RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling

Tumor-associated macrophages(TAMs)play crucial roles in tumor progression and immune responses.However,mechanisms of driving TAMs to antitumor function remain unknown.Here,transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12(RGS12)regulates pathologic processes and immune-related pathways.Mice with RGS12knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues,and extensive proliferation and invasion of oral cancer cells.RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length.Mechanistically,RGS12 associates with and activates MYC binding protein 2(MYCBP2)to degrade the cilia protein kinesin family member 2A(KIF2A)in TAMs.Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.

Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering

Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors(GFs), it makes stem cells the ideal agents for bone regeneration.Furthermore, platelet-rich plasma(PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future.

Carbon dioxide emissions from cities in China based on high resolution emission gridded data

Based on the China high resolution emission gridded data(1 km spatial resolution), this article is aimed to create a Chinese city carbon dioxide(CO_2) emission data set using consolidated data sources as well as normalized and standardized data processing methods. Standard methods were used to calculate city CO_2 emissions, including scope 1 and scope 2. Cities with higher CO_2 emissions are mostly in north, northeast, and eastern coastal areas. Cities with lower CO_2 emissions are in the western region. Cites with higher CO_2 emissions are clustered in the Jing-Jin-Ji Region(such as Beijing, Tianjin, and Tangshan), and the Yangtze River Delta region(such as Shanghai and Suzhou).The city per capita CO_2 emission is larger in the north than the south. There are obvious aggregations of cities with high per capita CO_2 emission in the north. Four cities among the top 10 per capita emissions(Erdos, Wuhai, Shizuishan, and Yinchuan) cluster in the main coal production areas of northern China. This indicates the significant impact of coal resources endowment on city industry and CO_2 emissions. The majority(77%) of cities have annual CO_2 emissions below 50 million tons. The mean annual emission, among all cities, is 37 million tons. Emissions from service-based cities, which include the smallest number of cities, are the highest. Industrial cities are the largest category and the emission distribution from these cities is close to the normal distribution. Emissions and degree of dispersion, in the other cities(excluding industrial cities and service-based cities), are in the lowest level. Per capita C02 emissions in these cities are generally below 20 t/person(89%) with a mean value of 11 t/person. The distribution interval of per capita CO_2 emission within industrial cities is the largest among the three city categories. This indicates greater differences among per capita CO_2 emissions of industrial cities. The distribution interval of per capita CO_2 emission of other cities is the lowest, indicating smaller differences of per capita CO_2 emissions among this city category. Three policy suggestions are proposed: first, city CO_2 emission inventory data in China should be increased,especially for prefecture level cities. Second, city responsibility for emission reduction, and partitioning the national goal should be established, using a bottom-up approach based on specific CO_2emission levels and potential for emission reductions in each city. Third, comparative and benchmarking research on city CO_2 emissions should be conducted, and a Top Runner system of city CO_2emission reduction should be established.

Open-circuit Fault-tolerant Control Strategy Based on Five-level Power Converter for SRM System

Switched reluctance motor power converters are prone to open-circuit faults because it need to withstand large voltages and currents.Due to the small number of traditional asymmetrical half bridge topology switches,it is difficult to carry out fault tolerant control when power converters has an open-circuit fault,resulting in larger output torque ripple.This paper presents a five-level power converter based on the traditional asymmetric half-bridge power converter.The five-level topology has more switching states and can work in multi-level mode.Based on the topology,different excitation and demagnetization voltages can be choose at different speeds.A fault-tolerance strategy is developed to decrease the influence of the open-circuit fault.The five-level power converter has four switches per phase,and two of them will be used in one of the operating mode.So the remaining two of the switches can be used for safe backup,enabling fault-tolerant control when an open-circuit occur.Since each phase of the five-level power converter proposed in this paper is independent of each other,a reasonable control strategy can be used to avoid the unbalance of the midpoint potential.Finally,the topology and fault-tolerant strategy proposed in this paper are verified by simulation and experiment.

Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of col agen-induced arthritis

IFT20 is the smallest member of the intraflagellar transport protein（IFT） complex B. It is involved in cilia formation. Studies of IFT20 have been confined to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro. However, how IFT20 regulates T-cell development and activation in vivo is still unknown. We deleted the IFT20 gene in early and later stages of T-cell development by crossing IFT20flox/flox（IFT20f/f） mice with Lck-Cre and CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation and in the development of T cell-mediated collagen-induced arthritis（CIA）. We found that both Lck-Cre/IFT20f/f and CD4-Cre/IFT20f/f mice were indistinguishable from their wild-type littermates in body size, as well as in the morphology and weight of the spleen and thymus. However, the number of CD4- and CD8-positive cells was significantly lower in thymus and spleen in Lck-Cre/IFT20f/f mice. Meanwhile, the incidence and severity of CIA symptoms were significantly decreased, and inflammation in the paw was significantly inhibited in Lck-Cre/IFT20f/f mice compared to Lck-Cre/IFT201/1littermates. Deletion IFT20 in more mature T cells of CD4-Cre/IFT20f/f mice had only mild effects on the development of T cells and CIA. The expression of IL-1b, IL-6 and TGF-b1 were significantly downregulated in the paw of Lck-Cre/IFT20f/f mice, but just slight decreased in CD4-Cre/IFT20f/f mice. These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

Stability Analysis of q-axis Rotor Flux Based Model Reference Adaptive System Updating Rotor Time Constant in Induction Motor Drives

q-axis rotor flux can be chosen to form a model reference adaptive system(MRAS)updating rotor time constant online in induction motor drives.This paper presents a stability analysis of such a system with Popov’s hyperstability concept and small-signal linearization technique.At first,the stability of q-axis rotor flux based MRAS is proven with Popov’s Hyperstability theory.Then,to find out the guidelines for optimally designing the coefficients in the PI controller,acting as the adaption mechanism in the MRAS,small-signal model of the estimation system is developed.The obtained linearization model not only allows the stability to be verified further through Routh criterion,but also reveals the distribution of the characteristic roots,which leads to the clue to optimal PI gains.The theoretical analysis and the resultant design guidelines of the adaptation PI gains are verified through simulation and experiments.

Foliar Application of Brassinolide Induced Regulation of Grain Yield and Quality,Antioxidant Responses and Aroma in Fragrant Rice

Brassinolide(BR)is a new green plant growth regulator.The present field study was conducted on two fragrant rice cultivars(i.e.,Meixiangzhan-2 and Xiangyaxiangzhan)to study the effects of foliar application of BR on fragrant rice performance.At the heading stage,BR solutions at 0.05,0.15,0.25 and 0.50 mg L-1 were sprayed on fragrant rice at 600 liters per hectare;these treatments were named as BR1,BR2,BR3 and BR4,respectively.The treatment sprayed with distilled water was taken as a control(CK).Compared with CK,the BR2 treatment significantly enhanced the chlorophyll concentration and net photosynthetic rate for Meixiangzhan-2,and Xiangyaxiangzhan.The BR3 and BR4 treatments increased the concentrations of chlorophyll a,chlorophyll b and carotenoid,and also enhanced net photosynthetic rate by 31.91%and 40.43%,respectively.Higher grain yields were recorded in the BR2 treatment than on CK on Meixiangzhan-2,while on Xiangyaxiangzhan,the BR3 and BR4 treatments increased grain yield compared with CK.In relation to CK,higher head rice rates were recorded in the BR2 treatment for Meixiangzhan-2,and in the BR3 and BR4 treatments for Xiangyaxiangzhan.BR treatments(BR2 for Meixiangzhan-2,BR3 and BR4 for Xiangyaxiangzhan)also significantly enhanced the activities of GPX,SOD and CAT by 10.22%to 23.00%,and reduced the malonaldehyde concentration.In addition,we observed that some BR treatments(BR2 for Meixiangzhan-2,BR3 and BR4 for Xiangyaxiangzhan)decreased the grain 2-acetyl-1-pyrroline concentration of fragrant rice.

Type Ⅱ collagen-positive progenitors are important stem cells in controlling skeletal development and vascular formation

