Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer.

Activating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC). An inducible Kras(G12D)-driven mouse model of PDAC has established a critical role for sustained Kras(G12D) expression in tumor maintenance, providing a model to determine the potential for and the underlying mechanisms of Kras(G12D)-independent PDAC recurrence. Here, we show that some tumors undergo spontaneous relapse and are devoid of Kras(G12D) expression and downstream canonical MAPK signaling and instead acquire amplification and overexpression of the transcriptional coactivator Yap1. Functional studies established the role of Yap1 and the transcriptional factor Tead2 in driving Kras(G12D)-independent tumor maintenance. The Yap1/Tead2 complex acts cooperatively with E2F transcription factors to activate a cell cycle and DNA replication program. Our studies, along with corroborating evidence from human PDAC models, portend a novel mechanism of escape from oncogenic Kras addiction in PDAC.

Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains recalcitrant to all forms of cancer treatment and carries a five-year survival rate of only 8%1. Inhibition of oncogenic KRAS (hereafter KRAS*), the earliest lesion in disease development that is present in more than 90% of PDACs, and its signalling surrogates has yielded encouraging preclinical results with experimental agents2-4. However, KRAS*-independent disease recurrence following genetic extinction of Kras* in mouse models anticipates the need for co-extinction strategies5,6. Multiple oncogenic processes are initiated at the cell surface, where KRAS* physically and functionally interacts to direct signalling that is essential for malignant transformation and tumour maintenance. Insights into the complexity of the functional cell-surface-protein repertoire (surfaceome) have been technologically limited until recently and-in the case of PDAC-the genetic control of the function and composition of the PDAC surfaceome in the context of KRAS* signalling remains largely unknown. Here we develop an unbiased, functional target-discovery platform to query KRAS*-dependent changes of the PDAC surfaceome, which reveals syndecan 1 (SDC1, also known as CD138) as a protein that is upregulated at the cell surface by KRAS*. Localization of SDC1 at the cell surface-where it regulates macropinocytosis, an essential metabolic pathway that fuels PDAC cell growth-is essential for disease maintenance and progression. Thus, our study forges a mechanistic link between KRAS* signalling and a targetable molecule driving nutrient salvage pathways in PDAC and validates oncogene-driven surfaceome annotation as a strategy to identify cancer-specific vulnerabilities.

METTL3-m6A methylation inhibits the proliferation and viability of type II alveolar epithelial cells in acute lung injury by enhancing the stability and translation efficiency of Pten mRNA.

BACKGROUND: The pathogenesis of acute lung injury (ALI) involves a severe inflammatory response, leading to significant morbidity and mortality. N6-methylation of adenosine (m6A), an abundant mRNA nucleotide modification, plays a crucial role in regulating mRNA metabolism and function. However, the precise impact of m6A modifications on the progression of ALI remains elusive. METHODS: ALI models were induced by either intraperitoneal injection of lipopolysaccharide (LPS) into C57BL/6 mice or the LPS-treated alveolar type II epithelial cells (AECII) in vitro. The viability and proliferation of AECII were assessed using CCK-8 and EdU assays. The whole-body plethysmography was used to record the general respiratory functions. M6A RNA methylation level of AECII after LPS insults was detected, and then the "writer" of m6A modifications was screened. Afterwards, we successfully identified the targets that underwent m6A methylation mediated by METTL3, a methyltransferase-like enzyme. Last, we evaluated the regulatory role of METTL3-medited m6A methylation at phosphatase and tensin homolog (Pten) in ALI, by assessing the proliferation, viability and inflammation of AECII. RESULTS: LPS induced marked damages in respiratory functions and cellular injuries of AECII. The m6A modification level in mRNA and the expression of METTL3, an m6A methyltransferase, exhibited a notable rise in both lung tissues of ALI mice and cultured AECII cells subjected to LPS treatment. METTL3 knockdown or inhibition improved the viability and proliferation of LPS-treated AECII, and also reduced the m6A modification level. In addition, the stability and translation of Pten mRNA were enhanced by METTL3-mediated m6A modification, and over-expression of PTEN reversed the protective effect of METTL3 knockdown in the LPS-treated AECII. CONCLUSIONS: The progression of ALI can be attributed to the elevated levels of METTL3 in AECII, as it promotes the stability and translation of Pten mRNA through m6A modification. This suggests that targeting METTL3 could offer a novel approach for treating ALI.

