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Abstract Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/−) mice did not show any significant changes in body weight or composition. However, Fadd+/− mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/− mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

Abstract The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal’s exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals’ investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.

Summary: Human cortical neurons (hCNs) exhibit high dendritic complexity and synaptic density, and the maturation process is greatly protracted. However, the molecular mechanism governing these specific features remains unclear. Here, we report that the hominoid-specific gene TBC1D3 promotes dendritic arborization and protracts the pace of synaptogenesis. Ablation of TBC1D3 in induced hCNs causes reduction of dendritic growth and precocious synaptic maturation. Forced expression of TBC1D3 in the mouse cortex protracts synaptic maturation while increasing dendritic growth. Mechanistically, TBC1D3 functions via interaction with MICAL1, a monooxygenase that mediates oxidation of actin filament. At the early stage of differentiation, the TBC1D3/MICAL1 interaction in the cytosol promotes dendritic growth via F-actin oxidation and enhanced actin dynamics. At late stages, TBC1D3 escorts MICAL1 into the nucleus and downregulates the expression of genes related with synaptic maturation through interaction with the chromatin remodeling factor ATRX. Thus, this study delineates the molecular mechanisms underlying human neuron development.

Abstract Pain, a comorbidity of anxiety disorders, causes substantial clinical, social, and economic burdens. Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain‐associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100 mg kg−1) in alleviating pain‐associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety‐like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress‐related hormones including corticosterone, corticotropin‐releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVNCRH) is reduced after propofol treatment. Interestingly, artificially activating PVNCRH neurons through chemogenetics interfered with the anxiety‐reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVNCRH neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of γ‐aminobutyric acid type A receptor β3 (GABAAβ3) subunits in PVNCRH neurons diminished the anxiety‐relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain‐associated anxiety‐like behaviors using a single dose of propofol.

Abstract Background Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. Results To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. Conclusion In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics. Graphical Abstract

Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague–Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFβ1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFβ1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. In vitro, peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.

Abstract Objective To quantify corneal nerve fiber parameters in a Mongolian population with diabetic peripheral neuropathy (DPN) by corneal confocal microscopy. Methods This study conducted a comprehensive evaluation of 114 participants from Hulunbuir between January 2020 and December 2021. The participants included healthy controls, Mongolian and Han patients with type 2 diabetes mellitus. Demographic, medical, and laboratory data were collected, and neuropathy was evaluated by confocal corneal microscopy. And compare various parameters between Han and Mongolian were performed using SPSS software. Results The average waist circumference of Mongolian diabetic patients was larger than that of Han diabetic patients (P

Abstract Paroxysmal kinesigenic dyskinesia (PKD) is associated with a disturbance of neural circuit and network activities, while its neurophysiological characteristics have not been fully elucidated. This study utilized the high‐density electroencephalogram (hd‐EEG) signals to detect abnormal brain activity of PKD and provide a neural biomarker for its clinical diagnosis and PKD progression monitoring. The resting hd‐EEGs are recorded from two independent datasets and then source‐localized for measuring the oscillatory activities and function connectivity (FC) patterns of cortical and subcortical regions. The abnormal elevation of theta oscillation in wildly brain regions represents the most remarkable physiological feature for PKD and these changes returned to healthy control level in remission patients. Another remarkable feature of PKD is the decreased high‐gamma FCs in non‐remission patients. Subtype analyses report that increased theta oscillations may be related to the emotional factors of PKD, while the decreased high‐gamma FCs are related to the motor symptoms. Finally, the authors established connectome‐based predictive modelling and successfully identified the remission state in PKD patients in dataset 1 and dataset 2. The findings establish a clinically relevant electroencephalography profile of PKD and indicate that hd‐EEG can provide robust neural biomarkers to evaluate the prognosis of PKD.

Summary: Amino acid formula (AAF) is increasingly consumed in infants with cow’s milk protein allergy; however, the long-term influences on health are less described. In this study, we established a mouse model by subjecting neonatal mice to an amino acid diet (AAD) to mimic the feeding regimen of infants on AAF. Surprisingly, AAD-fed mice exhibited dysbiotic microbiota and increased neuronal activity in both the intestine and brain, as well as gastrointestinal peristalsis disorders and depressive-like behavior. Furthermore, fecal microbiota transplantation from AAD-fed mice or AAF-fed infants to recipient mice led to elevated neuronal activations and exacerbated depressive-like behaviors compared to that from normal chow-fed mice or cow’s-milk-formula-fed infants, respectively. Our findings highlight the necessity to avoid the excessive use of AAF, which may influence the neuronal development and mental health of children.

Abstract Postoperative delirium (POD) is a complicated and harmful clinical syndrome. Traditional behaviour analysis mostly focuses on static parameters. However, animal behaviour is a bottom-up and hierarchical organizational structure composed of time-varying posture dynamics. Spontaneous and task-driven behaviours are used to conduct comprehensive profiling of behavioural data of various aspects of model animals. A machine-learning based method is used to assess the effect of dexmedetomidine. Fourteen statistically different spontaneous behaviours are used to distinguish the non-POD group from the POD group. In the task-driven behaviour, the non-POD group has greater deep versus shallow investigation preference, with no significant preference in the POD group. Hyperactive and hypoactive subtypes can be distinguished through pose evaluation. Dexmedetomidine at a dose of 25 μg kg−1 reduces the severity and incidence of POD. Here we propose a multi-scaled clustering analysis framework that includes pose, behaviour and action sequence evaluation. This may represent the hierarchical dynamics of delirium-like behaviours.

Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the anti-IgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in anti-IgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.