Type II collagen-positive(Col2^(+))cells have been reported as skeletal stem cells(SSCs),but the contribution of Col2^(+)progenitors to skeletal development both prenatally and postnatally during aging remains unclear.To address this question,we generated new mouse models with ablation of Col2^(+)cells at either the embryonic or postnatal stages.The embryonic ablation of Col2^(+)progenitors resulted in the death of newborn mice due to a decrease in skeletal blood vessels,loss of all vertebral bones and absence of most other bones except part of the craniofacial bone,the clavicle bone and a small piece of the long bone and ribs,which suggested that intramembranous ossification is involved in long bone development but does not participate in spine development.The postnatal ablation of Col2^(+)cells resulted in mouse growth retardation and a collagenopathy phenotype.Lineage tracing experiments with embryonic or postnatal mice revealed that Col2^(+)progenitors occurred predominantly in the growth plate(GP)and articular cartilage,but a limited number of Col2^(+)cells were detected in the bone marrow.Moreover,the number and differentiation ability of Col2^(+)progenitors in the long bone and knee joints decreased with increasing age.The fate-mapping study further revealed Col2^(+)lineage cells contributed to,in addition to osteoblasts and chondrocytes,CD31^(+)blood vessels in both the calvarial bone and long bone.Specifically,almost all blood vessels in calvarial bone and 25.4%of blood vessels in long bone were Col2^(+)lineage cells.However,during fracture healing,95.5%of CD31^(+)blood vessels in long bone were Col2^(+)lineage cells.In vitro studies further confirmed that Col2^(+)progenitors from calvarial bone and GP could form CD31^(+)vascular lumens.Thus,this study provides the first demonstration that intramembranous ossification is involved in long bone and rib development but not spine development.Col2^(+)progenitors contribute to CD31^(+)skeletal blood vessel formation,but the percentage differs between long bone and skull bone.The number and differentiation ability of Col2^(+)progenitors decreases with increasing age.

Single doses of p38 MAP kinase inhibitors or prednisolone affect CRP and IL-6 in patients with active Rheumatoid Arthritis (RA)

Purpose: To investigate the effects of single doses of losmapimod, dilmapimod (inhibitors of p38 MAPK) and prednisolone on biomarkers of systemic inflammation (serum C-reactive protein (CRP) and interleukin (IL)-6) in subjects with active rheumatoid arthritis (RA). Methods: Two randomized, double blind, placebo controlled, parallel group, single dose studies investigated the CRP and IL-6 dose-response relationships for losmapimod (study A) and dilmapimod and prednisolone (study B) in patients with active RA on stable weekly doses of methotrexate. CRP, IL-6 and other exploratory biomarkers were measured in blood at baseline and up to 72 hours post-dosing. Results: In study A, 51 subjects were randomized to receive losmapimod (7.5, 20 and 60 mg) or placebo and in study B, 77 subjects were randomized to receive dilmapimod (7.5, 15 and 25 mg) or prednisolone (10, 20 and 50 mg) or placebo. Single doses of prednisolone caused a decrease in circulating IL-6 detectable at 3 and 24 hours post-dose as well as a CRP single-dose relationship at 48 hours post-dose in patients with active RA. All doses of losmapimod produced a statistically significant reduction in serum IL-6, 3 hours post-dose but had no effect on CRP. Dilmapimod had no effect on IL-6 or CRP at any dose or time. Conclusion: This single-dose response clinical study design could be useful in the early clinical development of anti-inflammatory agents for the treatment of rheumatoid arthritis. Inhibition of both circulating IL-6 and CRP would increase confidence that a new chemical entity may have the potential to deliver clinical benefit in RA. Trial registration: [clinicaltrials.gov: NCT00256919 and NCT00134693].

Deficiency of Trp53 and Rb1 in myeloid cell lineage spontaneously develops acute myeloid leukemia in a mouse model

Acute myeloid leukemia(AML)is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic tissue.In recent decades,AML patients are significantly increased.In 2019 alone,21,450 new AML cases were diagnosed in the United States,with an estimated 10,920 deaths due to AML.What’s worse,AML occurs with an increasing incidence with advanced age,and the survival rate remains dismal with a median overall survival of only 5e10 months.Notwithstanding great advances in allogenic transplant and chemotherapy,the therapeutic outcomes are unfavorable due to the disease relapse and mortality rates.More importantly,the development of more specific and effective therapies was hampered in part by the lack of proper animal models for AML.Thus,management and elucidation of the pathological mechanism of AML remain an ongoing challenge,and the development of effective AML mouse models and treatment options are urgently needed.

