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Abstract Background Cholangiocarcinoma (CCA), a malignancy that arises from biliary epithelial cells, has a dismal prognosis, and few targeted therapies are available. Aurora B, a key mitotic regulator, has been reported to be involved in the progression of various tumors, yet its role in CCA is still unclarified. Methods Human CCA tissues and murine spontaneous CCA models were used to assess Aurora B expression in CCA. A loss‐of‐function model was constructed in CCA cells to determine the role of Aurora B in CCA progression. Subcutaneous and liver orthotopic xenograft models were used to assess the therapeutic potential of Aurora B inhibitors in CCA. Results In murine spontaneous CCA models, Aurora B was significantly upregulated. Elevated Aurora B expression was also observed in 62.3% of human specimens in our validation cohort (143 CCA specimens), and high Aurora B expression was positively correlated with pathological parameters of tumors and poor survival. Knockdown of Aurora B by siRNA and heteroduplex oligonucleotide (HDO) or an Aurora B kinase inhibitor (AZD1152) significantly suppressed CCA progression via G2/M arrest induction. An interaction between Aurora B and c‐Myc was found in CCA cells. Targeting Aurora B significantly reduced this interaction and accelerated the proteasomal degradation of c‐Myc, suggesting that Aurora B promoted the malignant properties of CCA by stabilizing c‐Myc. Furthermore, sequential application of AZD1152 or Aurora B HDO drastically improved the efficacy of gemcitabine in CCA. Conclusions Aurora B plays an essential role in CCA progression by modulating c‐Myc stability and represents a new target for treatment and chemosensitization in CCA.

A high atmospheric vapour pressure deficit (VPD) hinders calcium absorption in tomatoes (Solanum lycopersicum L.), which severely reduces tomato yield, crop water productivity (WPcrop), and quality. Although reducing the VPD is effective for increasing tomato yield and water productivity, regulating the VPD is costly. Therefore, this study aimed to explore the effects of VPD regulation (high VPD=2.22 kPa, low VPD=0.95 kPa) during different growth stages on tomato WPcrop, yield, and quality to identify a VPD management method that saves costs and enhances the above parameters. The results showed that the yield was significantly positively correlated with fruit calcium absorption. Decreasing the VPD during the fruit expansion stage and increasing it during the flowering stage significantly increased calcium accumulation in the fruits, thereby improving tomato WPcrop, yield, and quality. Additionally, a high VPD during the flowering stage increased stomatal conductance and mesophyll conductance, thereby increasing intercellular and chloroplast CO2 concentrations and enhancing plant photosynthetic capacity, and reduced the stem water potential, leaf water potential, and leaf relative water content, thereby increasing the water potential difference, leaf hydraulic conductance, and calcium absorption. By integrating game theory and the technique for order of preference by similarity to ideal solution method, a comprehensive analysis of tomato appearance, nutrients, and flavour quality revealed that growing plants under a high VPD during the seedling, flowering, and fruit ripening stages and a low VPD during the fruit expansion stage not only enhanced the comprehensive tomato quality value but also maximally reduced the humidification cost. Conclusively, controlling the environmental VPD at 2.22 kPa during the seedling, flowering, and fruit ripening stages and at 0.95 kPa during the fruit expansion stage can effectively increase tomato WPcrop, yield, and quality. This study provides a theoretical basis for the environmental regulation of high-quality, efficient, and water-conserving cultivation of greenhouse tomatoes.

Herba Epimedii’s leaves are highly valued in traditional Chinese medicine for their substantial concentration of flavonoids, which play a crucial role in manifesting the plant’s therapeutic properties. This study investigated the metabolomic, transcriptomic and proteomic profiles of leaves from two Herba Epimedii cultivars, Epipremnum sagittatum (J) and Epipremnum pubescens (R), at three different developmental stages. Metabolite identification and analysis revealed a total of 1,412 and 1,421 metabolites with known structures were found. Flavonoids made up of 33%, including 10 significant accumulated icariin analogues. Transcriptomic analysis unveiled totally 41,644 differentially expressed genes (DEGs) containing five encoded genes participated in icariin biosynthesis pathways. Totally, 9,745 differentially expressed proteins (DEPs) were found, including Cluster-47248.2.p1 (UDP-glucuronosy/UDP-glucosyltransferase), Cluster-30441.2.p1 (O-glucosyltransferase), and Cluster-28344.9.p1 (anthocyanidin 3-O-glucoside 2 “-O-glucosyltransferase-like) through proteomics analysis which are involved to icariin biosynthesis. Protein-protein interaction (PPI) assay exhibited, totally 12 proteins showing a strong relationship of false discovery rate (FDR)

