on their partners' parenting function.

Background: Diabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive., Results: We found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPARα signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to cardiac fibrosis and dysfunction in T1D mice. Additionally, transplant of faecal microbiota from healthy mice alleviated cardiac dysfunction in T1D mice, but this effect was abolished by FGF21 knockdown., Conclusions: Our study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator. Video Abstract., (© 2024. The Author(s).)

During infection viruses hijack host cell metabolism to promote their replication. Here, analysis of metabolite alterations in macrophages exposed to poly I:C recognises that the antiviral effector Protein Kinase RNA-activated (PKR) suppresses glucose breakdown within the pentose phosphate pathway (PPP). This pathway runs parallel to central glycolysis and is critical to producing NADPH and pentose precursors for nucleotides. Changes in metabolite levels between wild-type and PKR-ablated macrophages show that PKR controls the generation of ribose 5-phosphate, in a manner distinct from its established function in gene expression but dependent on its kinase activity. PKR phosphorylates and inhibits the Ribose 5-Phosphate Isomerase A (RPIA), thereby preventing interconversion of ribulose- to ribose 5-phosphate. This activity preserves redox control but decreases production of ribose 5-phosphate for nucleotide biosynthesis. Accordingly, the PKR-mediated immune response to RNA suppresses nucleic acid production. In line, pharmacological targeting of the PPP during infection decreases the replication of the Herpes simplex virus. These results identify an immune response-mediated control of host cell metabolism and suggest targeting the RPIA as a potential innovative antiviral treatment., (© 2024. The Author(s).)

Background: Human patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear., Methods: Lrp4 f/f mice were crossed with hGFAP-Cre and Nex-Cre mice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4 -/- ) and pyramidal neuron specific knockout mice (Nex-Lrp4 -/- ). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored., Results: We found that Lrp4 deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice with Lrp4 deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE., Conclusion: These results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE., (© 2024. The Author(s).)

Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T-cell receptor signaling and as such is an attractive target for cancer immunotherapy. Although the role of the HPK1 kinase domain (KD) has been extensively characterized, the function of its citron homology domain (CHD) remains elusive. Through a combination of structural, biochemical, and mechanistic studies, we characterize the structure-function of CHD in relationship to KD. Crystallography and hydrogen-deuterium exchange mass spectrometry reveal that CHD adopts a seven-bladed β-propellor fold that binds to KD. Mutagenesis associated with binding and functional studies show a direct correlation between domain-domain interaction and negative regulation of kinase activity. We further demonstrate that the CHD provides stability to HPK1 protein in cells as well as contributes to the docking of its substrate SLP76. Altogether, this study highlights the importance of the CHD in the direct and indirect regulation of HPK1 function., (© 2024. The Author(s).)

Objective: Sleep problems are a significant risk factor for identifying and preventing suicidal involvement among adolescents. However, there is limited evidence to assess the underlying mechanisms between them. This study investigated the longitudinal relationship between sleep problems and suicidal behavior and examined whether this relationship was moderated by negative emotions, low self-control, and nonsuicidal self-injury (NSSI)., Methods: From December 2020 onward, we assessed 1214 Chinese secondary school adolescents (60.7% were boys, aged 13-19 years) three times, 6 months apart., Results: In the direct effects model, sleep problems were found to have a positive impact on adolescent suicidal behavior. In the indirect effects model, we observed that sleep problems were associated with an elevated risk of suicidal behavior through several pathways: one-mediator path of negative emotions, low self-control, and NSSI, respectively; two-mediator path of negative emotions via low self-control, negative emotions via NSSI, and low self-control via NSSI, and three-mediator path from negative emotions to NSSI via low self-control., Conclusions: This longitudinal study provides evidence that sleep problems in adolescents may increase suicidal behavior by exacerbating negative emotions, weakening self-control, and promoting NSSI. The findings suggest sleep problems should be addressed in suicide prevention and intervention efforts for adolescents., (© 2024 American Association of Suicidology.)

