Search

This paper addresses the self-supervised learning of several critical factors in Visual Simultaneous Localization and Mapping (VSLAM) in low-level vision: interest point learning, descriptor learning, ego-motion estimation, and depth estimation. The key insight we have is that appearance and geometry constraints can be used to couple these fundamental vision issues. We propose a self-supervised framework for joint training of neural networks for multiple objectives to address complicated issues, simplify systems, and provide important information for deep monocular VSLAM systems. First, we input two adjacent images into pose and depth networks to obtain their corresponding depth maps and camera poses. Then, we employ a differentiable geometry module and utilize the depth maps and camera poses to generate pseudo-input images needed for the interest point network and construct the geometry loss. Further, we input the pseudo-input image and source image into the interest point network to obtain the corresponding interest points, descriptors, and scores. Subsequently, we construct the appearance loss. Finally, we combine the geometry and appearance losses to constrain the whole network in an unsupervised manner. The novelty of this paper is that it integrates the key information necessary in monocular VSLAM into a unified framework that takes into account interest point learning, descriptor learning, ego-motion estimation, and depth estimation at the same time. Without providing any ground truth, our model can combine sub-problems for self-supervised learning and achieve state-of-the-art performance in their respective domains. [ABSTRACT FROM AUTHOR]

Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection. Superoxide dismutase 3 is elevated in patients and animals infected by protozoan parasites such as Plasmodium. Here, Li et al. show that SOD3 expression is associated with experimental cerebral malaria and inhibition of host immune responses. [ABSTRACT FROM AUTHOR]

Background: The human sortilin protein is an important drug target and detection marker for cancer research. The sortilin from Toxoplasma gondii transports proteins associated with the apical organelles of the parasite. In this study, we aimed to determine the intracellular localization and structural domains of T. gondii sortilin, which may mediate protein transportation. Approaches to the functional inhibition of sortilin to establish novel treatments for T. gondii infections were explored. Methods: A gene encoding the sortilin protein was identified in the T. gondii genome. Immunoprecipitation and mass spectrometry were performed to identify the protein species transported by T. gondii sortilin. The interaction of each structural domain of sortilin with the transported proteins was investigated using bio-layer interferometry. The binding regions of the transported proteins in sortilin were identified. The effect of the sortilin inhibitor AF38469 on the infectivity of T. gondii was investigated. The binding site of AF38469 on sortilin was determined. Results: The subdomains Vps10, sortilin-C, and sortilin-M of the sortilin were identified as the binding regions for intracellular transportation of the target proteins. The sortilin inhibitor AF38469 bound to the Vps10 structural domain of T. gondii sortilin, which inhibited parasite invasion, replication, and intracellular growth in vitro and was therapeutic in mice infected with T. gondii. Conclusion: The Vps10, sortilin-C, and sortilin-M subdomains of T. gondii sortilin were identified as functional regions for intracellular protein transport. The binding region for the sortilin inhibitor AF38469 was also identified as the Vps10 subdomain. This study establishes sortilin as a promising drug target against T. gondii and provides a valuable reference for the development of anti-T. gondii drug-target studies. [ABSTRACT FROM AUTHOR]

Aim: Tyrosine decarboxylase (TDC) presented in the gut‐associated strain Enterococcus faecalis can convert levodopa (L‐dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L‐dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria‐mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L‐dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L‐dopa on Parkinson's disease (PD). Methods: Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis. Then, the inhibitory effects of PIP on L‐dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L‐dopa and PIP on 6‐hydroxydopamine (6‐OHDA)‐lesioned rats and tested the regulations of L‐dopa bioavailability and brain DA level by pharmacokinetics study and MALDI‐MS imaging. Finally, we evaluated the microbiota‐dependent improvement effect of PIP on L‐dopa availability using pseudo‐germ‐free and E. faecalis‐transplanted rats. Results: We found that PIP combined with L‐dopa could better ameliorate the move disorders of 6‐OHDA‐lesioned rats by remarkably improving L‐dopa availability and brain DA level than L‐dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L‐dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6‐OHDA‐lesioned rats. Conclusion: Oral administration of L‐dopa combined with PIP can improve L‐dopa availability and brain DA level in 6‐OHDA‐lesioned rats by suppressing intestinal bacterial TDC. [ABSTRACT FROM AUTHOR]

The uncertainty and unknowability of emerging infectious diseases have caused many major public health and security incidents in recent years. As a new tick‐borne disease, Dabieshan tick virus (DBTV) necessitate systematic epidemiological and spatial distribution analysis. In this study, tick samples from Liaoning Province were collected and used to evaluate distribution of DBTV in ticks. Outbreak points of DBTV and the records of the vector Haemaphysalis longicornis in China were collected and used to establish a prediction model using niche model combined with environmental factors. We found that H. longicornis and DBTV were widely distributed in Liaoning Province. The risk analysis results showed that the DBTV in the eastern provinces of China has a high risk, and the risk is greatly influenced by elevation, land cover, and meteorological factors. The risk geographical area predicted by the model is significantly larger than the detected positive areas, indicating that the etiological survey is seriously insufficient. This study provided molecular and important epidemiological evidence for etiological ecology of DBTV. The predicted high‐risk areas indicated the insufficient monitoring and risk evaluation and the necessity of future monitoring and control work. [ABSTRACT FROM AUTHOR]

Scale ambiguity is a difficulty in monocular visual odometry. This challenge has not yet been well solved, regardless of whether it is a traditional method or a learning-based method. Simultaneously, the performance of unsupervised monocular visual odometry in tricky situations is limited. To tackle these issues, we propose an accurate and efficient end-to-end system that can favorably deal with the problem of scale ambiguity in unsupervised monocular visual odometry, particularly in long-sequence videos in challenging environments. To acquire the depth map and optical flow, we first employ the depth network and the optical flow network. Then, we combine the optical flow information and the camera height using a ground plane geometric model to recover the absolute scale of the camera translation and depth map using our scale recovery algorithm. Finally, we use the recovered scale and our flow-depth loss to unify the training and testing processes across the entire network. Extensive experiments and analyses reveal that, when compared to existing unsupervised approaches, our method achieves state-of-the-art performance on the KITTI dataset not only for depth estimation and optical flow estimation but also for monocular visual odometry. [ABSTRACT FROM AUTHOR]