Abstract We disclose herein a strategy for the rapid synthesis of versatile organoselenium compounds under mild conditions. In this work, magnesium-based selenium nucleophiles are formed in situ from easily available organic halides, magnesium metal, and elemental selenium via mechanical stimulation. This process occurs under liquid-assisted grinding (LAG) conditions, requires no complicated pre-activation procedures, and operates broadly across a diverse range of aryl, heteroaryl, and alkyl substrates. In this work, symmetrical diselenides are efficiently obtained after work-up in the air, while one-pot nucleophilic addition reactions with various electrophiles allow the comprehensive synthesis of unsymmetrical monoselenides with high functional group tolerance. Notably, the method is applied to regioselective selenylation reactions of diiodoarenes and polyaromatic aryl halides that are difficult to operate via solution approaches. Besides selenium, elemental sulfur and tellurium are also competent in this process, which showcases the potential of the methodology for the facile synthesis of organochalcogen compounds.

Chicken yolk immunoglobulin (IgY), an immunologically active component, is used as an alternative to antibiotics for the treatment of enteritis. In this study, IgY was embedded in a W/O/W emulsion to overcome the digestive barrier and to investigate the protective effect of IgY against LPS-induced enteritis in mice. Four different hydrophilic emulsifiers (T80, PC, SC, and WPI) were selected to prepare separate W/O/W emulsions for encapsulating IgY. The results showed that the IgY-embedded double emulsion in the WPI group was the most effective. IgY embedded in the W/O/W emulsion could reduce the damage of LPS to the mouse intestine and prevent LPS-induced intestinal mucosal damage in mice. It increased the number of cup cells, promoted the expression of Muc2, and increased the mRNA expression levels of KLF3, TFF3, Itln1, and Ang4 (p < 0.05). It also enhanced the antioxidant capacity of the colon tissue, reduced the level of inflammatory factors in the colon tissue, and protected the integrity of the colon tissue. Stable embedding of IgY could be achieved using the W/O/W emulsion. In addition, the IgY-embedded W/O/W emulsion can be used as a dietary supplement to protect against LPS-induced enteritis in mice.

BackgroundAlveolar Rhabdomyosarcoma is a profoundly malignant soft-tissue sarcoma that predominantly affects children and adolescents. However, the medical field lacks consensus regarding the optimal surgical approach to be undertaken in cases where this tumor causes local bone destruction in the upper limb.Case descriptionA 17-year-old male presented a mass in his left forearm and CT and MRI indicated that the mass had penetrated the ulnar cortex and infiltrating the medulla, resulting in the formation of an eccentric trans-ventricular tumor focus. The sizable tumor affected the volar muscles of the forearm as well as the ulnar bone marrow, exerting pressure on the ulnar artery and vein. It was confirmed by needle biopsy that the mass is alveolar rhabdomyosarcoma. Following two courses of neoadjuvant chemotherapy, the tumor was widely excised en bloc. Autologous fibula with a vascular pedicle was utilized for reconstruction during the procedure. In the postoperative follow-up, no local recurrence of the tumor was observed. Furthermore, the patient retained satisfactory wrist flexion and pronation function in the left forearm.ConclusionsAlveolar rhabdomyosarcoma is an uncommon and highly aggressive form of soft tissue sarcoma. Scientific management necessitates a multidisciplinary approach, combining chemotherapy with surgery. In cases where the tumor invaded into compartment of the bone, careful consideration should be given to the boundaries of tumor resection, the extent of osteotomy, and the approach to musculoskeletal reconstruction when designing the surgical plan. Through reporting our own case and thoroughly reviewing previous clinical experiences, we aim to provide valuable insights for the treatment of this particular disease.

