Search

Objective: Panic disorder (PD) is a common disabling condition characterized by recurrent panic attacks. Emotional and behavioral impairments are associated with functional connectivity (FC) and network abnormalities. We used whole-brain FC, modular networks, and graph-theory analysis to investigate extensive network profiles in PD. Methods: Functional magnetic resonance imaging (fMRI) data from 82 subjects with PD and 97 healthy controls were included. Intrinsic FC between each pair of 160 regions, six intra-network, and 15 inter-network FCs were analyzed. Topological properties were explored. Results: PD patients showed altered FCs within the right insula, between frontal cortex-posterior cingulate cortex (PCC), frontal cortex-cerebellum, and PCC-occipital cortex (corrected p < 0.001). Lower connections within the sensorimotor network (SMN) and SMN-occipital network (OCN) were detected (p < 0.05). Various decreased global and local network features were found in PD (p < 0.05). In addition, significant correlations were found between PD symptoms and nodal efficiency (Ne) in the insula (r = -0.273, p = 0.016) and intra-insula FC (r = -0.226, p = 0.041). Conclusion: PD patients present with abnormal functional brain networks, especially decreased FC and Ne within the insula, suggesting that dysfunction of information integration plays an important role in PD.

ABSTRACTFlagella play a crucial role in the invasion process of Salmonella and function as a significant antigen that triggers host pyroptosis. Regulation of flagellar biogenesis is essential for both pathogenicity and immune escape of Salmonella. We identified the conserved and unknown function protein STM0435 as a new flagellar regulator. The ∆stm0435 strain exhibited higher pathogenicity in both cellular and animal infection experiments than the wild-type Salmonella. Proteomic and transcriptomic analyses demonstrated dramatic increases in almost all flagellar genes in the ∆stm0435 strain compared to wild-type Salmonella. In a surface plasmon resonance assay, purified STM0435 protein-bound c-di-GMP had an affinity of ~8.383 µM. The crystal structures of apo-STM0435 and STM0435&c-di-GMP complex were determined. Structural analysis revealed that R33, R137, and D138 of STM0435 were essential for c-di-GMP binding. A Salmonella with STM1987 (GGDEF protein) or STM4264 (EAL protein) overexpression exhibits completely different motility behaviours, indicating that the binding of c-di-GMP to STM0435 promotes its inhibitory effect on Salmonella flagellar biogenesis.

IntroductionDepression is a common psychological disorder, accompanied by a disturbance of the gut microbiota and its metabolites. Recently, microbiota-derived tryptophan metabolism and AMPK/mTOR pathway were found to be strongly linked to the development of depression. Shugan Hewei Decoction (SHD) is a classical anti-depression traditional Chinese medicine formula. Although, we have shown that SHD exerted antidepressant effects via cecal microbiota and cecum NLRP3 inflammasome, the specific mechanism of SHD on metabolism driven by gut microbiota is unknown. In this study, we focus on the tryptophan metabolism and AMPK/mTOR pathway to elucidate the multifaceted mechanisms of SHD.MethodsMale rats were established to the chronic unpredictable stress (CUS)/social isolation for 6 weeks, and SHD-L (7.34 g/kg/d), SHD-H (14.68 g/kg/d), Fructooligosaccharide (FOS) (3.15 g/kg/d) were given by intragastric administration once daily during the last 2 weeks. Behavioral experiments were carried out to evaluate the model. The colonic content was taken out for shotgun metagenomic sequencing combined with the untargeted metabolomics, the targeted tryptophan metabolomics. ELISA was used to detect the levels of zonula occludens 1 (ZO-1), Occludin in colon, as well as lipopolysaccharide (LPS), diamine oxidase (DAO), D-lactate (DLA) in serum. The expressions of mRNA and proteins of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway of autophagy were examined using RT-qPCR and Western blot in colon.ResultsSHD modulated gut microbiota function and biological pathways, which were related to tryptophan metabolism. In addition, SHD could regulate microbiota-derived tryptophan production (such as reduction of 3-HK, 3-HAA etc., increment of ILA, IAA etc.), which metabolites belong to kynurenine (KYN) and indole derivatives. Further, SHD reduced intestinal permeability and enhanced the intestinal barrier function. Moreover, SHD could upregulate the levels of AMPK, microtubule associated protein light chain 3 (LC3), autophagy related protein 5 (ATG5) and Beclin1, downregulate the levels of mTOR, p62, promoted autophagy in colon. Spearman’s analysis illustrated the close correlation between tryptophan metabolites and intestinal barrier, AMPK/mTOR pathway.ConclusionSHD may exert antidepressant-like effects by regulating microbiota-derived tryptophan metabolism, and triggering the AMPK/mTOR pathway of autophagy, enhancing the intestinal barrier function.

