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The concept of diagnosis and treatment of keratoconus is constantly updated. Today, we are not only concerned with how to delay the progress of the disease, but also with the preservation of useful vision for patients as well as improvement of visual quality. With the precise and individualized application of excimer laser and femtosecond laser technology in ophthalmology, corneal cross-linking combined with excimer laser ablation for the irregular cornea has become a new strategy for keratoconus. However, questions have been raised and caused ophthalmologists' thinking. Are patients with keratoconus who have progressively thinned corneas suitable for excimer laser ablation? Which is better when the combined strategy is applied, simultaneous or sequential surgery? Based on the research data from home and abroad, we comprehensively sort out various treatment methods for the focus issues. It is hoped that this article can provide guidance for the rational selection of an optimal clinical solution to keratoconus.如今圆锥角膜的诊疗理念不断更新，人们不仅关注于如何延缓圆锥角膜进展，也在努力提高患者的视觉质量。随着准分子激光和飞秒激光技术在眼科的应用，角膜胶原交联术联合不规则角膜准分子激光切削术的治疗方案已成为圆锥角膜治疗的新策略。然而已逐渐变薄的圆锥角膜患眼是否可再进一步行准分子激光切削、该方案两种手术同期和分期执行孰优孰劣等关键问题尚无定论，本文基于这两个关键问题展开论述，以期为临床合理选择最优化的解决方案提供指导。

Background Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients’ treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses. Methods Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany. Results Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. Conclusions This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

Scarce information is available about the seroprevalence of Toxoplasma gondii (T. gondii) and Neospora caninum (N. caninum) infections in goats in Hubei province, China. In the present study, the prevalence of T. gondii and N. caninum infections in goats were investigated in Hubei province, China between 2014 and 2015. A total 2007 serum samples were collected from 6 counties of Hubei province, China and were tested for antibodies to N. caninum and T. gondii by an enzyme-linked immunosorbent assay (ELISA) and an indirect agglutination test (IAT), respectively. Antibodies against T. gondii and N. caninum were detected in 13.4% and 3.9%, respectively in goats. 2% (41) serum samples were positive to both parasites. There was no apparent association of T. gondii and N. caninum infection with gender of the animals. There were significant differences of T. gondii (p0.01), N. caninum (p0.05) and both parasites (p0.01) infection with season. This is the first time that antibodies to T. gondii and N. caninum have been detected in goats in Hubei province, China.

Additional file 1: Supplementary-Text 1.a Collection and digitalization of the WSIs. Supplementary-Text 1.b Dataset-A, B, C and D. Supplementary-Text 1.c Patch-level performance and patient-level accuracy. Supplementary-Text 1.d Comparison of different architectures at patch-level. Supplementary-Text 1.e Comparison of different cluster sizes for aggregation of patch-level results. Supplementary-Table 1. Input patch size for common CNN. Supplementary-Table 2 Pathologist info. Supplementary-Table 3 List of AUCs of AI applied in CRC and other cancer types. Supplementary-Table 4 Overall performance of AI and pathologists in Human-AI contest. Supplementary-Table 5 Cohen’s Kappa coefficient for agreement among human experts and AI. Supplementary-Figure 1 Weakly-labeled and fully-labeled CRC patches. Supplementary-Figure 2.The distribution of cancerous area in multiple independent WSI datasets measured by the proportion of patches (P) containing cancer cells on the WSI. Supplementary-Figure 3 Heatmap produced by AI. Supplementary-Figure 4 Activation map produced by AI.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Summary Gas-bearing prediction of tight sandstone reservoir is difficult since the relationship between gas-bearing property and its seismic response is nonlinear. However, machine learning methods provide the potential for solving the issue. One main limitation of some intelligent methods is imperfect in interpretability, which makes the gas-bearing prediction questionable. This study introduces an improved kNN method to predict gas-bearing distribution based on a known database made from borehole-side seismic traces and the corresponding interpreted gas-bearing curves obtained from the measured well-logs. The method can output gas-bearing probability approximated by the occurrence frequency of gas-bearing samples in the first k samples which are the most like data to be predicted. Compared with outputting kNN classification results, outputting probability results can reserve the valid information. The method has a simple principle and strong interpretability. No network needs to be trained. It does not rely on big data. A numerical model designed based on petrophysical parameters in a field work area is used to test the method. The result demonstrates that the method is good at characterizing the reservoir morphology and location. When applied to the field data, the gas-bearing prediction distribution is basically consistent with the geological law of the work area.

Summary High-density multicomponent acquisition is perceived as the holy grail of land seismic, however, 3C is rarely considered when surveys are planned mainly because of the cost and bulkiness of 3C nodes and also the lack of land processing examples that could justify such spent, especially when it can be directed towards more proven benefits like increased trace density. Ironically, the availability and affordability of 3C data play a crucial role in developing the processing technology that could promote the acquisition of more 3C land surveys. The recent evolution in onshore nodal technology has brought to the market a variety of nodes of different sizes, shapes, and sensor types, some are small and light enough that even if combined in a 3C configuration remain smaller and lighter than a purpose-built 3C node. Acquiring a 1C, 2C or 3C survey with the same node’s inventory could be very attractive and could incite more users to attempt a 3C acquisition. In this paper, we demonstrate how piezoelectric nodes can be used in a 3C combination by comparing them to established geophone 3C sensors in a 2d S-wave survey. We also discuss the benefits and inconveniences of a such approach in land acquisition.