BackgroundCentral lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) are common, but management through prophylactic central lymph node dissection (pCLND) remains controversial. In this study, the independent predictors of CLNM in PTMC were retrospectively studied based on ultrasound and pathological data, and we aim to establish the prediction model to predict CLNM in PTMC.MethodsThis study included a total of 1,506 patients who underwent thyroid surgery for PTMC at the First Affiliated Hospital of Chongqing Medical University from 2015 to 2018. Ultrasound and clinicopathological features were summarized and analyzed. Univariate and multivariate analyses were performed to determine the risk factors associated with CLNM. The prediction model is established and verified according to the multivariate analysis results. The Kaplan–Meier curve was used to evaluate the effect of CLNM on survival.ResultsThe CLNM rate was 44.5% (670/1,506). Multivariate analysis showed that men, younger age, smaller diameter, ETE, microcalcification, without Hashimoto’s thyroiditis, and multifocal were independent risk predictors of CLNM. Nomogram has a good discriminative ability (C-index: 0.755 in the validation group), and the calibration effect is good. In the DCA curve, the CLNM prediction model performed better net benefit given any high-risk thresholds. The median follow-up time was 30 months (12–59 months), 116 cases were lost, and the follow-up rate was 92.8% (1,506/1,622). Of the 1,506 patients included, 12 (0.8%) experienced recurrence.ConclusionThe likelihood of CLNM can be objectively quantified before surgery by using this reliable and accurate nomogram that combines preoperative ultrasound with clinicopathological features. Clinicians can use this nomogram to assess central lymph node status in patients with PTMC and consider prophylactic CND in patients with high scores.

Abstract Immunotherapies have been explored in treating solid tumors, albeit with disparate clinical effects in distinct cancer types. Systematic interrogation of immune cells in the tumor microenvironment (TME) is vital to the prediction of immunotherapy response and the development of innovative immunotherapeutics. To comprehensively characterize the immune microenvironment in advanced biliary tract cancer (BTC), we utilized single-cell RNA sequencing in unselected viable cells from 16 matched samples, and identified nineteen cell subsets from a total of 45,851 cells, in which exhausted CD8+ T cells, macrophages, and dendritic cells (DCs) in BTC were shown to augment and communicate within the TME. Transcriptional profiles coupled with T cell receptor (TCR) sequences revealed that exhausted CD8+ T cells retained clonal expansion and high proliferation in the TME, and some of them highly expressed the endoplasmic reticulum stress (ER) response gene, XBP1, indicating the role of ER stress in remodeling TME. Functional assays demonstrated that XBP1 and common immune checkpoints (PD1, TIGIT) were significantly upregulated in CD8+ T cells cocultured within the TME of BTC cells (GBC-SD, HCCC-9810). When treating the coculture groups with the specific inhibitor of IRE1α-XBP1 (4μ8C), the downregulation of TIGIT was observed in the treatment group. Collectively, comprehensive transcriptome profiling provides deep insights into the immune atlas in advanced BTC, which might be instrumental in exploring innovative immunotherapy strategies.

Siliceous microplankton is an effective proxy for connecting modern and past marine environments; however, radiolarians have been understudied in Prydz Bay, Eastern Antarctica. This study investigated the changes in the siliceous microbiota fluxes and radiolarian assemblages captured in a 1-year time-series sediment trap (February 2014 to February 2015, ~490 m water depth) in the polynya of Prydz Bay. The results exhibited the strong seasonality in the radiolarian assemblages and the fluxes of radiolarians, diatoms, silicoflagellates and sponge spicules, with low numbers in winter and high numbers in summer. Seasonal variations in the sea ice and plankton community were critical in these patterns. The total radiolarian flux (TRF) displayed three peaks with higher flux than the annual average TRF over the year, all of which occurred in summer. These TRF peaks were mainly driven by seasonal fluctuations of sea ice, primary productivity, grazing pressure caused by phytophagous zooplankton and resuspension of small radiolarians in the surface sediments induced by modified Circumpolar Deep Water (mCDW) intrusion onto the shelf. There were also two notable low-TRF stages, mainly related to full sea-ice coverage and high grazing pressure. Two dominant assemblages were recognized by means of Q-factor analysis. Dominant assemblage one was composed of three small-sized taxa, Antarctissa sp., Phormacantha hystrix and Plectacantha oikiskos, which could be used as a proxy for primary productivity in the Marginal Ice Zone (MIZ) in Prydz Bay. Dominant assemblage two was composed of Antarctissa strelkovi and Antarctissa denticulata, with A. strelkovi dominating. The high flux and high relative abundance of A. strelkovi marked the extension of Ice Shelf Water (ISW) to the shelf area in Prydz Bay. These findings will provide new insights and reliable proxies for modern and paleoceanographic research in the Southern Ocean.

Abstract Background Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial. Methods We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing. Results These experiments showed that patient’s anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient’s antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice. Conclusions Overall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.

Examining iron (Fe) speciation in marine sediments is critical to understand Fe and carbon biogeochemical cycling in polar regions. In this study, we investigated the speciation of Fe in sediments from Prydz Bay and the adjacent Southern Ocean, and examined the factors controlling Fe speciation and its relationship with total organic carbon (TOC). Our results reveal that unreactive silicate Fe (FeU) is the dominant pool of total Fe (FeT), followed by poorly reactive sheet silicate Fe (FePRS), reducible crystalline Fe oxides (Feox2), easily reducible amorphous/poorly crystalline Fe oxides (Feox1), and magnetite (Femag), with carbonate-associated ferrous Fe (Fecarb) being the smallest pool. The highly reactive Fe (FeHR)/FeT ratios (0.13 ± 0.06) in our study area are among the lowest end-member globally, primarily due to weak bedrock weathering and slow glacier melting. The Feox1/FeT ratios are similar to those in continental shelf and marginal seas containing highly weathered materials, while the Feox2/FeT ratios are significantly lower. This result implicates that low temperature inhibits the aging of iceberg melting-sourced Feox1 potentially, and accordingly the regulation of weathering on the FeHR/FeT ratio is mainly reflected in Feox2/FeT ratio. There are no significant correlations between TOC and FeHR, Fecarb, Feox1 or Feox2 in the research region. Four distinct patterns of TOC/FeHR ratio can be discerned by summarizing the global data set: (a) high TOC/FeHR ratios (> 2.5) are likely the result of high marine primary productivity and low chemically weathered source materials; (b) low TOC/FeHR ratios (< 0.6) are caused by high rates of FeHR inputs and OC remineralization; (c) mid-range TOC/FeHR ratios (0.6 – 2.5) typical of most river particulates and marginal sea sediments indicate the same FeHR and OC sources and/or interactions between each other; (d) both low TOC and FeHR content is the result of low marine primary productivity and weak chemical weathering. Our findings provide new insights into the relationship between FeHR and TOC in polar sediments.