In this paper, the effect of Ce addition on high temperature oxidation behavior of hot-formed steel was studied by high temperature oxidation experiment. The structure and phase composition of surface oxide layer of specimens with different Ce content were systematically analyzed by SEM, EDS, XPS. The results showed that the addition of Ce promoted the formation of a dense oxide layer during the initial oxidation stage, and effectively weaken the oxidation degree of the steel surface. Meanwhile, the Ce2O3 particles segregation in Si–Cr rich phase reduced the concentration of vacancy defects in oxide layer and enhanced the adhesion between oxide layer and substrate. After Ce addition, the surface oxidation resistance of hot-formed steel is significantly improved.

Abstract Occlusion has always been a challenging research topic in the field of multi‐target tracking. The invisibility of the target in full occlusion increases the difficulty of continuous tracking, which makes the recovery failure when the target is re‐visible, and ultimately leads to a decrease in tracking accuracy. To address full occlusion problem, an effective multi‐object tracking algorithm with full occlusion handle and adaptive fusion features is proposed. Firstly, a spatio‐temporal model is established for full occlusion, and a simple, efficient and training‐free method is proposed to find full occluded targets. Secondly, local high discrimination features with better stability and independence is proposed to realize effective correlation between targets before and after the full occlusion. Finally, an adaptive feature fusion mechanism is proposed, which can adjust feature structure dynamically according to the occlusion state. The experimental results show that most evaluation metrics of the proposed algorithm are superior to those of some typical algorithms proposed in recent years under full occlusion tracking scenes. The proposed algorithm can realize accurate occluded targets identification and improve tracking robustness under short‐term, long‐term and frequent full occlusion.

Titanium alloys have gained popularity in implant dentistry for the restoration of missing teeth and related hard tissues because of their biocompatibility and enhanced strength. However, titanium corrosion and infection caused by microbial biofilms remains a significant clinical challenge leading to implant failure. This study aimed to evaluate the effectiveness of antibiofilm peptides 1018 and DJK-5 on the corrosion resistance of titanium in the presence of Streptococcus mutans. Commercially pure titanium disks were prepared and used to form biofilms. The disks were randomly assigned to different treatment groups (exposed to S. mutans supplied with sucrose) including a positive control with untreated biofilms, peptides 1018 or DJK-5 at concentrations of 5 μg/mL or 10 μg/mL, and a negative control with no S. mutans. Dynamic biofilm growth and pH variation of all disks were measured after one or two treatment periods of 48 h. After incubation, the dead bacterial proportion, surface morphology, and electrochemical behaviors of the disks were determined. The results showed that peptides 1018 and DJK-5 exhibited significantly higher dead bacterial proportions than the positive control group in a concentration dependent manner (p < 0.01), as well as far less defects in microstructure. DJK-5 at 10 μg/mL killed 84.82% of biofilms and inhibited biofilm growth, preventing acidification due to S. mutans and maintaining a neutral pH. Potential polarization and electrochemical impedance spectroscopy data revealed that both peptides significantly reduced the corrosion and passive currents on titanium compared to titanium surfaces with untreated biofilms, and increased the resistance of the passive film (p < 0.05), with 10 μg/mL of DJK-5 achieving the greatest effect. These findings demonstrated that antibiofilm peptides are effective in promoting corrosion resistance of titanium against S. mutans, suggesting a promising strategy to enhance the stability of dental implants by endowing them with antibiofilm and anticorrosion properties.

Glycosylated protein by transglutaminase-type could alter the structures and functional properties of proteins. However, the beneficial effects of glycosylated proteins against alcohol-induced intestinal injury remain unclear. Herein, the protective role and mechanism of glycosylated casein ameliorating alcohol-induced intestinal injury were assessed in vivo. The results showed that glycosylated casein and casein significantly relieved alcohol-induced oxidative stress and inflammatory responses in a concentration-dependent manner. The interventions of glycosylated casein and casein decreased serum parameters, improved the activities of antioxidant enzymes, reduced levels of inflammatory cytokines, and alleviated histopathological impairment in intestine tissues. Glycosylated casein and casein treatment downregulated protein expressions of TLR4, NF-κB p65, IKB-α, and MyD88 in mice, which activated the TLR4/NF-κB signaling pathway as a protective mechanism. More importantly, glycosylated caseinate showed a better effect against alcohol-induced intestinal injury than casein, suggesting that transglutaminase-mediated glycosylation of proteins is a useful technique to enforce protein biofunctions in the intestine.

Abstract Multi‐object tracking (MOT), which uses the context information of image sequences to locate, maintain identities and generate trajectories of multiple targets in each frame, is key technology in the field of computer vision. To address the problems of occlusion and scale variation in low‐viewpoint MOT, OsaMOT is proposed here. First, according to the global occlusion state of each frame, OsaMOT proposes the adaptive anti‐occlusion feature to enhance the awareness and adaptability for occlusion. At the same time, OsaMOT uses the cascade screening mechanism to reduce the “virtual new target” phenomenon due to the dramatic change in target features caused by scale variation and occlusion. Finally, considering that the occluded templates will affect the tracking performance, OsaMOT proposes an adaptive anti‐noise template update mechanism according to the partial occlusion state of the target, which improves the purity of the template library and further enhances the applicability to occlusion. The experimental results show that OsaMOT can weaken the influence of scale variation, partial occlusion, short‐term full occlusion and long‐term full occlusion in the low‐viewpoint tracking scenes. Most evaluation indexes of OsaMOT under low‐viewpoint tracking scenario are superior to those of some typical algorithms proposed in recent years, and the tracking robustness is improved.