Density Functional Theory and Raman Spectroscopy Studies of Adsorption Sites of Au Nanoparticles with Alectinib.

Alectinib is an ALK tyrosine kinase inhibitor, which is mainly used in patients with crizotinib-resistant nonsmall cell lung cancer. Alectinib has attracted much clinical attention for its longest progression-free survival time and the best therapeutic effect. The chemical adsorption of Au nanoclusters (AuNPs) with alectinib molecules is studied by density functional theory (DFT) and surface-enhanced Raman scattering spectroscopy (SERS) experiments. DFT/B3LYP-D3/6-311G** was used for optimization and vibration analysis of alectinib-Au6 complexes, as well as molecular electrostatic potential, frontier molecular orbital, and electro-optic-based charge transfer descriptors. Comparing the results of the DFT theory and SERS experiment, alectinib and AuNPs can form Au-N6 bonds primarily through chemical adsorption of N6 atoms, and the experimental results showed that the enhancement factor (EFCHEM) could reach 4.27. The results provide a theoretical basis for exploring the mechanism of chemical enhancement between AuNPs and alectinib.

Irf7 regulates the expression of Srg3 and ferroptosis axis aggravated sepsis-induced acute lung injury.

OBJECTIVE: To investigate the mechanism of action of Srg3 in acute lung injury caused by sepsis. METHODS: First, a sepsis-induced acute lung injury rat model was established using cecal ligation and puncture (CLP). RNA sequencing (RNA-seq) was used to screen for highly expressed genes in sepsis-induced acute lung injury (ALI), and the results showed that Srg3 was significantly upregulated. Then, SWI3-related gene 3 (Srg3) was knocked down using AAV9 vector in vivo, and changes in ALI symptoms in rats were analyzed. In vitro experiments were conducted by establishing a cell model using lipopolysaccharide (LPS)-induced BEAS-2B cells and coculturing them with phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells to analyze macrophage polarization. Next, downstream signaling pathways regulated by Srg3 and transcription factors involved in regulating Srg3 expression were analyzed using the KEGG database. Finally, gain-of-loss functional validation experiments were performed to analyze the role of downstream signaling pathways regulated by Srg3 and transcription factors involved in regulating Srg3 expression in sepsis-induced acute lung injury. RESULTS: Srg3 was significantly upregulated in sepsis-induced acute lung injury, and knocking down Srg3 significantly improved the symptoms of ALI in rats. Furthermore, in vitro experiments showed that knocking down Srg3 significantly weakened the inhibitory effect of LPS on the viability of BEAS-2B cells and promoted alternative activation phenotype (M2) macrophage polarization. Subsequent experiments showed that Srg3 can regulate the activation of the NF-κB signaling pathway and promote ferroptosis. Specific activation of the NF-κB signaling pathway or ferroptosis significantly weakened the effect of Srg3 knockdown. It was then found that Srg3 can be transcriptionally activated by interferon regulatory factor 7 (Irf7), and specific inhibition of Irf7 significantly improved the symptoms of ALI. CONCLUSIONS: Irf7 transcriptionally activates the expression of Srg3, which can promote ferroptosis and activate classical activation phenotype (M1) macrophage polarization by regulating the NF-κB signaling pathway, thereby exacerbating the symptoms of septic lung injury.

Improvement of LIBS signal stability for NaCl solution using femtosecond laser-induced water film.

This paper studies the analysis of Na element concentration in NaCl aqueous solution using laser-induced breakdown spectroscopy (LIBS). The NaCl solution is transformed to a thin water film. The water film can provide a stable liquid surface, and overcome the disadvantage that laser focusing position cannot be fixed due to liquid level fluctuation (when nanosecond laser is used as the excitation light source, there is serious liquid splash phenomenon, which affects the signal stability). And, femtosecond pulse laser is used to excite the water film to produce the plasma, avoiding liquid splashing. The measured emission lines are Na (I) at 589.0 nm and 589.6 nm. The calibration curves of sodium are plotted by measuring different concentrations of NaCl solution. The linear correlation coefficients of Na (I) lines at 589.0 nm and 589.6 nm are 0.9928 and 0.9914, respectively. In addition, the relative standard deviation is also calculated; its range is from 1.5% to 4.5%. The results indicate that the combination of femtosecond laser and water film can significantly improve the signal stability for liquid analysis in LIBS.