Abstract Background We aimed to report pregnancy outcomes of women with type 1 diabetes (T1D) in China, on which data were sparse. Methods This is a nationwide retrospective study conducted in 11 general medical centers in 8 cities across China. We investigated the clinical data of all women who attended these centers with a singleton pregnancy and whose pregnancy ended between 1 January 2004 and 31 December 2014. Pregnancies of women with pregestational T1D were ascertained and compared with those of women without T1D. Results From over 300 000 pregnancies over the 11‐year study period, we identified 265 singleton pregnancies of women with T1D. One maternal death was documented among 265 (0.37%) women with T1D and 83 among 318 486 (0.03%) women without T1D. Women with T1D suffered from higher rates of pregnancy loss (13.21% vs 2.92%, crude risk ratio [cRR] 5.08 [95% CI, 3.56‐7.26]) and preeclampsia (17.74% vs 4.20%, cRR 4.94 [95% CI, 3.60‐6.77]) compared with those without T1D. Infants of these women with T1D had elevated rates of neonatal death (5.65% vs 0.16%, cRR 37.36 [95% CI, 21.21‐65.82]) and congenital malformation(s) (8.26% vs 3.53%, cRR 2.46 [95% CI, 1.54‐3.93]) compared with those of women without T1D. No significant improvement in pregnancy outcomes in women with T1D was observed over the period 2004 to 2014. Conclusions Pregnancy outcomes were persistently poor in women with T1D during 2004 to 2014 in China. Pregnancy care needs to be improved to reduce adverse pregnancy outcomes among Chinese women with T1D.

Background: Anti-IgLON5 disease is a rare autoimmune disease of the central nervous system. It typically manifests as a chronic condition, characterized by cognitive impairments, movement disorders, and sleep disorders. The mechanisms underlying movement disorders in this disease remain poorly understood due to a lack of research. Furthermore, this disease exhibits both neuroimmune and neurodegenerative characteristics. The objective of this study is to explore the underlying mechanisms of movement disorders caused by anti-IgLON5 antibodies for the first time. Methods: Antibodies were purified from the serum of a confirmed patient of anti-IgLON5 disease. The passive transfer animal models were employed, where antibodies were continuously injected into the substantia nigra pars compacta (SNc) of the mouse midbrain using stereotactic injection to explore the mechanism of movement disorder. The effects of anti-IgLON5 antibodies on dopaminergic neurons in the SNc and neurodegeneration were examined through immunohistochemistry. Changes in neurotransmitter levels in the basal ganglia were assessed using high-performance liquid chromatography. Additionally, RNA-seq was employed to identify the differentially expressed genes associated with the short-term and long-term effects of anti-IgLON5 antibody on the SNc. Results: Mice injected with anti-IgLON5 antibodies in the SNc exhibited persistent movement impairments for up to 3 months. One week after antibody injection, the number of TH neurons significantly decreased compared to the control group, accompanied by reduced projection fibers in the basal ganglia and decreased dopamine levels. After 3 months of antibody injection, an increase in phosphorylated Tau was observed in the SNc of the midbrain. Additionally, long-term sustained activation of microglia was detected in the SNc. The differentially expressed genes of long-term effects of IgLON5 antibodies were different from their short-term effects on the SNc. Conclusion: Purified serum IgG from a patient with anti-IgLON5 antibodies can cause long-term movement disorder in mice. The movement disorders appear to be linked to the impaired dopaminergic pathway, and the increased p-Tau showed neurodegenerative changes induced by the anti-IgLON5 antibody.

Mg2SiO4 and MgSiO3 ceramics with superior microwave dielectric properties are considered to be promising candidates for 5G applications. However, a slight deviation from the stoichiometric Mg/Si ratio will significantly influence their microwave dielectric properties, which will hinder their practical applications. In this work, the xMgO-SiO2 (x = 1~2) ceramics were synthesized by a solid-state reaction method. The influence of the Mg/Si ratio x on the crystalline phase, microstructure, and microwave dielectric properties was investigated through X-ray diffraction (XRD), a scanning electron microscope (SEM), and the resonant cavity method. The XRD patterns revealed the coexistence of Mg2SiO4 and MgSiO3 within the x range of 1~2, which was further demonstrated by the energy-dispersive X-ray spectra. The SEM images show a typical polycrystalline morphology of ceramics with an inhomogeneous grain size distribution. It is found that the microwave dielectric properties fluctuate at both sides of the x range while those remain relatively stable with minor changes at the intermediate components, indicating an obvious low composition dependence helpful for practical applications. Further, a demonstrator of a microstrip patch antenna for 5G applications using the 1.5MgO-SiO2 ceramic was designed and fabricated, and a return loss of −16.2 dB was demonstrated, which demonstrated the potential applications.

Diabetes mellitus (DM) is a fast-growing chronic metabolic disorder that leads to significant health, social, and economic problems worldwide. Chronic hyperglycemia caused by DM leads to multiple devastating complications, including macrovascular complications and microvascular complications, such as diabetic cardiovascular disease, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. Numerous studies provide growing evidence that aberrant expression of and mutations in RNA-binding proteins (RBPs) genes are linked to the pathogenesis of diabetes and associated complications. RBPs are involved in RNA processing and metabolism by directing a variety of post-transcriptional events, such as alternative splicing, stability, localization, and translation, all of which have a significant impact on RNA fate, altering their function. Here, we purposed to summarize the current progression and underlying regulatory mechanisms of RBPs in the progression of diabetes and its complications. We expected that this review will open the door for RBPs and their RNA networks as novel therapeutic targets for diabetes and its related complications.