The factors that determine fibrosis progression or normal tissue repair are largely unknown. We previously demonstrated that autophagy inhibition-mediated epithelial–mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling. Here, we report that liver kinase B1 (LKB1) inactivation in ATII cells inhibits autophagy and induces EMT as a consequence. In IPF lungs, this is caused by the down-regulation of CAB39L, a key subunit within the LKB1 complex. 3D co-cultures of ATII cells and MRC5 lung fibroblasts coupled with RNA sequencing (RNA-seq) confirmed that paracrine signaling between LKB1-depleted ATII cells and fibroblasts augmented myofibroblast differentiation. Together, these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATII cells and contribute to fibrosis via aberrant epithelial–fibroblast crosstalk.

Abstract In clinical trials involving patients with HER2 (ERBB2 receptor tyrosine kinase 2) positive gastric cancer, the efficacy of the HER2-targeted drug lapatinib has proven to be disappointingly poor. Under the persistent pressure exerted by targeted drug therapy, a subset of tumor cells exhibit acquired drug resistance through the activation of novel survival signaling cascades, alongside the proliferation of tumor cells that previously harbored mutations conferring resistance to the drug. This study was undertaken with the aim of elucidating in comprehensive detail the intricate mechanisms behind adaptive resistance and identifying novel therapeutic targets that hold promise in the development of effective lapatinib-based therapies for the specific subset of patients afflicted with gastric cancer. We have successfully established a gastric cancer cell line with acquired lapatinib resistance, designated as HGC-27-LR cells. Utilizing comprehensive coding and noncoding transcriptome sequencing analysis, we have identified key factors that regulate lapatinib resistance in HGC-27 cells. We have compellingly validated that among all the lncRNAs identified in HGC-27-LR cells, a novel lncRNA (long noncoding RNA) named NONHSAT160169.1 was found to be most notably upregulated following exposure to lapatinib treatment. The upregulation of NONHSAT160169.1 significantly augmented the migratory, invasive, and stemness capabilities of HGC-27-LR cells. Furthermore, we have delved into the mechanism by which NONHSAT160169.1 regulates lapatinib resistance. The findings have revealed that NONHSAT160169.1, which is induced by the p-STAT3 (signal transducer and activator of transcription 3) nuclear transport pathway, functions as a decoy that competitively interacts with hsa-let-7c-3p and thereby abrogates the inhibitory effect of hsa-let-7c-3p on SOX2 (SRY-box transcription factor 2) expression. Hence, our study has unveiled the NONHSAT160169.1/hsa-let-7c-3p/SOX2 signaling pathway as a novel and pivotal axis for comprehending and surmounting lapatinib resistance in the treatment of HER2-positive gastric cancer.

Telekinesis, as commonly portrayed in science fiction literature and cinema, is a super power wherein users control and manipulate objects absent in physical interaction. In real world, enhancing human–robot interaction needs the synthesis of human intuitive processes with robotic arm. This paper introduces a robotic teleoperation system achieving the essence of telekinetic operations, combining the profound capabilities of augmented reality (AR) with the robotic arm operations. Utilizing AR, the proposed methodology offers operators with a visual feedback, facilitating a level of control surpassing the capacities of natural interfaces. By using AR-driven visual recognition, this system achieves operations in a virtual environment, subsequently actualized in the real world through the robotic arm. Through multiple experiments, we found that the system has a small margin of error in telekinesis operations, meeting the needs of remote operation. Furthermore, our system can operate on objects in the real world. These experiments underscore the capability of the remote control system to assist humans in accomplishing a wider range of tasks through the integration of AR and robotic arms, providing a natural human–robot interaction approach.

With fast advances in enhancing the focusing/imaging resolution of Fresnel zone plate lenses toward sub-10 nm, low diffraction efficiency in connection with their rectangular zone shape still remains a big issue in both soft and hard X-ray microscopy. In hard X-ray optics, encouraging progress has recently been reported in our earlier attempts of high focusing efficiency by 3D kinoform shaped metallic zone plates, formed by greyscale electron beam lithography. This paper addresses our efforts towards high focusing/imaging efficiency by developing a novel dielectric kinoform zone plate lens for soft X-rays. The effects of the zone materials and zone shapes on the focusing/imaging quality were first theoretically investigated by a modified thin-grating-approximation method, revealing superior efficiencies of dielectric kinoform zone plates over rectangular ones in metals. Optical characterizations of replicated dielectric kinoform zone plates by greyscale electron beam lithography demonstrate a focusing efficiency of 15.5% with a resolution of 110 nm in the water window of X-rays. Apart from high efficiency, the novel kinoform zone plate lenses developed in this work exhibit significant advantages over conventional zone plates, i.e. simplified process, low cost and no need for a beamstop.

