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Industrial robot provides a promising alternative in free-surface milling. However, due to its low stiffness, it is difficult to guarantee the machining quality. While existing research considers mainly the influence of robot posture on stiffness, the workpiece setup's influence is equally important. In this study, to ensure the overall workpiece's robot stiffness meets the requirement of stiffness threshold in robotic milling, a method for simultaneously optimizing the robot posture and the workpiece setup is proposed. Firstly, to evaluate the robot stiffness during machining, this work presents a new stiffness index considering the robot's rotational deformation. And then, an optimization model is established to optimize both the robot redundancy and the workpiece setup, considering the constraints of joint limitation, singularity-free and collision-free. Moreover, for complex free-surface, to obtain the minimum number of posture changes of the robot and workpiece under the premise of meeting the limit of stiffness threshold, this work constructs a minimum set covering problem, which is solved by a clustering algorithm and a greedy algorithm. Finally, simulations and experimental studies are conducted to validate the effectiveness of the proposed robot stiffness index and the proposed optimization method, showing that the robot stiffness is improved during a milling process of the entire workpiece.

In recent years, processing bodies (P-bodies) formed by liquid-liquid phase separation, have attracted growing scientific attention due to their involvement in numerous cellular activities, including the regulation of mRNAs decay or storage. These cytoplasmic dynamic membraneless granules contain mRNA storage and decay components such as deadenylase and decapping factors. In addition, different mRNA metabolic regulators, including m

With compression, both Bi2Te2Se and Bi2Se2Te followed the transformation path R3̄m → C2/m → C2/c → Im3̄m. With decreasing pressure from the site-disordered state, partial amorphization were observed in these compounds.

Guided by Global Natural Products Social molecular networking, two p-terphenyl derivatives and one 4,5-diphenyl-2-pyrone analogue, peniterphenyls A-C (1-3), together with five known p-terphenyl derivatives (4-8) and sulochrin (9), were obtained from a deep-sea-derived Penicillium sp. SCSIO41030. Their structures were elucidated using extensive NMR spectroscopic and HRESIMS data and by comparing the information with literature data. Peniterphenyl B (2) represented the first reported natural product possessing a 4,5-diphenyl-substituted 2-pyrone derivative. The p-terphenyl derivatives displayed inhibitory activities against HSV-1/2 with EC50 values ranging from 1.4 ± 0.6 to 9.3 ± 3.7 μM in Vero cells, which showed that they possessed antiviral activities with low cytotoxicity, superior to the current clinical drug acyclovir (EC50 3.6 ± 0.7 μM). Peniterphenyl A (1) inhibited HSV-1/2 virus entry into cells and may block HSV-1/2 infection through direct interaction with virus envelope glycoprotein D to interfere with virus adsorption and membrane fusion, and thus differs from the nucleoside analogues such as acyclovir. Our study indicated peniterphenyl A (1) could be a promising lead compound against HSV-1/2.

One new citrinin monomer derivative (1), and two new natural products α-pyrone analogues (2a and 2b), were isolated from the sponge derived fungus Penicillium sp. SCSIO 41302. Their structures were determined by extensive spectroscopic analysis, chiral-phase HPLC analysis, modified Mosher's method, ECD calculations, and X-ray single-crystal diffraction. Bioactivity screening showed that compounds 2b and 8 exhibited obvious inhibitory activities against pancreatic lipase and acetyl cholinesterase with IC50 values of 48.5 and 4.8 μM, respectively, which indicated that different chiral center between enantiomers (2a and 2b) might result in different biological activities (IC50 value against PL for 2a >100 μg/ml).