We examine whether the disclosure of tax-related uncertainty through unrecognized tax benefits (UTBs) resolves or exacerbates investors’ uncertainty about firm value based on evidence from investor trading behavior and information asymmetry around the time of the disclosure. We find that current year UTB additions are associated with reduced trading activity around the release of the 10-K and wider bid-ask spreads in the days following the 10-K release. We find no evidence of an association between UTB additions and contemporaneous abnormal returns. Our results suggest that UTB additions increase investor uncertainty and investors impound the information contained in UTBs into prices with a delay. Moreover, we find that our results are concentrated in firms that engage in greater tax avoidance and in firms with poorer financial reporting quality. We also find that the association between UTB additions and information asymmetry is concentrated among firms with low institutional ownership. Taken together, our results suggest that UTB disclosures increase short-term investor uncertainty about future firm value, which undermines the FASB’s goal of increasing the relevance and transparency of accounting for uncertain tax positions.

Background: According to the clinical manifestation, tuberculosis (TB) is divided into pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). The incidence rate of EPTB has increased in many countries. The demographic and clinical characteristics of EPTB in China remain still unclear. Materials and methods: We retrospectively analyzed the medical records of 5,624 hospitalized patients with positive M. tuberculosis culture between January 2008 and June 2013 in Shandong province. We investigated the epidemiological, demographic, and clinical characteristics of patients with EPTB. Results: Among 5,624 hospitalized TB patients with positive M. tuberculosis culture, 4,277 (76.05 %) had PTB, 618 (10.99 %) had EPTB, and 729 (12.96 %) had both PTB and EPTB. The proportion of EPTB increased significantly from 6.97 % in 2008 to 19.98 % in 2012 (p

BACKGROUND: People with childhood-onset disabilities face unique physical and social challenges in adulthood. Exercise interventions may improve physical performance in children, but there is a lack of research on adults. OBJECTIVE: To describe studies that investigate exercise interventions and to evaluate the quality of physical performance outcome measures for adults with childhood-onset disabilities. METHODS: Eligible studies reported on exercise interventions for adults (ages 16+) with cerebral palsy, spina bifida, or acquired brain injuries. Only randomized controlled trials published in English from 2008 to 2019 were included. MEDLINE, CINAHL, PEDro, EMBASE, and Cochrane Central Register of Controlled Trials were searched. Two reviewers independently screened studies and abstracted data. RESULTS: This scoping review included 4 trials reporting on cerebral palsy only. Three strength training programs found significant improvements in gait, and one mixed training program found significant improvements in strength and fitness. Only two outcome measures used are valid/reliable for adults (6 Minute Walk Test and Borg-20 Grades). CONCLUSION: Certain interventions may improve physical performance, but there is a lack of research on appropriate exercise interventions and physical performance outcome measures for adults with childhood-onset disabilities. Different exercise interventions should be investigated using larger sample sizes and outcome measures should be standardized.

Advanced porous materials are becoming widely utilized because they have multiple functions that can be readily customized through chemical modification. To more effectively use porous materials in new applications, accurate information related to the structure-property relationship of materials needs to be well-understood with atomic-level precision. Low-frequency vibrational motions, which result from intermolecular interactions, can provide significant insight into the structure-property relationship of advanced porous materials.

Background Regional longitudinal left ventricular (LV) dysfunction in patients with mitral regurgitation (MR) due to valve prolapse (MVP) with normal ejection fraction has been recently described, with data pointing at dysfunction of the LV base related to dilatation of the mitral annulus. Purpose To investigate degree and extent of regional LV dysfunction and its mechanisms in patients with MVP and severe acute (MRa, n=27) or chronic (MRc, n=41) MR and no coronary disease, undergoing surgical valve repair with 3 months follow-up (FU); 20 normal subjects were used as controls (N). Methods Speckle-tracking echocardiography was performed pre- (Bas), 1 week (1w) and 4 months (4mo) post-operatively to measure longitudinal global (GLPSS, %), regional (RPSS, %) and segmental (SPSS) peak systolic strain. Maximum and minimum mitral annulus (MA) diameters were measured with 3D echo at Bas. We also evaluated: LV end-diastolic volume index (EDVi, ml/m2); ejection fraction (EF, %); left atrial end-systolic volume index (LAVi, ml/m2); non-invasive pulmonary systolic pressure (PSP, mmHg). Results Risk factors (hypertension, diabetes, atrial fibrillation, smoke and previous stroke) were similar in MRc and MRa. At Bas EDVi was larger by definition in MRc (MRc: 102±21, MRa: 67±10 ml/m2, p Conclusions In patients with MVP and severe MR, there is a specific regional longitudinal dysfunction pattern prevalent at the LV base which may be related to the duration of MR but not to annular dilatation or morphology of the prolapsing leaflets. The dysfunction worsens greatly following acute reduction of preload after surgical repair and is still significant at 4mo FU. Funding Acknowledgement Type of funding source: None