Vector Control Strategy of a T-type Three-level Converter Driving a Switched Reluctance Motor

A novel 12 voltage vector control strategy for switched reluctance motors(SRM)with a T-type three-level converter is proposed in this study.Based on a causal analysis of torque ripple under the control of conventional six voltage vectors,six new voltage vectors are added for further reduction of torque ripple.An optimized control rule is adopted based on the division method of the 12 new voltage vectors.A zero-voltage vector is used to adjust the duration of the 12 voltage vectors,the time of which is varied at different parts of the vector sectors according to the torque error.In addition,the windings are connected in a delta configuration,therefore,the number of connections between the converter and SRM is reduced.Finally,the results of MATLAB/Simulink and RT-LAB are presented to verify the validity of the proposed scheme.

Modeling and experiment of grinding wheel axial profiles based on gear hobs

Hobbing is one of the crucial gear manufacturing processes with high precision and high efficiency.In order to improve the accuracy of hobbing and hob relief grinding,more precise grinding wheels are demanded for relief grinding in the production of gear hobs.In this paper,a new and accurate mathematical method for calculating the axial profile of grinding wheel based on the corresponding gear hob to be ground is proposed.Considering that most researches have been conducted to focus on the optimization of hob geometric feature and only can be applied to a specific type of hand of helix and rake angle of gear hobs.The method in this paper can be served as a general algorithm for generating axial profile of grinding wheels on the basis of the spatial envelope theory,the principle of coordinate system transformation,and studies on normal profile of single-tooth.The accuracy of grinding hobs is based on applying the approach in practical manufacturing.Taking two typical different kinds of pre-grinding gear hobs as examples for calculation and experiment,the results of tooth profile errors strengthen the position that the validity and feasibility of this method,it can be employed for gear hob design and grinding processing.

Improved Fractional-order Damping Method for Voltage-controlled DFIG System Under Weak Grid

When a doubly-fed induction generator(DFIG)is connected to a weak grid,the coupling between the grid and the DFIG itself will increase,which will cause stability problems.It is difficult to maintain the tracking accuracy and robustness of the phase-locked loop(PLL)in the weak grid,and the risk of instability of the current-controlled DFIG(CC-DFIG)system will increase.In this paper,a new type of voltage-controlled DFIG(VC-DFIG)mode is adopted,which is a grid-forming structure that can independently support the voltage and frequency with a certain adaptability in the weak grid.A small-signal impedance model of the VC-DFIG system is also established.The impedance of DFIG inevitably generates coupling with the grid impedance in the weak grid,especially in parallel compensation grids,and results in resonance.On the basis of the VC-DFIG,impedance stability analysis is performed to study the influences of the control structure and short-circuit ratio.Then,a feedforward damping method is proposed to modify the impedance of the VC-DFIG system at resonance frequencies.The proposed fractional order damping is utilized,which can enhance the robustness and rapidity of resonance suppression under parameter fluctuations.Finally,the experimental results are presented to validate the effectiveness of the proposed control strategy.

Macrophage RGS12 contributes to osteoarthritis pathogenesis through enhancing the ubiquitination

Ubiquitination has important functions in osteoarthritis(OA),yet the mechanism remains unclear.Here,we identify the regulator of G protein signaling 12(RGS12)in macrophages,which promotes the association between ubiquitin and IκB during inflammation.We also find that RGS12 promotes the degradation of IκB through enhancing the ubiquitination whereas the process can be inhibited by MG132.Moreover,the increased ubiquitination further inhibits the expression of MTAP,which can indirectly activate the phosphorylation of IκB.Finally,due to the degradation of IκB,the NF-κB translocates into the nucleus and further promotes the gene expression of cytokines such as IL1β,IL6,and TNFαduring inflammation.Importantly,RGS12 deficiency prevents ubiquitination and inflammation in surgically or chemically induced OA.We conclude that the lack of RGS12 in macrophages interferes with the ubiquitination and degradation of IκB,thereby preventing inflammation and cartilage damage.Our results provide evidence for the relevance of RGS12 in promoting inflammation and regulating immune signaling.

RGS12 inhibits the progression and metastasis of multiple myeloma by driving M1 macrophage polarization and activation in the bone marrow microenvironment

Dear Editor,Multiple myeloma(MM)is a malignant plasma cancer that grows in the bone marrow and migrates through the bloodstream.Fifty-eight percent of MM patients exhibit the phenotype of hepatomegaly,and 40%have myeloma cell infiltration in the liver[1].The occurrence and migration of MM are highly associated with the bone marrow microenvironment[2].A key in the develop-ment of MM is the evasion and suppression of the host immune system.Monocyte/macrophage-lineage cells are major components of the infiltrating leukocytes in tumors.