With the development of the Internet of Things (IoT) technology, massive amounts of sensor data in applications such as fire monitoring need to be transmitted to edge servers for timely processing. However, there is an energy-hole phenomenon in transmitting data only through terrestrial multi-hop networks. In this study, we focus on the data collection task in an unmanned aerial vehicle (UAV)-assisted mobile edge computing (MEC) network, where a UAV is deployed as the mobile data collector for the ground sensor nodes (SNs) to ensure high information freshness. Meanwhile, the UAV is equipped with an edge server for data caching. We first establish a rigorous mathematical model in which the age of information (AoI) is used as a measure of information freshness, related to both the data collection time and the UAV's flight time. Then a mixed-integer non-convex optimization problem is formulated to minimize the peak AoI of the collected data. To solve the problem efficiently, we propose an iterative two-step algorithm named the AoI-minimized association and trajectory planning (AoI-MATP) algorithm. In each iteration, the optimal SN-collection point (CP) associations and CP locations for the parameter ε are first obtained by the affinity propagation clustering algorithm. The optimal UAV trajectory is found using an improved elite genetic algorithm. Simulation results show that based on the optimized ε, the AoI-MATP algorithm can achieve a balance between data collection time and flight time, reducing the peak AoI of the collected data.

Diabetes mellitus (DM) causes damage to the central nervous system, resulting in cognitive impairment. Fibroblast growth factor 21 (FGF21) exhibits the potential to alleviate neurodegeneration. However, the therapeutic effect of intracerebroventricular (i.c.v) FGF21 infusion on diabetes-induced cognitive decline (DICD) and its potential mechanisms remain unclear. In this study, the impact of FGF21 on DICD was explored, and 1H nuclear magnetic resonance (NMR)-based metabolomics plus 13C NMR spectroscopy in combine with intravenous [1-13C]-glucose infusion were used to investigate the underlying metabolic mechanism. Results revealed that i.c.v FGF21 infusion effectively improved learning and memory performance of DICD mice; neuron loss and apoptosis in hippocampus and cortex were significantly blocked, suggesting a potential neuroprotective role of FGF21 in DICD. Metabolomics results revealed that FGF21 modulated DICD metabolic alterations related to glucose and neurotransmitter metabolism, which are characterized by distinct recovered enrichment of [3-13C]-lactate, [3-13C]-aspartate, [4-13C]-glutamine, [3-13C]-glutamine, [4-13C]-glutamate, and [4-13C]- γ-aminobutyric acid (GABA) from [1-13C]-glucose. Moreover, diabetes-induced neuron injury and metabolic dysfunctions might be mediated by PI3K/AKT/GSK-3β signaling pathway inactivation in the hippocampus and cortex, which were activated by i.c.v injection of FGF21. These findings indicate that i.c.v FGF21 infusion exerts its neuroprotective effect on DICD by remodeling cerebral glucose and neurotransmitter metabolism by activating the PI3K/AKT/GSK-3β signaling pathway., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Left-behind childre (LBC) in China are deeply concerned by society because of their high risk of emotional and behavioral problems. Depression and nonsuicidal self-injury are the most harmful and worrying negative emotional and behavioral problems in LBC. Unfortunately, LBCs are in unfavorable environments for a long time and are prone to negative interpersonal interactions. Child maltreatment and bullying victimization, as the two most typical negative interpersonal interactions in family and school environments, maybe the key risk factors for depression and nonsuicidal self-injury among LBCs. However, we are less known of the longitudinal effects of child maltreatment and bullying victimization on LBC's depression and nonsuicidal self-injury and their underlying mechanisms., Aims: This study used a two-year longitudinal design with three-time points to investigate the longitudinal effects of child maltreatment and bullying victimization on depression, nonsuicidal self-injury, and the mediating role of negative thoughts and self-compassion., Materials & Methods: A sample of 592 LBC (390 were males, Mage at time 1 = 9.56, SDage = 0.65; 202 were females, Mage at time 1 = 9.43, SDage = 0.63) completed a set of questionnaires at three-time points. This study used SPSS software (version 25.0) and MPLUS software (version 8.3) for all analyses., Results: (1) Child maltreatment not only affects depression and nonsuicidal self-injury but also affects depression and nonsuicidal self-injury through negative thoughts. Child maltreatment affects depression through self-compassion and does not affect nonsuicidal self-injury. (2) Bullying victimization affects depression and nonsuicidal self-injury through negative thoughts and bullying victimization further affects depression through self-compassion but does not affect nonsuicidal self-injury., Conclusion: This study revealed the effects of negative interpersonal interactions (child maltreatment, bullying victimization) on LBC's adverse emotions and behaviors, and their underlying mechanisms, which helps to provide parents, schools, and psychoeducational workers with a new perspective on intervention., (© 2023 Wiley Periodicals LLC.)