Bolt connection structure is a common form of connecting large and complex equipment. Its object contact surfaces under normal and tangential loads will appear in the form of slip and adhesion, which affects the service life of mechanical equipment. Bolted connection structures cause changes in stiffness and damping, which have great impacts on the dynamic characteristics. Experimental studies and numerical simulations have difficulty predicting the overall performance of bolts in a timely manner, hence cannot ensure the reliability and safety of complex equipment. In order to improve the overall performance of complex equipment, it is necessary to study the contact theory model of bolt connection structures. Based on the relationship between friction force and velocity in the classical friction model, the mathematical expressions of restoring force and tangential displacement in the kinetic theory model are deduced to predict the stiffness degradation of the bolted structure and to characterise the kinetic properties and laws of the bolted structure. From the perspective of theoretical calculation, it makes up for the situation in which it is difficult to measure the performance of bolts due to the existence of spanning scale and provides theoretical support for the reliability of connecting complex equipment. This paper summarises and analyses the contact theory model of bolt connection structures, ranging from macroscopic to microscopic; describes the static friction model, kinetic friction model, statistical summation contact model, fractal contact model; and analyses the influencing factors of the microscopic contact mechanism. The advantages and disadvantages of the kinetic theoretical models are described, the manifestation of friction and the relationship between tangential force–displacement are discussed, and the key research directions of the kinetic theoretical models of bolted structures in the future are elucidated.

IntroductionTumor immunotherapy targeting PD-L1 has emerged as one of the powerful tools for tumor therapy. Numerous studies indicate that tumor-targeted drugs critically have an influence on the interaction between the immune system and tumors by changing the expression of PD-L1, which is beneficial for immunotherapy. Our study provided novel evidence for improving the drug regimen in tumor targeted therapy and immunotherapy.MethodsThe expression of PD-L1 on SKBR3, MDA-MB-231, MCF7, 4T1, MC38 and B16 cells was evaluated by flow cytometry after treatment with six preclinical targeted drugs (ARN-509, AZD3514, Galeterone, Neratinib, MLN8237 and LGK974). AURKA was knockdowned by using the specific siRNA or CRISPR-Cas9 technology. In the 4T1-breast tumor and colorectal cancer xenograft tumor models, we determined the number of infiltrated CD3+ and CD8+ T cells in tumor tissues by IHC.ResultsWe found that AURKA inhibitor MLN8237 promoted the expression of PD-L1 in a time- and concentration-dependent manner while exerted its antitumor effect. Knockdown of AURKA could induce the upregulation of PD-L1 on SKBR3 cells. MLN8237-induced PD-L1 upregulation was mainly associated with the phosphorylation of STAT3. In the 4T1-breast tumor xenograft model, the infiltrated CD3+ and CD8+ T cells decreased after treatment with MLN8237. When treated with MLN8237 in combination with anti-PD-L1 antibody, the volumes of tumor were significantly reduced and accompanied by increasing the infiltration of CD3+ and CD8+ T cells in colorectal cancer xenograft tumor model.DiscussionOur data demonstrated that MLN8237 improved the effect of immunology-related therapy on tumor cells by interacting with anti-PD-L1 antibody, which contributed to producing creative sparks for exploring the possible solutions to overcoming drug resistance to tumor targeted therapy.

