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Hybrid metal halide materials with charming phase transition behaviors have attracted considerable attention. In former works, much attention has been focused on the phase transition triggered by the order–disorder or displacement motions of the organic component. However, manipulating the variation of the inorganic component to achieve the phase transition has rarely been reported. Herein, two novel organic–inorganic hybrid materials, [THPM]n[AgX2]n(THPM = 3,4,5,6-tetrahydropyrimidin-1-ium, X = I for 1and Br for 2) with the [AgX2]nn–anionic chain structure, were synthesized. At 293 K, the [AgX2]nn–chains in 1were constructed by the tetramer units of Ag atoms, while that in 2was assembled by the dimer structure. Upon heating to 355 K, owing to the variation of the metallophilic interaction between adjacent Ag atoms, a unique transformation process from tetramer to dimer in [AgI2]nn–chains of 1can be detected and endow 1with a giant anisotropic thermal expansion with linear strain of ∼7% and shear strain of ∼20%, which can be used as a mechanical actuator for switching. Alternatively, for 2, no phase transition process can be observed upon the temperature variation. This work provides an effective approach to design phase transition materials triggered by the inorganic part.

Efficient access to multiple functionalized allenes via a three component 1,4-alkylcyanation of enynes with cyclic alcohol derivatives in the presence of trimethylsilyl cyanide (TMSCN) under copper/photoredox dual catalysis has been developed. Both easily transformable aldehyde and cyano groups were introduced to tetra-substituted allenes through light-induced C–C bond cleavage of cyclic butanol and pentanol derivatives. The reactions proceeded smoothly under mild conditions with broad functional groups tolerance.

To improve energy efficiency and reduce pollution emissions of ports with electricity and hydrogen substitution, this paper proposes a collaborative scheduling method of port integrated energy and container logistics considering electric and hydrogen-powered transport. By analyzing the coupling relationship between energy production and consumption in a port that deploys electric and hydrogen-powered transport, the scheduling optimization models of the port integrated energy system (PIES) and the port container logistic system (PCLS) are collaboratively established and rendered as a mixed-integer bi-level programming model. Moreover, to simplify the complexity of PCLS scheduling which involves the allocation and operation of each type of container logistics equipment, an assembly line of port container logistics (ALPCL) model based on flexible job-shop scheduling (FJSS) is further constructed. Then, a distributed algorithm based on the Benders decomposition (BD) embedded with an improved non-dominated sorting genetic (INSGA-II) is designed to realize optimal dispatch with limited data exchange and great solution efficiency. The results of case studies demonstrate the effectiveness of the proposed method for economic and environmental benefits, including a reduction in scheduling costs and pollution emissions. This method can also achieve co-improvement of energy and logistics efficiency.

Human pluripotent stem cell-derived β cells (hPSC-β cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-β cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-β cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-β cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome. Importantly, remodeling lipid metabolism, especially downregulating the metabolic activity of ceramides, the central hub of sphingolipid metabolism, is critical for β cell maturation. Limiting intracellular accumulation of ceramides in hPSC-β cells remarkably enhanced their function, as indicated by improvements in insulin processing and glucose-stimulated insulin secretion. In summary, our findings provide insights into the maturation of human pancreatic β cells and highlight the importance of ceramide homeostasis in function acquisition.

Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment1,2. However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates3. In this study, we generated islets from human chemically induced pluripotent stem cells (hCiPSC-islets) and show that a one-dose intraportal infusion of hCiPSC-islets into diabetic non-human primates effectively restored endogenous insulin secretion and improved glycemic control. Fasting and average pre-prandial blood glucose levels significantly decreased in all recipients, accompanied by meal or glucose-responsive C-peptide release and overall increase in body weight. Notably, in the four long-term follow-up macaques, average hemoglobin A1c dropped by over 2% compared with peak values, whereas the average exogenous insulin requirement reduced by 49% 15 weeks after transplantation. Collectively, our findings show the feasibility of hPSC-islets for diabetic treatment in a preclinical context, marking a substantial step forward in clinical translation of hPSC-islets.