Lecai Xiong,1 Yanhong Wei,2 Xiao Zhou,1 Peng Dai,1 Yi Cai,1 Xuefeng Zhou,1 Ming Xu,1 Jinping Zhao,1 Hexiao Tang1 1Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Department of Rheumatology and Immunology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, People’s Republic of ChinaCorrespondence: Hexiao TangThe Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of ChinaTel +86-15102723563Email thx1245@sina.comPurpose: The occurrence and development of lung adenocarcinoma (LUAD) are related to many factors. Multiple researches showed that the renin-angiotensin system (RAS) plays an important role in lung cancer. This research mainly focuses on angiotensin II receptor 1 (AT1R) encoding gene AGTR1, an important part of the RAS.Methods: We comprehensively evaluated the expression of AGTR1 in pan-cancer based on RNA sequencing data obtained from The Cancer Genome Atlas (TCGA). We explored the correlation of AGTR1 with clinicopathological features, prognosis and tumor microenvironment in LUAD. We also explored the mechanism through enrichment analysis and verified it with cell lines and tissue samples.Results: We found that AGTR1 was less expressed in most tumors and related to prognosis based on the TCGA database. To further explore its mechanism, we mainly focused on LUAD. Combined with the verification results in the GEO database, AGTR1 was associated with a better prognosis in LUAD. High expression of AGTR1 was associated with less lymph node metastasis (P=0.007) and MET mutation (P=0.019). High expression of AGTR1 was related to the anti-tumor immune microenvironment with high infiltration of B cells, myeloid dendritic cells, monocytes, and low infiltration of myeloid-derived suppressor cells (all P< 0.05). Enrichment analysis and in vitro verification results showed that AGTR1 was likely to play a role in LUAD through the PI3K/AKT3 pathway. Finally, we verified the above results through tissue samples and the construction of AGTR1 overexpressing cells.Conclusion: AGTR1 inhibits the progression of lung adenocarcinoma through the PI3K/AKT3 pathway.Keywords: AGTR1, tumor suppressor gene, TCGA, lung adenocarcinoma, AKT3

High-quality hafnium disilicide (HfSi2) has been successfully synthesized using a high-pressure and high-temperature (HPHT) method at 3 GPa and 1573 K in a DS6 × 10 MN cubic press. The modest synthesis temperature is aided by significant decreases in both liquidus and solidus temperatures at high pressure for the Si-rich portion of the Hf-Si binary system. The in situ high-pressure X-ray diffraction study yielded a bulk modulus of B0 = 124.4 ± 0.8 GPa with a fixed B0' = 4.0 for HfSi2, which exhibits a dramatically anisotropic compressibility, with a and c axes nearly twice as incompressible as the b axis. The bulk HfSi2 as synthesized has a Vickers hardness of 6.9 ± 0.1 GPa and high thermal stability of 1163 K in air, indicating its hard and refractory ceramic properties. The core-level XPS data of Hf 4f and Si 2p have been collected on the bulk samples of HfSi2, HfSi, and Hf, as well as Si powder to examine the Hf-Si bonding in hafnium silicides. The Hf 4f7/2 binding energies are 15.0 and 14.8 eV for bulk HfSi2 and HfSi, respectively.

A new glyoxylate-containing benzene derivative, methyl 2-(4-hydroxy-3-(3'-methyl-2'-butenyl)phenyl)-2-oxoacetate (1), together with ten known compounds (2-11), were isolated from the marine algicolous fungus, Aspergillus sp. SCSIO 41304. Their planar structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analysis and comparing with literature data. Compound 1 was isolated as a new fungal secondary metabolite, possessing a methyl glyoxylate moiety R-CO-CO-OCH3, which is rare in natural sources. All the isolated compounds (1-11) were tested for their antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among these compounds, aspulvinone H (4) showed moderate inhibition against AChE and PL with IC50 values of 25.95 and 47.06 μM, respectively. Further molecular docking simulation exhibited that compound 4 could well bind to the catalytic pockets of the AChE and PL.