As a new promising detection technology in the terahertz research field, the terahertz time-domain spectroscopy (THz-TDS) has very broad application potential in many fields because its advantage on the characteristic spectrum, wide spectrum and non-destructive analysis of interested substances. In this paper, the terahertz absorption spectra of gases mixed with 12CO and 13CO in the spectrum range of 0.5–2.5 THz are measured by terahertz time-domain spectroscopy for the first time. Several isotopologues can be clearly distinguished based on the difference in their rotational energies and the consequent terahertz spectrum. The experimental results show that 12CO and 13CO have obvious characteristic absorption peaks in the spectrum range of 0.5–2.5 THz due to the difference in rotational energy, and the rotational constant B can be calculated according to the experimental values to distinguish the two gaseous isotopologues. The frequency positions of the characteristic absorption peak measured by this experiment and the rotation constant B calculated according to the experimental values are compared with those previous theoretical calculations and experimental results, and they are in good agreement. This result lays a foundation for developing more sophisticated terahertz instruments to the detection of different isotopologues. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common tumors in the world. Cholesterol plays an important role in the pathogenesis of tumors. One of the cholesterol transporters, scavenger receptor class B type 1 (SR‐B1), a multi‐ligand membrane receptor protein, is expressed in the intestines which also highly expressed in various tumors. But the potential mechanism of SR‐B1 in CRC development has not been reported. Aims: This study aimed to clarify the importance of SR‐B1 in the development and prognosis of CRC as much as possible to provide a possible strategy in CRC treatment. Materials & Methods: In this study, we used SR‐B1 gene knockdown mice to study the effect of SR‐B1 on colitis‐induced or APCmin/+‐induced CRC. The expression of related molecules were detected through the immunohistochemistry and hematoxylin–eosin staining, western blot analysis, and Flow cytometry. The gene expression and microbiota in microenvironment of CRC mice were analyzed through eukaryotic mRNA sequencing and 16S rRNA high‐throughput sequencing. Results: The results showed that SR‐B1 knockdown reduced the tumor load of colitis‐induced or APCmin/+‐induced CRC. SR‐B1 knockdown improved the immune microenvironment by affecting the level of tumor‐associated macrophage (TAM), mononuclear myeloid‐derived suppressor cells (M‐MDSCs), granulocytic myeloid‐derived suppressor cells (G‐MDSCs), programmed cell death‐ligand 1 (PD‐L1), and human leukocyte antigen class I‐B (HLA‐B), and also reduced the level of low‐density lipoprotein receptor (LDL‐R), and increased the level of ATP binding cassette transporter A1 (ABCA1) to regulate the cholesterol metabolism, and regulated the expression of related genes and intestinal microbiota. SR‐B1 knockdown can also trigger the anti‐CRC effect of anti‐PD 1 in colitis‐induced CRC. Discussion: SR‐B1 deficiency significantly improved the immunity in tumor microenvironment of colitis‐induced or APCmin/+‐induced CRC. In addition, the microbiota changes caused by SR‐B1 deficiency favor improving the immune response to chemotherapeutic drugs and anti‐PD1 therapy. The mechanism of action of SR‐B1 deficiency on the development of CRC still needs further in‐depth research. Conclusion: This study provides a new treatment strategy for treating CRC by affecting the expression of SR‐B1 in intestine. [ABSTRACT FROM AUTHOR]

Background: Interruption of parasite reproduction by targeting migrating schistosomula is a promising strategy for managing schistosomiasis. Hepatic schistosomula proteins previously identified based on second-generation schistosome DNA sequencing were found to hold excellent potential for schistosomiasis japonica diagnosis and as vaccine candidates. However, there are still many unknown schistosomula proteins that warrant further investigations. Herein, a novel schistosomula protein, the Schistosoma japonicum erythroid Krüppel-like factor (SjEKLF/KLF1), was explored. Methods: Sequence alignment was carried out to detect the amino acid sequence characteristics of SjEKLF. The expression profile of SjEKLF was determined by western blot and immunofluorescence analysis. Enzyme-linked immunosorbent assay was used to determine the antigenicity of SjEKLF in hosts. Mice immunised with recombinant SjEKLF were challenged to test the potential value of the protein as an immunoprotective target. Results: SjEKLF is defined as EKLF/KLF1 for its C-terminal DNA-binding domain. SjEKLF is mainly expressed in hepatic schistosomula and male adults and located within the intestinal intima of the parasites. Notably, high levels of SjEKLF-specific antibodies were detected in host sera and SjEKLF exhibited outstanding sensitivity and specificity for schistosomiasis japonica immunodiagnosis but failed to distinguish between ongoing infection and previous exposure. In addition, SjEKLF immunisation reduced the infection in vivo, resulting in decreased worm and egg counts, and alleviated body weight loss and hepatomegaly in infected mice. Conclusions: Overall, these findings demonstrate that SjEKLF is critical for the infection of S. japonicum and may be a potential target to help control S. japonicum infection and transmission. [ABSTRACT FROM AUTHOR]

Polygalae radix (PR) is a well-known traditional Chinese medicine that is used to treat depression, and polygalae radix oligosaccharide esters (PROEs) are the main active ingredient. Although gut microbiota are now believed to play key role in depression, the effects of PROEs on depression via modulation of gut microbiota remain unknown. In this article, we investigate the effect of PROEs on the gut microbiota of a depression rat and the possible mechanism responsible. The depression rat model was induced by solitary rearing combined with chronic unpredictable mild stress (CUMS). The depression-like behavior, the influence on the hypothalamic–pituitary–adrenal (HPA) axis, the contents of monoamine neurotransmitter in the hippocampus, and the quantity of short-chain fatty acids (SCFAs) in the feces were each assessed, and the serum levels of lipopolysaccharide (LPS) and interleukin-6 (IL-6) were measured by ELISA. Additionally, ultrastructural changes of the duodenal and colonic epithelium were observed under transmission electron microscope, and the gut microbiota were profiled by using 16S rRNA sequencing. The results show that PROEs alleviated the depression-like behavior of the depression model rats, increased the level of monoamine neurotransmitters in the brain, and reduced the hyperfunction of the HPA axis. Furthermore, PROEs regulated the imbalance of the gut microbiota in the rats, relieving intestinal mucosal damage by increasing the relative abundance of gut microbiota with intestinal barrier protective functions, and adjusting the level of SCFAs in the feces, as well as the serum levels of LPS and IL-6. Thus, we find that PROEs had an antidepressant effect through the restructuring of gut microbiota that restored the function of the intestinal barrier, reduced the release of intestinal endotoxin, and constrained the inflammatory response. [ABSTRACT FROM AUTHOR]

