Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients

Summary:The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease.Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic.In this study,we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia(FOP)patients who underwent lung surgery and served as controls.We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients.In contrast to the FOP patients,Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients.This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients.In summary,our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity.Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.

A novel launch dynamics measurement system for multiple launch rocket system and comparative analysis with numerical simulations

In this paper,a novel launch dynamics measurement system based on the photoelectric sensor pair is built.The actual muzzle time(i.e.a time duration that originates from the initial movement to the rocket’s departure from the muzzle)and the muzzle velocity are measured.Compared with the classical methods,the actual muzzle time is obtained by eliminating the ignition delay.The comparative analysis method is proposed with numerical simulations established by the transfer matrix method for multibody systems.The experiment results indicate that the proposed measurement system can effectively measure the actual muzzle time and reduce the error of classical methods,which match well with the simulation results showing the launch dynamics model is reliable and helpful for further analysis and design of the MLRS.

An efficient and modular modeling for launch dynamics of tubed rockets on a moving launcher

This paper develops a modular modeling and efficient formulation of launch dynamics with marching fire(LDMF)using a mixed formulation of the transfer matrix method for multibody systems(MSTMM)and Newton-Euler formulation.Taking a ground-borne multiple launch rocket systems(MLRS),the focus is on the launching subsystem comprising the rocket,flexible tube,and tube tail.The launching subsystem is treated as a coupled rigid-flexible multibody system,where the rocket and tube tail are treated as rigid bodies while the flexible tube as a beam with large motion.Firstly,the tube and tube tail can be elegantly handled by the MSTMM,a computationally efficient order-N formulation.Then,the equation of motion of the in-bore rocket with relative kinematics w.r.t.the tube using the Newton-Euler method is derived.Finally,the rocket,tube,and tube tail dynamics are coupled,yielding the equation of motion of the launching subsystem that can be regarded as a building block and further integrated with other subsystems.The deduced dynamics equation of the launching subsystem is not limited to ground-borne MLRS but also fits for tanks,self-propelled artilleries,and other air-borne and naval-borne weapons undergoing large motion.Numerical simulation results of LDMF are given and partially verified by the experiment.

Adaptive control of track tension estimation using radial basis function neural network

Track tension is a major factor influencing the reliability of a track.In order to reduce the risk of track peel-off,it is necessary to keep track tension constant.However,it is difficult to measure the dynamic tension during off-road operation.Based on the analysis of the relation and external forces depending on free body diagrams of the idler,idler arm,road wheel and road arm,a theoretical estimation model of track tension is built.Comparing estimation results with multibody dynamics simulation results,the rationality of track tension monitor is validated.By the aid of this monitor,a track tension control system is designed,which includes a self-tuning proportional-integral-derivative(PID)controller based on radial basis function neural network,an electro-hydraulic servo system and an idler arm.The tightness of track can be adjusted by turning the idler arm.Simulation results of the vehicle starting process indicate that the controller can reach different expected tensions quickly and accurately.Compared with a traditional PID controller,the proposed controller has a stronger anti-disturbance ability by amending control parameters online.

A New Method of Establishing Orthotopic Bladder Transplantable Tumor in Mice

Objective The present study aims to find a convenient, rapid, and stable method to establish bladder tumor in mice. Methods Female Balb/C-nu-nu nude mice （or female T739 mice） were narcotized by sodium pentobarbital at a dosage of 60 mg/ kg. The stylet of the 24# venous retention needles was bent in a 5° to 7° angle at a distance of 15 mm from the needlepoint to form a circle with 2.61 mm to 3.66 mm radius when the stylet is rotated. The pipe casing was lubricated with liquid paraffin, and inserted into the bladder cavity. The drift angle stylet was inserted into the pipe casing slowly, rotated for five times, and then pulled out. A cell 6 suspension （0.1 mL） of approximately lx10 T24 cells （or BTT cells） was then injected imme＆ately. Results A total of 60 T739 mice and 60 Balb/C-nu-nu nude mice were inoculated with BTT cells and T24 cells, respectively. The bladder tumor incidence and the average survival time of the tumor-bearing mice were 100% and （26.69±9.24） d and 100% and （34.59±9.8） d for the T739 mice and Balb/C-nu-nu nude mice, respectively. Conclusions Using the drift angle stylet to injure the mucous membrane of the urinary bladder can establish a stable bladder transplantable tumor model in mice.