Two-dimensional transition metal dichalcogenides (TMDs), as flexible and stretchable materials, have attracted considerable attention in the field of novel flexible electronics due to their excellent mechanical, optical, and electronic properties. Among the various TMD materials, atomically thin MoS 2 has become the most widely used material due to its advantageous properties, such as its adjustable bandgap, excellent performance, and ease of preparation. In this work, we demonstrated the practicality of a stacked wafer-scale two-layer MoS 2 film obtained by transferring multiple single-layer films grown using chemical vapor deposition. The MoS 2 field-effect transistor cell had a top-gated device structure with a (PI) film as the substrate, which exhibited a high on/off ratio (10 8 ), large average mobility (∼8.56 cm 2 V -1 s -1 ), and exceptional uniformity. Furthermore, a range of flexible integrated logic devices, including inverters, NOR gates, and NAND gates, were successfully implemented via traditional lithography. These results highlight the immense potential of TMD materials, particularly MoS 2 , in enabling advanced flexible electronic and optoelectronic devices, which pave the way for transformative applications in future-generation electronics., (© 2023 IOP Publishing Ltd.)

Mixed-ligand metal-organic frameworks (MOFs) are usually synthesized from two or more organic ligands as initial reactants, and MOFs synthesized from one organic ligand precursor through partial in situ reactions remain very limited. Herein, by introducing an imidazole-tetrazole bifunctional ligand, 5-(4-imidazol-1-yl-phenyl)-2 H -tetrazole (HIPT), as a single ligand and performing in situ hydrolysis of the tetrazolium group, a mixed-ligand Co(II)-MOF based on HIPT and 4-imidazol-1-yl-benzoic acid (HIBA), [Co 2 (μ 3 -O)(IPT)(IBA)]· x solvent (Co-IPT-IBA), was constructed and applied to capture I 2 and methyl iodide vapours. Single crystal structural analyses reveal that Co-IPT-IBA exhibits a 3D porous framework with 1D channels based on the relatively few reported ribbon-like rod SBUs. The nitrogen adsorption-desorption isotherms indicate that the BET surface area of Co-IPT-IBA is 168.5 m 2 g -1 and it possesses both micropores and mesopores. Due to its porosity, nitrogen-rich conjugated aromatic rings, and Co(II) ions, Co-IPT-IBA was applied to capture iodine molecules in vapour and exhibited an adsorption capacity of 2.88 g g -1 . By combining the IR, Raman, XPS and grand canonical Monte Carlo (GCMC) simulation results, it was deduced that the tetrazole ring, coordination water molecules, and the redox potential of Co 3+ /Co 2+ facilitate iodine capture. The presence of mesopores was also responsible for the high iodine adsorption capacity. In addition, Co-IPT-IBA showed the ability to capture methyl iodide in vapours with a moderate capacity of 625 mg g -1 . The transformation of crystalline Co-IPT-IBA to amorphous MOFs may be due to the methylation reaction. This work represents a relatively rare example of methyl iodide adsorption by MOFs.

Abundant research has shown that self-compassion robustly contributes to adults' psychological well-being. Meanwhile, a few studies have shown that self-compassion is rooted in early experiences with parents. However, it is unclear whether interactions with partners and children affect adults' self-compassion, and the role of their self-compassion in interactions with significant others. This study examined bidirectional longitudinal relationships between Chinese parents' marital satisfaction, parenting stress, and self-compassion following a three-wave longitudinal design. A sample of 322 Chinese father-mother dyads (father's M age  = 35.84, SD age  = 5.76; mother's M age  = 34.32, SD age  = 5.46) completed a set of questionnaires at three time points. The results showed that marital satisfaction positively predicted the fathers' and mothers' self-compassion, while parenting stress did not significantly predict the parents' self-compassion; In contrast, parents' self-compassion did not significantly predict marital satisfaction or parenting stress. Additionally, there was a bidirectional relationship between marital satisfaction and parenting stress in fathers and mothers. Finally, mothers' marital satisfaction positively mediated the relationship between parenting stress and self-compassion/next-stage parenting stress. This study revealed that adults' self-compassion can develop from caring and supportive relationships, including marital relationships. Highlighting key mechanisms of marital satisfaction, such as increasing self-compassion and reducing parenting stress, may contribute to the improvement of adults' mental health., (© 2022 Family Process Institute.)

