Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis

Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status:5-year follow-up of a prospective cohort study

Objective:We investigated the relation between man papillomavirus(HPV)integration status and the immediate risk of cervical intraepithelial neoplasia(CIN),as well as the triage strategy based on HPV integration test.Methods:4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective,population-based,clinical observational study to evaluate the triage performance of HPV integration.Cervical exfoliated cells were collected for HPV testing and cytologic test.If high-risk HPV was positive,HPV integration test was performed at baseline,2-year and 5-year follow-up.Results:At baseline,HPV integration was positively correlated with the severity of cervical pathology,ranging from 5.0%(15/301)in normal diagnosis,6.9%(4/58)in CIN1,31.0%(9/29)in CIN2,70%(14/20)in CIN3,and 100%(2/2)in cervical cancer(P<0.001).Compared with cytology,HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+,higher specificity(92.8%[90.2%-95.4%]vs.75.5%[71.2%-79.8%],P<0.001)and higher positive predictive value(36.4%[22.1%-50.6%]vs.15.2%[8.5%-21.8%],P<0.001).HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy(10.7%[44/410]vs.27.3%[112/410],P<0.001).The HPV integration-negative group exhibited the lowest immediate risk for CIN3+(1.6%)and accounted for the largest proportion of the total population(89.3%),when compared with the normal cytology group(risk,1.7%;proportion,72.7%).Conclusion:As a key molecular basis for the development of cervical cancer,HPV integration might be a promising triage strategy for HPV-positive patients.

Experience of Clinical Management for Pregnant Women and Newborns with Novel Coronavirus Pneumonia in Tongji Hospital,China

Based on the New Diagnosis and Treatment Scheme for Novel Coronavirus Infected Pneumonia(Trial Edition 5),combined with our current clinical treatment experience,we recently proposed a revision of the first edition of“Guidance for maternal and fctal management during pneumonia epidemics of novel coronavirus infection in the Wuhan Tongji Hospital".This article focused on the issues of greatest concern of pregnant women including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection diagnostic criteria,inspection precautions,drug treatment options,indications and methods of termination of pregnancy,postpartum fever,breastfeeding considerations,mode of mother-to-child transmission,neonatal isolation and advice on nconatal nursing,to provide valuable experience for better management of SARS-CoV-2 infection in pregnant women and newborns.

Expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics

Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.

Advances in photothermal conversion of carbon dioxide to solar fuels

Converting carbon dioxide(CO_(2)) into useful fuels or chemical feedstocks is important for achieving peak carbon emission and carbon neutrality.Recently,photothermal catalysis has been extensively studied and applied due to its advantages over traditional heat-driven catalysis.In this review,we focus on photothermal catalysis of thermodynamically uphill reactions that convert CO_(2)into value-added products.We first introduce the fundamentals of photothermal catalysis for CO_(2)reduction,including the definition and classification of photothermal catalysis,followed by their photothermal conversion processes.The structure design of different types of photothermal catalysts is summarized.The superior performance of photothermal catalytic conversion of CO_(2)is illustrated and discussed,including improved CO_(2)activation,tunable selectivity towards different solar fuel products,and resistance to sintering and coking.Finally,the perspectives and challenges in this cutting-edge field are presented with the aim of advancing understanding of the underlying mechanisms and inspiring rational design of photothermal catalysts for highly efficient solar-to-fuel conversion.

Expression of C-Kit & PDGFRα and correlation with chemotherapy resistance in ovarian serous carcinomas:a clinical study

Objective： To investigate the expression of C-Kit and PDGFRa and their correlation with chemotherapy resistance in ovarian serous carcinoma. Methods： We undertook SP immunohistochemical technique to examine the expression of C-Kit and PDGFRa in 59 cases with ovarian serous carcinomas, using archival paraffin-embedded specimens. Then we observed the correlation with chemotherapy resistance. Results： C-Kit and PDGFRa immunostainings were observed posi- tively expressed in 57.63% and 66.10% cases. C-Kit expression was statistically correlated with the progression of disease after first-line chemotherapy （P 〈 0.05）, but PDGFRa was not statistically significant （P 〉 0.05）. There were great difference between of C-Kit and PDGFRa expressions in samples of different differentiated and clinical stages of ovarian serous carcinomas （P 〈 0.01 or P 〈 0.05）. Conclusion： C-Kit is statistically correlated with chemotherapy resistance, while PDGFRa is not correlated.

Solar Energy and Residential Building Integration Technology and Application

Building energy saving needs solar energy, but the promotion of solar energy has to be integrated with the constructions. Through analyzing the energy-saving significance of solar energy, and the status and features of it, this paper has discussed the solar energy and building integration technology and application in the residential building, and explored a new way and thinking for the close combination of the solar technology and residence.