CONTEXT:Transition from the pediatric to the adult health care system is a complex process that should include medical, psychosocial, educational, recreational, and vocational considerations.OBJECTIVE:In this systematic review, we aim to synthesize the evidence on transitional care interventions (TCIs) to improve the quality of life (QoL) for adolescents and young adults with childhood-onset disabilities, including neurodevelopmental disorders.DATA SOURCES:Four electronic databases (Medline, Embase, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature) were searched.STUDY SELECTION:In the included studies, researchers examined TCIs for adolescents and young adults (12–24 years of age) with childhood-onset disabilities. Studies were experimental, quasi-experimental, and observational studies published in the last 26 years.DATA EXTRACTION:Two reviewers independently completed study screening, data extraction, and risk-of-bias assessment.RESULTS:Fifty-two studies were included. Five studies reported on QoL, but statistically significant improvements were noted in only 1 of these studies. Significant improvements were also found in secondary outcomes including disability-related knowledge and transitional readiness. TCIs targeted patients, families and/or caregivers, and health care providers and exhibited great heterogeneity in their characteristics and components.LIMITATIONS:Inconsistent reporting on interventions between studies hindered synthesis of the relationships between specific intervention characteristics and outcomes.CONCLUSIONS:Although there is limited evidence on the impact of TCIs on the QoL for youth with childhood-onset disabilities, there is indication that they can be effective in improving patient and provider outcomes. The initiation of transition-focused care at an early age may contribute to improved long-term health outcomes in this population.

Cell-based immunotherapies using T cells that are engineered to express a chimeric antigen receptor (CAR-T cells) are an effective treatment option for several B cell malignancies. Compared with most drugs, CAR-T cell products are highly complex, as each cell product is composed of a heterogeneous mixture of millions of cells. The biodistribution and kinetics of CAR-T cells, following administration, are unique given the ability of T cells to actively migrate as well as replicate within the patient. CAR-T cell therapies also have multiple mechanisms of action that contribute to both their antitumor activity and their toxicity. This review provides an overview of the unique pharmacology of CAR-T cells, with a focus on CD19-targeting and B cell maturation antigen (BCMA)-targeting CAR-T cells.

The biosynthesis and transport of nicotine has been shown to be coordinately upregulated by jasmonate (JA). MYC2, a member of basic helix-loop-helix (bHLH) transcription factor family, is well-documented as the core player in the JA signalling pathway to regulate diverse plant development processes. Four MYC2 genes were found in the tobacco genome, NtMYC2a/2b and 1a/1b. In this study, we tested whether one of them, NtMYC2a, acts as a 'master switch' in the regulation of nicotine biosynthesis and transport in tobacco. We generated NtMYC2a knockout tobacco plants using the CRISPR-Cas9 technique and analysed the effect of NtMYC2a knockout on expression of the nicotine biosynthesis genes (NtAO, NtQS, NtPMT1a, NtQPT2, NtODC2, NtMPO1, NtA622 and NtBBLa) and transport genes (NtMATE2 and NtJAT1), as well as leaf accumulation of nicotine in the NtMYC2a knockout plants. We found that all the nicotine biosynthesis and transport genes tested in this study were significantly downregulated (>50% reduction compared with wild-type control) in the NtMYC2a knockout plants. Moreover, the leaf nicotine content in knockout plants was dramatically reduced by ca 80% compared with the wild-type control. These results clearly show that NtMYC2a acts as a 'master switch' to coordinate JA-induced nicotine accumulation in tobacco and suggests that NtMYC2a might play an important role in tobacco nicotine-mediated defence against herbivory.

With the continuous development of cancer treatment, the immune checkpoint inhibitors have been applied to the treatment of a variety of malignant tumors, which improved the patient's survival time and quality of life. However, immune-related adverse reactions occur inevitably. Like chemotherapeutics and targeted drugs, immunosuppressants can also cause cardiovascular events that affect the mortality of cancer patients. With the extension of the survival time of cancer patients, it will increasingly become a key factor which affects the prognoses of these diseases. This review focuses on the cardiotoxic mechanism, clinical manifestation, and future direction of immune checkpoint inhibitors during cancer treatment.随着恶性肿瘤治疗的不断发展，免疫检查点抑制剂已应用于多种恶性肿瘤的治疗，使患者的生存时间和生活质量有所改善，但在应用的过程中不可避免地发生免疫相关不良反应。与化疗药物和靶向药物相同，免疫抑制剂也会引起心血管事件，从而影响肿瘤患者的死亡率。随着肿瘤患者生存时间的延长，会日益成为影响这类疾病预后的关键因素。文章重点论述免疫检查点抑制剂在肿瘤治疗过程中引起的心脏毒性机制、临床表现以及未来发展方向。.

The root bark of Pseudolarix kaempferi, a famous traditional Chinese medicine, has been commonly used in China to treat skin diseases caused by fungal infections. To evaluate its pharmatherapeutic quality, a sensitive, simple and accurate high-performance liquid chromatography (HPLC) method was developed for the quantitative analysis of three major bioactive diterpenoids, pseudolaric acids A-C in P. kaempferi. A Zorbax XDB RP-C18 (4.6 mm×250 mm, 5 μm) was used in this HPLC system, with UV detection at 260 nm. A gradient elution was effected by a mobile phase composed of acetonitrile and 1% aqueous acetic acid, where acetonitrile concentration was changed from 30% to 60% in 30 min. These three constituents were well resolved by this method with good linear relationships in the range of 0.982-98.2 μg/mL for pseudolaric acid A, 0.618-61.8 μg/mL for pseudolaric acid B, and 1.052-105.2 μg/mL for pseudolaric acid C, respectively. The correlation coefficients of the calibration curves were all over 0.999. In addition, these three compounds in six batches of the root barks of P. kaempferi were quantitatively determined to evaluate the effectiveness of this method.