Highly Improving the Accuracy of Clustering (HIAC) algorithm is designed to enhance clustering accuracy by introducing a gravitational force between data objects, drawing them closer together, and employing a decision graph to establish a weight threshold for differentiating neighbor classes and outliers. Despite its strengths, HIAC faces two shortcomings: (1) its inability to generate effective decision graphs for small-scale datasets and (2) the non-smooth probability curve within the decision graph, making threshold determination by visual inspection both difficult and imprecise. This study presents an improved adaptive algorithm based on Kernel Density Estimation (KDE-AHIAC). This approach automatically selects the bandwidth based on the density and distribution of the data, utilizing the kernel density function to create a decision graph that applies to any dataset. For threshold selection, we introduce an adaptive calculation method that leverages the smoothness and continuity of the kernel density curve, replacing the observational approach. Additionally, we incorporate an outlier test model using Analysis of Similarity (ANOSIM) to avert misclassification of valid samples as outliers. Through comprehensive experimentation, we tested KDE-AHIAC and found that it offers notable improvements over HIAC. KDE-AHIAC enhances the clustering accuracy of the dataset by 66.05% compared to the original data and by 6.22% over HIAC. [ABSTRACT FROM AUTHOR]

The improved fuzzy c-means (IFCM) algorithm is an effective technique for handling the "uniform effect" in imbalanced data clustering; it adjusts the weight of each class based on the fuzzy size between clusters. However, the IFCM algorithm produces a "siphon effect" as the imbalance rate increases. It misclassifies the samples in small classes into large ones. Our analysis shows that this effect occurs because all samples have the same weight value of the same classes, the membership values are polarized, resulting in the model failing to converge to the correct interval. Thus, we propose an imbalanced fuzzy c-means clustering based on edge modification (EM-IFCM) algorithm to alleviate the "siphon effect" of the IFCM algorithm. It exhibits stronger inter-class separability by dynamically adjusting the weight of the samples to enhance the influence of edge samples on the model. In addition, we analyze the effectiveness and complexity of the algorithm and proved its convergence. Finally, we conduct extensive experiments on synthesis, machine-learning, and image-segmentation datasets and compare the results with those of six algorithms. The experimental results show that EM-IFCM has higher accuracy and exhibits an imbalance rate that is at least 1.94 times higher than that of the other algorithms. [ABSTRACT FROM AUTHOR]

An intermolecular controllable Pd-catalyzed spirocyclization of isocyano cycloalkenes has been developed, offering efficient and selective approaches toward spirocyclic hydropyrrole scaffolds. 2-Azaspiro-1,7-dienes could be obtained through a “chain-walking” process with aryl/vinyl iodides as electrophiles, while the normal Heck product 2-azaspiro-1,6-dienes were selectively generated when aryl triflates were used as the coupling partner of isocyanides. Mechanistic studies suggested that the counteranion of the Pd(II) intermediate played a crucial role in the regioselectivity control. Dihydropyrrole-fused 5,6,7-membered spirocycles were switchably accessed under mild conditions with wide functional group tolerance.

Because of its excellent dose distribution, proton therapy is becoming increasingly popular in the medical application of cancer treatment. A synchrotron-based proton therapy facility was designed and constructed in Shanghai. The synchrotron, beam delivery system, and other technical systems were commissioned and reached their expected performances. After a clinical trial of 47 patients was finished, the proton therapy facility obtained a registration certificate from the National Medical Products Administration. The characteristics of the accelerator and treatment systems are described in this article.

A compact interdigital H-mode drift-tube linac (IH-DTL) with the alternating-phase-focusing (APF) method, working at 325 MHz was designed for an injector of a proton medical accelerator. When fed in with a proper RF (radio frequency) power, the DTL cavity could establish the corresponding electromagnetic field to accelerate the “proton bunches” from an input energy of 3 MeV to an output energy of 7 MeV successfully, without any additional radial focusing elements. The gap-voltage distribution which was obtained from the CST®Microwave Studio software simulations of the axial electric field was compared with that from the beam dynamics, and the errors met the requirements within ± 5%. In this paper, the RF design procedure and key results of the APF IH-DTL, which include the main RF characteristics of the cavity, frequency sensitivities of the tuners, and coupling factor of the RF power input coupler are presented.

Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.