Butyrolactone I (BTL-I), a butenolide compound isolated from land or marine-derived fungi, has been reported to show diverse activities. To further study the pharmaceutical potential of BTL-I, transcriptome and bioinformatics analysis of BTL-I treated HepG2 cells were taken. BTL-I was revealed with lipid metabolism regulatory activity and confirmed by increasing the mRNA expression of related genes, such as LXRα and its target gene UGT1A1. However, the obvious chemical carcinogenesis of BTL-I was also disclosed. BTL-I could significantly increase the mRNA and protein levels of oncogenes such as CYP1A1. Molecular docking of BTL-I and its analogs were performed to understand the active or toxic effects. Although BTL-I showed attractive activities, enough attention must be paid to its adverse effects in its further development.

Tuning eutectoid carbides through tailoring austenitization parameters offers an alternative pathway for the ductility enhancement of high-speed steels. This study probes the origin of austenitization-dependent eutectoid reaction and revisits the role of primary carbides in the annealing process. The increase of austenitization temperature and/or duration produces more rod-shaped eutectoid carbides while suppressing their granular counterparts, corresponding to a transition of eutectoid transformation from a divorced mode to a lamellar manner. Primary carbides can serve as chemical conditioners of the austenite as well as nucleation substrates of eutectoid carbides. Austenitization conditions determine the dissolution of primary carbides and concurrently affect the two essential factors of eutectoid reaction modes, i.e., the inter-particle spacing and the undercooling, thereby causing the austenitization dependence of eutectoid carbides in high-speed steels.

Malaymycin (1), a new cyclopentenone-containing tetrahydroquinoline alkaloid, and mccrearamycin E (2), a geldanamycin analogue bearing a rare ring-contracted cyclopentenone moiety, and a C2-symmetric macrodiolide (7) were isolated from Streptomyces malaysiensis SCSIO41397. Their structures including absolute configurations were determined by detailed analyses of NMR and HRMS data and ECD calculations. The occurrence of mccrearamycin E (2) bearing a ring-contracted cyclopentenone is rare in the geldanamycin class. All isolated compounds were evaluated for their cytotoxicities against five cancer cell lines. As a result, compounds 1, 4, 5, and 7 showed cytotoxicity against some or all of the five cancer cell lines with IC50 values ranging from 0.067 to 7.2 μM. In particular, compound 1 inhibited the growth of C42B and H446 cell lines with IC50 values of 67 and 70 nM, respectively. Malaymycin (1) significantly induced cell cycle arrest at the G0/G1 phase in C42B cell lines and caused cell shrinkage and inhibited the expression of the androgen receptor (AR) at both the mRNA and protein levels in a dose-dependent manner. Further examination by qRT-PCR analysis showed that 1 strongly suppressed the expression of AR target genes KLK2 and KLK3 in the C42B and 22RV1 cell lines, which suggested that 1 might be a promising potential lead compound for the development of a treatment for the castration-resistant prostate cancer (CRPC).