The purpose of this study was to investigate the expression level of EphA3 in nasopharyngeal carcinoma (NPC) and its effect on the proliferative capacity of NPC. Meanwhile, the underlying mechanism by which EphA3 prompts NPC malignant progression was further explored.In this study, the expression of EphA3 in 42 pairs of tumor tissue specimens and paracancerous ones collected from NPC patients was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the interplay between EphA3 expression and clinical indicators, as well as prognosis of NPC patients was analyzed. Meanwhile, qRT-PCR was also applied to further verify EphA expression in NPC cell lines. In addition, EphA knockdown model was constructed in NPC cell lines, CNE2, and 6-10B, and the impacts of EphA on NPC cell functions was assessed through Cell Counting Kit-8 (CCK-8), cell colony formation, as well as 5-Ethynyl-2'- deoxyuridine (EdU) assays. Finally, a potential interplay between EphA3 and FOG2 was also investigated.In this study, qRT-PCR results revealed that EphA3 expression levels in tumor tissues of patients with NPC were markedly higher than those in adjacent tissues. Compared with patients with low expression of EphA3, those with highly expressed EphA3 had a more advanced pathological stage. In addition, in vitro experiments showed that knocking down EphA3 notably attenuated the proliferation capacity of NPC cells. Subsequently, it was found that the expression of FOG2 in NPC cells was remarkably decreased both in NPC cell lines and tissues, which had a negative correlation with EphA3. Finally, cell recovery experiment revealed a mutual regulation between EphA3 and FOG2, which then together affected the malignant progression of NPC.EphA3 is significantly relevant to pathological staging and poor prognosis of patients with NPC and may enhance the proliferation ability of NPC cells by modulating FOG2.

Summary ? 2019 ? 12 ?????????,COVID-19(??????)?????????????????? COVID-19 ?????(???????)?????????????????? ??????????????,?????????????,?????????????????????????????????????????? ?????????????????????????????????????,???????,???????? COVID-19 ???,??????????????? COVID-19 ??,????????????,????????? ????????????? N95 ???????????????????????? CT ???? COVID-19 ????,??????????????????????????????,???????????????????,????????? COVID-19 ?????,?????????????????????????? ???????????????COVID-19 ????????????????????????????????????????,?????(?????????????????)????????????????????????????,????????????,????????????? ????????,?? 2020 ? 2 ? 20 ?,??????????????? ???????: ????? 2019 ????????????????: ???????

Summary Since cases first emerged in December 2019, COVID‐19 (a type of coronavirus) has rapidly become pandemic. This fast‐tracked paper (published quickly) from China on COVID‐19 is written by dermatologists at the epicentre of the outbreak in Wuhan. Dermatology clinic staff may be at risk because protective equipment is not routinely available, and skin lesions might possibly transmit the virus indirectly. These authors suggest preventive measures based on experience in this and previous coronavirus outbreaks. Online consultation for non‐urgent patients reduces the numbers of patients attending clinics. Nurse‐led triage, to identify patients with possible COVID‐19, at the entrances of hospital and skin clinics directs patients with a cough or fever to a specific COVID‐19 area and a dermatologist is consulted if the fever might be related to skin disease. Clinic staff wear N95 masks and observe hand hygiene during consultations. Patients are admitted to a ward only if routine blood tests and chest CT scans exclude COVID‐19. Triage will not detect patients who are showing no symptoms but who are developing the disease, so the hospital should provide an on‐call expert team to discuss inpatients suspected or diagnosed with COVID‐19 and refer them to radiology, respiratory or intensive care colleagues as required. Confirmed cases are managed following local policies. Skin disorders in COVID‐19 inpatients can usually be managed remotely using photographs, email and teleconferencing. If necessary a multidisciplinary team (a team of medical staff from different specialties) can meet in the clean area of the isolation ward. If the dermatologist must see the patient, all records should be provided in advance to minimise exposure time. With these precautions, as of 20th February 2020 no infected patients were detected in the Wuhan Dermatology Department. This is a summary of the study: Emergency management for preventing and controlling nosocomial infection of 2019 novel coronavirus: implications for the dermatology department, Linked Article: Tao et al. Br J Dermatol 2020; 182:1477–1478