Ultrafast dynamics on fluorescence quenching of rhodamine 6G by graphene oxide.

Fluorescence quenching of rhodamine 6G by graphene oxide (GO) was investigated using steady-state fluorescence spectroscopy and ultrafast time-resolved absorption spectroscopy. The steady-state fluorescence spectra showed that rhodamine 6G fluorescence was effectively quenched by titrating the GO to the rhodamine 6G solutions. For lower GO concentrations, transient dynamic curves followed two-exponential decay parameters. For higher GO concentrations, the dynamic curves could not be fitted well, and three-exponential decay parameters were appropriate. The results indicated that there was a new transition process (electron transfer) in the exited rhodamine 6G and GO solution.

Assessing the Security of Campus Networks: The Case of Seven Universities.

The network security situation of campus networks on CERNET (China Education and Research Network) has received great concern. However, most network managers have no complete picture of the network security because of its special management and the rapid growth of network assets. In this investigation, the security of campus networks belonging to seven universities in Wuhan was investigated. A tool called "WebHunt" was designed for campus networks, and with its help, the network security risks were found. Differently from existing tools for network probing, WebHunt can adopt the network scale and special rules of the campus network. According to the characteristics of campus websites, a series of functions were integrated into WebHunt, including reverse resolution of domain names, active network detection and fingerprint identification for software assets. Besides, WebHunt builds its vulnerability intelligence database with a knowledge graph structure and locates the vulnerabilities through matching knowledge graph information. Security assessments of seven universities presents WebHunt's applicability for campus networks. Besides, it also shows that many security risks are concealed in campus networks, such as non-compliance IP addresses and domain names, system vulnerabilities and so on. The security reports containing risks have been sent to the relevant universities, and positive feedback was received.

Simultaneously Performed, Totally Endoscopic Left Atrial Myxoma Resection and Lobectomy.

The patient was a 69-year-old male patient with cancer in the right lung and whose preoperative examination showed left atrial myxoma. Simultaneous surgery for both cardiac myxoma resection and a lobectomy by totally endoscopic surgery without robotic assistance was performed. First, the cardiac tumor on the heart was removed using a cardiopulmonary bypass (CPB), then a lobectomy without any new incisions was performed. This case provides evidence that in individual select patients, a left atrial myxoma resection and lobectomy can be performed under total endoscopy at the same time.

Effects of inclusion level and amino acid supplementation on energy values of soybean oil determined with difference or regression methods in growing pigs.

OBJECTIVE: This study was conducted to evaluate the effects of inclusion level and amino acid (AA) supplementation on energy values of soybean oil (SO) as determined by difference method or regression method when fed to growing pigs. METHODS: Thirty-six barrows (initial BW: 28.0 ± 1.3 kg) were randomly assigned to one of 6 dietary treatments, which included 2 control diets formulated using a basal diet with or without AA supplementation, and 4 experimental diets with 5% or 10% SO addition in the 2 control diets, respectively. All pigs were individually housed in metabolism crates for 19 d, and during the last 5 d, total urine and feces production were collected. The nutrient digestibility in diets and the digestible energy (DE) and metabolizable energy (ME) values of SO were determined using the difference method and the regression method, respectively. RESULTS: Our results showed that there were no interaction effects (p > 0.05) between AA supplementation and SO inclusion levels on energy values of SO and dietary nutrient digestibility. The DE and ME values of SO determined by the difference method were not affected (p > 0.05) by AA supplementation, however, the ME value of SO increased (p < 0.05) as the inclusion level of SO increased. Moreover, the energy values of SO determined using the regression method were close to those determined using difference method with 10% SO inclusion, but were greater than those obtained using difference method with 5% SO inclusion. CONCLUSION: We concluded that the DE and ME values of SO increased with the inclusion level but were not affected by AA supplementation in the range of 0% to 10%. The difference method can substitute for the regression method to determine the DE and ME values of SO when the inclusion level is 10%, but not at 5% inclusion level.

MALAT1 promoted cell proliferation and migration via MALAT1/miR-155/MEF2A pathway in hypoxia of cardiac stem cells.