A review on image-based rendering

Image-based rendering is important both in the field of computer graphics and computer vision,and it is also widely used in virtual reality technology.For more than two decades,people have done a lot of work on the research of image-based rendering,and these methods can be divided into two categories according to whether the geometric information of the scene is utilized.According to this classification,we introduce some classical methods and representative methods proposed in recent years.We also compare and analyze the basic principles,advantages and disadvantages of different methods.Finally,some suggestions are given for research directions on image-based rendering techniques in the future.

RON in hepatobiliary and pancreatic cancers:Pathogenesis and potential therapeutic targets

The receptor protein tyrosine kinase RON belongs to the c-MET proto-oncogene family.Research has shown that RON has a role in cancer pathogenesis,which places RON on the frontline of the development of novel cancer therapeutic strategies.Hepatobiliary and pancreatic(HBP)cancers have a poor prognosis,being reported as having higher rates of cancer-related death.Therefore,to combat these malignant diseases,the mechanism underlying the aberrant expression and signaling of RON in HBP cancer pathogenesis,and the development of RON as a drug target for therapeutic intervention should be investigated.Abnormal RON expression and signaling have been identified in HBP cancers,and also act as tumorigenic determinants for HBP cancer malignant behaviors.In addition,RON is emerging as an important mediator of the clinical prognosis of HBP cancers.Thus,not only is RON significant in HBP cancers,but also RON-targeted therapeutics could be developed to treat these cancers,for example,therapeutic monoclonal antibodies and small-molecule inhibitors.Among them,antibody-drug conjugates have become increasingly popular in current research and their potential as novel anti-cancer biotherapeutics will be determined in future clinical trials.

Some issues in diagnostics of solar chromospheric magnetic fields with the Mg b_2 line

Up to now, exact measurements of chromospheric magnetic fields have not been as successful as those done in the photosphere. We are currently engaging in diagnostics of chromospheric magnetic fields with the Mg b2 line by employing the Multi-Channel Solar Telescope at Huairou Solar Observing Station. Therefore, how to improve accuracy in the measurement is the main issue of our present study. To this end, we first study linear calibration coefficients for longitudinal and transverse components of chromospheric fields, which vary with wavelength, in the case of a weak field assumption. Then the polarization crosstalk introduced by instruments is analyzed in detail with two numerical simulation methods. Comparisons of the po- larization signals between cases with and without correction are presented. The result indicates that polarization accuracy is greatly improved after crosstalk correction.

Prostate Cancer Detection with Multiparametric Magnetic Resonance Imaging： Prostate Imaging Reporting and Data System Version 1 versus Version 2

Background：Prostate Imaging Reporting and Data System （PI-RADS） is a globally acceptable standardization for multiparametric magnetic resonance imaging （mp-MRI） in prostate cancer （PCa） diagnosis.The American College of Radiology revised the PI-RADS to address the limitations of version 1 in December 2014.This study aimed to determine whether the PI-RADS version 2 （PI-RADS v2） scoring system improves the diagnostic accuracy of mp-MRI of the prostate compared with PI-RADS v1.Methods：This retrospective study was approved by the institutional review board.A total of 401 consecutive patients,with clinically suspicious Pca undergoing 3.0 T mp-MRI （T2-weighted imaging ＋ diffusion-weighted imaging ＋ DCE） before transrectal ultrasound-guided biopsy between June 2013 and July 2015,were included in the study.All patients were scored using the 5-point PI-RADS scoring system based on either PI-RADS v1 or v2.Receiver operating characteristics were calculated for statistical analysis.Sensitivity,specificity,and diagnostic accuracy were compared using McNemar＇s test.Results：Pca was present in 150 of 401 （37.41%） patients.When we pooled data from both peripheral zone （PZ） and transition zone （TZ）,the areas under the curve were 0.889 for PI-RADS v1 and 0.942 for v2 （P =0.0001）.Maximal accuracy was achieved with a score threshold of 4.At this threshold,in the PZ,similar sensitivity,specificity,and accuracy were achieved with v 1 and v2 （all P 〉 0.05）.In the TZ,sensitivity was higher for v2 than for v1 （96.36% vs.76.36%,P =0.003）,specificity was similar for v2 and v1 （90.24% vs.84.15%,P =0.227）,and accuracy was higher for v2 than for v1 （92.70% vs.81.02%,P =0.002）.Conclusions：Both v1 and v2 showed good diagnostic performance for the detection of Pca.However,in the TZ,the performance was better with v2 than with v1.