Most of the existing blind super-resolution(SR) methods explicitly estimate the kernel in pixel space, which usually has a large deviation and results in poor SR performance. As a seminal work, DASR learns abstract representations to distinguish various degradations in the feature space, which effectively reduces degradation estimation bias. Therefore, we also employ the feature space to extract degradation representations for an ancient painting. However, most of the blind SR mehods, including DASR, are committed to removing degradations introduced by kernels, downsampling and additive noise. Among them, downsampling degradation is often accompanied by unpleasant artifacts. To address this issue, the paper designs a high-resolution(HR) representation encoder EHRbased on contrastive learning to distinguish artifacts introduced by downsampling. Moreover, to optimize the ill-posed nature of blind SR, we propose a contrastive regularization(CR)to minimize the contrastive loss based on VGG-19. With the help of CR, the SR images are pulled closer to the HR images and pushed far away from bicubic LR observations. Benefiting from these improvements, our method consistently achieves higher quantitative performance and better visual quality with more natural textures than state-of-the-art approaches on a specialized painting dataset.

Background Depression, one of the most frequent complications after stroke, increases the disease’s burden and physical disability. Poststroke depression (PSD) is a multifactorial disease with genetic, environmental and biological factors involved in its occurrence. Genetic studies on PSD to date have mainly focused on the monoamine system and brain-derived neurotrophic factors. However, understanding is still limited about the influence of the single nucleotide polymorphism (SNP) of other neurotrophic factors on PSD.Aims The present study aimed to investigate the relationship between seven vascular endothelial growth factor (VEGF) family gene variants that occur with PSD.Methods A multicentre candidate gene study from five hospitals in Jiangsu Province from June 2013 to December 2014 involved 121 patients with PSD and 131 patients with non-PSD. Demographic characteristics and neuropsychological assessments were collected. The χ2 test was used to evaluate categorical variables, while the independent t-test was applied to continuous variables. SNPs in seven genes (VEGFA, VEGFB, KDR, FLT-1, IGF-1, IGF-1R and PlGF) were genotyped. Single-marker association for PSD was analysed by χ2 tests and logistic regression using SPSS and PLINK software.Results Patients with PSD included more women and those with lower education levels, lower body mass indexes, lower Mini-Mental State Examination scores, and higher scores on the 17-item Hamilton Depression Rating Scale than non-PSD patients. Ninety-two SNPs with seven genes were genotyped and passed quality control. The rs7692791 CC genotypes, the C allele of KDR and the rs9282715 T allele of IGF-1R increased the risk for PSD (χ2=7.881, p=0.019; χ2=4.259, p=0.039; χ2=4.222, p=0.040, respectively). In addition, the SNP rs7692791 of KDR was significantly associated with PSD by the logistic regression of an additive model (p=0.015, OR=9.584, 95% CI: 1.549 to 59.31).Conclusions Patients with rs7692791 C allele carriers or the CC genotype of KDR and the rs9282715 T allele of IGF-1R may have PSD susceptibility. Findings such as these may help clinicians to identify the high-risk population for PSD earlier and, thus, enable them to provide more timely interventions.Trial registration number ChiCTR-OCH-13003133.

Upon entering host cells, Salmonella quickly turns off flagella biogenesis to avoid recognition by the host immune system. However, it is not clear which host signal(s) Salmonella senses to initiate flagellum control. Here, we demonstrate that the acid signal can suppress flagella synthesis and motility of Salmonella, and this occurs after the transcription of master flagellar gene flhDC and depends on the anti-FlhDC factor YdiV. YdiV expression is activated after acid treatment. A global screen with ydiV promoter DNA and total protein from acid-treated Salmonella revealed a novel regulator of YdiV, the acid-related transcription factor CadC. Further studies showed that CadCC, the DNA binding domain of CadC, directly binds to a 33 nt region of the ydiV promoter with a 0.2 μM KD affinity. Furthermore, CadC could separate H-NS-ydiV promoter DNA complex to form CadC-DNA complex at a low concentration. Structural simulation and mutagenesis assays revealed that H43 and W106 of CadC are essential for ydiV promoter binding. No acid-induced flagellum control phenotype was observed in cadC mutant or ydiV mutant strains, suggesting that flagellum control during acid adaption is dependent on CadC and YdiV. The intracellular survival ability of cadC mutant strain decreased significantly compared with WT strain while the flagellin expression could not be effectively controlled in the cadC mutant strain when surviving within host cells. Together, our results demonstrated that acid stress acts as an important host signal to trigger Salmonella flagellum control through the CadC-YdiV-FlhDC axis, allowing Salmonella to sense a hostile environment and regulate flagellar synthesis during infection.