Silicon encapsulated in conductive layers has proven to be an excellent method for retaining the high capacity of silicon in lithium-ion batteries (LIBs) throughout cycling. This study presents an ultra-fast, single-step, and scalable method for synthesizing graphene@Fe–Si nanoparticles via an atmospheric pressure surface-wave-sustained plasma. The verification of the synthesized nanoparticles, encompassing graphene cladding and silicon nanoparticles encapsulated in iron, was conducted through energy-dispersive x-ray spectroscopy mapping, line scanning in the transmission electron microscopy mode, and high-resolution transmission electron microscopy. Additionally, Raman spectroscopy corroborated the identity of the cladding as graphene. This study provides a viable strategy for the industrial production of anode materials for high-performance LIBs. [ABSTRACT FROM AUTHOR]

Graph Convolution Network (GCN) algorithms have greatly improved the accuracy of skeleton-based human action recognition. GCN can utilize the spatial information between skeletal joints in subsequent frames better than other deep learning algorithms, which is beneficial for achieving high accuracy. However, the traditional GCN algorithms consume lots of computation for the stack of multiple primary GCN layers. Aiming at solving the problem, we introduce a lightweight network, a Differential Learning and Parallel Convolutional Networks (DL-PCN), whose key modules are Differential Learning (DLM) and the Parallel Convolutional Network (PCN). DLM features a feedforward connection, which carries the error information of GCN modules with the same structure, where GCN and CNN modules directly extract the original information from the input data, making the spatiotemporal information extracted by these modules more complete than that of GCN and CNN tandem structure. PCN comprises GCN and Convolution Neural Network (CNN) in parallel. Our network achieves comparable performance on the NTU RGB+D 60 dataset, the NTU RGB+D 120 dataset and the Northwestern-UCLA dataset while considering both accuracy and calculation parameters. [ABSTRACT FROM AUTHOR]

Background: Malaria caused by Plasmodium species is a prominent public health concern worldwide, and the infection of a malarial parasite is transmitted to humans through the saliva of female Anopheles mosquitoes. Plasmodium invasion is a rapid and complex process. A critical step in the blood-stage infection of malarial parasites is the adhesion of merozoites to red blood cells (RBCs), which involves interactions between parasite ligands and receptors. The present study aimed to investigate a previously uncharacterized protein, PbMAP1 (encoded by PBANKA_1425900), which facilitates Plasmodium berghei ANKA (PbANKA) merozoite attachment and invasion via the heparan sulfate receptor. Methods: PbMAP1 protein expression was investigated at the asexual blood stage, and its specific binding activity to both heparan sulfate and RBCs was analyzed using western blotting, immunofluorescence, and flow cytometry. Furthermore, a PbMAP1-knockout parasitic strain was established using the double-crossover method to investigate its pathogenicity in mice. Results: The PbMAP1 protein, primarily localized to the P. berghei membrane at the merozoite stage, is involved in binding to heparan sulfate-like receptor on RBC surface of during merozoite invasion. Furthermore, mice immunized with the PbMAP1 protein or passively immunized with sera from PbMAP1-immunized mice exhibited increased immunity against lethal challenge. The PbMAP1-knockout parasite exhibited reduced pathogenicity. Conclusions: PbMAP1 is involved in the binding of P. berghei to heparan sulfate-like receptors on RBC surface during merozoite invasion. [ABSTRACT FROM AUTHOR]

Ticks are vectors and reservoirs of a variety of pathogens including protozoa, bacteria and viruses which cause tick-borne diseases (TBDs) in humans and livestock. TBDs pose serious constraints to the improvement of livestock production in tropical and subtropical regions of the world. Despite their wide distribution, information on the tick and pathogen relationship is scarce in Tanzania. We used nested PCR and sequencing to screen pathogens of public and veterinary health importance in ticks collected by flagging from four districts of Tanzania. In total, 2021 ticks comprising nine species were identified. DNA from ticks was pooled according to tick species, developmental stage, and location, then screened for Babesia bigemina, Babesia bovis, Theileria parva and Coxiella burnetii. Out of 377 pools, 34.7% were positive for at least one pathogen. Theileria parva was the most abundant with a minimum infection rate (MIR) of 2.8%, followed by B. bigemina (MIR = 1.8%) and B. bovis (MIR = 0.8%). Multiple pathogens detection was observed in 7.2% of the tested pools. However, PCR screening of individual tick DNA revealed that only 0.3% of the examined pools had co-infection. DNA of C. burnetii was never detected in any tick DNA pool. The MIR of tick-borne pathogens (TBPs) differed significantly among districts, seasons, tick species, and tick developmental stages. Sequence analysis showed that B. bigemina RAP-1a, B. bovis SBP-4, and T. parva p104 genes were conserved among pathogens in the four districts. Despite the absence of C. burnetii in ticks, considering its pathogenic potential, it is essential to continue monitoring for its possible recurrence in ticks. This information adds to the knowledge of TBPs epidemiology and will contribute to the scientific basis for planning future control strategies. [ABSTRACT FROM AUTHOR]

Identification of promising schistosome antigen targets is crucial for the development of anti-schistosomal strategies. Schistosomes rely on their neuromuscular systems to coordinate important locomotory behaviors. Tyrosine hydroxylase (TH) is critical in the initial rate-limiting step in biosynthesis of catecholamine, the important neuroactive agents, which promote the lengthening of the worm through muscular relaxation and are therefore of great importance to the movement of the organism both within and between its hosts. THs from both Schistosoma mansoni and Schistosoma japonicum and their enzyme activities have been discovered; however, the role of these proteins during infection have not been explored. Herein, a recombinant protein of the nonconserved fragment of S. japonicum TH (SjTH) was produced and the corresponding polyclonal antibody was generated. The expression and antigenicity of SjTH were detected by qRT-PCR, western blotting, immunofluorescence assays, and ELISA. Mice immunized with the recombinant SjTH were challenged with cercariae to evaluate the immunoprotective value of this protein. Our results showed SjTH not only distributed in the head associated with the central nervous system, but also expressed along the tegument and the intestinal intima, which are involved in the movement, coupling and digestion of the parasites and associated with the peripheral nervous system. This protein can effectively stimulate humoral immune responses in mammalian hosts and has high potential as a biomarker for schistosomiasis immunodiagnosis. Furthermore, immunization with recombinant SjTH showed to reduce the worm and egg burden of challenged mice, and to contribute to the systemic balance of the Th1/Th2 responses. Taken together, these results suggest that SjTH is an important pathogenic molecule in S. japonicum and may be a possible target for anti-schistosomal approaches. Author summary: Schistosomiasis is still a disease imposing great threat to human life and which is far from elimination. The identification and function of many schistosome antigens remains limited, which constrains the development of schistosomiasis vaccines and new diagnostics markers. Schistosomes rely on their neuromuscular systems to coordinate important locomotory behaviors. Tyrosine hydroxylase (TH) is critical for normal physiological and neuropathological conditions, which are of great importance to the movement of the parasites both within and between its hosts. THs from both S. mansoni and S. japonicum and their enzyme activities have been discovered, however, the role of these proteins during infection have not been explored. In this study we show SjTH may be expressed in the head, on the tegument surface, and along the intestinal intima of the parasites, associated with both central nervous system and peripheral nervous system. This protein effectively stimulates the host immune response and exhibited highly encouraging performance for schistosomiasis immunodiagnosis. We also show that immunization with the recombinant SjTH was able to protect mice from a challenge S. japonicum infection. Overall, these results indicate the SjTH holds potential value as an immunoprotection target. [ABSTRACT FROM AUTHOR]