Accumulating evidence revealed that hypoxia contributed to many human diseases, including ischemic myocardium and heart failure (HF). In recent years, the roles of hypoxia in stem cell survival and cardiac biology have been studied extensively. However, the underlying molecular mechanisms remain to be elucidated. As a leading cause of HF, ischemic heart disease was correlated with hypoxia. In this study, we firstly constructed the hypoxia cell model by CoCl2 in cardiac stem cells (CSCs) and found that hypoxia induced the cell proliferation and migration potential in CSCs. Then, we demonstrated that the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was promoted in CoCl2 -induced CSCs hypoxia model. Furthermore, we found that knockdown of MALAT1 inhibited the cell proliferation and migration in CoCl2 -induced CSCs hypoxia model. In addition, we revealed that MALAT1 regulated the microRNA-155 (miR-155) expression in CSCs under both the normal and hypoxia conditions and further, manipulation of the miR-155 expression affected the role of MALAT1 in CoCl2 -induced CSCs hypoxia cell model. We then illustrated that miR-155 regulated the myocyte enhancer factor 2A (MEF2A) expression in CSCs under both the normal and hypoxia conditions and further, changing the expression of MEF2A affected the role of miR-155. Finally, we demonstrated that MALAT1 regulated the MEF2A expression and exerted its role via modulation of the MALAT1/miR-155/MEF2A pathway. Taken together, our study illustrated that MALAT1 promoted the cell proliferation and migration in CoCl2 -induced CSCs hypoxia model, acting mechanistically by promoting MEF2A expression via "sponging" miR-155.

Spectral resolved study of filamentation effect on the nonlinear absorption in carbon disulfide.

A Z-scan system using spectrometers as detectors is established to investigate nonlinear absorption and white light continuum separately, in which absorption coefficient that is coincident with previous work was obtained. After Z-scan experiments, spot photographs were captured to further study the spatial properties of filaments in CS2, and we obtained similar space between dual filaments with previous work. Using the experimental setup, we find that plasma generation is the main effect impacting the nonlinear absorption and refraction process, and this impact can be eliminated in the case of CS2. Therefore, effect of filamentation can be neglected for CS2. Though it is easy to generate filaments in CS2 at relatively low intensity, fitting the Z-scan curve with three-photon model at 800 nm for CS2 is reasonable. In addition, the thickness of sample can affect extracted absorption coefficient of CS2 by affecting the length of filamentation.

Advanced glycation end products of bovine serum albumin affect the cell growth of human umbilical vein endothelial cells via modulation of MEG3/miR-93/p21 pathway.

Advanced glycation end products of BSA (AGE-BSA) contribute to the pathogenesis of diabetic vascular diseases. However, the roles and underlying mechanisms of AGE-BSA in diabetic vascular diseases remain largely unclear. Long non-coding RNAs (lncRNAs) are widely identified and known as gene regulators. However, the roles of lncRNAs in diabetic vascular disease are still vague. In this study, we sought to investigate the contributions of lncRNAs in human umbilical vein endothelial cells (HUVECs) treated with AGE-BSA. We first demonstrated that AGE-BSA reduced the cell viability and inhibited the cell proliferation of HUVECs. Then, we found that lncRNA MEG3 was up-regulated in HUVECs treated with AGE-BSA. Furthermore, inhibition of MEG3 restored the AGE-BSA-induced repression of cell viability and proliferation. In addition, our results revealed that MEG3 played its role via modulation of miR-93 expression in HUVECs treated with AGE-BSA. Furthermore, we illustrated that miR-93 played its role via regulation of p21 in HUVECs treated with AGE-BSA. Ultimately, our study displayed that AGE-BSA exerted its function via modulation of MEG3/miR-93/p21 pathway in HUVECs. Thus, for the first time, we identified the MEG3/miR-93/p21 axis in HUVECs treated with AGE-BSA, which might be a novel regulatory network in diabetic vascular cells, and possess the potential therapeutic value for diabetes mellitus.

LncRNA-MALAT1 promotes CPC proliferation and migration in hypoxia by up-regulation of JMJD6 via sponging miR-125.