Neuroinflammation and anhedonia in major depressive disorder (MDD) are closely connected, though the exact mechanism is unclear. This study aimed to investigate the relationships between cytokines, C-reactive protein (CRP), cortisol, and anhedonia, revealing the potential predictive value in identifying anhedonic MDD. In total, 66 patients with MDD (29 with anhedonia and 37 without anhedonia) and 66 healthy controls (HCs) were included. The severity of depression and anhedonia was evaluated using the Hamilton Rating Scale for Depression-24 (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS), respectively. Serum cytokines were measured using flow cytofluorometric kits, while CRP and cortisol were measured using enzyme-linked immunosorbent assay kits. We found higher serum levels of interleukin-2 (IL-2), IL-6, and cortisol in MDD than in HC where anhedonic MDD was highest. CRP and IL-6 were positively associated with anhedonia, and cortisol levels were related to both anhedonia and depression. A combination of IL-6, CRP, and cortisol had optimal predictive value for distinguishing anhedonic MDD. Anhedonic MDD has unique neuroendocrine-immune characteristics compared with those without anhedonia. The combination of IL-6, CRP, and cortisol might be an early marker to distinguish anhedonic MDD.

ABSTRACT Bacterial flagellin activates the host immune system and triggers pyroptosis. Salmonella reduces flagellin expression when it survives within host cells. Here, we found that the UMPylator YdiU significantly altered the Salmonella flagellar biogenesis process upon host cell entry. The expression levels of class II and class III flagellar genes, but not the class I flagellar genes flhDC, were dramatically increased in a ΔydiU strain compared to wild-type (WT) Salmonella in a host-simulating environment. A direct interaction between YdiU and FlhDC was detected by bacterial two-hybrid assay. Furthermore, YdiU efficiently catalyzed the UMPylation of FlhC but not FlhD, FliA, or FliC. UMPylation of FlhC completely eliminated its DNA-binding activity. In vivo experiments showed that YdiU was required and sufficient for Salmonella flagellar control within host cells. Mice infected with the ΔydiU strain died much earlier than WT strain-infected mice and developed much more severe inflammation and injury in organs and much higher levels of cytokines in blood, demonstrating that early host death induced by the ΔydiU strain is probably due to excessive inflammation. Our results indicate that YdiU acts as an essential factor of Salmonella to mediate host immune escape. IMPORTANCE Salmonella is an important facultative pathogen of foodborne illness and typhoid fever in humans. Flagella allow bacterial motility and are required for Salmonella to successfully invade the host cells. In parallel, flagellin triggers the host immune system. Salmonella reduces flagellar biogenesis to avoid detection within host cells by a largely unknown mechanism. Here, we report that the UMPylator YdiU inhibits flagellin expression in response to host signals in an UMPylation-dependent manner. The target of YdiU is the major flagellar transcription factor FlhDC. YdiU UMPylates the FlhC subunit on its Ser31 residue and prevents FlhDC from binding to flagellar genes, thus switching off flagellar biogenesis. Our results reveal a novel mechanism by which Salmonella adopts posttranslational modification to shut down flagellar synthesis as a strategy to achieve immune escape.

ABSTRACT Iron limitation is a universal strategy of host immunity during bacterial infection. However, the mechanisms by which pathogens antagonize host nutritional immunity have not been fully elucidated. Here, we identified a requirement for the UMPylator YdiU for this process in Salmonella. The expression of YdiU was dramatically induced by the metal starvation signal. The intracellular iron content was much lower in the ΔydiU strain than in wild-type Salmonella, and the ΔydiU strain exhibited severe growth defect under metal deficiency environments. Genome-wide expression analyses revealed significantly decreased expression of iron uptake genes in ΔydiU strain compared with the wild-type strain. Interestingly, YdiU did not affect the expression level of the major iron uptake regulator Fur but directly UMPylated Fur on its H118 residue in vivo and in vitro. UMPylation destroyed the Fur dimer, promoted Fur aggregation, and eliminated the DNA-binding activity of Fur, thus abolishing the ability of Fur to inhibit iron uptake. Restricting Fur to the deUMPylated state dramatically eliminates Salmonella iron uptake in iron deficiency environments. In parallel, YdiU facilitates Salmonella survival within host cells by regulating the iron uptake pathway. IMPORTANCE Salmonella is the major pathogen causing bacterial enteric illness in both humans and animals. Iron availability is strictly controlled upon Salmonella entry into host cells. The mechanisms by which Salmonella balances the acquisition of sufficient iron while preventing a toxic overload has not been fully understood. Here, we reveal a novel regulation process of iron acquisition mediated by the UMPylator YdiU. Fur acts as the central regulator of bacterial iron homeostasis. YdiU UMPylates Fur on H118 and prevents Fur from binding to target DNA, thus activating the expression of iron uptake genes under iron-deficient conditions. We describe the first posttranslational modification-based regulation of Fur and highlight a potential mechanism by which Salmonella can adapt to eliminate host nutritional immunity.