Background ATP-dependent chromatin remodelling complexes are responsible for establishing and maintaining the positions of nucleosomes. Chromatin remodellers are targeted to chromatin by transcription factors and non-coding RNA to remodel the chromatin into functional states. However, the influence of chromatin remodelling on shaping the functional epigenome is not well understood. Moreover, chromatin remodellers have not been extensively explored as a collective group across two-dimensional and three-dimensional epigenomic layers. Results Here, we have integrated the genome-wide binding profiles of eight chromatin remodellers together with DNA methylation, nucleosome positioning, histone modification and Hi-C chromosomal contacts to reveal that chromatin remodellers can be stratified into two functional groups. Group 1 (BRG1, SNF2H, CHD3 and CHD4) has a clear preference for binding at ‘actively marked’ chromatin and Group 2 (BRM, INO80, SNF2L and CHD1) for ‘repressively marked’ chromatin. We find that histone modifications and chromatin architectural features, but not DNA methylation, stratify the remodellers into these functional groups. Conclusions Our findings suggest that chromatin remodelling events are synchronous and that chromatin remodellers themselves should be considered simultaneously and not as individual entities in isolation or necessarily by structural similarity, as they are traditionally classified. Their coordinated function should be considered by preference for chromatin features in order to gain a more accurate and comprehensive picture of chromatin regulation. Electronic supplementary material The online version of this article (10.1186/s13072-019-0258-9) contains supplementary material, which is available to authorized users.

As a conventional mobile assistance device, a wheelchair makes people suffer from skin injuries such as bed sores and ulcer, owing to sitting on a wheelchair for a long period. And the wheelchair is barely able to adapt to complex terrains, such as stairs. With the development of robotic technology, the rise of lower-limb exoskeleton robotics provides a new means of motion assistance, and provides training of motor ability. However, it can't support a user to compete long-distance movement because a user need consume much energy to keep balance. Considering the merits and demerits of wheelchairs and exoskeletons, we propose a novel hybrid motion assistant robot that combines both. The biggest challenge is the design of a mechanism that can transform the robot from a wheelchair into an exoskeleton, as well as the reverse transformation. To achieve this goal, the mechanism must be able to achieve three configurations: the wheelchair configuration, the support configuration, and the exoskeleton configuration. To reduce the weight of the robot and make it more compact, the linkages and actuators in the mechanism are designed to be reusable when the configuration changes. The mechanism is designed based on the analysis of functional requirements, and distributed synthesis of the mechanism is adopted. The kinematics and statics of every configuration are discussed in detail, to obtain the most reasonable dimensions using the particle swarm optimization algorithm. The mechanism performance is simulated and verified using ADAMS software. Finally, an experimental prototype is constructed for preliminary tests.

DNA replication timing is known to facilitate the establishment of the epigenome, however, the intimate connection between replication timing and changes to the genome and epigenome in cancer remain largely uncharacterised. Here, we perform Repli-Seq and integrated epigenome analyses and demonstrate that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing. A subset of altered replication timing domains are conserved across cancers from different tissue origins. Notably, late-replicating regions in cancer cells display a loss of DNA methylation, and a switch in heterochromatin features from H3K9me3-marked constitutive to H3K27me3-marked facultative heterochromatin. Finally, analysis of 214 prostate and 35 breast cancer genomes reveal that late-replicating regions are prone to cis and early-replication to trans chromosomal rearrangements. Together, our data suggests that the nature of chromosomal rearrangement in cancer is related to the spatial and temporal positioning and altered epigenetic states of early-replicating compared to late-replicating loci., The connection between DNA replication timing and changes that occur to the epigenome in cancer are still poorly understood. Here, the authors perform Repli-Seq and integrated epigenome analyses and find that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing.

Currently, the therapeutic effect on patients with liver cancer is associated with disease development. Meanwhile, the efficacy in patients with advanced liver cancer is far from satisfactory. Therefore, the aim of this study was to explore the association of disease condition with changes in liver function indexes, intestinal flora, and plasma endotoxin (ET) and vascular endothelial growth factor (VEGF) levels in patients with liver cancer.A total of 300 patients with primary liver cancer in our hospital were enrolled in this study. All patients were divided into three groups, including early liver cancer group, middle liver cancer group, and advanced liver cancer group. Peripheral blood was collected from each subject to detect liver function indexes, procalcitonin (PCT), plasma ET, and VEGF levels. Furthermore, mid-posterior-segment stools were collected from 15 cases in each group, and sent to the company for detection of intestinal flora.Liver function indexes in peripheral blood of patients with liver cancer changed with the changes in disease condition. With the progression of liver cancer, the level of aspartate aminotransferase (AST) increased significantly, and the highest was observed in advanced liver cancer patients [(91.18±10.34) U/L] (p=0.046). However, the level of plasma total protein declined significantly, which was (24.83±1.75) g/L in advanced liver cancer patients (p=0.035). The changes in total bilirubin were significantly associated with the progression of liver cancer (p=0.003). The abundance of Clostridiales, Firmicutes, and Streptococcus in the intestinal tract was high in early liver cancer group. The abundance of Ruminococcaceae, Pasteurellaceae, Tanticharoenia, and Vagococcus in the intestinal tract was high in middle liver cancer group. Meanwhile, the abundance of Bifidobacteriales, Actinobacteria, Barnesiella, Porphyromonadaceae, and Pseudomonadales in the intestinal tract was high in advanced liver cancer group. In patients with liver cancer, the level of Enterobacteriaceae was positively correlated with that of Firmicutes (r=0.36, p=0.003), whereas it was negatively correlated with Lactobacillus (r=-0.72, p=0.021). The level of Lactobacillus was positively correlated with that of Ruminococcaceae (r=0.39, p=0.043), whereas it was negatively correlated with that of Firmicutes (r=-0.27, p=0.019). In addition, the level of PCT markedly rose in advanced liver cancer group [(6.89±0.35) ng/mL] (p=0.021). The level of ET increased significantly with the development of liver cancer, with the highest level observed in advanced liver cancer group [(0.71±0.09) EU/mL] (p=0.004). The level of VEGF also increased remarkably with the aggravation of liver cancer, and the highest was found in advanced liver cancer group [(112.33±2.11) μmol/L], showing differences among groups (p0.05).With the progression of liver cancer, the abundance of Barnesiella, etc., rose and that of Ruminococcaceae, etc., declined in the intestinal tract. Meanwhile, the composition of intestinal flora was changed, and the levels of plasma ET and VEGF increased.