Native Medicinal Plant Richness Distribution Patterns and Environmental Determinants of Xinjiang, Northwest China

Objective To comprehensively map the distribution patterns of native medicinal plants of Xinjiang Uygur Autonomous Region, China; To find the environmental determinants and to give suggestions for the conservation planning of medicinal plants in Xinjiang region. Methods Firstly, we compiled the distribution data of native medicinal plants at a county level in Xinjiang region, including the source plants of Chinese Materia Medica （CMM）, Uygur Medicine （UM）, and Kazak Medicine （KM）; Secondly, we divided the distribution data into grid with a resolution of 0.1~ x 0.1~ and overlaid it on the topography and climate data in Arcgis 10.0; Finally, we analyzed the correlations of medicinal plant richness and environmental variables with ordinary least square （OLS） regressions and partial regressions. Results UM has more non-native species in Xinjiang region than KM. The species richness of medicinal plants is high in Altay Mountains, western Tianshan Mountains, and part of Kunlun Mountains. The richness of medicinal plants is highly correlated with the vascular plant species richness and climate, and further, the independent effects of vascular plant species richness are higher than the independent effects of climate. The whole plant, root ＆ rhizome, and seed ＆ fruit are more frequently used than stem and leaf for CMM in Xinjiang region. Conclusion The distribution patterns of medicinal plants are concordant with vascular plant species, which could be carefully considered in the conservation planning of this region. Taking full advantage of current nature reserves is a low-costing approach to the conservation of medicinal plants although they were not originally established for medicinal plant protection. Nevertheless, it is urgent to further study the distributions and protection status of medicinal plants in the nature reserves of Xinjiang region.

Towards a scientific rationale for traditional properties of Chinese medicinal plants: “natures” and “flavors”

Objective: According to theory of Chinese medicine property, the ecological environment shapes properties(natures and flavors) of Chinese materia medica(CMM) and there are close relationships between certain natures and flavors. However, to date these observations have not been validated scientifically in the context of the whole flora of a region. The present study aims to address this gap.Methods: We collected geographical distributions of 3637 vascular plant species native to the Xinjiang region of northwest China, of which around 812 are medicinal plants. The CMM property characters of these medicinal plants were also collected. All medicinal plants were then analyzed in the occurrence of their natures(cold, cool, neutral, warm, and hot) and flavors(sweet, bitter, sour, salty, and pungent). Possible correlations between these properties and environmental factors, notably climate, as well as correlations with plant species richness of the wider native flora of Xinjiang were then investigated using permutation test and regression.Results: Cold species(38.5%) were more numerous than warm(21.0%) and neutral(22.3%), while bitter species(43.3%) were more numerous than pungent(25.6%), sweet(22.4%) and sour(6.7%) ones. Species with bitter flavor were most commonly also cold(48.6%) in nature, sour flavor usually coincided with cold(44.2%) or cool nature(26.0%), whereas pungent or sweet species tended to be warm(34.4%, 28.4%) or neutral(27.8%, 28.4%). The percentages of species of cold/cool nature, bitter flavor were higher in mountainous regions, and the percentages of warm/neutral and pungent/sweet/sour were higher in basins. The percentages of species of cold/cool, bitter were positively correlated with actual evapotranspiration(AET),and also plant species richness but had a bell-shaped relationship with potential evapotranspiration(PET),whereas the inverse situation was shown for warm/neutral and pungent/sweet/sour species.Conclusion: Analysis of the data in Xinjiang region of China supports the qualitative observations concerning natures and flavors in traditional theory of Chinese medicine property. Specifically,(i) certain natures and flavors co-occur more frequently than if randomly distributed;(ii) correlations between proportions of natures and flavors and climatic variables suggest a role for the environment in shaping the properties of CMM.