Deep brain stimulation (DBS) is a clinical intervention for the treatment of movement disorders. It has also been applied to the treatment of psychiatric disorders such as depression, anorexia nervosa, obsessive-compulsive disorder, and schizophrenia. Psychiatric disorders including schizophrenia, bipolar disorder, and major depression can lead to psychosis, which can cause patients to lose touch with reality. The ventral tegmental area (VTA), located near the midline of the midbrain, is an important region involved in psychosis. However, the clinical application of electrical stimulation of the VTA to treat psychotic diseases has been limited, and related mechanisms have not been thoroughly studied. In the present study, hyperlocomotion and stereotyped behaviors of the mice were employed to mimic and evaluate the positive-psychotic-like behaviors. We attempted to treat positive psychotic-like behaviors by electrically stimulating the VTA in mice and exploring the neural mechanisms behind behavioral effects. Local field potential recording and in vivo fiber photometry to observe the behavioral effects and changes in neural activities caused by DBS in the VTA of mice. Optogenetic techniques were used to verify the neural mechanisms underlying the behavioral effects induced by DBS. Our results showed that electrical stimulation of the VTA activates local gamma-aminobutyric acid (GABA) neurons, and dopamine (DA) neurons, reduces hyperlocomotion, and relieves stereotyped behaviors induced by MK-801 (dizocilpine) injection. The results of optogenetic manipulation showed that the activation of the VTA GABA neurons, but not DA neurons, is involved in the alleviation of hyperlocomotion and stereotyped behaviors. We visualized changes in the activity of specific types in specific brain areas induced by DBS, and explored the neural mechanism of DBS in alleviating positive psychotic-like behaviors. This preclinical study not only proposes new technical means of exploring the mechanism of DBS, but also provides experimental justification for the clinical treatment of psychotic diseases by electrical stimulation of the VTA.

ObjectiveTo investigate the relationship between diabetic peripheral neuropathy (DPN) and gait abnormality in diabetic patients.MethodsRelated research concerning the gait of diabetic patients with and without DPN was collected and analyzed by searching PubMed, Embase, and Web of Science. Statistical analysis was performed by using RevMan 5.3 software.ResultsTwenty-one studies were included in this meta-analysis, consisting of 499 diabetic neuropathy patients and 467 diabetes controls without neuropathy. Meta-analysis results showed lower gait velocity, shorter stride length, longer stride time, longer stance time, and higher maximum knee extension moment in the DPN group, compared with their counterparts.ConclusionAmong diabetic patients, those complicated with DPN possess lower gait velocity, shorter stride length, longer stride time, longer stance time, and higher maximum knee extension moment.

AimTo explore the relationship between genomic DNA methylation and diabetic chronic complications.Methods299 patients with type 2 diabetes mellitus (T2DM) hospitalized in the Second Affiliated Hospital of Soochow University were enrolled. We divided the patients into different complications groups and corresponding non-complication groups. Clinical and biochemical parameters were compared between the two groups. The level of genomic DNA methylation in leukocytes was determined by high-performance liquid chromatography-tandem mass spectrometry.Results(1) Age, duration of diabetes, creatinine (Cr), blood urea nitrogen (BUN), genomic DNA methylation, 24- hour urine total protein (24-hUTP), and intima-media thickness (IMT) were significantly higher in the carotid plaque (CP) group. Waist-to-hip ratio (WHR), body mass index (BMI), estimated glomerular- filtration rate (eGFR), and albumin (Alb) were significantly lower in the CP group. Gender, age and BMI were the influencing factors of CP. (2) Age, duration, Cr, BUN, urinary microalbumin creatinine ratio (UACR), systolic blood pressure (SBP), TCSS, and 24- hUTP were significantly higher in the diabetic retinopathy (DR) group. eGFR, 2h postprandial C- peptide, and Alb were lower in the DR group. Age, duration, Cr, Alb, SBP, and the presence of DN were the influencing factors of DR. (3) Age, duration, HbA1c, BUN, TCSS, SBP, and IMT(R) were significantly higher in the diabetic nephropathy (DN) group. 2h postprandial C-peptide, and Alb were lower in the DN group. HbA1c, BUN, DR, and HBP were the influencing factors of DN. (4) Age, duration, total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), Cr, BUN, uric acid (UA), and SBP were significantly higher in the diabetic peripheral neuropathy (DPN) group. The level of genomic DNA methylation and eGFR were significantly lower in the DPN group. Age, duration, LDL-C, UA, the presence of DR, and the genomic DNA methylation level were the influencing factors for DPN. Incorporating the level of genomic DNA methylation into the prediction model could improve the ability to predict DPN on the basis of conventional risk factors.ConclusionLow level of genomic DNA methylation is a relatively specific risk factor for DPN in patients with T2DM and not a contributing factor to the other chronic complications.

Alzheimer's disease (AD) has raised extensive concern in healthcare and academia as one of the most prevalent health threats to the elderly. Due to the irreversible nature of AD, early and accurate diagnoses are significant for effective prevention and treatment. However, diverse clinical symptoms and limited neuroimaging accuracy make diagnoses challenging. In this article, we built a brain network for each subject, which assembles several commonly used neuroimaging data simply and reasonably, including structural magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and amyloid positron emission tomography (PET). Based on some existing research results, we applied statistical methods to analyze (i) the distinct affinity of AD burden on each brain region, (ii) the topological lateralization between left and right hemispheric sub-networks, and (iii) the asymmetry of the AD attacks on the left and right hemispheres. In the light of advances in graph convolutional networks for graph classifications and summarized characteristics of brain networks and AD pathologies, we proposed a regional brain fusion-graph convolutional network (RBF-GCN), which is constructed with an RBF framework mainly, including three sub-modules, namely, hemispheric network generation module, multichannel GCN module, and feature fusion module. In the multichannel GCN module, the improved GCN by our proposed adaptive native node attribute (ANNA) unit embeds within each channel independently. We not only fully verified the effectiveness of the RBF framework and ANNA unit but also achieved competitive results in multiple sets of AD stages' classification tasks using hundreds of experiments over the ADNI clinical dataset.