One-step synthesis of carbon-supported copper nanoparticles from biomass for N-arylation of pyrazole

Carbon-supported copper catalyst was prepared for the first time in one-step with copper nitrate and corn stalk through calcination under different temperatures. Uniformly dispersed nanoparticles were obtained and were identified to be Cu（0） and Cu（Ⅰ） in XRD patterns. Excellent catalytic activity and selectivity were achieved in the N-arylation of pyrazole under ligand and protection gas free conditions. About90.4% of product yield was achieved with only 0.5 mol% of copper catalyst（Cu-C-300）, which was considerably more efficient than previous reports. XPS results suggested that the N-arylation of pyrazole activity was closely related to the surface Cu（Ⅰ） species.

Promotion effect of adsorbed water/OH on the catalytic performance of Ag/activated carbon catalysts for CO preferential oxidation in excess H_2

Activated carbon （AC） supported silver catalysts were prepared by incipient wetness impregnation method and their catalytic performance for CO preferential oxidation （PROX） in excess H2 was evaluated. Ag/AC catalysts, after reduction in H2 at low temperatures （≤200 ℃） following heat treatment in He at 200 ℃ （He200H200）, exhibited the best catalytic properties. Temperature-programmed desorption （TPD）, X-ray diffraction （XRD） and temperature-programmed reduction （TPR） results indicated that silver oxides were produced during heat treatment in He at 200 ℃ which were reduced to metal silver nanoparticles in H2 at low temperatures （≤200 ℃）, simultaneously generating the adsorbed water/OH. CO conversion was enhanced 40% after water treatment following heat treatment in He at 600 ℃. These results imply that the metal silver nanoparticles are the active species and the adsorbed water/OH has noticeable promotion effects on CO oxidation. However, the promotion effect is still limited compared to gold catalysts under the similar conditions, which may be the reason of low selectivity to CO oxidation in PROX over silver catalysts. The reported Ag/AC-S-He catalyst after He200H200 treatment displayed similar PROX of CO reaction properties to Ag/SiO2. This means that Ag/AC catalyst is also an efficient low-temperature CO oxidation catalyst.

Calcification-associated molecular traits and therapeutic strategies in hormone receptor-positive HER2-negative breast cancer

Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2−)breast cancer remain unclear.Methods:We retrospectively collected mammography records of an HR+/HER2−breast cancer cohort(n=316)with matched clinicopathological,genomic,transcriptomic,and metabolomic data.On the basis of mammographic images,we grouped tumors by calcification status into calcification-negative tumors,tumors with probably benign calcifications,tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy.We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results:Among the different statuses,tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores,estrogen receptor(ER)pathway activation,lipid metabolism,and sensitivity to endocrine therapy.Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes,elevated lymph node metastasis incidence,Ki-67 staining scores,genomic instability,cell cycle pathway activation,and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors.Conclusions:Our research established links between tumor calcifications and molecular features,thus proposing potential precision treatment strategies for HR+/HER2−breast cancer.

One-Pot Upgrading Polyethylene and CO_(2)to Aromatics via Tandem Catalysis

Polyolefins have the largest share in plastic waste,so it is vital to transform these end-of-life wastes into highly valued products.We present here a new catalytic method to produce aromatics using PE as a carbon source.Our results indicate that polyethylene(PE)and CO_(2)can be converted into aromatics and CO simultaneously,achieving a high transformation rate and a 64.0%selectivity toward aromatics below 400℃ by Cu-Fe_(3)O_(4)and Zn/ZSM-5 tandem catalysis.Notably,the established theoretical limit of 50%selectivity toward aromatics in PE aromatization is surpassed.This is attributed to the coexistence of reverse water-gas shift,which converts another feed,CO_(2),with hydrogen to produce valuable CO,confirmed by^(13)C isotope studies.It consumes excessive hydrogen generated during PE aromatization to produce CO and mitigates the production of light alkanes from hydrogen transfer reactions,thereby augmenting the formation of aromatic compounds.Our research offers a new approach to valorizing two prevalent waste carbon sources:waste plastic and CO_(2),which is useful for designing a new strategy for upcycling waste carbon resources.