The success or failure of executing the watershed ecological compensation (WEC) policy is primarily contingent on incentive designs. How do different contractual designs influence the actions of micro-individuals in WEC? How may individuals be enticed to engage in WEC project? Taking the first inter-provincial WEC-Xin'an River Basin (XRB) pilot in China as a case, this study investigates the impacts of government-oriented, market-oriented, and incentive-cooperation contracts on individuals' behavior based on the framework of Stackelberg games. Subsequently, differences in efforts and profits of diverse individuals are compared and analyzed for each contract. The case-specific numerical example is then utilized to validate theoretical outcomes and to support subsequent key insights. First, the government-oriented contract exhibits effectiveness in bolstering the efforts and interests of micro-individuals, whereas it also places the government under tremendous financial strain. Second, the market-oriented contract formed by the output contribution rate assists in overcoming deficiencies of excurrent government-oriented contract. But it remains controversial if, in the absence of government inspection, investors that devote more cooperative-efforts are not rewarded with further dividends, ultimately diminishing their enthusiasm for the WEC-XRB project. Lastly, the incentive-cooperation contract reinforced by market dominance is advantageous for improving the efficacy of water resource management under the existing government-oriented policy relying on command-and-control instruments., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Here we investigate the function of the innate immune molecule protein kinase R (PKR) in intestinal inflammation. To model a colitogenic role of PKR, we determine the physiological response to dextran sulfate sodium (DSS) of wild-type and two transgenic mice strains mutated to express either a kinase-dead PKR or to ablate expression of the kinase. These experiments recognize kinase-dependent and -independent protection from DSS-induced weight loss and inflammation, against a kinase-dependent increase in the susceptibility to DSS-induced injury. We propose these effects arise through PKR-dependent alteration of gut physiology, evidenced as altered goblet cell function and changes to the gut microbiota at homeostasis that suppresses inflammasome activity by controlling autophagy. These findings establish that PKR functions as both a protein kinase and a signaling molecule in instituting immune homeostasis in the gut., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yim, Chakrabarti, Kessler, Morimoto, Wang, Sooraj, Ahmed, de la Motte, Silverman, Williams and Sadler.)

T Helper 17 (Th17) cells are adaptive immune cells that play myriad roles in the body. Immune-endocrine interactions are vital in endocrine organs during pathological states. Th17 cells are known to take part in multiple autoimmune diseases over the years. Current evidence has moved from minimal to substantial that Th17 cells are closely related to endocrine organs. Diverse tissue Th17 cells have been discovered within endocrine organs, including gut, adipose tissue, liver and bone, and these cells are modulated by various secretions from endocrine organs. Th17 cells in these endocrine organs are key players in the process of an array of metabolic disorders and inflammatory conditions, including obesity, insulin resistance, nonalcoholic fatty liver disease (NAFLD), primary sclerosing cholangitis (PSC), osteoporosis and inflammatory bowel disease (IBD). We reviewed the pathogenetic or protective functions played by Th17 cells in various endocrine tissues and identified potential regulators for plasticity of it. Furthermore, we discussed the roles of Th17 cells in crosstalk of gut-organs axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zi, Wang, Gao and He.)

During the heterotrophic cultivation of microalgae, a cooled process against temperature rise caused by the metabolism of exogenous organic carbon sources greatly increases cultivation cost. Furthermore, microalgae harvesting is also a cost-consuming process. Cell harvesting efficiency is closely related to the characteristics of the algal cells. It may be possible to change cell characteristics through controlling culture conditions to make harvesting easier. In this study, the mesophilic Chlorella pyrenoidosa was found to be a thermal-tolerant species in the heterotrophic mode. The cells could maintain their maximal specific growth rate at 40°C and reached 1.45 day -1 , which is equivalent to that of cultures at 35°C but significantly higher than those cultured at lower temperatures. Interestingly, the cells cultured at 40°C were much easier to be harvested than those at lower temperatures. The harvesting efficiency of the cells cultured at 40°C reached 96.83% after sedimentation for 240 min, while the cells cultured at lower temperatures were reluctant to settle. Likely, the same circumstance occurred when cells were harvested by centrifugation or flocculation. The promotion of cell harvesting for cells cultured at high temperatures was mainly attributed to increased cell size and decreased cell surface charge. To the best of our knowledge, this is the first report that cells cultured at high temperatures can promote microalgae harvesting. This study explores a new approach to simplify the cultivation and harvesting of microalgae, which effectively reduces the microalgae production cost., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dai, Wang, Zhu, Yang, Jiao, Sun and Wang.)