To explore the expression and significance of miR-223 in mice with pulmonary fibrosis.The rats were separated into a control group (n=15), a sham operation group (n=15), and a model group (n=45) (which was then divided into a 3-day group, a 7-day group, and a 14-day group, with 15 rats in each group). The rat model of pulmonary fibrosis was established. The rats in the model group were injected with bleomycin solution, while those in the control group and sham operation group were given the same operation and injected with the same amount of normal saline. After observing the pulmonary function indexes of the rats on the 3rd, 7th and 14th days after modeling, the rats were sacrificed by cervical dislocation, the pulmonary inflammation and fibrosis of the rats were observed, and the HYP (hydroxyproline) content and miR-223 expression level were determined. Pearson correlation analysis was employed to analyze the correlation between miR-223 and HYP.The pulmonary inflammation score of the model group was significantly higher than that of the sham group and the control group, and the pulmonary inflammation of the model group significantly increased with the increase of time (p0.05). The pulmonary fibrosis score in the model group was markedly higher than that in the rest two groups, and the pulmonary fibrosis in the model group elevated significantly with the passage of time (p0.05). The relevant pulmonary function indexes of the model group rats were significantly lower than those of the other two groups, and the pulmonary function of the model group rats gradually decreased with time (p0.05). As to the HYP, it presented notably higher content in the model group than in the remaining two groups, and its content in the model group rats increased significantly with time (p0.05). The expression of miR-223 decreased with the increase of fibrosis (p0.05), and the expression level of miR-223 was negatively correlated with the HYP content (p0.05).MiR-572 targeted CDH1 to promote cell metastasis in WT by suppressing EMT.

As a newly epidemic, 2019 coronavirus disease (COVID-19) with a concentrated outbreak poses a great challenge to medical treatment. The severe and critical patients are complex complicatied with the psychological problems, and the medical staff are overworked and under tremendous psychological pressure. The surgeon participated in emergency medical rescue could provide professional treatment for the patients combined with surgical diseases, as well as specialized training for the non-surgeon crew, to reduce surgical-related mortality. With the advantages of good team consciousness, strong aseptic concept and good psychological quality, the surgeons can quickly adapt to and carry out rescue work under the premise of good self-protection. Surgeons need to develop critical care management concepts and focus on the critical care support equipment. Some suggestions are put forward for the standardized training of resident surgeons to cultivate compound talents. It is hoped that this article can lead to the thinking of how to participate in the emergency medical rescue of infectious diseases among surgeons and provide some enlightenment for future surgical education.作为新发传染病，集中暴发的新型冠状病毒肺炎（COVID-19）对医疗救治提出很大挑战。尤其是重型及危重型患者病情复杂，合并较多心理问题，而医务人员超负荷工作同时承受巨大心理压力。外科医师参与应急医疗救援，可对患者合并的外科疾病进行专科处理，同时对非外科医师培训COVID-19治疗过程中常见的外科相关问题，降低外科相关病死率。外科医师结合自身特点，扬长补短，利用团队意识佳、无菌观念强及心理素质好的优势，在做好自身防护的前提下快速适应并开展救援工作；同时建立重症管理观念，重点掌握疫情相关重症支持设备，针对疫情特点快速转型。建议结合外科住院医师规范化培训培养复合型外科人才。希望上述思考可以对外科医师更好地参与传染病应急医疗救援及外科教育提供参考。.