With the gradual deepening of mining depth, sudden ground pressure disasters such as rock burst and collapse caused by deep high stress and high rock pressure are major hidden dangers affecting mine safety production. Microseismic monitoring technology has been widely applied in the field of mine ground pressure disaster warning. The existing microseismic monitoring system has some problems, such as inaccurate automatic recognition and classification of waveform signals, low quality and low efficiency of manual processing. In this paper, the automatic classification of vibration signals in the process of mining is studied, and the automatic classification results are uploaded to the cloud service platform in real time, which solves the technical bottleneck of the existing microseismic monitoring system. Meanwhile, the real-time monitoring of mine ground pressure safety is guaranteed based on the cloud service platform of microseismic monitoring.

Sudden ground pressure disasters caused by deep mining such as rock burst and cave-in are major hidden dangers affecting safety production underground mine. The safe and stable operation of ground pressure safety monitoring platform is of great significance for mine safety production. However, many small and medium-sized mining enterprises make slow progress in the construction of the online monitoring platform for ground pressure safety due to the limitations of enterprise scale, capital capacity and other factors. With the development of The Times, SaaS model (software as a service model) develops rapidly with the advantages of Internet, multiple leasing, service and scalability. Through SaaS model, it effectively solves the problem of building a low-cost and high-reliability online ground pressure monitoring platform for Chinese small and medium-sized mining enterprises.

Touch can positively modulate cognitive performance and emotional response. Here the authors demonstrate that enriched tactile experience improves memory and reduces anxiety in adult mice by remodelling the pathway from the primary somatosensory cortex to the dentate gyrus.

Graph clustering is a fundamental task in data analysis and has attracted considerable attention in recommendation systems, mapping knowledge domain, and biological science. Because graph convolution is very effective in combining the feature information and topology information of graph data, some graph clustering methods based on graph convolution have achieved superior performance. However, current methods lack the consideration of structured information and the process of graph convolution. Specifically, most of existing methods ignore the implicit interaction between topology information and feature information, and the stacking of a small number of graph convolutional layers leads to insufficient learning of complex information. Inspired by graph convolutional network and auto-encoder, we propose a deep graph structured clustering network that applies a deep clustering method to graph structured data processing. Deep graph convolution is employed in the backbone network, and evaluates the result of each iteration with node feature and topology information. In order to optimize the network without supervision, a triple self-supervised module is designed to help update parameters for overall network. In our model, we exploit all information of the graph structured data and perform self-supervised learning. Furthermore, improved graph convolution layers significantly alleviate the problem of clustering performance degradation caused by over-smoothing. Our model is designed to perform on representative and indirect graph datasets, and experimental results demonstrate that our model achieves superior performance over state-of-the-art models.

Endothelial cells are the fundamental components of blood vessels that regulate several physiological processes including immune responses, angiogenesis, and vascular tone. Endothelial dysfunction contributes to the development of various diseases such as acute lung injury, and endothelial inflammation is a vital part of endothelial dysfunction. Dauricine is an extract isolated from Menispermum dauricum DC, a traditional Chinese medical plant that can be used for pharyngitis. In this work, we found that IL-1β-induced overexpression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin was inhibited by dauricine in primary human umbilical vein endothelial cells (HUVECs). Correspondingly, adhesion of human acute monocytic leukemia cell line (THP-1) to HUVECs was decreased by dauricine. Further studies showed that dauricine inhibited the activation of nuclear factor-κB (NF-κB) pathway in HUVECs stimulated with IL-1β. In vivo, dauricine protected mice from lipopolysaccharide (LPS)-induced acute lung injury. In lung tissues, the activation of NF-κB pathway and the expression of its downstream genes (ICAM-1, VCAM-1, and E-selectin) were decreased by dauricine, consistent with what was found in vitro. In summary, we concluded that dauricine could alleviate endothelial inflammation by suppressing NF-κB pathway, which might serve as an effective candidate for diseases related with endothelial inflammation.

Anaerobic oxidation of methane (AOM), an important biological process to reduce global methane emissions to the atmosphere, can utilize methane as an electron donor to reduce sulfate, nitrate, nitrite, iron, manganese, AQDS (9,10-anthraquinone-2,6-disulfonate), etc.; thus, AOM has been a hot topic in global climate change research in recent years. In addition, nitrogen deposition of terrestrial ecosystems can input more nitrogen to nitrogen-limited peatlands, which could impact the AOM process. However, the effect of nitrogen addition on AOM is not well studied. Here, we investigated the effects of two forms of nitrogen on the vertical distribution (0–100 cm) of AOM in the Zoige peatlands (China) using an anaerobic incubation experiment. The results show that the concentrations of inorganic nitrogen species changed with nitrogen addition, but it did not significantly promote the potential of AOM. The cumulative AOM of treatments without nitrogen (CK) and ammonium chloride (Nred) was 2343.43 ± 18.96 µg·g−1 and 2340.76 ± 16.11 µg·g−1, respectively, which were significantly higher than that of sodium nitrate (Nox) addition treatment (2098.13 ± 13.59 µg·g−1). In addition, the potential of AOM increased with depth, but different soil layers had different responses to the two forms of nitrogen, which could reflect the variable need for different forms of nitrogen in the different soil layers. The soil water content (SWC), dissolved organic carbon (DOC), iron content (Fe3+), and pH played important roles in the potential of AOM in the Zoige peatlands. Overall, our results found that nitrogen addition did not increase the potential of AOM, but instead had an inhibitory effect on it. This study provides a basis for understanding the response of AOM to nitrogen addition in peatlands, which has important implications for global climate change.

Regardless of its good electron-transfer ability and chemical stability, pure Zn2SnO4 (ZSO) still has intrinsic deficiencies of a narrow spectral response region, poor absorption ability, and high photo-activated carrier recombination rate. Aiming to overcome the deficiencies above-mentioned, we designed a facile hydrothermal route for etching ZSO nanoparticles in a dilute acetic acid solution, through which efficient oxygen vacancy defect engineering was accomplished and SnO2−x nanocrystals were obtained with an ultrafine particle size. In comparison with the untreated ZSO nanoparticles, the specific surface area of SnO2−x nanocrystals was substantially enlarged, subsequently leading to the notable augmentation of active sites for the photo-degradation reaction. Aside from the above, it is worth noting that SnO2−x nanocrystals were endowed with a broad spectral response, enhancing light absorption capacity and the photo-activated carrier transfer rate with the aid of oxygen vacancy defect engineering. Accordingly, SnO2−x nanocrystals exhibited significantly enhanced photoactivity toward the degradation of the organic dye rhodamine B (RhB), which could be imputed to the synergistic effect of increasing active sites, intensified visible-light harvesting, and the separation rate of the photo-activated charge carrier caused by the oxygen vacancy defect engineering. In addition, these findings will inspire us to open up a novel pathway to design and prepare oxide compound photocatalysts modified by oxygen vacancy defects in pursuing excellent visible-light photoactivity.