2D semiconductors, such as molybdenum disulfide (MoS 2 ), have attracted tremendous attention in constructing advanced monolithic integrated circuits (ICs) for future flexible and energy-efficient electronics. However, the development of large-scale ICs based on 2D materials is still in its early stage, mainly due to the non-uniformity of the individual devices and little investigation of device and circuit-level optimization. Herein, a 4-inch high-quality monolayer MoS 2 film is successfully synthesized, which is then used to fabricate top-gated (TG) MoS 2 field-effect transistors with wafer-scale uniformity. Some basic circuits such as static random access memory and ring oscillators are examined. A pass-transistor logic configuration based on pseudo-NMOS is then employed to design more complex MoS 2 logic circuits, which are successfully fabricated with proper logic functions tested. These preliminary integration efforts show the promising potential of wafer-scale 2D semiconductors for application in complex ICs., (© 2022 Wiley-VCH GmbH.)

Introduction: Hiccup is a common disease that not only occurred on adults but also on infants, which can severely do harm to patients' physical and psychological health. Metoclopramide has been reported to have effects on intractable hiccup. However, there is a limited evidence that describes the efficacy and safety of metoclopramide in the treatment of intractable hiccup. The aim of this article is to obtain evidence on the effectiveness and safety of metoclopramide in treating patients with intractable hiccup., Methods and Analysis: We will search the following databases, including PubMed, Cochrane Library, Embase, Web of Science, CBM, Wan-fang, VIP database, CNKI and MEDLINE from their inception to 11 November 2021. All the randomised controlled trials associated with metoclopramide in treating intractable hiccup will be included. Articles screened, selected and extracted will be performed by two researchers independently. The risk of bias will be assessed by using the Cochrane Collaboration. We will carry out the meta-analysis by using RevMan V.5.4 software., Prospero Registration Number: CRD42021293000., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The topic of school bullying has become an important issue over the world. Being in disadvantaged situations of fathers' absence, prior research suggested that left-behind children (LBC) with absent fathers in China are more vulnerable to get involved in school bullying (bullying or being bullied). In addition, fathers' absence brings much pressure to single stay-at-home mothers, leading to more maternal psychologically controlling parenting. Following a three-wave longitudinal design, this study aimed to examine the developmental relationship between maternal psychological control and father-absent LBC's bullying/victimization as well as its mechanism. A total of 348 father-absent LBC aged 7-11 years in China completed a battery of questionnaires at three-time points. The results indicated that there are reciprocal effects between maternal psychological control and father-absent LBC's bullying/victimization. Specifically, maternal psychological control at T1 predicted father-absent LBC's victimization at T2; children's victimization at T2 predicted maternal psychological control at T3; maternal psychological control predicted later children's bullying perpetration stably from T1 to T2 and from T2 to T3; children's bullying at T2 predicted maternal psychological control at T3. Two vicious circles happened in the above relationships. Current findings highlight the stronger effects of mothers' negative parenting on children's school bullying, which bring inspiration for future family education and school intervention.

Objectives: To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission., Methods: A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points., Results: On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism., Conclusions: The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