Background and purpose: The prognosis of malignant melanoma (MM) in China and Asia is significantly worse than that of European and American populations, mainly because acral melanoma (AM) is inferior to cutaneous melanoma (CM) in terms of biological behavior, clinical features, prognosis, and efficacy of drugs (mainly immunotherapy). Certain changes have occurred in the last 5 years in the choice of surgical and drug-adjuvant treatment for MM. This study retrospectively analyzed the survival outcomes of Chinese CM and AM patients after surgical treatment in a single cancer center for the past five years. Methods:Data of melanoma patients undergoing surgical treatment were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. The basic clinical characteristics, pathological features, lymph node tumor burden and survival information were carefully collected from medical document. Patients with mucosal subtype, unknown primary sites, or follow-up less than 6 months were excluded. Survival analysis and multivariable Cox regression analysis were performed to explore prognosis and associated risk factors. Results:Totally 585 patients were enrolled, including 397 AM and 188 CM patients. The median age was 59 (19-89) years, and 54% were female. AM and CM patients differed in gender, age, primary tumor location, gene mutation distribution and adjuvant therapy, but not in tumor burden associated factors including the Breslow thickness, ulceration and lymph node involvment. The median follow-up time was 24 months, and the median relapse-free survival (mRFS) was 36 months, with 1-year and 2-year RFS of 75.6% and 61.2%, respectively. However, there was no statistically significant difference in prognosis between the two subtypes. Primary ulceration (HR=2.265, 95% CI: 1.257-4.080), NRAS mutation (HR=1.816, 95% CI: 1.211-2.725) and advanced N stage (HR of N1, N2 and N3 versus N0 were 1.850, 4.085 and 4.191, respectively) were independent prognostic risk factors for RFS in AM; while the protective factors were female (HR=0.636, 95% CI: 0.433-0.933) and upper extremity primary lesions (HR=0.259, 95% CI: 0.105-0.639). Independent risk factors for RFS in CM included primary ulceration (HR=4.073, 95% CI: 1.718-9.654), and later N stage (HR=5.482, 95% CI: 2.385-12.601 for N3 stage). Conclusion: High tumor burden of primay lesion still deteriorates overall outcomes for both AM and CM, while harboring NRAS mutation might suggest even worse outcome for AM.

Abstract Vitiligo is the most common human skin depigmenting disorder. It is mediated by endogenous autoreactive CD8 + T cells that destruct skin melanocytes. This disease has an estimated prevalence of 1% of the global population and currently has no cure. Animal models are indispensable tools for understanding vitiligo pathogenesis and for developing new therapies. Here, we describe a vitiligo mouse model which recapitulates key clinical features of vitiligo, including epidermis depigmentation, CD8 + T cell infiltration in skin, and melanocyte loss. To activate endogenous autoreactive cytotoxic CD8 + T cells targeting melanocytes, this model relies on transient inoculation of B16F10 melanoma cells and depletion of CD4 + regulatory T cells. At cellular level, epidermal CD8 + T cell infiltration and melanocyte loss start as early as Day 19 after treatment. Visually apparent epidermis depigmentation occurs 2 months later. This protocol can efficiently induce vitiligo in any C57BL/6 background mouse strain, using only commercially available reagents. This enables researchers to carry out in-depth in vivo vitiligo studies utilizing mouse genetics tools, and provides a powerful platform for drug discovery.

Radial fuel relocation due to fuel fragmentation can significantly change the heat split, further affecting the thermal performance and safety of dual-cooled annular fuels. Considering the rarity of in-pile irradiation data for annular fuels, three different fuel relocation and its recovery models were developed based on modifications of relocation models for solid fuel rods or the mechanistic relocation simulation of pre-fragmented, interacting and deformable fuel fragments. The three relocation models were implanted into the fuel performance analysis code FROBA-ANNULAR, and thermo-mechanical simulation was carried out to investigate the influence of fuel relocation on gap size variation and heat split variation in an annular fuel. The results indicate that different relocation models lead to significant difference on the prediction of gap size and heat split. Relocation models developed through mechanistic simulation of pre-fragmented fragments seems to be more reasonable, compared with the other two models developed based on unreasonable and extreme assumptions. Mechanistic simulation results indicate that radial relocation of fragmented annular fuels can be bidirectional even at the initial burnup stages, resulting in the reduction of gap sizes of both internal and external fuel-cladding gaps. In addition, it was found that the gap size variation due to radial fuel relocation significantly changed the heat split and matching-rate between heat split and flow flux distribution, exerting an influence on fuel temperature and MDNBR.