Weiyong Hong,1,2 Ying Gao,2 Bang Lou,2 Sanjun Ying,2 Wenchao Wu,2 Xugang Ji,2 Nan Yu,2 Yunlong Jiao,2 Haiying Wang,1 Xuefeng Zhou,1 Anqin Li,3 Fangyuan Guo,2 Gensheng Yang2 1Department of Pharmacy, Taizhou Municipal Hospital, Taizhou, 318000, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China; 3Zhejiang Share Bio-Pharm Co., Ltd, Hangzhou, 310019, People’s Republic of ChinaCorrespondence: Fangyuan Guo; Gensheng YangCollege of Pharmaceutical Science, Zhejiang University of Technology, #18 Chaowang Road, Hangzhou, 310014, People’s Republic of ChinaTel +86571-88871077Fax +86571-88320913Email guofy@zjut.edu.cn; yanggs@zjut.edu.cnPurpose: To develop microchannel-based preparation of curcumin (Cur)-loaded hybrid nanoparticles using enzyme-targeted peptides and star-shaped polycyclic lipids as carriers, and to accomplish a desirable targeted drug delivery via these nanoparticles, which could improve the bioavailability and antitumor effects of Cur.Methods: The amphiphilic tri-chaintricarballylic acid-poly (ϵ-caprolactone)-methoxypolyethylene glycol (Tri-CL-mPEG) and the enzyme-targeted tetra-chain pentaerythritol-poly (ϵ-caprolactone)-polypeptide (PET-CL-P) were synthesized. The Cur-loaded enzyme-targeted hybrid nano-delivery systems (Cur-P-NPs) were prepared by using the microfluidic continuous granulation technology. The physicochemical properties, release behavior in vitro, and stability of these Cur-P-NPs were investigated. Their cytotoxicity, cellular uptake, anti-proliferative efficacy in vitro, biodistribution, and antitumor effects in vivo were also studied.Results: The particle size of the prepared Cur-P-NPs was 146.1 ± 1.940 nm, polydispersity index was 0.175 ± 0.014, zeta potential was 10.1 ± 0.300 mV, encapsulation rate was 74.66 ± 0.671%, and drug loading capacity was 5.38 ± 0.316%. The stability of Cur-P-NPs was adequate, and the in vitro release rate increased with the decrease of the environmental pH. Seven days post incubation, the cumulative release values of Cur were 52.78%, 67.39%, and 98.12% at pH 7.4, pH 6.8 and pH 5.0, respectively. Cur-P-NPs exhibited better cell entry and antiproliferation efficacy against U251 cells than the Cur-solution and Cur-NPs and were safe for use. Cur-P-NPs specifically targeted tumor tissues and inhibited their growth (78.63% tumor growth inhibition rate) with low toxic effects on normal tissues.Conclusion: The enzyme-targeted hybrid nanoparticles prepared in the study clearly have the tumor-targeting ability. Cur-P-NPs can effectively improve the bioavailability of Cur and have potential applications in drug delivery and tumor management.Keywords: enzyme targeting, nanoparticle fabrication, mouse model, growth inhibition

A new azaphthalide derivative, (S)-3-hydroxy-2,7-dimethylfuro [3,4-b]pyridin-5(7H)-one (1), and a new phthalide derivative, (S)-7-hydroxy-3-((S)-1-hydroxyethyl)isobenzofuran-1(3H)-one (2), were isolated from the coral-derived fungus Aspergillus sp. SCSIO41405, together with eight known compounds (3–10). Their structures, including absolute configurations, were determined by NMR and MS spectroscopic analyses, optical rotation, calculated electronic circular dichroism (ECD) and X-ray crystal data. The isolated compounds were examined for antibacterial and enzyme inhibition activities. Compounds 7 and 8 exhibited weak antibacterial activities, and 10 displayed moderate inhibition on pancreatic lipase with an IC50 value of 15.6 μg/mL.

Selenium cathode has been demonstrated as a promising candidate of cathode material for low‐cost and high‐energy density potassium ion batteries (PIBs). Nevertheless, their applications are prevented by poor electrochemical performance due to the shuttle effect of high‐order polyselenides, the sluggish diffusion of bigger K+, and the huge volumetric expansion during cycling. In this work, we design a multifunctional Se host (N‐HCNS) by grafting ZIF‐8‐derived microporous carbon onto the surface of N‐doped porous carbon nanosheets. The obtained N‐HCNS carbon matrix integrates conductivity, captivity, and immobility abilities, which inhibits the polyselenides shuttle, improves the Se utilization, and buffers the volume change during cycling. The 3D hollow carbon skeleton enhances the infiltration of electrolytes. As an cathode for PIBs, the Se@N‐HCNS electrode delivers an unprecedented life‐span (260 mAh g−1 at 1.0 A g−1 after 2000 cycles) and exhibits a remarkable rate capacity (339 mAh g−1 at 5.0 A g−1). Density functional theory (DFT) calculation reveals the effective adsorption of K2Se with pyridine and pyrrole nitrogen doping in carbon matrix. The unique synergetic design of electrode not only gives insight into the reaction mechanism but also highly emphasizes the potential capabilities of N‐doped carbon in K‐Se batteries.