Chronic stress is a significant cause of depression, anxiety, and intestinal mucosal injury. Gut microbiota disturbances are also associated with these disorders. Shugan Hewei Decoction (SHD), which is a traditional Chinese medicine formula developed by our team, has shown superior therapeutic effects in the treatment of depression, anxiety, and functional gastrointestinal diseases caused by chronic stress. In this study, we investigated the modulatory effect of SHD on the cecal microbiota and cecum mucosal NOD-like receptor protein 3 (NLRP3) inflammasome in a chronic unpredictable stress (CUS)/social isolation rat model. After the SHD intervention, the CUS model rats showed improvements in their depressive- and anxiety-like behaviors, as well as sustained body weight growth and improved fecal characteristics. SHD improved the cecal microbiota diversity and changed the abundance of six microbial genera. A Spearman’s correlation analysis showed a strong correlation between the NLRP3 inflammasome and CUS-perturbed cecal biomarker microbiota. SHD regulated the excessive expression of NLRP3, ASC, caspase-1, interleukin-1β (IL-1β), and IL-18 in the serum and cecum mucosa induced by CUS, as well as the activation of the Toll-like receptor 4/nuclear factor-κB signaling cascades. Our results reveal the pharmacological mechanisms of SHD and provide a validated therapeutic method for the treatment of depression, anxiety, and cecum mucosal injury.

As the complexity and cost of industrial systems continue to increase, so does the need for the safety and reliability of industrial systems. In recent years, in the field of mechanical fault diagnosis, methods based on deep learning are gradually gaining popularity. The traditional deep learning method assumes that the training set and the test set belong to the same working condition, which is contrary to the actual industrial process. In order to improve the general ability of the fault diagnosis model, researchers start to study the domain adaptation method. However, most domain adaptation methods do not impose constraints on the test set, which leads to the occurrence of the domain mismatch problem. This paper proposes a multi-source consistency domain adaptation neural network MCDANN, which uses sub-domain division alignment and multi-source prediction consistency to achieve fine-grained domain matching and improve the transfer accuracy of the model. This paper conducts domain adaptation experiments on the open-source bearing fault dataset CWRU and DIRG bearing dataset and compares them with other classical methods. Experiments show that in the case of a signal-to-noise ratio of −4, the MCDANN model achieves an average diagnostic accuracy of more than 96% on the CWRU dataset and the DIRG dataset on noisy fault signals from the target domain, and is superior in almost all fields than other adaptive models.

As an important part of human cultural heritage, many ancient paintings have suffered from various deteriorations that have led to texture blurring, color fading, etc. Single image super-resolution (SISR) which aims to recover a high-resolution (HR) version from a low-resolution (LR) input is actively engaged in the digital preservation of cultural relics. Currently, only traditional super-resolution is widely studied and used in cultural heritage, and it is difficult to apply learning-based SISR to unique historical paintings because of the absence of both ground truth and datasets. Fortunately, the recently proposed ZSSR method suggests that it is feasible to generate a small dataset and extract self-supervised information from a single image. However, when applied to the preservations of historical paintings, the performance of ZSSR is highly limited due to the lack of image knowledge. To address the above issues and to unleash the great potential of learning-based methods in heritage conservation, we present Ref-ZSSR, which is the first attempt to combine zero-shot and reference-based methods to achieve SISR. In our model, both global and local multi-scale similar information is fully exploited from the painting itself. In an end-to-end manner, this information provides consistent artistic style image knowledge and helps synthesize SR images with sharp texture details. Compared with the ZSSR method, our approach shows improvement in both precision (approximately 4.68 dB for scale ×2) and visual perception. It is worth mentioning that all image knowledge required in our method can be extracted from the painting itself, i.e., external examples are not required. Therefore, this approach can be easily generalized to any damaged historical paintings, broken murals, noisy old photos, incomplete art works, etc.

BackgroundSubjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI) are regarded to be at high risk of converting to Alzheimer’s disease (AD). Amplitude of low-frequency fluctuations (ALFF) can reflect functional deterioration while diffusion tensor imaging (DTI) is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.MethodsWe analyzed ALFF under slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz) bands and white matter fiber integrity among normal controls (CN), SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.ResultsFor ALFF calculation, ascended ALFF values were detected in the lingual gyrus (LING) and superior frontal gyrus (SFG) within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus (UF) in aMCI patients and within the superior longitudinal fasciculus (SLF) in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.ConclusionsSCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression.

BackgroundSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) were considered to be a continuum of Alzheimer’s disease (AD) spectrum. The abnormal topological architecture and rich-club organization in the brain functional network can reveal the pathology of the AD spectrum. However, few studies have explored the disrupted patterns of diverse club organizations and the combination of rich- and diverse-club organizations in SCD and aMCI.MethodsWe collected resting-state functional magnetic resonance imaging data of 19 SCDs, 29 aMCIs, and 28 healthy controls (HCs) from the Alzheimer’s Disease Neuroimaging Initiative. Graph theory analysis was used to analyze the network metrics and rich- and diverse-club organizations simultaneously.ResultsCompared with HC, the aMCI group showed altered small-world and network efficiency, whereas the SCD group remained relatively stable. The aMCI group showed reduced rich-club connectivity compared with the HC. In addition, the aMCI group showed significantly increased feeder connectivity and decreased local connectivity of the diverse club compared with the SCD group. The overlapping nodes of the rich club and diverse club showed a significant difference in nodal efficiency and shortest path length (Lp) between groups. Notably, the Lp values of overlapping nodes in the SCD and aMCI groups were significantly associated with episodic memory.ConclusionThe present study demonstrates that the network properties of SCD and aMCI have varying degrees of damage. The combination of the rich club and the diverse club can provide a novel insight into the pathological mechanism of the AD spectrum. The altered patterns in overlapping nodes might be potential biomarkers in the diagnosis of the AD spectrum.

Summary: Sensing stressful conditions and adjusting the cellular metabolism to adapt to the environment are essential activities for bacteria to survive in variable situations. Here, we describe a stress-related protein, YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine-5′-monophosphate to a protein tyrosine/histidine residue, an unusual modification defined as UMPylation. Mn2+ serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+ binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function. Consistent with the recent finding that YdiU acts as an AMPylator, we further demonstrate that the self-AMPylation of YdiU padlocks its chaperone-UMPylation activity. A detailed mechanism is proposed based on the crystal structures of Apo-YdiU and YdiU-AMPNPP-Mn2+ and on molecular dynamics simulation models of YdiU-UTP-Mn2+ and YdiU-UTP-peptide. In vivo data demonstrate that YdiU effectively protects Salmonella from stress-induced ATP depletion through UMPylation.

Study on fish behavior is essential to fishery development and water environment protection. Quantitative analysis of fish behavior is impossible without information on fish trajectories. Although the computer vision techniques have provided an effective approach to the collection of fish trajectories, it is still challenging to track fish groups accurately and robustly due to fish appearance variations and frequent occlusions. In this paper, a skeleton-based method for 3-D tracking of fish group is proposed. First, skeleton analysis is performed to simplify the top- and side-view objects into representation of feature points. Next, the feature points under the top view are associated to obtain the top-view trajectories of objects. Finally, the epipolar constraint and the motion continuity constraint are used to match the top-view trajectories with the side-view feature points, thereby obtaining the 3-D trajectories of objects. Experimental results demonstrate the ability of the proposed method to track fish group more effectively than other state-of-the-art methods.

Abstract Natural killer (NK) cells represent a subset of lymphocytes that contribute to innate immunity and have been reported to play a role in autoimmune uveitis. However, the mechanisms regulating NK cellular function in this condition remain unclear. Herein, we investigated the status of NK cells in experimental autoimmune uveitis (EAU). We found that the number of CD83+CD3−NK1.1+ cells was increased in the inflamed eyes and spleens of the EAU mouse model. At the recovery stage of EAU, serum concentrations of soluble CD83 (sCD83) were increased. sCD83 treatment relieved retinal tissue damage and decreased the number of infiltrating NK cells in inflamed eyes. Further analysis of the effects of sCD83 treatment in EAU revealed that it reduced: 1) the expressions of CD11b and CD83 in NK cells, 2) the percent of CD11bhighCD27lowCD3−NK1.1+ cells and 3) the secretion of granzyme B, perforin and IFN-γ in NK cells as demonstrated both in vivo and in vitro. When sCD83 treated-NK cells were transferred into EAU mice, retinal tissue damage was relieved. These results demonstrate sCD83 down-regulate NK cellular function and thus provide important, new information regarding the means for the beneficial effects of this agent in the treatment of autoimmune uveitis.

Abstract Previous studies have indicated that the level of glial cell line-derived neurotrophic factor (GDNF) may be correlated with stroke and depression. Here, we investigated whether GDNF can be a discriminant indicator for post stroke depression (PSD). 159 participants were divided into four groups: PSD, stroke without depression (Non-PSD), major depressive disorder (MDD) and normal control (NC) group, and the protein and mRNA expression levels of GDNF in serum were measured. The results showed that only MDD group had statistical difference in protein and mRNA levels compared with the other three groups (Bonferroni test, P

Abstract Mental disorders are severe, disabling conditions with unknown etiology and are commonly misdiagnosed when clinical symptomology criteria are solely used. Our previous work indicated that combination of serum levels of multiple proteins in tissue plasminogen activator (tPA)-brain-derived neurotrophic factor (BDNF) pathway improved accuracy of diagnosis of major depressive disorder (MDD). Here, we measured serum levels of tPA, plasminogen activator inhibitor-1 (PAI-1), BDNF, precursor-BDNF (proBDNF), tropomyosin-related kinase B (TrkB) and neurotrophin receptor p75 (p75NTR) in patients with paranoid schizophrenia (SZ, n = 34), MDD (n = 30), bipolar mania (BM, n = 30), bipolar depression (BD, n = 22), panic disorder (PD, n = 30), and healthy controls (HCs, n = 30) by Enzyme-linked immunosorbent assay kits. We used receiver operating characteristic (ROC) curve to analyze diagnostic potential of these proteins. We found, compared with HCs, that serum tPA and proBDNF were lower in SZ, BM and BD; TrkB was lower in SZ and BD; and p75NTR was declined in SZ and BM. ROC analysis showed that combined serum level of tPA, PAI-1, BDNF, proBDNF, TrkB and p75NTR was better than any single protein in accuracy of diagnosis and differentiation, suggesting that the combination of multiple serum proteins levels in tPA-BDNF pathway may have a potential for a diagnostic panel in mental disorders.