For biped robots, the ability to maintain balance under external forces is an essential requirement. Inspired by human beings' behaviors to resist external forces, a compliant-resistant balance-control method is proposed to keep the biped robot balance subjected to an external force. A model-free trajectory generator is designed based on the central pattern generator (CPG) to generate compliant-resistant human-like behavior. The CPG pattern generator generates the desired pulse signal utilizing Matsuoka's CPG. The signal modulator applies the defined signal to the robot's center of mass (CoM) to generate the workspace trajectory when standing on double feet. Moreover, when standing on single foot, the output signal of the CPG will directly act on the hip joint of the robot to generate the joint space trajectory. Furthermore, the motion engine calculates the workspace trajectory into joint sequence values. The proposed control strategy can generate defined pulse signals to realize compliant-resistant balance control for biped robots. The control strategy proposed in this paper is verified in the NAO simulation environment. [ABSTRACT FROM AUTHOR]

Dihydroartemisinin (DHA), a potent antimalarial drug, also exhibits distinct property in modulation on Treg and B cells, which has been recognized for decades, but the underlying mechanisms remain understood. Herein we revealed that DHA could promote Treg proliferation, meanwhile, suppress B cell expansion in germinal centers, and consequently decrease the number of circulating plasma cells and the content of serum immunoglobulins. Further, DHA-activated Treg significantly mitigated lipopolysaccharide-induced and malaria-associated inflammation. All these scenarios were attributed to the upregulation of c-Fos expression by DHA and enhancement of its interaction with target genes in both Treg and circulating plasma cells with bilateral cell fates. In Treg, the c-Fos-DHA complex upregulated cell proliferation-associated genes and promoted cell expansion; whereas in plasma cells, it upregulated the apoptosis-related genes resulting in decreased circulating plasma cells. Thus, the bilateral immunoregulatory mechanism of DHA was elucidated and its application in the treatment of autoimmune diseases is further justified. Dihydroartemisinin (DHA) promotes Treg cell proliferation and suppresses plasma cell expansion through direct interaction and activation of c-Fos, underling the bilateral immunoregulatory mechanism of DHA. [ABSTRACT FROM AUTHOR]

Background: Perivascular epithelioid cell tumor (PEComa) occurring in the female genital tract are rare, and typically found in the uterine corpus. PEComa occurring in the cervix is extremely rare, and very few cases have been reported till now. Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported. Case presentation: A 55-year-old postmenopausal woman presented with abnormal vagina discharge for 3 months. A liquid-based cytology test was performed. Microscopically, some loosely cohesive epithelioid cells were uniform with abundant clear cytoplasm, showing predominantly round or oval nuclei with finely stippled chromatin. Distinct round nucleoli were visible in some cells, notably with numerous melanin pigments in the cytoplasm. The cytopathological features were well correlated with cell block and histopathological findings. Upon immunohistochemistry (IHC), the tumor cells were positive for HMB45 and TFE3, focally positive for MelanA, while negative for muscle marker. Fluorescence in situ hybridization (FISH) confirmed TFE3 gene rearrangement. The final pathological diagnosis was PEComa identified by the liquid-based cytology, cell block, cervical biopsy, IHC and FISH result. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for 2 years with no evidence of disease. Conclusion: The cytologic characteristics of the tumor can provide sufficient clues for PEComa diagnosis, which includes loosely cohesive, epithelioid morphology with abundant clear or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigments. This will help cytopathologists to recognize this rare tumor that occurred in the cervix, and the combination of predictive morphology evaluation, immunophenotype, and molecular testing can achieve the definitive diagnosis of PEComa. [ABSTRACT FROM AUTHOR]

Scavenger receptor class B type 1 (SR−B1), a multiligand membrane receptor, is expressed in a gradient along the gastrocolic axis. SR−B1 deficiency enhances lymphocyte proliferation and elevates inflammatory cytokine production in macrophages. However, whether SR−B1 affects intestinal metabolites is unclear. In this study, we detected metabolite changes in the intestinal tissue of SR−B1−/− mice, including amino acids and neurotransmitters, by ultra−performance liquid chromatography quadrupole time−of−flight mass spectrometry (UHPLC−Q−TOF/MS) and HPLC. We found that SR−B1−/− mice exhibited changes in intestinal lipid metabolites and metabolic pathways, including the glycerophospholipid, sphingolipid, linoleic acid, taurine, and hypotaurine metabolic pathways. SR−B1 deficiency influenced the contents of amino acids and neurotransmitters in all parts of the intestine; the contents of leucine (LEU), phenylalanine (PHE), tryptophan (TRP), and tyrosine (TYR) were affected in all parts of the intestine; and the contents of 3,4−dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were significantly decreased in both the colon and rectum. In summary, SR−B1 deficiency regulated intestinal lipids, amino acids, and neurotransmitter metabolism in mice. [ABSTRACT FROM AUTHOR]