This was the “News & Views” story in the journal Nature that was most popular online in 2020. The relative contribution of stress to greying of the hair is not known. Hair color is determined by melanocyte cells derived from melanocyte stem cells (MeSCs) located in a part of the hair follicle called the bulge. This paper, published in Nature in January 2020, was authored by Ya-Chieh Hsu's research group at Harvard University, with Bing Zhang as the first author [1]. Zhang et al. report that noradrenaline - a neurotransmitter molecule involved in the “fight or flight” response to stress — is released from neurons of the sympathetic nervous system. MeSC proliferation and differentiation increase markedly under extreme stress or on exposure to a high level of noradrenaline, resulting in a mass migration of melanocytes away from the bulge and leaving no remaining stem cells to replace them,① thus causing greying. This work by Zhang et al. provides a better understanding of how stress influences other stem cells as well as clues for finding ways to stop and reverse the effects of stress.①① Original source in Chinese: Ji Hu, Stress turns hair white, Bulletin of National Natural Science Foundation of China. 35 (2) (2021) 247-248

The peatlands of the Zoige Plateau are an important global carbon source that is currently under threat as a result of drainage for grazing. How drainage affects the microbial diversity and activity in peatlands is unclear. This study examined the response of microbial communities at two sites to short-term drainage (3 years) and long-term drainage (48 years) in combination with three different water table treatments. Our objective was to examine the changes in the physicochemical properties of the soil, composition of bacterial and fungal communities, and microbial activity. Our results indicated that (1) both duration of drainage and water table drawdown had significant effects on the diversity and composition of the bacterial and fungal communities in the soil, and certain bacteria were replaced by fungal decomposers; (2) duration of drainage affected the structure of fungal communities more than that of bacterial communities, and interactions between microbial species were more complex in peatlands with long-term drainage; (3) drainage significantly altered concentrations of dissolved inorganic nitrogen (NH4+-N and NO3−-N), and these changes correlated with structure of bacterial and fungal communities as well as with changes in abundance of certain dominant microbial species; and (4) fungal communities explained a larger part of microbial activity than bacterial communities. Overall, these findings suggest that fungi play a much more important role than bacteria in microbial-mediated ecosystem functioning in peatlands undergoing drainage.

The effect of bran on rheological property of wheat flour was researched. The national trial strong gluten variety Jinmai 92 was used as raw material to grind flour.The bran addition were 5%, 10%, 15%, 20%, 25% and 30% with pure flour as negative control group and pure bran as positive control group.The rheological properties were determined by electronic farinograph, electronic extensograph and automatic bubblerin accordance with GB/T 14614-2006, GB/T 14615-2006 and GB/T 14614.4-2005. The results showed thatalong with the bran addition changed from 30% to 5%, the sedimentation value, farinograph stabilizing time and extensograph energy increased gradually, the maximum bubble pressure and Dmax gradually decreased, and blowing curve length, bubble inflation index and bubble deformation energy decreased at first then upward, the ratio of stretch ratio and bubble curve increased first and then decreased. As the bran addition was 5%~25%, the dough strength hreached the level of medium or moderately strong which can be used to make noodles or steamed bread.

Background: Despite the fundamental clinical significance of general anaesthesia, the cortical mechanism underlying anaesthetic-induced loss of consciousness (aLOC) remains elusive. Methods: Here, we measured the dynamics of two major cortical neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate, through in vivo two-photon imaging and genetically encoded neurotransmitter sensors in a cell type-specific manner in the primary visual (V1) cortex. Findings: We found a general decrease in cortical GABA transmission during aLOC. However, the glutamate transmission varies among different cortical cell types, where in it is almost preserved on pyramidal cells and is significantly reduced on inhibitory interneurons. Cortical interneurons expressing vasoactive intestinal peptide (VIP) and parvalbumin (PV) specialize in disinhibitory and inhibitory effects, respectively. During aLOC, VIP neuronal activity was delayed, and PV neuronal activity was dramatically inhibited and highly synchronized. Interpretation: These data reveal that aLOC resembles a cortical state with a disrupted excitatory-inhibitory network and suggest that a functional inhibitory network is indispensable in the maintenance of consciousness. Funding: This work was supported by the grants of the National Natural Science Foundation of China (grant nos. 81620108012 and 82030038 to H.D. and grant nos. 31922029, 61890951, and 61890950 to J.H.).

Summary: Morphine is commonly used to relieve moderate to severe pain, but repeated doses cause opioid tolerance. Here, we used ATP sensor and fiber photometry to detect prefrontal ATP level. It showed that prefrontal ATP level decreased after morphine injection and the event amplitude tended to decrease with continuous morphine exposure. Morphine had little effect on prefrontal ATP due to its tolerance. Therefore, we hypothesized that the analgesic effect of morphine might be related to ATP in the medial prefrontal cortex (mPFC). Moreover, local infusion of ATP partially antagonized morphine analgesia. Then we found that inhibiting P2X7R in the mPFC mimicked morphine analgesia. In morphine-tolerant mice, pretreatment with P2X4R or P2X7R antagonists in the mPFC enhanced analgesic effect. Our findings suggest that reduction of prefrontal purinergic signaling is necessary for the morphine analgesia, which help elucidate the mechanism of morphine analgesia and may lead to the development of new clinical treatments for neuropathic pain.

