Frozen Natural Orbitals for the State-Averaged Driven Similarity Renormalization Group.

We present a reduced-cost implementation of the state-averaged driven similarity renormalization group (SA-DSRG) based on the frozen natural orbital (FNO) approach. The natural orbitals (NOs) are obtained by diagonalizing the one-body reduced density matrix from SA-DSRG second-order perturbation theory (SA-DSRG-PT2). We consider three criteria to truncate the virtual NOs for the subsequent electron correlation treatment beyond SA-DSRG-PT2. An additive second-order correction is applied to the SA-DSRG Hamiltonian to reintroduce correlation effects from the discarded orbitals. The FNO SA-DSRG method is benchmarked on 35 small organic molecules in the QUEST database. When keeping 98-99% of the cumulative occupation numbers, the mean absolute error in the vertical transition energies due to FNO is less than 0.01 eV. Using the same FNO threshold, we observe a speedup of 9 times compared to the conventional SA-DSRG implementation for nickel carbonyl with a quadruple-ζ basis set. The FNO approach enables nonperturbative SA-DSRG computations on chloroiron corrole [FeCl(C19H11N4)] with more than 1000 basis functions, surpassing the current limit of a conventional implementation.

Validation of a Tool-Based Visual Anorectal Examination Advanced Simulator for the Early Detection of Colorectal Cancer.

Rectal examination through proctoscopy or rigid sigmoidoscopy is a common investigation in clinical practice. It is an important diagnostic tool for the workup and management of anorectal pathologies. Performing the examination can be daunting not only for patients but also for junior doctors. There are associated risks with the procedure, such as pain, diagnostic failure, and perforation of the bowel. Simulation-based training is recognised as an important adjunct in clinical education. It allows students and doctors to practice skills and techniques at their own pace in a risk-free environment. These skills can then be transferred to and developed further in clinical practice. There is extensive research published regarding the role of simulation-based training in endoscopy, however, we identified no published study regarding simulation-based training in rigid sigmoidoscopy or proctoscopy. This study aims to establish the initial face, content, and construct validity of a tool-based visual anorectal examination advanced simulator model for proctoscopy and rigid sigmoidoscopy. This innovative, highly realistic simulated environment aims to enhance the training of healthcare professionals and improve the efficiency of detecting and diagnosing distal colorectal disease.

Network Pharmacology Analysis and Experiments Validation of the Inhibitory Effect of JianPi Fu Recipe on Colorectal Cancer LoVo Cells Metastasis and Growth.

OBJECTIVE: To analyze the active compounds, potential targets, and diseases of JianPi Fu Recipe (JPFR) based on network pharmacology and bioinformatics and verify the potential biological function and mechanism of JPFR in vitro and in vivo. METHODS: Network pharmacology databases including TCMSP, TCM-PTD, TCMID, and DrugBank were used to screen the active compounds and potential drug targets of JPFR. Cytoscape 3.7 software was applied to construct the interaction network between active compounds and potential targets. The DAVID online database analysis was performed to investigate the potential effective diseases and involved signaling pathways according to the results of the GO function and KEGG pathways enrichment analysis. To ensure standardization and maintain interbatch reliability of JPFR, High Performance Liquid Chromatography (HPLC) was used to establish a "chemical fingerprint." For biological function validation, the effect of JPFR on the proliferation and migration of CRC cells in vitro was investigated by CCK-8 and transwell and wound healing assay, and the effect of JPFR on the growth and metastasis of CRC cells in vivo was detected by building a lung metastasis model in nude mice and in vivo imaging. For the potential mechanism validation, the expressions of MALAT1, PTBP-2, and ß-catenin in CRC cells and transplanted CRC tumors were detected by real-time PCR, western blot, and immunohistochemical staining analysis. RESULTS: According to the rules of oral bioavailability (OB) > 30% and drug-likeness (DL) > 0.18, 244 effective compounds in JPFR were screened out, as well as the corresponding 132 potential drug targets. By the analysis of DAVID database, all these key targets were associated closely with the cancer diseases such as prostate cancer, colorectal cancer, bladder cancer, small cell lung cancer, pancreatic cancer, and hepatocellular carcinoma. In addition, multiple signaling pathways were closely related to JPFR, including p53, Wnt, PI3K-Akt, IL-17, HIF-1, p38-MAPK, NF-κB, PD-L1 expression and PD-1 checkpoint pathway, VEGF, JAK-STAT, and Hippo. The systematical analysis showed that various active compounds of JPFR were closely connected with Wnt/ß-catenin, EGFR, HIF-1, TGFß/Smads, and IL6-STAT3 signaling pathway, including kaempferol, isorhamnetin, calycosin, quercetin, medicarpin, phaseol, spinasterol, hederagenin, beta-sitosterol, wighteone, luteolin, and isotrifoliol. For in vitro experiments, the migration and growth of human CRC cells were inhibited by the JPFR extract in a dose-dependent way, and the expression of MALAT1, PTBP-2, ß-catenin, MMP7, c-Myc, and Cyclin D1 in CRC cells were downregulated by the JPFR extract in a dose-dependent way. For in vivo metastasis experiments, the numbers of lung metastasis were found to be decreased by the JPFR extract in a dose-dependent manner, and the expressions of metastasis-associated genes including MALAT1, PTBP-2, ß-catenin, and MMP7 in the lung metastases were downregulated dose dependently by the JPFR extract. For the orthotopic transplanted tumor experiments, the JPFR extract could inhibit the growth of orthotopic transplanted tumors and downregulate the expression of c-Myc and Cyclin D1 in a dose-dependent manner. Moreover, the JPFR extract could prolong the survival time of tumor-bearing mice in a dose-dependent manner. CONCLUSIONS: Through effective network pharmacology analysis, we found that JPFR contains many effective compounds which may directly target cancer-associated signaling pathways. The in vitro and in vivo experiments further confirmed that JPFR could inhibit the growth and metastasis of CRC cells by regulating ß-catenin signaling-associated genes or proteins.

A Multireference Quantum Krylov Algorithm for Strongly Correlated Electrons.

We introduce a multireference selected quantum Krylov (MRSQK) algorithm suitable for quantum simulation of many-body problems. MRSQK is a low-cost alternative to the quantum phase estimation algorithm that generates a target state as a linear combination of non-orthogonal Krylov basis states. This basis is constructed from a set of reference states via real-time evolution; thus, avoiding the numerical optimization of parameters. An efficient algorithm for the evaluation of the off-diagonal matrix elements of the overlap and Hamiltonian matrices is discussed and a selection procedure is introduced to identify a basis of orthogonal references that ameliorates the linear dependency problem. Preliminary benchmarks on linear H6, H8, and BeH2 indicate that MRSQK can predict the energy of these systems accurately using very compact Krylov bases.

Catalytic asymmetric trifluoromethylthiolation of carbonyl compounds via a diastereo and enantioselective Cu-catalyzed tandem reaction.

Although recent progress has been made in introducing an SCF3 functionality into a variety of molecules, enantioselective trifluoromethylthiolation remains challenging, especially the α-trifluoromethylthiolation of carbonyl compounds. The present study describes a diastereo and enantioselective Cu-catalyzed tandem 1,4-addition/trifluoromethylthiolation of acyclic enones. The tandem reaction enables the asymmetric integration of the -SCF3 group to carbonyl compounds, establishing chiral tertiary α-carbon centers and affording α-SCF3-ß-substituted carbonyl compounds in 50-92% yields with up to 20 : 1 dr and 96% ee.