The scramjet isolator length is a very important influence factor on the stability of scramjet engines. The effects of the isolator length on the pseudo-shock wave (PSW) were studied through a numerical method. The steady and unsteady PSW characteristics were analyzed to explore the influence mechanism of the isolator length. The numerical model was validated with the existing experimental results, and the validation results show that the numerical model has high accuracy. The effects of the structural variation of the PSW on self-excited oscillation were explored at different isolator lengths. Result shows that increasing the isolator length increases the length of the PSW. The leading shock becomes stable with the increasing of PSW length, and the following shocks become unstable. This phenomenon indicates that the unsteady characteristics of self-excited oscillation are closely related to the PSW structure. The influence mechanism of isolator length is represented by the amplitude difference of the leading and following shocks caused by the PSW structure variation. [ABSTRACT FROM AUTHOR]

Objective: This study was aimed at investigating the immunoregulatory effects of trypanosomal lipophosphoglycan (LPG) anchored to trypanosome membranes, including the formation of neutrophil extracellular traps (NETs) and neutrophil cytokine release after parasite infection. The interaction of cell surface TLR receptors with LPG, which signals cellular responses during Trypanosma brucei infection, was systematically investigated. Methods: The cytokine expression profile in neutrophils after exposure to T. brucei LPG, and the involvement of TLR2, TLR4, p38 MAP kinase, and NF-κB in NET formation were studied with molecular immunological approaches including quantitative PCR, western blotting and immunofluorescence. Results: T. brucei-derived LPG induced phosphorylation of p38 MAP kinase and NF-κB, thereby stimulating neutrophil secretion of IL-1β, IL-8, and TNF-a. The blockade of Toll-like receptor 2/4 and specific inhibitors of MyD88, p38 MAP kinase, and NF-κB decreased cytokine release and the phosphorylation of both kinases. Furthermore, the exposure of neutrophils containing LPG to IL-1β and LPG-induced cell supernatants promoted the release of NETs. Conclusion: Our findings suggest that T. brucei LPG activates neutrophil IL-1β secretion via the TLR-mediated p38 MAP kinase and NF-κB pathways, thereby promoting the formation of LPG-stimulated NETs. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s13238-021-00833-y [ABSTRACT FROM AUTHOR]

The immunomodulatory potential of dihydroartemisinin (DHA) has recently been highlighted; however, the potential mechanism remains to be clarified. Single-cell RNA sequencing was explored in combination with cellular and biochemical approaches to elucidate the immunomodulatory mechanisms of DHA. In this study, we found that DHA induced both spleen enlargement and rearrangement of splenic immune cell subsets in mice. It was revealed that DHA promoted the reversible expansion of effective regulatory T cells and interferon-γ+ cytotoxic CD8+ T cells in the spleen via induction of superoxide dismutase 3 (SOD3) expression and increased phosphorylation of c-Jun N-terminal kinases (JNK) and its downstream activator protein 1 (AP-1) transcription factors. Further, SOD3 knockout mice were resistant to the regulatory effect of DHA. Thus, DHA, through the activation of the SOD3-JNK-AP-1 axis, beneficially regulated immune cell heterogeneity and splenic immune cell homeostasis to treat autoimmune diseases. [ABSTRACT FROM AUTHOR]

6D object pose estimation is a longstanding computer vision problem. Existing deep learning-based methods have achieved inspiring results in this task. However, large-scale training data with annotations is extremely needed to guarantee these methods’ performance, and acquiring real 6D object pose annotations is fairly labor-intensive and time-consuming. To overcome this drawback, we propose a semi-supervised pose estimation method using labeled synthetic data and unlabeled real data. For unlabeled real data, we form a self-supervised pipeline by minimizing the distance between the input point cloud, which is under ground-truth pose, and the model points transformed based on predicted pose. The labeled synthetic data is used to supervise the network to converge correctly. And we utilize a feature mapping to eliminate the domain gap between the real and synthetic features to further enhance the network’s performance. Moreover, we propose an attention-based pose estimation network, which can concentrate more on the distinguishing features, thus improving the accuracy of pose estimation. Experiments show that our proposed semi-supervised method is able to achieve good performance without the real annotations and outperforms all other methods relying on synthetic data or self-supervision strategy, indicating that the proposed method is effective. [ABSTRACT FROM AUTHOR]

Metschnikowia bicuspidata is a globally distributed pathogenic yeast with a wide range of aquatic hosts. A new strain, M. bicuspidata LNES0119, isolated from the Chinese mitten crab Eriocheir sinensis , has caused a serious reduction in production and marked economic loss for the aquaculture industry in China. Therefore, the whole-genome sequence of M. bicuspidata LNES0119 was sequenced using Illumina and Oxford Nanopore technology; whole-genome annotation and comparative genomic analyses of this pathogen were performed as well. A high-quality genome of M. bicuspidata LNES0119 was 16.13 Mb in size, with six scaffolds and six contigs, and encoded 5,567 putative predicted genes. Of these, 1,467 genes shared substantial homology with genes in the pathogen–host interactions database. Comparative genomic analyses of three M. bicuspidata strains and one non-pathogenic yeast, M. aff. pulcherrima , showed 331 unique genes in M. bicuspidata LNES0119, 30 of which were putatively related to pathogenicity. Overall, we identified several meaningful characteristics related to pathogenicity and virulence that may play essential roles in the infection and pathogenicity of M. bicuspidata LNES0119. Our study will aid in identifying potential targets for further exploration of the molecular basis of the pathogenicity of M. bicuspidata as well as the therapeutic intervention of M. bicuspidata infection. [ABSTRACT FROM AUTHOR]

6D object pose estimation for texture-less objects from RGB images remains challenging, especially in occlusion scenarios. Instead of localizing sparse keypoints by regressing their image coordinates or heatmaps, which are sensitive to occlusion, we introduce GeoPose, a novel reconstruction guided pose estimation pipeline that predicts dense correspondences and leverages geometric consistency effectively. We first design a dense reconstruction network (ReconNet) to reconstruct pixel-wise object coordinates in normalization space. Dense 2D-3D correspondences are generated intuitively by our explicit parameterization for 3D object models, which dismisses keypoint selection efforts. These 2D-3D correspondences are then utilized to estimate 6D poses by the PnP algorithm with RANSAC iterations. Furthermore, a novel Cycle Loss is proposed to provide 3D prior supervision, which significantly correlates with the pose estimation task by guiding geometric consistency between reconstruction (pixel to 3D) and reprojection (3D to pixel). In addition, a training data augmentation method is proposed to handle the insufficiency of 6D datasets, the acquisition of which is error-prone and time-consuming. Extensive experiments demonstrate that, compared with existing RGB-based methods, our GeoPose can achieve state-of-the-art (SOTA) 6D pose estimation performance on the LINEMOD, Occlusion LINEMOD and T-LESS datasets. [ABSTRACT FROM AUTHOR]

