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Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota–brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. We found that SD-induced gut dysbiosis, inflammatory responses, and cognitive impairment in humans. Moreover, the absence of the gut microbiota suppressed inflammatory response and cognitive impairment induced by SD in germ-free (GF) mice. Transplantation of the “SD microbiota” into GF mice activated the Toll-like receptor 4/nuclear factor-κB signaling pathway and impaired cognitive function in the recipient mice. Mice that harbored “SD microbiota” also exhibited increases in neuroinflammation and microglial activity in the hippocampus and medial prefrontal cortex. These findings indicate that gut dysbiosis contributes to both peripheral and central inflammatory processes and cognitive deficits that are induced by SD, which may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.

The treatments for early-onset scoliosis (EOS) remain great challenges for spine surgeons. This study aimed to comprehensively review the treatments for EOS, especially the advancements made in the last decade. Current studies on EOS were retrieved through a search on PubMed, UpToDate, the Web of Science Core Collection and Scopus were reviewed. The most pertinent information related to the current treatments for EOS was collected. The foci of treatments for EOS have included creating a well-developed thoracic cavity, improving lung volume, and improving pulmonary function. Conservative treatments include bracing, casting, halo-gravity traction, and physiotherapy. Serial casting is the most effective conservative treatment for EOS. Surgical treatments mainly include growth-friendly techniques, which are generally classified into three types according to the amount of correction force applied: distraction-based, compression-based, and growth-guided. The distraction-based systems include traditional or conventional growing rods, magnetically controlled growing rods, and vertical expandable prosthesis titanium ribs. The compression-based systems include vertebral body stapling and tethering. The growth-guided systems include the Shilla system and modern Luque trolley. In addition, some newer techniques have emerged in recent years, such as posterior dynamic deformity correction (ApiFix). For EOS patients presenting with sharp deformities in a long, congenital spinal deformity, a hybrid technique, one-stage posterior osteotomy with short segmental fusion and dual growing rods, may be a good choice. Hemivertebra resection is the gold standard for congenital scoliosis caused by single hemivertebra. Although the patient's growth potential is preserved in growth-friendly surgeries, a high complication rate should be expected, as well as a prolonged treatment duration and additional costs. Knowledge about EOS and its treatment options is rapidly expanding. Conservative treatments have specific limitations. For curves requiring a surgical intervention, surgical techniques may vary depending on the patients' characteristics, the surgeon's experience, and the actual state of the country.

Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder. The pathogenesis of IBD is not yet clear. Studies have shown that the imbalance between T helper 17 (Th17) and regulatory T (Treg) cells, which differentiate from CD4+ T cells, contributes to IBD. Th17 cells promote tissue inflammation, and Treg cells suppress autoimmunity in IBD. Therefore, Th17/Treg cell balance is crucial. Some regulatory factors affecting the production and maintenance of these cells are also important for the proper regulation of the Th17/Treg balance; these factors include T cell receptor (TCR) signaling, costimulatory signals, cytokine signaling, bile acid metabolites, and the intestinal microbiota. This article focuses on our understanding of the function and role of the balance between Th17/Treg cells in IBD and these regulatory factors and their clinical significance in IBD.

Autoimmune diseases encompass a wide range of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, which cause inflammation and multiple organ involvement. However, its pathogenesis remains unelucidated. Furthermore, the cumulative medical and economic burden of autoimmune diseases is on the rise, making these diseases a ubiquitous global phenomenon that is predicted to further increase in the coming decades. Coumarins, a class of aromatic natural products with benzene and alpha-pyrone as their basic structures, has good therapeutic effects on autoimmune diseases. In this review, we systematically highlighted the latest evidence on coumarins and autoimmune diseases data from clinical and animal studies. Coumarin acts on immune cells and cytokines and plays a role in the treatment of autoimmune diseases by regulating NF-κB, Keap1/Nrf2, MAPKs, JAK/STAT, Wnt/β-catenin, PI3K/AKT, Notch and TGF-β/Smad signaling pathways. This systematic review will provide insight into the interaction of coumarin and autoimmune diseases, and will lay a groundwork for the development of new drugs for autoimmune diseases.

Background The key to modern drug discovery is to find, identify and prepare drug molecular targets. However, due to the influence of throughput, precision and cost, traditional experimental methods are difficult to be widely used to infer these potential Drug-Target Interactions (DTIs). Therefore, it is urgent to develop effective computational methods to validate the interaction between drugs and target. Methods We developed a deep learning-based model for DTIs prediction. The proteins evolutionary features are extracted via Position Specific Scoring Matrix (PSSM) and Legendre Moment (LM) and associated with drugs molecular substructure fingerprints to form feature vectors of drug-target pairs. Then we utilized the Sparse Principal Component Analysis (SPCA) to compress the features of drugs and proteins into a uniform vector space. Lastly, the deep long short-term memory (DeepLSTM) was constructed for carrying out prediction. Results A significant improvement in DTIs prediction performance can be observed on experimental results, with AUC of 0.9951, 0.9705, 0.9951, 0.9206, respectively, on four classes important drug-target datasets. Further experiments preliminary proves that the proposed characterization scheme has great advantage on feature expression and recognition. We also have shown that the proposed method can work well with small dataset. Conclusion The results demonstration that the proposed approach has a great advantage over state-of-the-art drug-target predictor. To the best of our knowledge, this study first tests the potential of deep learning method with memory and Turing completeness in DTIs prediction.