The detection of heavy metals, such as Hg 2+ and Fe 3+ , is of great significance. In this work, fluorescent small-molecule BODIPY (BY-3) bearing CC group was synthesized firstly. And then, the chitosan-based polymer sensor CY-1 was synthesized through the spontaneous NH 2 /C≡C click reaction. The synthesized CY-1 can effectively bind and recognize Hg 2+ /Hg + by the -C=N groups formed in the click reaction. Moreover, the macromolecular sensors CS-1 and CS-2 were synthesized by incorporating another recognition sites to CY-1. These synthesized macromolecular sensors can not only recognize Hg 2+ /Hg + , but also effectively recognize Fe 3+ /Fe 2+ . All of them exhibited significant quenching effect, visible to the naked eye under UV irradiation. The detection limit of CY-1 for Hg 2+ was 1.51 × 10 -6  mol/L, and the detection limit of CS-2 for Fe 3+ was 2.30 × 10 -6  mol/L. The BODIPY-chitosan sensors synthesized in this work have the functions of removing heavy metal ions besides the identifying ability. The maximum adsorption capacity of 1 g chitosan to Hg 2+ was 108 mg as the best one. This article provides a new method to prepare macromolecular sensors for the detection and removal of heavy metal ions. As a useful natural polymer, chitosan's application scope was enlarged., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sexual dimorphism exists in the onset and development of type 1 diabetes (T1D), but its potential pathological mechanism is poorly understood. In the present study, we examined sex-specific changes in the gut microbiome and host metabolome of T1D mice via 16S rRNA gene sequencing and nuclear magnetic resonance (NMR)-based metabolomics approach, and aimed to investigate potential mechanism of the gut microbiota-host metabolic interaction in the sexual dimorphism of T1D. Our results demonstrate that female mice had a greater shift in the gut microbiota than male mice during the development of T1D; however, host metabolome was more susceptible to T1D in male mice. The correlation network analysis indicates that T1D-induced host metabolic changes may be regulated by the gut microbiota in a sex-specific manner, mainly involving short-chain fatty acids (SCFAs) metabolism, energy metabolism, amino acid metabolism, and choline metabolism. Therefore, our study suggests that sex-dependent "gut microbiota-host metabolism axis" may be implicated in the sexual dimorphism of T1D, and the link between microbes and metabolites might contribute to the prevention and treatment of T1D., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Whether financial agglomeration is conducive to improving the green efficiency of water resources is of great significance for China to realize water saving and consumption reduction, and green sustainable development. Based on the panel data of 30 provinces in China from 2006 to 2017, this paper uses the SBM model with undesirable output to measure the green efficiency of water resources in China and empirically examines the impact of financial agglomeration on the green efficiency of water resources. The results show that the green efficiency of water resources in China presents the "N" type fluctuation characteristic, and the overall trend is increasing. The mean value of green efficiency of water resources in China fluctuates around 0.6, which is at a medium level, and there is still a large room for improvement. Secondly, there are obvious spatial differences in China's green efficiency of water resources, showing a gradient of "Eastern>Central>Western." Thirdly, at the national level, financial agglomeration has a significant positive impact on the green efficiency of water resources, and there is an inverted "U"-shaped relationship between financial agglomeration and green efficiency of water resources. Fourthly, at the regional level, the impact of financial agglomeration on green efficiency of water resources has significant regional differences. Finally, based on the above conclusions, specific proposals for financial agglomeration to improve the green efficiency of water resources are put forward., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the present study, a comparative study on the influence of different laminated stacks driven by aomic layer deposition (ALD) on the interfacial and electrcial properties of high- k /Ge gate stacks passivated by trimethylaluminum (TMA) has been performed in detail via X-ray photoelectron spectroscopy (XPS) and electrical measurements. XPS measurements indicate that HfO 2 /Al 2 O 3 /Ge gate stacks can effectively inhibit the formation of Ge suboxides and a low- k germanate layer. Compared to Al 2 O 3 /HfO 2 and HfO 2 /Al 2 O 3 /HfO 2 gate stacks, the HfO 2 /Al 2 O 3 /Ge metal oxide semiconductor (MOS) capacitors exhibited improved electrical performance, including a maximum permittivity of 18.15, disappearing hysteresis, an almost neglected flat band voltage of 0.01 V, and a minimum leakage current density of 3.82 × 10-8 A/cm 2 at room temperature. Especially, the leakage current mechanisms of Ge-MOS capacitors based on different laminated stacks measured at room temperature and low temperature (77-327 K) have been comprehensively analyzed. By comparing three different laminated gate stacks, it can be inferred that HfO 2 /Al 2 O 3 /Ge gate stacks have a potential application prospect in Ge-based microelectronic devices.