Background: Antigens of migrating schistosomula are promising candidates as schistosomiasis vaccine targets, since immune attack on hepatic schistosomula would interrupt the parasites life cycle and reduce egg burden on the host.Methods: In this study, we report a collection of Schistosoma japonicum schistosomula proteins (SjScPs) that are highly expressed in hepatic schistosomula. The expression characteristics, antigenicity and immune protection of these proteins were studied by western blot, ELISA, immunofluorescence and challenge assays.Results: We found that several of these SjScPs were highly antigenic and could effectively stimulate humoral immune responses in both human and other mammalian hosts. In particular, SjScP25, SjScP37, SjScP41, SjScP80, and SjScP88 showed high potential as biomarkers for schistosomiasis immunodiagnosis. Furthermore, we demonstrated that immunization with several of the recombinant SjScPs were able to protect mice from S japonicum challenge infection, with SjScP25 generating the most protective results.Conclusions: Our work represents a group of novel schistosome immunogens, which may be promising schistosomiasis japonica diagnosis and vaccine candidates. [ABSTRACT FROM AUTHOR]

3D skeleton data has been widely used in action recognition as the skeleton-based method has achieved good performance in complex dynamic environments. The rise of spatio-temporal graph convolutions has attracted much attention to use graph convolution to extract spatial and temporal features together in the field of skeleton-based action recognition. However, due to the huge difference in the focus of spatial and temporal features, it is difficult to improve the efficiency of extracting the spatiotemporal features. In this paper, we propose a channel attention and multi-scale neural network (CA-MSN) for skeleton-based action recognition with a series of spatio-temporal extraction modules. We exploit the relationship of body joints hierarchically through two modules, i.e., a spatial module which uses the residual GCN network with the channel attention block to extract the high-level spatial features, and a temporal module which uses the multi-scale TCN network to extract the temporal features at different scales. We perform extensive experiments on both the NTU-RGBD60 and NTU-RGBD120 datasets to verify the effectiveness of our network. The comparison results show that our method achieves the state-of-the-art performance with the competitive computing speed. In order to test the application effect of our CA-MSN model, we design a multi-task tandem network consisting of 2D pose estimation, 2D to 3D pose regression and skeleton action recognition model. The end-to-end (RGB video-to-action type) recognition effect is demonstrated. The code is available at https://github.com/Rh-Dang/CA-MSN-action-recognition.git. [ABSTRACT FROM AUTHOR]

Cherry tomato (Solanum lycopersicum) is popular with consumers over the world due to its special flavor. Soluble solids content (SSC) and firmness are two key metrics for evaluating the product qualities. In this work, we develop non-destructive testing techniques for SSC and fruit firmness based on hyperspectral images and the corresponding deep learning regression model. Hyperspectral reflectance images of over 200 tomato fruits are derived with the spectrum ranging from 400 to 1,000 nm. The acquired hyperspectral images are corrected and the spectral information are extracted. A novel one-dimensional (1D) convolutional ResNet (Con1dResNet) based regression model is proposed and compared with the state of art techniques. Experimental results show that, with a relatively large number of samples our technique is 26.4% better than state of art technique for SSC and 33.7% for firmness. The results of this study indicate the application potential of hyperspectral imaging technique in the SSC and firmness detection, which provides a new option for non-destructive testing of cherry tomato fruit quality in the future. [ABSTRACT FROM AUTHOR]

Real-time and high-performance segmentation is a crucial but challenging perception task for computationally constrained robots, such as the humanoid NAO robot used in the RoboCup Soccer Standard Platform League. However, most existing convolutional neural network (CNN)-based models for semantic segmentation suffer from massive computational costs, which prevents them from being applied to performing real-time inference with a NAO. In this article, we first publish meticulously annotated datasets for training and evaluating semantic segmentation models. Then, we propose a fast downsampling module that downsamples the image while maintaining the spatial information and a novel dense learning module that learns high-level semantic information while recovering the spatial details. Based on these operations, by using a multiscale fusion method to recover the resolution, we propose a more efficient and real-time segmentation model called RoboSeg primarily aimed at offering better speed and accuracy tradeoffs. Finally, to accommodate practical engineering applications, we offer a promising deployment guideline for the CNN model describing how to deploy it on computational resource-limited robots and achieve real-time performance. The experimental results show that the RoboSeg exceeds the state-of-the-art networks in RoboCup scene segmentation: we attain a mean IoU of 87.35% and a pixel accuracy of 96.88% on our dataset using a model that contains only 0.29M parameters and performs just 0.73 GFLOPs. Under the proposed deployment strategies, the network can run at above 30 FPS on NAO robots with downsampled frames. [ABSTRACT FROM AUTHOR]

To achieve adaptive gait planning of humanoid robots, a hierarchical central pattern generator (H-CPG) model with a basic rhythmic signal generation layer and a pattern formation layer is proposed to modulate the center of mass (CoM) and the online foot trajectory. The entrainment property of the CPG is exploited for adaptive walking in the absence of a priori knowledge of walking conditions, and the sensory feedback is applied to modulate the generated trajectories online to improve walking adaptability and stability. The developed control strategy is verified using a humanoid robot on sloped terrain and shows good performance. [ABSTRACT FROM AUTHOR]

Babesiosis poses a serious threat to immunocompromised individuals and the major etiological species of Babesia for human babesiosis is Babesia microti. Merozoites are a critical stage in the life cycle of Babesia microti. Several merozoite proteins have been demonstrated to play important roles in this process; however, most of the merozoite proteins of B. microti remain unknown. In the present study, we identified a novel merozoite protein of B. microti with similar structure to the thioredoxin (Trx)-like domain of the Trx family, which was named as B. microti Trx-like protein (Bm TLP). Western blot assays demonstrated that this protein was expressed by B. microti during the erythrocytic infection process, and its expression peaked on day 7 post-infection in vivo. Immunofluorescence assay further showed that this protein is mainly expressed in B. microti merozoites. Bm TLP hold both heparin- and erythrocyte-binding properties, which are critical functions of invasion-related proteins. Immunization with recombinant Bm TLP imparted significant protection against B. microti infection in mice. Taken together, these results suggest that the novel merozoite protein, Bm TLP, is an important pathogenic molecule of B. microti and may be a possible target for the design of babesiosis control strategy. [ABSTRACT FROM AUTHOR]