The death of cardiomyocytes after myocardial infarction (MI) often leads to ventricular remodeling as well as heart failure (HF). The cardiac progenitor cells (CPCs) have the ability to regenerate functional heart muscle in patients after MI, which provides a promising method for MI-induced HF therapy. However, to date, CPCs can easily lose their proliferation ability in the infarcted myocardium. Therefore, exploring the mechanism for CPC proliferation is essential for CPC-based therapy in MI-induced HF. A previous study indicated that a hypoxic environment is essential for CPC proliferation, but the mechanism is not yet clear. In this work, we discovered that CoCl2-induced hypoxia can promote CPC proliferation and migration. Additionally, long non-coding RNA MALAT1 expression was significantly up-regulated in the CoCl2-induced hypoxia CPC model. MALAT1 suppression inhibited CPC proliferation and migration under hypoxic conditions. In addition, MALAT1 acted as a sponge for miR-125. The miR-125 inhibitor restored the proliferation and migration potentials of CPCs after a MALAT1 knockdown in hypoxia. A further study demonstrated that JMJD6 was a target of miR-125 whose expression was negatively regulated by miR-125. JMJD6 knockdown blocked miR-125 inhibitor's protective effect on CPC function in hypoxia. Ultimately, our finding demonstrated that MALAT1 can modulate CPC proliferation and migration potential through the miR-125/JMJD6 axis in hypoxia. Our finding provided a new regulatory mechanism for CPC proliferation in hypoxia, which provided a new target for MI-induced HF therapy.

Long non-coding RNA H19 contributes to hypoxia-induced CPC injury by suppressing Sirt1 through miR-200a-3p.

Cardiomyocyte death is the chief obstacle that prevents the heart function recovery in myocardial infarction (MI)-induced heart failure (HF). Cardiac progenitor cells (CPCs)-based myocardial regeneration has provided a promising method for heart function recovery after MI. However, CPCs can easily lose their proliferation ability due to oxygen deficiency in infarcted myocardium. Revealing the underlying molecular mechanism for CPC proliferation is critical for effective MI therapy. In the present study, we set up a CoCl2-induced hypoxia model in CPCs. We found that the expression of long non-coding RNA H19 was significantly down-regulated in CPCs after hypoxia stimuli. In addition, H19 suppression attenuated the proliferation and migration of CPCs under hypoxia stress. Furthermore, we discovered that H19 regulated the proliferation and migration of CPCs through mediating the expression of Sirt1 which is a target of miR-200a-3p under hypoxia. In conclusion, our findings demonstrate a novel regulatory mechanism for the proliferation and migration of CPCs under hypoxia condition, which provides useful information for the development of new therapeutic targets for MI therapy.

Additivity of values for phosphorus digestibility in corn, soybean meal, and canola meal in diets fed to growing pigs.

OBJECTIVE: This study was conducted to determine the apparent and standardized total tract digestibility (ATTD and STTD) of phosphorus (P) in corn, soybean meal (SBM), and canola meal (CM), and additivity of values for ATTD and STTD of P in corn, SBM, and CM in diets fed to growing pigs. METHODS: Thirty-six growing barrows (initial body weight of 21.6±1.7 kg) were placed in metabolism crates and allotted to a completely randomized design with 6 diets and 6 pigs per diet. Six diets were formulated using corn, SBM or CM as the sole source of P, or corn and SBM, or corn and CM, or corn, SBM, and CM as the P source in each diet, respectively. Fecal samples were collected for 5 d following a 7 d adaptation period to the diets. RESULTS: Values for ATTD and STTD of P in corn, SBM, and CM in growing pigs were 33.12% and 37.76%, 50.19% and 56.62%, 34.93% and 39.45%, respectively. The ATTD and STTD of P in SBM were greater (p<0.05) than those in corn and CM. However, there were no differences in the ATTD or STTD of P between corn and CM. The determined STTD of P in the mixture of corn and SBM, corn and CM, and corn, SBM, and CM is not different from the calculated STTD values. CONCLUSION: Values for STTD of P in corn, SBM, and CM are additive in their mixture fed to growing pigs.

Comparative digestibility of nutrients and amino acids in high-fiber diets fed to crossbred barrows of Duroc boars crossed with Berkshire×Jiaxing and Landrace×Yorkshire.