Background: The early progression continuum of Alzheimer’s disease (AD) has been considered to advance through subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI). Altered functional connectivity (FC) in the default mode network (DMN) is regarded as a hallmark of AD. Furthermore, the DMN can be divided into two subnetworks, the anterior and posterior subnetworks. However, little is known about distinct disruptive patterns in the subsystems of the DMN across the preclinical AD spectrum. This study investigated the connectivity patterns of anterior DMN (aDMN) and posterior DMN (pDMN) across the preclinical AD spectrum.Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the FC in the DMN subnetworks in 20 healthy controls (HC), eight SCD, 11 naMCI, and 28 aMCI patients. Moreover, a correlation analysis was used to examine associations between the altered connectivity of the DMN subnetworks and the neurocognitive performance.Results: Compared to the HC, SCD patients showed increased FC in the bilateral superior frontal gyrus (SFG), naMCI patients showed increased FC in the left inferior parietal lobule (IPL), and aMCI patients showed increased FC in the bilateral IPL in the aDMN; while SCD patients showed decreased FC in the precuneus, naMCI patients showed increased FC in the left middle temporal gyrus (MTG), and aMCI patients also showed increased FC in the right middle frontal gyrus (MFG) in the pDMN. Notably, the FC between the ventromedial prefrontal cortex (vmPFC) and the left MFG and the IPL in the aDMN was associated with episodic memory in the SCD and aMCI groups. Interestingly, the FC between the posterior cingulated cortex (PCC) and several regions in the pDMN was associated with other cognitive functions in the SCD and naMCI groups.Conclusions: This study demonstrates that the three preclinical stages of AD exhibit distinct FC alternations in the DMN subnetworks. Furthermore, the patient group data showed that the altered FC involves cognitive function. These findings can provide novel insights for tailored clinical intervention across the preclinical AD spectrum.

In this paper, a combined organic Rankine cycle (ORC) system that can effectively utilize the cold energy of Liquefied Nature Gas (LNG) and the waste heat of dual fuel (DF) marine engine was proposed. Particularly, the engine exhaust gas and the jacket cooling water of the DF marine engine were used as heat sources. Firstly, a thorough assessment of thermo-economic performance was conducted for the combined ORC system using 11 environmentally friendly working fluids (WFs). Afterwards, the effects of evaporation and condensation pressures on the net output work, energy efficiency, exergy efficiency, total investment cost and payback period were examined. Furthermore, the thermo-economic performances of the ORC system were optimized via multi-objective optimization with a genetic algorithm. Finally, exergy destructions and investment costs of each component under the optimal operating conditions were analyzed to make suggestions for further improvement. The results show that R1150-R1234yf-R600a and R170-R1270-R152a are the two most promising WF combinations. The exergy destruction of the combined ORC system mainly exists in heat exchangers. Through WF optimization, the exergy destruction in the intermediate heat exchanger was reduced by 18.99%. The proportion of expanders investment cost could be greater than 50% and the payback period of the combined ORC system varies in the range of 7.68−9.43 years. This study demonstrated that the selection of WF and the optimization of operating conditions had important potential to improve thermo-economic performances of ORC systems.

Soluble CD83 (sCD83) is the extracellular domain of the membrane-bound CD83 molecule, and known for its immunoregulatory functions. Whether and how sCD83 participates in the pathogenesis of uveitis, a serious inflammatory disease of the eye that can cause visual disability and blindness, is unknown. By flow cytometry and imaging studies, we show that sCD83 alleviates experimental autoimmune uveitis (EAU) through a novel mechanism. During onset and recovery of EAU, the level of sCD83 rises in the serum and aqueous humor, and CD83+ leukocytes infiltrate the inflamed eye. Systemic or topical application of sCD83 exerts a protective effect by decreasing inflammatory cytokine expression, reducing ocular and splenic leukocyte including CD4+ T cells and dendritic cells (DCs). Mechanistically, sCD83 induces tolerogenic DCs by decreasing the synaptic expression of co-stimulatory molecules and hampering the calcium response in DCs. These changes are caused by a disruption of the cytoskeletal rearrangements at the DC–T cell contact zone, leading to altered localization of calcium microdomains and suppressed T-cell activation. Thus, the ability of sCD83 to modulate DC-mediated inflammation in the eye could be harnessed to develop new immunosuppressive therapeutics for autoimmune uveitis.