外生技术条件下教育与产出关系的研究

教育对经济增长产生影响的重要途径之一是教育促进了生产技术的进步。以往的研究通常把技术进步看作是教育水平提高的结果,而忽略了技术本身具有的特征,即,技术是由企业外生选定的,而在选定技术条件下企业需要有接受过相应教育的劳动者与之相匹配。本文以此为出发点构建了包含企业外生技术、劳动者个人选择和社会教育水平三个因素的市场均衡模型,来研究教育投入与产出的关系。结论是人均产出的边际增长率随着外生技术水平的提高而增加,但是随着教育水平的提高先增加后减少,该结论为教育经济学中的"K-L之谜"做出了解答。最后本文采取宏观和微观数据进行了实证分析,计算出教育投入增长的最优路径,并建议政府应鼓励国家层面的创新。

Cobalt phthalocyanine-graphene complex for electro-catalytic oxidation of dopamine

Cobalt phthalocyanine-graphene （CoPc-Gr） complex are fabricated through 7r-Tr interaction of each components, with CoPc adsorbed/inserted on/in the graphene sheets. The obtained complex could be used in the electro-chemical detection of various medicines. CoPc-Gr modified glassy electrode shows excellent response to the electro-oxidation of dopamine （DA） and ascorbic acid （AA）, much better than those of CoPc, graphene oxide （GrO） or graphene （Gr） modified electrode. Significantly, the detection of dopamine is a diffusion-controlled process, highly selective, and has a low detection limit and broad linear range.

Next-generation antibody-drug conjugates revolutionize the precise classification and treatment of HER2-expressing breast cancer

The concept of antibody±drug conjugations(ADCs)can be tracked back to the early 20^(th) century when the renowned immunologist,Paul Ehrlich,proposed the idea of a"magic bullet",which utilizes ADCs for targeted destruction of microorganisms and tumor cells^(1).After nearly one century of development,ADCs have emerged as a rather promising approach in the treatment of cancer,especially breast cancer,which is the most common malignant tumor in women^(2).

Characterization and application of a recombinant dopa decarboxylase from Harmonia axyridis for the efficient biosynthesis of dopamine

Here,a dopa decarboxylase(DDC)from Harmonia axyridis was heterogeneously expressed in Escherichia coli for the efficient biosynthesis of dopamine.For the production of recombinant DDC,the cultivation conditions including IPTG concentration,temperature and induction time were optimized and obtained an optimal specific enzyme activity of 51.72 U·mg^(-1) crude extracts.After the purification of DDC with a recovery yield of 68.79%,its activity was further characterized.The Vmax,Km,Kcat,and Kcat/Km of DDC for d ihyd roxy pheny la la nine(dopa)were 0.02 mmol·ml^(-1)·s^(-1),2.328 mmol·ml^(-1),10435.90 s^(-1) and4482.77 ml,mmol respectively.The highest DDC activity was observed at the condition of pH 7.5 and 45℃.With the purified DDC,the feasibility to produce dopamine from L-dopa was evaluated.The optimal yield was determined at the following bioconversion conditions:pH of 7,0,the reaction temperature of 40℃,0.4 mmol·L^(-1) of PLP and 4 g·L^(-1) of L-dopa,Subsequently,a fed-batch process for the production of dopamine was developed and the effect of oxygen was evaluated.The titer,yield and productivity of dopamine reached up to 21.99 g·L^(-1)80.88%and 14.66 g·L^(-1)·h^(-1) at 90 min under anaerobic condition.

Correlation between Load of HPV 16 DNA in Cervical Cancer and HPV 16 DNA in Lymph Nodes

OBJECTIVE To determine the association between viral loadof human papillomavirus 16 (HPV16) DNA in the primary focusof cervical carcinoma and HPV16 DNA in pelvic lymph nodes.METHODS The HPV16 DNA load was measured by fluorescentquantitation polymerase chain reaction (FQ-PCR) in 17 primaryfoci. HPV16 DNA was detected by polymerase chain reaction(PCR) using HPV16 type-specific primers in 296 pelvic lymphnodes which were from 17 cases of cervical cancer.RESULTS The viral load of HPV16 DNA showed statisticallysignificant differences between tumors with a diameter of < 4cm and ≥ 4 cm (P < 0.05). Seven of 17 cervical cancer cases hadHPV16 DNA positive lymph nodes, designated as the positivegroup, while the remaining 10 without positive lymph nodes wasdesignated the negative group. The average load of HPV16 DNAshowed no significant difference between the 2 groups (P > 0.05).The load of HPV16 in the primary lesion was not associated withthat in the lymph nodes. There were 38 HPV16 DNA positivenodes in the total 296 nodes. The rate of positivity of HPV16 DNAin lymph nodes showed statistically significant differences inconsideration of maximum tumor diameter, tumor differentiation,histologic type, depth of myometial infiltration and the metastaticstatus of the nodes, respectively (P < 0.05).CONCLUSION Viral load of HPV16 in the primary cancer focuscorrelated with the quantity of tumor cells in the primary focusbut not with the existence of HPV DNA positive lymph nodes.Detection of HPV DNA may help to find the early metastases thatcannot be evaluated histopathologically, but the prognostic valueof HPV positive lymph nodes needs further examination.