BackgroundAnkylosing spondylitis (AS), a common chronic inflammatory disease, is a prototype of spondyloarthritis affecting sacroiliac joints and spine with or without peripheral arthritis and other systemic symptoms[1]. Environmental factors, especially microorganisms have been suggested to implicate with AS pathogenesis[2].ObjectivesUtilizing 16S rRNA genes sequencing on the feces of untreated AS patients and healthy controls (HCs), our study aimed to provide an in-depth understanding of AS gut microbiota and identifying a feasible diagnostic strategy for AS.MethodsFecal samples were collected from 62 AS patients and 62 age-and-gender- matched HCs. Microbial genome was extracted from approximately 250mg fresh fecal samples from all participants using QIAamp PowerFecal DNA Kit (Qiagen). The V3-V4 variable regions of bacterial 16S rRNA genes were sequenced with the Illumina Miseq PE300 system. QIIME2 based pipeline was used to process the raw sequence data. Alpha and beta diversities were assessed using result from QIIME2, and comparisons of gut microbiome profile were performed using linear discriminant analysis (LDA) effect size (LEfSe) to examine differences between AS and HCs. R (version 4. 0.1) was used for comparative statistics, and pearson’s correlation was used to assess the correlations between the relative abundances of bacterial genera and clinical parameters; correlations with pResultsAS for alpha-diversity, ACE and Chao1 indices were lower in AS compared with those HCs(Figure 1A, pB, p=0.003, ANOSIM). Fecal microbial communities in AS differed significantly from those in HCs, driven by higher abundances of Escherichia-Shigella, Turicibacter, Enterococcus, et al. and a lower abundance of Agathobacter, Roseburia, Eubacterium_eligens_group, et al (Figure 1C, p+T cell and Agathobacter, B cell and Agathobacter, Streptococcus, Th1 and Prevotella, CAG−352, Th2 and Agathobacter, Th17 and Prevotella, Agathobacter, IL-2 and Agathobacter, IL-4 and Agathobacter, IL-6 and Lachnospiraceae_UCG−004, Muribaculaceae, IL-17 and Eubacterium_hallii_group, IFN-gama and Phascolarctobacterium.There were negative correlations between total lymphocytes and Escherichia−Shigella, CD4+T cell and Enterobacteriaceae, Th2 cell and Escherichia−Shigella, IL-10 and CAG−352, Ruminococcus (Figure 2, pFigure 1.Feature of gut microbiota in AS patients and HCs. (A) Alpha-diversity assessed by richness (Chao1, ACE) and diversity (Shannon, Simpson), Median estimates compared across cohorts. (B) PCoA plot based on the Bray curtis distance of gut microbiota samples from AS patients vs. HC group(p=0.003, ANOSIM). (C) Panel demonstrated the average relative abundance of different genus in AS and HCs. (D) Distribution of gut microbiota at genus level.Figure 2.Correlations between the relative abundance of significantly different bacteria and clinical variables. *pConclusionHuman gut microbiome in patients with AS differed from that of the HCs. Characters of bacteria communities were associated with disease activity.References[1]Simone D, Al Mossawi M H, Bowness P. Progress in our understanding of the pathogenesis of ankylosing spondylitis [J]. Rheumatology (Oxford), 2018, 57(suppl_6): vi4-vi9.[2]Zhou C, Zhao H, Xiao X Y, et al. Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis [J]. J Autoimmun, 2020, 107(102360.AcknowledgementsThis project was supported by the National Natural Science Foundation of China (No. 82001740).Disclosure of InterestsNone declared

For solar system boundary exploration mission, this paper designed an X-ray pulsar-based navigation (XNAV) scheme. The Fisher information matrix is used to choose optimal pulsar observation configuration. Based on the selected pulsar configuration, the accuracy of pulsar navigation and stellar angle navigation is compared. Besides, the navigation performance of XNAV is verified by the orbits of voyager 1, voyager 2 and pioneer 10 respectively. Simulation results show that the pulsar navigation could provide accurate positioning results for solar system boundary explorers.

A high-speed radiation imaging system based on an image converter of liquid scintillator filled capillary arrays has been developed, which is sensitive to x rays, gamma rays, and neutrons. This imaging system has advantages of both high spatial resolution and high sensitivity because increasing the thickness of the image converter only leads to little deterioration on imaging resolution. The capillary arrays have dimensions of 150 mm diameter and 50 mm thickness, with 100 µm diameter of each capillary. The fluorescence decay time of the filled liquid scintillator based on the mixture of p-xylene and 2,5-diphenyloxazole has been evaluated to be ∼3 ns with the single photon method under the gamma ray excitation. The spatial resolution has been experimentally evaluated to be about 1.15 and 0.6 mm, under excitation of x rays and neutrons, respectively. The imaging system has been applied for diagnosing the dynamic x-ray spot generated by the rod pinch. Two frames in single shot with 15 ns temporal resolution and 20 ns inter-frame separation time have been obtained, which show the spatiotemporal distribution of the electrons bombarding the tungsten rod, indicating the ability of this imaging system in diagnosing dynamic radiation objects. In addition, the technique of capillary arrays provides a promising path for applications of advanced liquid scintillators in the field of radiation imaging.

The back-streaming neutrons (Back-n) facility at China Spallation Neutron Source (CSNS) provides an excellent white neutron source for accurate nuclear data measurements. At Back-n, the GAmma spectrometer with GErmanium Array (GAEA) in planning is designed to measure neutron-induced cross-sections, nuclear structure, and in-beam nuclear spectroscopy. As GAEA consists of various detectors, developing and maintaining the readout electronics for this spectrometer is challenging. A prototype of readout electronics based on the universal digital readout platform is proposed in this paper. The digitizer in the platform consists of a data processing carrier and a signal acquire mezzanine. Different mezzanines are designed to accommodate various detectors in GAEA. The carrier's firmware also has a universal part for data readout and a reconfigurable module for real-time data processing. In order to synchronize all digitizers, a time synchronization module is designed, based upon which a global synchronous network is constructed with PXIe chassis. Critical signals as the clock, trigger, and control can be synchronously distributed over this network with high precision, significantly simplifying the whole readout electronics. Several tests were carried out to evaluate the prototype. The measured FWHM of the 22Na characteristic peak at 1274.5 keV is better than 0.15% for the HPGe detector. The measured time resolution of the readout electronics is 34.7 ps. Test results show that the performance of the readout electronics can meet GAEA requirements.