Background: Asthma is a chronic disease appeared to be associated with depression. But the underpinnings of depression in asthma remain unknown. In order to understand the neural mechanisms of depression in asthma, we used cerebral blood flow (CBF) to probe the difference between depressed asthmatic (DA) and non-depressed asthmatic (NDA) patients.Methods: Eighteen DA patients, 24 NDA patients and 57 healthy controls (HC) received pulsed arterial spin labeling (pASL) scan for measuring CBF, resting-state functional magnetic resonance imaging (rs-fMRI) scan, severity of depression and asthma control assessment, respectively.Results: Compared to NDA, DA patients showed increased regional CBF (rCBF) in the right cerebellum posterior lobe. Compared to HC, DA, and NDA patients all showed significantly decreased rCBF in the right cerebellum posterior lobe.Conclusions: We showed the first evidence of altered rCBF in the right cerebellum posterior lobe in asthma using pASL, which appeared to be involved in the neuropathology in asthma.Clinical Trial Registration: An investigation of therapeutic mechanism in asthmatic patients: based on the results of Group Cognitive Behavioral Therapy (Registration number: ChiCTR-COC-15007442) (http://www.chictr.org.cn/usercenter.aspx).

Background and Purpose. Recent studies suggest that abnormal structure and function in the brain network were related to cognitive and emotional impairment in hyperthyroid patients (HPs). The association between altered voxel-mirrored homotopic connectivity (VMHC) and neuropsychological impairment in HPs remains unclear. This study is aimed at investigating the association between the disrupted functional coordination and psychological dysfunction in hyperthyroidism. Method. Thirty-three hyperthyroid patients and thirty-three matched healthy controls (HCs) were recruited, and they received resting-state functional magnetic resonance imaging (fMRI) scans and neuropsychological evaluation. The VMHC value was computed to reveal the functional coordination between homotopic regions in both groups. The neurobehavioral relevancy method was employed to explore the relationship between the altered VMHC and emotional, cognition measures. Further receiver operating characteristic (ROC) curve analysis was adopted to examine the power of changed regional VMHC in classifying the patients with hyperthyroidism. Results. Compared with the HCs, the HPs exhibited significantly declined VMHC values in the bilateral medial frontal gyrus (MeFG). The interhemispheric asynchrony in the MeFG was positively correlated with Z scores of episodic memory. The ROC analysis further determined that abnormal VMHC in the MeFG could efficiently distinguish the HPs from the HCs (area under the curve AUC=0.808, P

Objective. To explore the underlying mechanism of depression in asthmatic patients, the ReHo in the insula and its FC was used to probe the differences between depressed asthmatic (DA) and nondepressed asthmatic (NDA) patients. Methods. 18 DA patients, 24 NDA patients, and 60 healthy controls (HCs) received resting-state fMRI scan, severity of depression, and asthma control assessment. Results. DA patients showed increased FC between the left ventral anterior insula (vAI) and the left middle temporal gyrus compared with both NDA and HC groups. In addition, compared with HCs, the DA and NDA patients both exhibited increased FC between the left vAI and the right anterior cingulate cortex (ACC), decreased FC between the left vAI and the bilateral parietal lobe, and increased FC between the right vAI and the left putamen and the right caudate, respectively. Furthermore, the increased FC between the left vAI and the right ACC could differentiate HCs from both DA and NDA patients, and the increased FC between the right vAI and both the left putamen and the right caudate could separate NDA patients from HCs. Conclusions. This study confirmed that abnormal vAI FC may be involved in the neuropathology of depression in asthma. The increased FC between the left vAI and the left MTG could distinguish DA from the NDA and HC groups.

BACKGROUND: Major depressive disorder (MDD) is associated with decreased function of cortico-limbic circuits, which play important roles in the pathogenesis of MDD. Abnormal functional connectivity (FC) with the amygdala, which is involved in cortico-limbic circuits, has also been observed in MDD. However, little is known about connectivity alterations in late-onset depression (LOD) or whether disrupted connectivity is correlated with cognitive impairment in LOD. METHODS AND RESULTS: A total of twenty-two LOD patients and twenty-two matched healthy controls (HC) underwent neuropsychological tests and resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and FC with bilateral amygdala seeds were used to analyze blood oxygen level-dependent fMRI data between two groups. Compared with HC, LOD patients showed decreased ReHo in the right middle frontal gyrus and left superior frontal gyrus. In the LOD group, the left amygdala had decreased FC with the right middle frontal gyrus and the left superior frontal gyrus in the amygdala positive network, and it had increased FC with the right post-central gyrus in the amygdala negative network. However, significantly reduced FC with the right amygdala was observed in the right middle occipital gyrus in the amygdala negative network. Further correlative analyses revealed that decreased FC between the amygdala and the right middle occipital gyrus was negatively correlated with the verbal fluency test (VFT, r = -0.485, P = 0.022) and the digit span test (DST, r = -0.561, P = 0.007). CONCLUSIONS: Our findings of reduced activity of the prefrontal gyrus and abnormal FC with the bilateral amygdala may be key markers of cognitive dysfunction in LOD patients.