Formation mechanism of Fe-based amorphous powders produced by spark erosion

Spark erosion is a convenient,flexible,and low-cost method to quickly produce fine powders of metals,alloys,and semiconductors in size ranging from nearly a hundred micrometers to submicrometer by repetitive spark discharges.Due to the complexity of the powder-forming journey,normally accompanied by high temperature,high pressure,decomposition,diffusion and rapid quenching caused by discharge plasma,the mechanisms of powder formation and possible contaminant infiltration are still controversial,posing a significant challenge to control particle size and chemical composition of the powder produced by this method.In this study,Fe-based amorphous powders in different particle-size distributions with high sphericity were fabricated by spark erosion under different discharge-energy conditions.The max-imum particle size of the resultant powders can be correlated with discharge parameters,crater depth,and crater radius,respectively.A multi-ring-breakup model is proposed to reveal the particle-size distribution of the powder formed from the electrode melt under a single-pulse discharge.Furthermore,a dielectric-element infiltration model is provided to quantitatively evaluate the infiltration mass ratio of the contaminant elements,stemming from the decomposed products of dielectric liquid,in the resultant powder with different particle sizes.The models verified through the experimental data are significant for the development of high-performance fine Fe-based amorphous powder with controlled particle size and chemical composition.

Long-term functional maintenance of primary hepatocytes in vitro using macroporous hydrogels engineered through liquid-liquid phase separation

Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after isolation.Inspired by the macroporous structures found in native liver tissues,here we develop synthetic hydrogel scaffolds that closely mimic the liver’s structural organization through the phase separation between polyethylene glycol(PEG)and polysaccharides.Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties,providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates.Compared to two-dimensional hepatocyte cultures,enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days,as evidenced by quantitative reverse-transcription–polymerase chain reactions(qRT-PCR),immunofluorescence,and enzyme linked immunosorbent assay(ELISA)analyses.Protein sequencing data further confirmed the establishment of cell–cell interactions among hepatocytes when cultured in our hydrogels.Notably,these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes,particularly in the Notch and tumor necrosis factor(TNF)signaling pathways.These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering.

一类Manakov方程组的几何刻画

众所周知,矩阵非线性Schrödinger方程规范等价于从R^(1)到Grassmann流形的Schrödinger流方程.本文证明,在物理学中同样有重要应用的一类可积Manakov方程组中的混合型方程组规范等价于从^(R1)到伪复射影空间G_(2,1)=U(2,1)/U(1,1)×U(1)的Schrödinger流方程.从而,结合已知的结果,得到Manakov方程组中的三类可积方程组可由Schrödinger流给出的统一的几何刻画,为后续关于一般的Manakov方程组的几何研究打下基础.

Construction of 3D hollow NiCo-layered double hydroxide nanostructures for high-performance industrial overall seawater electrolysis

Green hydrogen production via seawater electrolysis holds a great promise for carbon-neutral energy production. However, the development of efficient and low-cost bifunctional electrocatalysts for seawater electrolysis at an industrial level remains a significant challenge. Herein, we report a facile approach based on one-dimensional (1D) cobalt carbonate hydroxide (CCH) nanoneedles (NNs) as skeleton and zeolitic imidazolate framework-67 (ZIF-67) as a sacrificial template to construct a self-supported NiCo layered double hydroxide (NiCo LDH) heterostructure nanocage (CCH@NiCo LDH) anchoring on the carbon felt (CF). The NiCo LDHs have hollow features, consisting of ultrathin layered hydroxide nanosheets. Benefiting from the structural advantages, unique carbon substrate and desirable composition, three-dimensional (3D) NiCo LDH nanocages exhibit superior performance as a bifunctional catalyst for overall seawater splitting at an industrial level and good corrosion resistance in alkaline media. In the alkaline seawater (1 M KOH + 0.5 M NaCl), it exhibits low overpotentials of 356 mV for hydrogen evolution reaction (HER) and 433 mV for oxygen evolution reaction (OER) at 400 mA·cm^(−2), much better than most of reported non-noble metal catalysts. Consequently, the obtained CF electrode loading of CCH@NiCo LDH exhibits outstanding performance as anodes and cathodes for overall alkaline seawater splitting, with remarkably low cell voltages of 1.56 and 1.89 V at current densities of 10 and 400 mA·cm^(−2), respectively. Moreover, the robust stability of 100 h is also demonstrated at above 200 mA·cm^(−2) in alkaline seawater. Our present work demonstrates significant potential for constructing effective cost-efficient and non-noble-metal bifunctional electrocatalyst and electrode for industrial seawater splitting.