When using the beam scanning method for particle beam therapy, the target volume is divided into many iso-energy slices and is irradiated slice by slice. Each slice may comprise thousands of discrete scanning beam positions. An optimized scanning path can decrease the transit dose and may bypass important organs. The minimization of the scanning path length can be considered as a variation of the traveling salesman problem; the simulated annealing algorithm is adopted to solve this problem. The initial scanning path is assumed as a simple zigzag path; subsequently, random searches for accepted new paths are performed through cost evaluation and criteria-based judging. To reduce the optimization time of a given slice, random searches are parallelized by employing thousands of threads. The simultaneous optimization of multiple slices is realized by using many thread blocks of general-purpose computing on graphics processing units hardware. Running on a computer with an Intel i7-4790 CPU and NVIDIA K2200 GPU, our new method required only 1.3 s to obtain optimized scanning paths with a total of 40 slices in typically studied cases. The procedure and optimization results of this new method are presented in this work.

As a new type of anticancer drug, the effect of histone deacetylase inhibitors (HDACIs) in cancer clinical therapy is disappointing owing to drug resistance. P-glycoprotein (P-gp) is clearly recognized as a multidrug resistance protein. However, the relationship between P-gp and sodium butyrate (SB), a kind of HDACIs, has not been investigated. In this study, we found that SB increased mRNA and protein expression of P-gp in lung cancer cells and the underlying mechanisms were elucidated. We found that SB treatment enhanced the mRNA and protein expression of STAT3 rather than that of β-catenin, Foxo3a, PXR, or CAR, which were reported to directly regulate the transcription of ABCB1, a P-gp-encoding gene. Interestingly, inhibition of STAT3 expression obviously attenuated SB-increased P-gp expression in lung cancer cells, indicating that STAT3 played an important role in SB-mediated P-gp upregulation. Furthermore, we found that SB increased the mRNA stability of ABCB1. In summary, this study showed that SB increased P-gp expression by facilitating transcriptional activation and improving ABCB1mRNA stability. This study indicated that we should pay more attention to HDACIs during cancer clinical therapy.

The laying quail is a worldwide breed which exhibits high economic value. In our current study, the vasoactive intestinal peptide receptor-1 (VIPR-1) was selected as the candidate gene for identifying traits of egg production. A single nucleotide polymorphism (SNP) detection was performed in 443 individual quails, including 196 quails from the H line, 202 quails from the L line, and 45 wild quails. The SNPs were genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Two mutations (G373T, A313G) were detected in all the tested quail populations. The associated analysis showed that the SNP genotypes of the VIPR-1gene were significantly linked with the egg weight of G373T and A313G in 398 quails. The quails with the genotype GG always exhibited the largest egg weight for the two mutations in the H and L lines. Linkage disequilibrium (LD) analysis indicated that G373T and A313G loci showed the weakest LD. Seven main diplotypes from the four main reconstructed haplotypes were observed, indicating a significant association of diplotypes with egg weight. Quails with the h1h2 (GGGT) diplotype always exhibited the smallest egg weight and largest egg number at 20 weeks of age. The overall results suggest that the alterations in quails may be linked with potential major loci or genes affecting reproductive traits.

Among the various scanning techniques, spot and raster scanning are the most frequently adopted. Raster scanning turns off the beam only when each isoenergy slice irradiation is completed. This feature intrinsically solves the leakage dose and frequent beam-switching problems encountered during spot scanning. However, to shorten the delivery time of raster scanning, a sophisticated dose control strategy is required to guarantee dose distribution. In this study, a real-time compensation method with raster scanning for synchrotron systems was designed. It is characterized by a small spot-spacing planning strategy and real-time subtraction of the transient number of particles delivered between two planning-spot positions from the planned number of particles of the subsequent raster point. The efficacy of the compensation method was demonstrated by performing accurate raster scanning simulations with an in-house simulation code and accurate final dose evaluations with a commercial treatment planning system. Given the similar dose evaluation criteria under a practical high scanning speed, compared with the spot scanning method, the total delivery time of the compensated raster scanning method was significantly shortened by 53.3% in the case of irradiating a cubical target and by 28.8% in a pelvic case. Therefore, it can be concluded that real-time compensated raster scanning with a fast scanning configuration can significantly shorten the delivery time compared to that of spot scanning. It is important to reduce the pressure on patients caused by prolonged immobilization and to improve patient throughput capacity at particle therapy centers.