The development of malaria vaccines and medicines depends on the discovery of novel malaria protein targets, but the functions of more than 40% of P. falciparum genes remain unknown. Asexual parasites are the critical stage that leads to serious clinical symptoms and that can be modulated by malaria treatments and vaccines. To identify critical genes involved in the development of Plasmodium parasites within erythrocytes, the expression profile of more than 5,000 genes distributed across the 14 chromosomes of the PF3D7 strain during its six critical developmental stages (merozoite, early-ring, late-ring, early trophozoite, late-trophozoite, and middle-schizont) was evaluated. Hence, a qRT-PCR-based transcriptome of the erythrocytic developmental process of P. falciparum was revealed. Weighted gene coexpression network analyses revealed that a large number of genes are upregulated during the merozoite release process. Further gene ontology analysis revealed that a cluster of genes is associated with merozoite and may be apical complex components. Among these genes, 135 were comprised within chromosome 14, and 80% of them were previously unknown in functions. Western blot and immunofluorescence assays using newly developed corresponding antibodies showed that some of these newly discovered proteins are highly expressed in merozoites. Further invasion inhibition assays revealed that specific antibodies against several novel merozoite proteins can interfere with parasite invasion. Taken together, our study provides a developmental transcriptome of the asexual parasites of P. falciparum and identifies a group of previously unknown merozoite proteins that may play important roles in the process of merozoite invasion. [ABSTRACT FROM AUTHOR]

Medical information is private, and medical data are valuable for medical research. Thus, medical information sharing is challenging because the data might be manipulated improperly and revealed during the operational process. The accuracy and integrity of medical information should be guaranteed throughout the sharing process. Medical institutions require shared information for scientific research and development; however, the issue of privacy inhibits the sharing process. In this article, we propose a new business process and a blockchain-based platform for medical information sharing. Our method exploits the advantages of blockchain in medical information recording and sharing. Information can be stored, shared, and credibly verified among parties in the distributed network. In addition, we propose a new consensus algorithm and a universal anonymous sharing model. These methods improve the efficiency and security of medical information sharing between users. In this way, both the information and the traces of the transaction can be stored in a distributed manner to prevent manipulation and fraud. Consequently, the value of medical information can be fully utilized. [ABSTRACT FROM AUTHOR]

Alternating current (ac) impedance spectra facilitate lithium-ion battery management. Realizing a low-cost and low-complexity onboard impedance measuring system is a vital issue for the management based on the ac impedance. In the article, a novel impedance measuring system combined with a high-power dual active bridge (DAB) converter and distributed sampling units is proposed and verified. The DAB converter is designed to generate the ac disturbance to ensure a quasi-steady measurement of the battery impedance. The distributed signal sampling units simultaneously measure the voltage and current of all the series-connected battery cells in a module to measure their impedance. The measured impedance in a frequency range of 0.1–500 Hz shows the feasibility of the system. The root-mean-square errors of the measured impedance phase from 0.2 to 200 Hz and the magnitude from 0.1 to 500 Hz are less than 6.9% and 4.0%, respectively. The errors in some frequency ranges are slightly larger, which are analyzed. The novelty is reflected in that the system is easily integrated into a bidirectional onboard charger and compatible with the battery management system, thus reducing costs and complexity. It provides a basis for the onboard application of the battery impedance. [ABSTRACT FROM AUTHOR]

Summary: Life prediction facilitates efficient management and timely maintenance of lithium‐ion batteries. Challenges are still faced in eliminating the effects of battery temperature or state of charge (SOC) on the life indicator to form a life prediction method for complex onboard working conditions. To fulfill the research gap, this paper focuses on three novelties about the life indicator, effect elimination, and life prediction method. First, impedance spectra at different temperatures, SOC, and aging cycles are comprehensively studied by experiments. By fitting the spectra with an equivalent circuit model, changes of ohmic resistance, solid electrolyte interphase resistance, and charge transfer resistance (CTR) are analyzed in detail. CTR is determined as a novel life indicator, and an empirical model describing the changing trend of CTR with aging cycles is established. Second, a multi‐factor coupled CTR model is applied to eliminate the strong effects of temperature and SOC during the prediction. Third, the tracking of the effects and the changing trend of the CTR with the aging cycles form a composite life prediction method with dual time scales. The results show that the battery life can be accurately predicted and the errors converge to within ±5% even though the indicator CTR is obtained at different temperatures and SOC. With this method, life prediction no longer depends on the indicator obtained in a specific state. It has great potential to broaden the implementation of life prediction for onboard conditions. [ABSTRACT FROM AUTHOR]

Trypanosoma brucei brucei is the causative agent of African animal trypanosomosis, which mainly parasitizes the blood of the host. Lipophosphoglycan (LPG), a polymer anchored to the surface of the parasites, activates the host immune response. In this study, we revealed that T. brucei LPG stimulated neutrophils to form neutrophil extracellular traps (NETs) and release the reactive oxygen species (ROS). We further analyzed the involvement of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) and explored the activation of signaling pathway enzymes in response to LPG stimulation. During the stimulation of neutrophils by LPG, the blockade using anti-TLR2 and anti-TLR4 antibodies reduced the phosphorylation of c-Jun N-terminal kinase (JNK), the release of DNA from the NETs, and the burst of ROS. Moreover, the addition of JNK inhibitor and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor exhibited similar effects. Our data suggest that T. brucei LPG activates the phosphorylation of JNK through TLR2 and TLR4 recognition, which causes the formation of NETs and the burst of ROS. [ABSTRACT FROM AUTHOR]

In product inspection scenarios, the objects have different characteristics of textures and different potential anomalies. Still, traditional methods cannot precisely segment structural anomalies and achieve optimal performance on all object categories. This article introduces a flexible multilevel image reconstruction (MLIR) framework for the unsupervised anomaly segmentation task. The MLIR integrates multiple generators with different downsampling ratios to serve as multiple reconstruction levels and leverage an adjustable perceptual similarity measurement to obtain the featurewise reconstruction errors, overcoming the challenge of detecting multiscale anomalies. Leveraging embeddings with different receptive fields for reconstruction, generators perform differently on the same target. Therefore, we depend on the reconstruction uncertainty to propose an adaptive attention-level transition (ALT) strategy that optimizes the detection performance automatically according to the target’s category. ALT adjusts the weights of both reconstruction levels and feature measurement scales simultaneously to utilize features at a consistent level for reconstruction and anomaly detection (AD). This strategy remarkably improves the system’s adaptivity for different applications. Moreover, we propose reducing the signal-to-noise ratio (SNR) of the images by adding pepper noise so that the reconstruction process is framed as an image denoising task, which improves feature extraction and image restoration robustness. We conduct extensive experiments on the MVTec AD dataset and demonstrate that the proposed method performs satisfactorily to different categories and achieves the state-of-the-art (SOTA) performance. [ABSTRACT FROM AUTHOR]