In this work, a series of ternary HfTiO and TiAlO films and quaternary HfTiAlO films prepared with different stoichiometric ratios via atomic layer deposition (ALD) were deposited on Si substrates. The interfacial properties, band alignments, and electrical characteristics were analyzed to evaluate the electrical performance of the corresponding metal-oxide-semiconductor (MOS) capacitors. Based on the characterization data, it can be noted that the permittivity of HfTiO increases on increasing the Ti content, while the deterioration of the film quality leads to an increased leakage current. For TiAlO, as the Al content increased gradually, the interface quality improved, but the corresponding permittivity was sacrificed. As for HfTiAlO, the addition of Ti and Al jointly in HfO 2 could improve the interface performance, enlarge the energy band offset, enhance the dielectric constant, and reduce the leakage current simultaneously. The interfacial analysis and electrical characterization demonstrated that HfTiAlO with an ALD cycle ratio of Hf : Ti : Al = 6 : 1 : 1 had the most excellent film quality, interface performance and electrical properties, including a larger dielectric constant of 28.8, a larger conduction band offset with Si of 2.47 eV, and the lowest leakage current density of 1.11 × 10 -5 A cm -2 ., Competing Interests: The authors declare no conflict of interest statement., (This journal is © The Royal Society of Chemistry.)

In this work, the effects of different Dy-doping concentrations and annealing temperatures on the interfacial chemistry and electrical properties of TMA-passivated HfDyO x /Ge gate stacks have been investigated systematically. The microstructural, optical, interfacial chemistry, and electrical characteristics of sputtering-driven HfDyO x gate dielectrics have been characterized by means of X-ray diffraction (XRD), UV-Vis transmission spectroscopy, X-ray photoelectron spectroscopy (XPS), and electrical measurements. This work reveals that the interfacial chemistry evolution takes place via two competing processes, including oxide growth and oxide desorption. XPS analyses have confirmed that the 10 W-deposited targeted gate dielectrics display optimized interface characteristics, which can be attributed to the suppressed unstable Ge oxides and inhibition effects on inter-diffusion at the interface. Electrical observations show that the 10 W-driven HfDyO x /Ge MOS device without annealing treatment exhibits optimized electrical performance, including a larger permittivity of 22.4, a smaller flat band voltage of 0.07 V, vanishing hysteresis, a lowest oxide charge density of ∼10 11 cm -2 , and a lowest leakage current density of 2.31 × 10 -8 A cm -2 . Furthermore, the influences of doping and annealing conditions on the leakage current conduction mechanisms (CCMs) of HfDyO x /Ge MOS capacitors have also been investigated systematically. All of the experimental results indicate that TMA-passivated HfDyO x /Ge gate stacks with appropriate doping concentrations demonstrate potential application prospects for Ge-based MOSFET devices., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Hypermethylated-in-Cancer 1 (Hic1) is a tumor suppressor gene frequently inactivated by epigenetic silencing and loss-of-heterozygosity in a broad range of cancers. Loss of HIC1, a sequence-specific zinc finger transcriptional repressor, results in deregulation of genes that promote a malignant phenotype in a lineage-specific manner. In particular, upregulation of the HIC1 target gene SIRT1, a histone deacetylase, can promote tumor growth by inactivating TP53. An alternate line of evidence suggests that HIC1 can promote the repair of DNA double strand breaks through an interaction with MTA1, a component of the nucleosome remodeling and deacetylase (NuRD) complex. Using a conditional knockout mouse model of tumor initiation, we now show that inactivation of Hic1 results in cell cycle arrest, premature senescence, chromosomal instability and spontaneous transformation in vitro. This phenocopies the effects of deleting Brca1, a component of the homologous recombination DNA repair pathway, in mouse embryonic fibroblasts. These effects did not appear to be mediated by deregulation of Hic1 target gene expression or loss of Tp53 function, and rather support a role for Hic1 in maintaining genome integrity during sustained replicative stress. Loss of Hic1 function also cooperated with activation of oncogenic KRas in the adult airway epithelium of mice, resulting in the formation of highly pleomorphic adenocarcinomas with a micropapillary phenotype in vivo. These results suggest that loss of Hic1 expression in the early stages of tumor formation may contribute to malignant transformation through the acquisition of chromosomal instability.

Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3. In contrast, removal of Suz12 or Eed destabilizes canonical PRC2 function and ablates NKT cell development completely. We further show that Ezh2 directly methylates the NKT cell lineage defining transcription factor PLZF, leading to its ubiquitination and subsequent degradation. Sustained PLZF expression in Ezh2-deficient mice is associated with the expansion of a subset of NKT cells that cause immune perturbation. Taken together, we have identified a chromatin-independent function of Ezh2 that impacts on the development of the immune system., (© 2017 The Authors.)