Suppression of vortex-induced vibrations of a flexible riser by adding helical strakes

3-D computational fluid dynamics/ computational structure dynamics (CFD/CSD) numerical two-way coupling simulations are conducted for a flexible rise in order to study the dynamic response performance of the riser with and without helical strakes exposed to the vortex-induced vibration (VIV). The VIV responses of a PVC riser without helical strakes are computed and compared with experimental data, to verify the accuracy of the present two-way coupling method. Subsequently, the dynamic behaviors of a short PVC riser with different kinds of helical strakes are studied. The vibration amplitudes along the riser, the trajectories of the riser's monitor point and the vortex shedding contours are obtained in a series of simulations. The helical strakes5 VIV suppression mechanisms are found involving the breaking of the vortex structures and the reduction of the vortex shedding frequency of the bare riser. Moreover, a good suppression effect can be achieved by attaching the helical strake structure with a reasonable geometrical configuration (such as the appropriate strake height, strake pitch, the number of starts and strake coverages) to the flexible riser. The effect is also diverse at different reduced velocity (Ur). The remarkable effect is found at Ur = l for the short riser, with about 97% reduction in the transverse vibration response.

Hilar cholangiocarcinoma: Pathology and tumor biology

Hilar cholangiocarcinoma,first described by Klatskin in 1965,is a relatively rare tumor arising from the bile ducts.The histomorphological features of hilar cholangiocarcinoma are identical with other extra-and intra-hepatic bile duct carcinomas.The most common disease associated with cholangiocarcinoma is primary sclerosing cholangitis.The development of cholangiocar-cinoma is a multistep process associated with several mutations in oncogenes and tumor-suppressor genes.Based on macroscopic appearance,three distinct subtypes have been described:sclerosing,nodular,and papillary.Microscopically,more than 95%of tumors are adenocar-cinomas.Hilar cholangiocarcinoma is a slowly growing tumor and tends to spread longitudinally along the bile ducts with neural,perineural,and subepithelial extension.Lymph node invasion can be found in 30%–50%patients at the time of diagnosis,but blood-born metastases are rare and usually occur at late stages.

Anti-N-methyl-D-aspartate receptor encephalitis in a 17-year-old female patient with 3 years of follow-up

To the Editor:Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a potentially lethal autoimmune disease characterized by prominent psychiatric symptoms and seizures.It usually occurs in young female patients with ovarian teratomas.[1] Here,we describe a severe case of anti-NMDAR encephalitis.The patient was originally misdiagnosed as psychosis and did not improve within the first 4 weeks of first-line immunotherapy.Although she did not continue to receive second-line immunotherapy,the patient still recovered well and had no recurrence or tumor observed during 3 years of follow-up.

Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors

A series of novel amide derivatives bearing an indazole moiety were synthesized and evaluated for their in vitro S-adenosylL-homocysteine hydrolase（SAHase） inhibitory activity. Among these compounds, 8b,8m, 8r and 8w showed better or similar inhibitory effects compared to the positive control aristeromycin. These results provide a novel lead for the discovery of more potent non-adenosine analogs as SAHase inhibitors.

Correction to“A Classification of Spectrum-determined Circulant Digraphs”

We find an error in the proof of Lemma 4 in[3].This makes that Theorem 2 and Corollary 3 in[3]are also wrong,and the next counterexample shows this.