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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

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.

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

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.

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.

Background: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. Methods: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. Results: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. Conclusions: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China. [ABSTRACT FROM AUTHOR]