Misalignment between the instantaneous center of rotation (ICR) of human joint and the ICR of wearable robotic exoskeleton widely exists among most of exoskeletons widely used in rehabilitation, which results in discomfort, even endangers human safety. In order to alleviate it, this study focuses on the solution of misalignment in knee joint of lower limb exoskeletons, and proposes a compliant five-bar parallel mechanism, which offers two mobility in sagittal plane, as well as the torsional springs mounted on this mechanism, have the potential to automatically adjust the ICR of output link connected to thigh with respect to the basis link connected to shank. To reach this goal, we build the stiffness model of the mechanism and optimize its variables. And the self-alignment of the compliant five-bar parallel mechanism is verified via experimental investigations.

An experiment was conducted to determine the effects of soy isoflavone daidzein on ruminal fermentation, microbial protein synthesis and rumen bacterial community in beef cattle. Six rumen-cannulated adult beef cattle were assigned to three blocks according to similar body weight in a randomised block design, with two cattle each block. Each block randomly received one of the two dietary treatments: control (basal concentrate) and daidzein (supplementation with 500 mg daidzein/kg basal concentrate). High-throughput sequencing data showed that supplemental daidzein increased the relative abundance of bacteria belonging to phylum Bacteroidetes (p = .050), but reduced and tended to reduce the relative abundance of phylum Spirochaetae (p = .030) and Firmicutes (p = .080). At the genus level, the relative abundance of Prevotella (p = .036), RC9_gut_group (p = .019), Succinivibrio (p = .093) and Ruminobacter (p = .085) were increased or tended to be increased by daidzein supplementation. However, supplemental daidzein reduced or tended to reduce some uncultured and unclassified bacteria genus belonging to Ruminococcaceae (p = .028), Prevotellaceae (p = .088) and Lachnospiraceae (p = .068). The ruminal pH (p = .023) and ammonia-N (p = .031) concentration were lower in the daidzein group than in the control group, but the daidzein group tended to have greater ruminal total VFA (p = .063) concentration. Supplemental daidzein increased urinary excretion of allantoin (p = .005) and total purine derivatives (p = .007). Current results suggest that supplemental daidzein can affect ruminal fermentation by changing ruminal microbial community, increase the production of VFA and enhance microbial protein synthesis in the rumen, showing the potential of daidzein for improving ruminal fermentation in beef cattle.

The Hybrid Illinois Device for Research and Applications (HIDRA) is a toroidal fusion device at the University of Illinois at Urbana–Champaign, Urbana, IL, USA. HIDRA is the former WEGA stellarator that was operated at the Max Planck Institut fur Plasmaphysik, Greifswald, Germany. The machine is a five-period, $l=2, m=5$ stellarator, with major radius $R_{0}=0.72$ m, and minor radius $a=0.19$ m. Initial heating is achieved with 2.45-GHz electron cyclotron resonance heating and an on-axis magnetic field of $B_{0}=0.087$ T that can go as high as $B_{0}=0.5$ T. HIDRA has the ability to operate as both a stellarator and a tokamak, initially operating in the stellarator mode. The focus of research on HIDRA will be doing dedicated studies on plasma-material interactions (PMIs) using the wealth of knowledge and experience at the Center for Plasma Material Interactions, Urbana, IL, USA. In early 2016, the first experiments were performed on HIDRA. This paper presents some of the first results obtained from the machine such as initial magnetic fields’ measurements and plasma discharges. It also shows the development of the control system being currently implemented and introduces HIDRA-materials analysis tool, the in situ PMI facility that will be mounted on HIDRA in the near future to further enhance the diagnostics and material testing experiments meant to be conducted on the machine.

Topographic correction of surface reflectance in rugged terrain areas is the prerequisite for the quantitative application of remote sensing in mountainous areas. Physics-based radiative transfer model can be applied to correct the topographic effect and accurately retrieve the reflectance of the slope surface from high quality satellite image such as Landsat8 OLI. However, as more and more images data available from various of sensors, some times we can not get the accurate sensor calibration parameters and atmosphere conditions which are needed in the physics-based topographic correction model. This paper proposed a semi-empirical atmosphere and topographic corrction model for muti-source satellite images without accurate calibration parameters.Based on this model we can get the topographic corrected surface reflectance from DN data, and we tested and verified this model with image data from Chinese satellite HJ and GF. The result shows that the correlation factor was reduced almost 85 % for near infrared bands and the classification overall accuracy of classification increased 14 % after correction for HJ. The reflectance difference of slope face the sun and face away the sun have reduced after correction.

We investigate the topological properties of a trimerized parity–time ( P T ) symmetric non-Hermitian rhombic lattice. Although the system is P T -symmetric, the topology is not inherited from the Hermitian lattice; in contrast, the topology can be altered by the non-Hermiticity and depends on the couplings between the sublattices. The bulk–boundary correspondence is valid and the Bloch bulk captures the band topology. Topological edge states present in the two band gaps and are predicted from the global Zak phase obtained through the Wilson loop approach. In addition, the anomalous edge states compactly localize within two diamond plaquettes at the boundaries when all bands are flat at the exceptional point of the lattice. Our findings reveal the topological properties of the P T -symmetric non-Hermitian rhombic lattice and shed light on the investigation of multi-band non-Hermitian topological phases.