Background Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients’ lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. Methods Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. Results Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Conclusion This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

The apple target recognition algorithm is one of the core technologies of the apple picking robot. However, most of the existing apple detection algorithms cannot distinguish between the apples that are occluded by tree branches and occluded by other apples. The apples, grasping end-effector and mechanical picking arm of the robot are very likely to be damaged if the algorithm is directly applied to the picking robot. Based on this practical problem, in order to automatically recognize the graspable and ungraspable apples in an apple tree image, a light-weight apple targets detection method was proposed for picking robot using improved YOLOv5s. Firstly, BottleneckCSP module was improved designed to BottleneckCSP-2 module which was used to replace the BottleneckCSP module in backbone architecture of original YOLOv5s network. Secondly, SE module, which belonged to the visual attention mechanism network, was inserted to the proposed improved backbone network. Thirdly, the bonding fusion mode of feature maps, which were inputs to the target detection layer of medium size in the original YOLOv5s network, were improved. Finally, the initial anchor box size of the original network was improved. The experimental results indicated that the graspable apples, which were unoccluded or only occluded by tree leaves, and the ungraspable apples, which were occluded by tree branches or occluded by other fruits, could be identified effectively using the proposed improved network model in this study. Specifically, the recognition recall, precision, mAP and F1 were 91.48%, 83.83%, 86.75% and 87.49%, respectively. The average recognition time was 0.015 s per image. Contrasted with original YOLOv5s, YOLOv3, YOLOv4 and EfficientDet-D0 model, the mAP of the proposed improved YOLOv5s model increased by 5.05%, 14.95%, 4.74% and 6.75% respectively, the size of the model compressed by 9.29%, 94.6%, 94.8% and 15.3% respectively. The average recognition speeds per image of the proposed improved YOLOv5s model were 2.53, 1.13 and 3.53 times of EfficientDet-D0, YOLOv4 and YOLOv3 and model, respectively. The proposed method can provide technical support for the real-time accurate detection of multiple fruit targets for the apple picking robot.

A bstract We propose to utilize angularity distributions in Higgs boson decay to probe light quark Yukawa couplings at e + e − colliders. Angularities τ a are a class of 2-jet event shapes with variable and tunable sensitivity to the distribution of radiation in hadronic jets in the final state. Using soft-collinear effective theory (SCET), we present a prediction of angularity distributions from Higgs decaying to quark and gluon states at e + e − colliders to NNLL + 𝒪( α s ) accuracy. Due to the different color structures in quark and gluon jets, the angularity distributions from H → and H → gg show different behaviors and can be used to constrain the light quark Yukawa couplings. We show that the upper limit of light quark Yukawa couplings could be probed to the level of ~ 15% of the bottom quark Yukawa coupling in the Standard Model in a conservative analysis window far away from nonperturbative effects and other uncertainties; the limit can be pushed to ≲ 7 – 9% with better control of the nonperturbative effects especially on gluon angularity distributions and/or with multiple angularities.

Higher-order topological insulators have recently witnessed rapid progress in various fields ranging from condensed matter physics to electric circuits. A well-known higher-order state is the second-order topological insulator in three dimensions with gapless states localized on the hinges. A natural question in the context of nonlinearity is whether solitons can exist on the hinges in a second-order topological insulator. Here we theoretically demonstrate the existence of stable solitons localized on the hinges of a second-order topological insulator in three dimensions when nonlinearity is involved. By means of systematic numerical study, we find that the soliton has strong localization in real space and propagates along the hinge unidirectionally without changing its shape. We further construct an electric network to simulate the second-order topological insulator. When a nonlinear inductor is appropriately involved, we find that the system can support a bright soliton for the voltage distribution demonstrated by stable time evolution of a voltage pulse.

Accumulating evidence suggests that both sleep loss and gut dysbiosis can lead to metabolic disorders. However, less is known about the impact of total sleep deprivation (SD) and sleep recovery on the composition, function, and metabolic dynamics of the gut microbiota. Specific-pathogen free Sprague-Dawley rats were subjected to 48 h of SD with gentle handling and then allowed to recover for 1 week. Taxonomic profiles of fecal microbiota were obtained at baseline, 24 h of SD, 48 h of SD, and 1 week of recovery. We used 16 rRNA gene sequencing to analyze the gut microbial composition and function and further characterize microbiota-derived metabolites in rats. The microbiota composition analysis revealed that gut microbial composition and metabolites did not change in the rats after 24 h of SD but were significantly altered after 48 h of SD. These changes were reversible after 1 week of sleep recovery. A functional analysis was performed based on Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations, indicating that 19 KEGG pathways were significantly altered in the gut microbiota in SD rats. These functional changes occurred within 24 h of SD, were more apparent after 48 h of SD, and did not fully recover after 1 week of sleep recovery. These results indicate that acute total SD leads to significant compositional and functional changes in the gut microbiota, and these changes are reversible.