Formaldehyde is a carcinogen with highly toxic effect on organisms. ADH5 gene encodes the human formaldehyde dehydrogenase and is important to the detoxification of formaldehyde. The purpose of this work was to establish a platform to study ADH5 genetic markers induced by formaldehyde. After analyzing ADH5 SNPs database of Chinese Population, the three specific SNP sites : rs1154409,rs28730619,rs1154414 were sequenced in Human immortalized B lymphocytes of Chinese Han population by DNA sequencing. The real-time reverse transcription polymerase chain reaction (RT-PCR) approach was used to estimate expression of ADH5 mRNAs influenced by SNPs structure in human immortalized lymphocytes. Different immortalized B lymphocytes lines are gained by genotyping of multiple SNP sites of ADH5 gene. The mRNA expression of ADH5 could up regulate by 0.0005% formaldehyde for 48h exposure. But it showed rs1154409,rs28730619,rs1154414 SNPs has no association with the expression of ADH5 mRNA induced by formaldehyde. The human immortality lymphocytes model might be an efficient tool in a detection of genetic biomarkers of susceptibility to chemicals. The further research should be explored in the protein expression in more cell lines.

To evaluate the combined cytotoxicity effects between functionalized multi-walled carbon nanotubes (MWCNTs-PC) and cigarette smoke solution (CSS), 16-HBE cells was used as the target cells and exposed to various concentrations of MWCNTs-PC and CSS combined together. Cell proliferation, cell apoptosis, DNA damage were detected by Methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, single cell gel electrophoresis assay (SCGE) and micronuclear assay, respectively. The dose-dependent cytotoxic and genetic effects of CSS were found in our study. However, compared to the control group, the MWCNTs-PC exposed groups showed no significant difference in all concentration, with or without CSS exposure. It suggests that the MWCNTs-PC did not influence cellular toxicity or DNA damage of CSS on 16-HBE cells. No combined cytotoxic effects between NWCNTs-PC and CSS were found in this study.

The widespread explored application of water soluble carbon nanotubes makes it important to understand their potential toxic effects on health. This study investigates the effects of phosphoryl choline grafted water soluble multi-walled carbon nanotubes (MWCNTs-PC) on human bronchial epithelial (16-HBE) cells by different cytotoxicity methods in vitro. Various concentrations of MWCNTs-PC were incubated with 16-HBE cells, the effects of cell proliferation, cell apoptosis, cell cycle and DNA damage were detected by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, single cell gel electrophoresis assay (SCGE) and micronuclear assay, respectively. Compared with the control group, there were no significant differences in the changes of cell proliferation, cell apoptosis, cell cycle and DNA damage. Within the experimental concentrations of MWCNTs-PC, no obviously cytotoxicity and DNA damage was observed on 16-HBE cells in this study.

The spatial resolution of a commercial two-dimensional (2D) ionization chamber (IC) array is limited by the size of the individual detector and the center-to-center distance between sensors. For dose distributions with areas of steep dose gradients, inter-detector dose values are derived by the interpolation of nearby detector readings in the conventional mathematical interpolation of 2D IC array measurements. This may introduce significant errors, particularly in proton spot scanning radiotherapy. In this study, by combining logfile-based reconstructed dose values and detector measurements with the Laplacian pyramid image blending method, a novel method is proposed to obtain a reformatted dose distribution that provides an improved estimation of the delivered dose distribution with high spatial resolution. Meanwhile, the similarity between the measured original data and the downsampled logfile-based reconstructed dose is regarded as the confidence of the reformatted dose distribution. Furthermore, we quantify the performance benefits of this new approach by directly comparing the reformatted dose distributions with 2D IC array detector mathematically interpolated measurements and original low-resolution measurements. The result shows that this new method is better than the mathematical interpolation and achieves gamma pass rates similar to those of the original low-resolution measurements. The reformatted dose distributions generally yield a confidence exceeding 95%.

The collection efficiency of monitor parallel plate ionization chambers is the main uncertainty in the beam control of pencil beam scanning systems. Existing calculation methods for collection efficiency in photon or passive scattering proton systems have not considered the characteristics of non-uniform charge density in pencil beam scanning systems. In this study, Boag’s theory was applied to a proton pencil beam scanning system. The transverse distribution of charge density in the ionization chamber was considered to be a Gaussian function and an analytical solution was derived to calculate collection efficiency in the beam spot area. This calculation method is called the integral method and it was used to investigate the effects of beam parameters on collection efficiency. It was determined that collection efficiency is positively correlated with applied voltage, beam size, and beam energy, but negatively correlated with beam current intensity. Additionally, it was confirmed that collection efficiency is improved when the air filling the monitor parallel plate ionization chamber is replaced with nitrogen.

In the original article the authors affiliations are incorrectly published.