This article presents a flexible optical goniometer for the measurement of single-axis joint angular displacement. The design philosophy behind the apparatus lies that the agent's angular displacement is converted to the laser's distance measurement thanks to geometric conversion. We propose a dual-laser ranging model for joint angle measurement with the aid of a reference plane. This model converts the agent's rotational angle to the distance of laser range measurements under triangular constraints. Compared with the commonly used rotary encoders, the proposed sensor shows its competence in easy installation and flexible deployment. Furthermore, a model parameter calibration approach is introduced to decrease the angular measurement error. Extensive validation experiments with a prototype sensor on a robot arm prove the aforementioned claims and show that the prototype sensor can reach an angular precision of 0.3° with a measurement range of −30° – 30°. [ABSTRACT FROM AUTHOR]

Lithium‐ion battery cells are usually connected in series or parallel to form modules to meet power and energy requirements for specific applications. Inconsistency of the cells' performance, i.e., capacity and internal resistance, is initially formed during production. Then the inconsistency evolves in the lifespan. Herein, the performance and inconsistency evolution of the series and parallel modules for the design and management guide are investigated. A quantitative analysis of the performance and inconsistency is made. The performance and inconsistency evolution are investigated experimentally. Based on it, the trend judgment of the inconsistency evolution is derived. It is found that the cell performance in series modules is self‐divergent, especially in the later stage of the aging process. And the divergence becomes more severe with an unreasonable equalization, such as the traditional cell voltage equalization. Equalization of the cell performance is needed to cut off the vicious circle. For the parallel module, self‐convergence of the performance exists. The better‐performing cells in the module withstand a larger current, making their performance decay faster and finally becoming consistent with the cells with worse initial performance. Meanwhile, the parallel module performance also decays significantly. Therefore, maintaining the cells' consistency is still necessary for the parallel modules. [ABSTRACT FROM AUTHOR]

This paper investigates the distributed formation control problem of multiple nonholonomic wheeled mobile robots within real environments. The formation pattern of the system adopts leader–follower structure and the communication topology among the multirobot system is modeled by a directed graph. Slippage is hard to avoid due to the possible existence of ice, sand, or muddy roads. To overcome the effect of slippage, an adaptive trajectory tracking controller for leader robot is designed, such that the leader robot can keep up with the virtual reference trajectory and estimate the real value of unknown slipping ratio accurately. In addition, it is difficult for each follower robot to obtain leader’s states in a large formation system, so distributed formation controllers are designed based on distributed observers. It is shown that the proposed controllers can realize formation objective and overcome the slippage constraints at the same time. Finally, the effectiveness of the proposed controllers is verified by simulation results. [ABSTRACT FROM AUTHOR]

In this paper, an online foot position compensator (FPC) is proposed for improving the robustness of humanoid walking based on orbital energy conservation and discrete control Lyapunov function (DCLF), with which the asymptotic stability of the humanoid system can be maintained and, thus, the foot placement control is achieved. The online FPC is developed based on linear model predictive control (MPC) by replanning the trajectories of the center of mass (CoM) and properly placing the footsteps to resist external disturbances and recover the walking posture. To further improve the robustness of the humanoid robots to suppress strong external disturbance, a strategy of upper body posture control is proposed. The presented controller stabilizes the humanoid robot by utilizing hip joints to modulate the upper body posture online. Webots simulations and real experiments on a full-body NAO humanoid robot verify the effectiveness of the proposed methods. [ABSTRACT FROM AUTHOR]

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8+ T cell antitumor activity. Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion, we also found a non-canonical function of LDLR in CD8+ T cells: LDLR interacts with the T-cell receptor (TCR) complex and regulates TCR recycling and signaling, thus facilitating the effector function of cytotoxic T-lymphocytes (CTLs). Furthermore, we found that the tumor microenvironment (TME) downregulates CD8+ T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs. Moreover, genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+ T cells by alleviating the suppressive effect on CD8+ T cells and consequently inhibit tumor progression. While previously established as a hypercholesterolemia target, this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well. [ABSTRACT FROM AUTHOR]

The "milky disease" of the Chinese mitten crab, Eriocheir sinensis , is a highly lethal fungal disease caused by Metschnikowia bicuspidata infection. To elucidate the immune responses of the hemolymph of E. sinensis to M. bicuspidata infection, a comparative analysis of the hemolymph of E. sinensis infected with M. bicuspidata and that treated with phosphate buffered saline was performed using label-free quantitative proteomics. A total of 429 proteins were identified. Using a 1.5-fold change in expression as a physiologically significant benchmark, 62 differentially expressed proteins were identified, of which 38 were significantly upregulated and 24 were significantly downregulated. The upregulated proteins mainly included cytoskeleton-related proteins (myosin regulatory light chain 2, myosin light chain alkali, tubulin α-2 chain, and tubulin β-1 chain), serine protease and serine protease inhibitor (clip domain-containing serine protease, leukocyte elastase inhibitor, serine protein inhibitor 42Dd), catalase, transferrin, and heat shock protein 70. Upregulation of these proteins indicated that phenoloxidase system, phagocytosis and the ROS systems were induced by M. bicuspidata. The downregulated proteins were mainly organ and tissue regeneration proteins (PDGF/VEGF-related factor protein, integrin-linked protein kinase homing pat-4 gene) and hemagglutination-associated proteins (hemolymph clottable protein, hemocyte protein-glutamine gamma-glutamyltransferase). Downregulation of these proteins indicated that M. bicuspidata inhibited hemocyte regeneration and hemolymph agglutination. Fifteen differentially expressed proteins related to immunity were verified using a parallel reaction monitoring method. The expression trend of these proteins was similar to that of the proteome. To the best of our knowledge, this is the first report on the proteome of E. sinensis in response to M. bicuspidata infection. These results not only provide new and important information on the immune response of crustaceans to yeast infection but also provide a basis for further understanding the molecular mechanism of complex host pathogen interactions between crustaceans and fungi. [ABSTRACT FROM AUTHOR]