Transforming growth factor-β1 (TGF-β1)/Smad signaling has a central role in the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2 is anti-fibrotic. However, these Smads form heterogeneous complexes, the functions of which are poorly understood. Here we studied Smad complex function in renal fibrosis using the mouse model of unilateral ureteric obstruction. Mice heterozygous for Smad3/4 (Smad3/4 +/- ) exhibited substantial protection from renal fibrosis through day 7 of obstruction, whereas Smad2/3 +/- and Smad2/4 +/- mice showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an early event following obstruction in wild-type mice, which involved nuclear phosphorylation of the linker regions of Smad3. Significantly, Smad3 or Smad4 deficiency decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3 linker phosphorylation, and fibrosis but at different degrees. In vitro, TGF-β1 stimulation of collagen I promoter activity involved formation of Smad3/Smad4/CDK9 complexes, and overexpression of each component gave additive increases in collagen promoter activity. Co-administration of a CDK9 inhibitor and Smad3-specific inhibition achieved better protection from TGF-β1-induced fibrotic response in vitro and renal interstitial fibrosis in vivo. Thus formation of Smad3/Smad4/CDK9 complex drives renal fibrosis during ureteral obstruction. Formation of this complex represents a novel target for antifibrotic therapies.

Inflammation is critical for host defense, but without appropriate control, it can cause chronic disease or even provoke fatal responses. Here we identify a mechanism that limits the inflammatory response. Probing the responses of macrophages to the key sensory Toll-like receptors, we identify that the Broad-complex, Tramtrack and Bric-a-brac/poxvirus and zinc finger (BTB/POZ), transcriptional regulator promyelocytic leukemia zinc finger (PLZF) limits the expression of inflammatory gene products. In accord with this finding, PLZF-deficient animals express higher levels of potent inflammatory cytokines and mount exaggerated inflammatory responses to infectious stimuli. Temporal quantitation of inflammatory gene transcripts shows increased gene induction in the absence of PLZF. Genome-wide analysis of histone modifications distinguish that PLZF establishes basal activity states of early response genes to maintain immune homeostasis and limit damaging inflammation. We show that PLZF stabilizes a corepressor complex that encompasses histone deacetylase activity to control chromatin. Together with our previous demonstration that PLZF promotes the antiviral response, these results suggest a strategy that could realize one of the major goals of immune therapy to retain immune resistance to pathogens while curbing damaging inflammation.

Background: The role of naturally occurring regulatory T cells (Treg) in the control of the development of systemic lupus erythematosus (SLE) has not been well defined. Therefore, we dissect the phenotypically heterogeneous CD4(+)FoxP3(+) T cells into subpopulations during the dynamic SLE development. METHODLOGY/PRINCIPAL FINDINGS: To evaluate the proliferative and suppressive capacities of different CD4(+) T cell subgroups between active SLE patients and healthy donors, we employed CD45RA and CD25 as surface markers and carboxyfluorescein diacetatesuccinimidyl ester (CFSE) dilution assay. In addition, multiplex cytokines expression in active SLE patients was assessed using Luminex assay. Here, we showed a significant increase in the frequency of CD45RA(+)FoxP3(low) naive Treg cells (nTreg cells) and CD45RA(-)FoxP3(low) (non-Treg) cells in patients with active SLE. In active SLE patients, the increased proportions of CD45RA(+)FoxP3(low) nTreg cells were positively correlated with the disease based on SLE disease activity index (SLEDAI) and the status of serum anti-dsDNA antibodies. We found that the surface marker combination of CD25(+)CD45RA(+) can be used to defined CD45RA(+)FoxP3(low) nTreg cells for functional assays, wherein nTreg cells from active SLE patients demonstrated defective suppression function. A significant correlation was observed between inflammatory cytokines, such as IL-6, IL-12 and TNFα, and the frequency of nTreg cells. Furthermore, the CD45RA(+)FoxP3(low) nTreg cell subset increased when cultured with SLE serum compared to healthy donor serum, suggesting that the elevated inflammatory cytokines of SLE serum may promote nTreg cell proliferation/expansion., Conclusions/significance: Our results indicate that impaired numbers of functional CD45RA(+)FoxP3(low) naive Treg cell and CD45RA(-)FoxP3(low) non-suppressive T cell subsets in inflammatory conditions may contribute to SLE development. Therefore, analysis of subsets of FoxP3(+) T cells, using a combination of FoxP3, CD25 and CD45RA, rather than whole FoxP3(+) T cells, will help us to better understand the pathogenesis of SLE and may lead to the development of new therapeutic strategies.