AimTo develop and validate a CpG-based classifier for preoperative discrimination of early and advanced-late stage colorectal cancer (CRC).MethodsWe identified an epigenetic signature based on methylation status of multiple CpG sites (CpGs) from 372 subjects in The Cancer Genome Atlas (TCGA) CRC cohort, and an external cohort (GSE48684) with 64 subjects by LASSO regression algorithm. A classifier derived from the methylation signature was used to establish a multivariable logistic regression model to predict the advanced-late stage of CRC. A nomogram was further developed by incorporating the classifier and some independent clinical risk factors, and its performance was evaluated by discrimination and calibration analysis. The prognostic value of the classifier was determined by survival analysis. Furthermore, the diagnostic performance of several CpGs in the methylation signature was evaluated.ResultsThe eight-CpG-based methylation signature discriminated early stage from advanced-late stage CRC, with a satisfactory AUC of more than 0.700 in both the training and validation sets. This methylation classifier was identified as an independent predictor for CRC staging. The nomogram showed favorable predictive power for preoperative staging, and the C-index reached 0.817 (95% CI: 0.753–0.881) and 0.817 (95% CI: 0.721–0.913) in another training set and validation set respectively, with good calibration. The patients stratified in the high-risk group by the methylation classifier had significantly worse survival outcome than those in the low-risk group. Combination diagnosis utilizing only four of the eight specific CpGs performed well, even in CRC patients with low CEA level or at early stage.ConclusionsOur classifier is a valuable predictive indicator that can supplement established methods for more accurate preoperative staging and also provides prognostic information for CRC patients. Besides, the combination of multiple CpGs has a high value in the diagnosis of CRC.

Objective. The purpose of this study was to explore the effect of the SOST gene polymorphisms on body composition in Chinese nuclear families with male offspring. Methods. 1,016 individuals were recruited from 335 Chinese nuclear families with male offspring. The nuclear families consist of at least one male offspring aged 18 to 44. We genotyped the 10 tagged single-nucleotide polymorphisms (SNPs) in SOST gene (rs7220711, rs865429, rs851057, rs1708635, rs2023794, rs1234612, rs74252774, rs1634330, rs851058, and rs1513670) in all the above people. We used dual-energy X-ray absorptiometry to measure the composition of the human body. The quantitative transmission disequilibrium test (QTDT) was used to analyze the associations of the SNPs with the body composition. Results. QTDT analysis showed that rs1634330 was significantly associated with trunk LM P

Background. Triglyceride-glucose (TyG) index is a convenient indicator of insulin resistance. It has been shown to be associated with macrovascular and microvascular complications in nonhospitalized diabetic patients. However, whether TyG index is a risk factor of diabetes vascular complications in hospitalized type 2 diabetic patients is unclear. We sought to explore the association between TyG index and the risk of macrovascular and microvascular complications in a large Chinese cohort of hospitalized patients. Method. A total of 4,721 patients with type 2 diabetes (T2D) who were hospitalized in the Department of Endocrinology, Kunshan Hospital Affiliated to Jiangsu University were enrolled between January 2015 and November 2020. TyG index was calculated as lnfasting triglycerides mg/dL×fasting glucose mg/dL/2. Measures of macrovascular complications included brachial-ankle pulse wave velocity (ba-PWV) and ankle-brachial index (ABI), whilst urine microalbumin (MAU), chronic kidney disease (CKD), and diabetic retinopathy (DR) were evaluated for microvascular complications. Logistic regressions were used to examine the association between TyG index and diabetes complications. Results. In univariate logistic regressions, higher TyG index was significantly (p

Objective To explore the predictive value of prepregnancy body mass index (pBMI) and early gestational fasting blood glucose (eFBG) in gestational diabetes mellitus (GDM). Methods This case–control study enrolled pregnant women at 6 to 16 weeks of gestation. The pBMI, eFBG and glycosylated haemoglobin (HbA 1c ) was recorded in the first trimester of pregnancy. Receiver-operating characteristic (ROC) curve analysis was used to measure the efficacy of factors that predict GDM. Results A total of 2119 pregnant women were enrolled in this study. Of these, 386 were diagnosed with GDM and 1733 did not have GDM. The age (odds ratio [OR] 1.16; 95% confidence interval [CI] 1.13, 1.20), pBMI (OR 1.12; 95% CI 1.07, 1.17) and eFBG (OR 5.37; 95% CI 3.93, 7.34) were independent risk factors for GDM occurrence. The areas under the ROC curve of eFBG, pBMI and eFBG + pBMI were 0.68 (95% credibility interval 0.65, 0.71), 0.66 (95% credibility interval 0.63, 0.69) and 0.71 (95% credibility interval 0.69, 0.74), respectively. The area under the curve of eFBG + pBMI was significantly higher than that of eFBG or pBMI alone. Conclusion The combination of eFBG and pBMI had a high predictive value for GDM.

To meet the transportation requirements of heavy-haul trains, it is necessary to consider the use of prestressed reinforced concrete ballastless tracks. Therefore, the CRTSIII SBT (China Railway Track System III-type slab ballastless track) has been considered for its convenient construction and geometric adjustment. Considering the problems existing in the base plate of CRTSIII SBT in heavy-haul applications, an indoor test and simulation were conducted to explore the cracking phenomenon of the base plate concrete under fatigue load. The reliability of the simulation was verified through the experimental results. A fatigue crack development law of the base plate structure was established. Furthermore, the influence of the load position, the thickness of self-compacting concrete and axle loads on the fatigue damage of the base plate structure were investigated. For the CRTSIII SBT subjected to heavier axle loads, it is appropriate to thicken the self-compacting concrete layer and strengthen the concrete and steel reinforcement at the plate end to reduce fatigue damage and cracks. The research results can serve as a basis for the optimization of the CRTSIII SBT base plate structure in heavy-haul railway applications.

Depression is a common affective disorder characterized by significant and persistent low mood. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, is reported to have a rapid and durable antidepressant effect, but the mechanisms are unclear. Protein phosphorylation is a post-translational modification that plays a crucial role in cell signaling. Thus, we present a phosphoproteomics approach to investigate the mechanisms underlying stress-induced depression and the rapid antidepressant effect of ketamine in mice. We analyzed the phosphoprotein changes induced by chronic unpredictable mild stress (CUMS) and ketamine treatment in two known mood control centers, the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). We initially obtained >8,000 phosphorylation sites. Quantitation revealed 3,988 sites from the mPFC and 3,196 sites from the NAc. Further analysis revealed that changes in synaptic transmission-related signaling are a common feature. Notably, CUMS-induced changes were reversed by ketamine treatment, as shown by the analysis of commonly altered sites. Ketamine also induced specific changes, such as alterations in synapse organization, synaptic transmission, and enzyme binding. Collectively, our findings establish a signaling framework for stress-induced depression and the rapid antidepressant effect of ketamine.