Covalent organic frameworks (COF) hold great promise in filtration and separation but combining facile processing, high crystallinity and high separation performance remains challenging. Here, the authors demonstrate that heterocrystalline COF membranes in which high-crystalline regions are tightly linked by low-crystalline regions can improve molecular sieving properties at high solvent flux.

Measurement(s) Lonicera japonica • RNA sequencing • genome assembly • sequence annotation Technology Type(s) SMRT Sequencing • RNA sequencing • Hi-C • biomolecular annotation design Factor Type(s) Genotype Sample Characteristic - Organism Lonicera japonica Sample Characteristic - Environment occurrence Sample Characteristic - Location Shandong Province

X-ray microscopes are powerful tools in the nano-inspection of materials owing to their ultra-high resolution at the molecular level. However, the focusing efficiency of binary zone plate lenses as key components in such probes is merely 5% in practice, hindering their application in advanced scientific research. Although kinoform zone plate lenses are in principle supposed to possess high efficiency beyond binary ones, little progress has been reported so far due to the shortage of both a theoretical calculation approach and greyscale lithography for generating fine three-dimensional (3D) kinoform zones of the lenses. This paper reports our theoretical work for a modified beam propagation method to compute the focusing performance and state-of-the-art 3D greyscale electron beam lithography for kinoform zone plate lenses. Three different zone shapes – binary, kinoform and top-flat kinoform (nicknamed the trapezoid-kinoform) – were compared both theoretically and experimentally. Theoretical calculations suggest, for the first time, that the trapezoid-kinoform zone plate gives rise to the highest focusing efficiency among the three lenses, which was proved by optical characterization of the fabricated lens with hard X-rays. As high as 40% of the focusing efficiency by Au trapezoid-kinoform lenses with resolution of 250 nm at 8 keV has been achieved, which is two times higher than that of binary zone plate lenses. The origin of the enhanced efficiency in the trapezoid-kinoform zone plate lens was explained by the joint contributions from both the refraction through the kinoform slope and the diffraction through the top flat part of the trapezoid-kinoform zone plate. Such a breakthrough in focusing efficiency sheds light on the further development of X-ray lenses with both high resolution and high efficiency.

Stress concentration often occurs around bolt holes in load-bearing joint structures of large complex equipment, ships, aerospace and other complex machinery fields, which is an important mechanical factor leading to the failure of joint structures. It is of great engineering significance to study the phenomenon of stress concentration on connected structures for the safety of large and complex equipment; meanwhile, the layout of bolts seriously affects the stress around holes. Many scholars have studied the layout optimization of multi-bolted structures through experiments and simulations, but few algorithms have been applied to the layout optimization of bolted structures. And most of the studied types of multi-bolt structures are symmetrical. Therefore, in this paper, the gray wolf algorithm is used to optimize the layout of nickel steel plate connectors with a bolt layout in triangular position, and the optimal objective function is found based on the hole circumferential stress of the nickel steel plate, maximum shear stress of the bolt and bending stress of the nickel steel plate. Comparing the optimal values obtained by the fruit fly optimization algorithm, particle swarm optimization algorithm, gray wolf optimization algorithm, multiverse optimization algorithm and wind driven optimization algorithm, the accuracy of selecting the gray wolf algorithm for optimization is verified. A multi-bolt connection structure model was established in ABAQUS, and the surface stress before and after optimization was compared to verify the correctness of the gray wolf algorithm applied to the structure layout optimization of the nickel steel flat bolt connection. The results show that under the force of 15 KN, compared with the original bolt structure layout, the optimized upper side nickel steel plate bore peripheral stress is reduced by 73.1 MPa, and the optimization rate is 24%; bolt stress is reduced by 47.7 MPa, and the optimization rate is 12.5%; when the load is less than 18 KN, the optimization effect of both the upper nickel steel plate and bolt group is more than 10%. When the load is greater than 18 KN, the optimization effect is reduced, and when the load is greater than 21 KN, the nickel steel plate has exceeded the yield limit. Due to the existence of fixed constraints, the optimization of the lower nickel steel plate is not obvious. The results of this study can provide data and theoretical support for the layout optimization of the nickel steel flat bolt connection structure, and help to improve reliability analysis and health monitoring in complex assembly fields such as large complex equipment and aerospace.