OBJECTIVE: This experiment was conducted to determine the differences in the apparent ileal (AID) and total tract digestibility (ATTD) of nutrients and indispensable amino acids (IAA) in high-fiber diets with wheat middlings, rice bran or alfalfa meal fed to Duroc×(Landrace× Yorkshire) (DLY) and Duroc× (Berkshire×Jiaxing) (DBJ) growing barrows. METHODS: Eighteen DLY and 18 DBJ growing barrows were randomly allotted to a 2×3 factorial arrangement involving 2 crossbreeds and 3 high-fiber diets. The experiment lasted 15 d with 10 d for diets adaptation, 3 d for feces collection and 2 d for digesta collection. Three diets were based on corn and soybean meal with 25% wheat middlings, rice bran and alfalfa meal respectively. RESULTS: DBJ had a greater (p<0.05) AID of isoleucine, leucine, lysine, phenylalanine and valine and a lower (p<0.05) AID of methionine than DLY. The hindgut disappearance of acid detergent fiber for DBJ was greater (p<0.05) than DLY. The ATTD of gross energy, dry matter, organic matter, neutral detergent fiber and acid detergent fiber in wheat middlings diet were greater (p<0.05) than in rice bran and alfalfa meal diets. The hindgut disappearance of neutral detergent fiber and acid detergent fiber in wheat middlings diet or rice bran diet were the highest or lowest (p<0.05), and those of alfalfa meal diet were the middle. Barrows fed rice bran diet had a greater (p<0.05) hindgut disappearance of gross energy, dry matter and organic matter and lower hindgut disappearance of neutral detergent fiber and acid detergent fiber than barrows fed alfalfa meal diet. CONCLUSION: DBJ growing barrows showed a significant higher digestibility of fiber in the hindgut and most IAA in the small intestine compared with DLY barrows. The digestibilities of chemical constituents and IAA were affected by the diets formulated with different fiber sources.

Oligosaccharides are a key factor in prediction of amino acid digestibility in soybean meal of different origins when fed to growing pigs.

OBJECTIVE: The objective of this experiment was to determine apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of crude protein (CP) and amino acid (AA) in 15 sources of soybean meal (SBM) produced from soybeans from different countries and subsequently to establish equations for predicting the AID and SID in SBM based on their chemical composition. METHODS: Eighteen barrows (57.9±6.1 kg) fitted with a simple T-cannula were allotted into three 6×6 Latin square designs. Each period comprised a 6-d adaption period followed by a 2-d collection of ileal digesta. The 15 test diets included SBM as a sole source of AA in the diet. Another nitrogen-free diet was used to measure basal endogenous losses of CP and AA. Chromic oxide (0.3%) was used as an inert marker in each diet. RESULTS: The AID of lysine in SBM from China and USA tended to be greater than in SBM from Brazil (p<0.10). The SID of valine and proline in SBM from China was greater than in SBM from Brazil (p<0.05). The SID of lysine, threonine, cysteine and glycine in SBM from China tended to be greater than in SBM from Brazil (p<0.10). From a stepwise regression analysis, a series of AID and SID prediction equations were generated. The best fit equations for lysine in SBM were: AID lysine = 1.16 sucrose-1.81 raffinose+82.10 (R2 = 0.69, p<0.01) and SID lysine = 1.14 sucrose-1.93 raffinose-0.99 ether extract (EE)+85.26 (R2 = 0.77, p<0.01). CONCLUSION: It was concluded that under the conditions of this experiment, the oligosaccharides (such as sucrose and raffinose) can be used to predict the AID and SID of AA in SBM with reasonable accuracy.

Facile Synthesis of DendriMac Polymers via the Combination of Living Anionic Polymerization and Highly Efficient Coupling Reactions.

Two DendriMac polymers (Dendri-hydr and Dendri-click) are efficiently and conveniently synthesized via the combination of living anionic polymerization (LAP) and hydrosilylation/click chemistry. Based on the end-capping of DPE derivatives (DPE-SiH and DPE-DA) toward polymeric anions, the polymeric core and arms are effectively synthesized, and the base polymers can be regarded as polymeric bricks. Hydrosilylation and click chemistry are used as coupling reactions to construct the DendriMac polymers with high efficiency and convenience. The numbers of branched arms are calculated by SEC as 5.84 and 6.08 for Dendri-hydr and Dendri-click, respectively, which indicate that the DendriMac architectures exhibit high structural integrity. Because of its independence, high efficiency, and convenience, the whole construction can be regarded as the "building of polymeric bricks."