With the gradual increase of the cargo weight of heavy-haul trains, the traditional ballasted track with the accumulation of stone and ballast has been unable to meet its structural safety requirements. From the comparison of the three common ballastless tracks in China, it can be seen that the low-vibration track (LVT) has the advantages of reasonable structure, low cost, and easy maintenance. Therefore, the design and research of heavy-haul railways are focused on, and it is urgent to study the applicability of LVT in heavy-haul railways. Method: By improving the slope of the short side of the LVT support block, the support block has a better load bearing capacity, so as to achieve the purpose of bearing a larger axle load. Through 1:1 full-scale model test and finite element simulation, the static mechanical properties of Improved LVT (ILVT) and Traditional LVT (TLVT) are compared and analyzed. Result: Compared with TLVT, ILVT has smaller vertical displacement and track gauge changes when subjected to the same load. The proven and reliable finite element model also shows that ILVT’s load sharing is less affected. In the case of achieving the same deformation, ILVT can withstand greater vertical and lateral loads. Conclusions: Compared with the TLVT, the ILVT design can reduce the vertical displacement of the rail and the supporting block, better control the track subsidence, and improve the driving safety of the LVT. At the same time, ILVT improves the anti-overturning ability of the rail and support block under lateral load, reduces the expansion of the gauge and the lateral spacing of the support block, and improves the stability of the track structure. ILVT can also be considered for the weight of 40t and other large axle load, and has broad application prospects.

The surfaces of rivers are considered important sources of atmospheric methane (CH4), however research on this topic is still constrained, especially in freshwater rivers and with the consideration of spatial heterogeneity. Three regions (upper reaches, midstream and downstream) were selected to examine the CH4 fluxes from a freshwater river surface in a mangrove forest wetland from 2012 to 2013, using floating chambers. Results showed that the CH4 fluxes varied significantly among the three regions, with the lowest fluxes at downstream (0.50 ± 0.20 mg m−2 h−1), and highest at upper reaches (1.19 ± 0.36 mg m−2 h−1). The average emission rate at midstream was 0.95 ± 0.37 mg m−2 h−1. The methane flux also varied with seasons, with higher flux in rain-abundant seasons. On average, the CH4 flux in our research river was 0.88 ± 0.31 mg m−2 h−1, which was less than other tropical rivers. In addition, we found that the CH4 flux was significantly correlated with the water characteristics of temperature and atmospheric pressure. Thereby, this study quantified the methane emission from a freshwater river surface in a tropical mangrove forest, enriching the existing knowledge of river surface CH4 flux.

The alpine meadow of Zoige Plateau plays a key role in local livestock production of cattle and sheep. However, it remains unclear how animal grazing or its intensity affect nitrous oxide (N2O) emissions, and the main driving factors. A grazing experiment including four grazing intensities (G0, G0.7, G1.2, G1.6 yak ha−1) was conducted between January 2013 and December 2014 to evaluate the soil nitrous oxide (N2O) fluxes under different grazing intensities in an alpine meadow on the eastern Qinghai–Tibet Plateau of China. The N2O fluxes were examined with gas collected by the static chamber method and by chromatographic concentration analysis. N2O emissions in the growing seasons (from May to September) were lower than that in non-growing seasons (from October to April) in 2013, 1.94 ± 0.30 to 3.37 ± 0.56 kg N2O ha−1 yr−1. Annual mean N2O emission rates were calculated as 1.17 ± 0.50 kg N2O ha−1 yr−1 in non-grazing land (G0) and 1.94 ± 0.23 kg N2O ha−1 yr−1 in the grazing land (G0.7, G1.2, and G1.6). The annual mean N2O flux showed no significant differences between grazing treatments in 2013. However, there were significantly greater fluxes from the G0.7 treatment than from the G1.6 treatment in 2014, especially in the growing season. Over the two years, the soil N2O emission rate was significantly negatively correlated with soil water-filled pore space (WFPS) and dissolved organic carbon (DOC) content as well as positively correlated with soil available phosphorus (P). No relationship was observed between soil N2O emission rate and temperature or rainfall. Our results showed that the meadow soils acted as a source of N2O for most periods and turned into a weak sink of N2O later during the sampling period. Our results highlight the importance of proper grazing intensity in reducing N2O emissions from alpine meadow. The interaction between grazing intensity and N2O emissions should be of more concern during future management of pastures in Zoige Plateau.

Abstract The present study was designed to investigate the roles of P2X3 receptors in dorsal root ganglion (DRG) neurons in colonic hypersensitivity and the effects of alpha-lipoic acid (ALA) on P2X3 receptor activity and colonic hypersensitivity of diabetic rats. Streptozotocin (STZ) was used to induce diabetic model. Abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) was recorded as colonic sensitivity. ATP-induced current density of colon-specific DRG (T13-L2 DRGs) neurons was measured with whole-cell patch clamp. The expression of P2X3Rs of T13-L2 DRGs was measured by western blot analysis. The results showed that AWR scores significantly increased after STZ injection. P2X3R expression and ATP current density of T13-L2 DRG neurons were enhanced in diabetic rats. Intraperitoneal injection with ALA once a day for 1 week remarkably reduced P2X3R expression and ATP current density in diabetic rats. Importantly, ALA treatment attenuated colonic hypersensitivity in diabetic rats. Our data suggest that STZ injection increases expression and function of P2X3 receptors of colon-specific DRG neurons, thus contributing to colonic hypersensitivity in diabetic rats. Administration of ALA attenuates diabetic colonic hypersensitivity, which is most likely mediated by suppressing expression and function of P2X3 receptors in DRGs of diabetic rats.