Previous studies found that 5-aminolevulinic acid (ALA) and abscisic acid (ABA) can mitigate damage from adversity by enhancing photosynthesis. However, it is not clear whether they have positive effects on iron utilization and chlorophyll synthesis of tomato seedlings under low-temperature stress. To investigate the possible functional relationship between ABA and ALA and elucidate the possible mechanisms of action of ALA to alleviate low-temperature stress in tomato seedlings, this experiment analyzed the effects of ALA and ABA on chlorophyll synthesis in tomato seedling leaves sprayed with exogenous of ALA (25 mg·L−1) or ABA (100 µM) under low-temperature stress (8–18 °C/8–12 °C, day/night). The results show that exogenous ALA increased the Fv/Fm of tomato leaves by 5.31% and increased the accumulation of iron and chlorophyll by 101.15% and 15.18%, respectively, compared to the low-temperature treatment alone, and tomato resistance of low-temperature stress was enhanced. Meanwhile, exogenous application of ALA increased the ABA content by 39.43%, and subsequent application of exogenous ABA revealed that tomato seedlings showed similar effects to exogenous ALA under low-temperature stress, with increased accumulation of iron and chlorophyll in tomato seedlings, which eventually increased the maximum photochemical efficiency of PS II. Under low-temperature stress, application of exogenous ABA significantly reduced ALA content, but the expression of key enzyme genes (PPGD, HEMB1, HEME1, and HEMF1), precursors of chlorophyll synthesis by ALA, was significantly elevated, presumably because the increased activity of these enzymes after external application of ABA accelerated ALA consumption. In conclusion, ABA may crosstalk with ALA to improve the photochemical efficiency and low temperature resistance of tomatoes by regulating chlorophyll synthesis and iron accumulation.

Abstract Background The current study was conducted to investigate the individual and combined occurrence of aflatoxin B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEN) in feeds from various Provinces of China during 2018 to 2020. A total of 3,507 feed samples, including 2,090 feed ingredients and 1,417 complete feed samples, were collected from different areas of China for mycotoxins analysis. Results The individual contamination of AFB1, DON and ZEN were present in more than 81.9%, 96.4% and 96.9% of feed samples, respectively, with average concentration ranges of AFB1 between 1.2–27.4 μg/kg, DON between 458.0–1,925.4 μg/kg and ZEN between 48.1–326.8 μg/kg. Notably, 0.9%, 0.5% and 0.1% of feed ingredients, and 1.2–12.8%, 0.9–2.9% and 0–8.9% of complete feeds for pigs, poultry and ruminants with AFB1, ZEN and DON that exceeded China’s safety standards, respectively. Moreover, more than 81.5% of feed ingredients and 95.7% of complete feeds were co-contaminated with various combinations of these mycotoxins. Conclusion This study indicates that the feeds in China were universally contaminated with AFB1, DON and ZEN during the past 3 years. These findings highlight the significance of monitoring mycotoxin contaminant levels in the domestic animal feed, and the importance of carrying out feed administration and remediation strategies for mycotoxin control.

Developing biomarkers for accurately predicting the efficacy of immune checkpoint inhibitor (ICI) therapies is conducive to avoiding unwanted side effects and economic burden. At the moment, the quantification of programmed cell death ligand 1 (PD-L1) in tumor tissues is clinically used as one of the combined diagnostic assays of response to anti-PD-1/PD-L1 therapy. However, the current assays for evaluating PD-L1 remain imperfect. Recent studies are promoting the methodologies of PD-L1 evaluation from rough to precise. Standardization of PD-L1 immunohistochemistry tests is being promoted by using optimized reagents, platforms, and cutoff values. Combining novel in vivo probes with PET or SPECT will probably be of benefit to map the spatio-temporal heterogeneity of PD-L1 expression. The dynamic change of PD-L1 in the circulatory system can also be realized by liquid biopsy. Consider PD-L1 expressed on non-tumor (immune and non-immune) cells, and optimized combination detection indexes are further improving the accuracy of PD-L1 in predicting the efficacy of ICIs. The combinations of artificial intelligence with novel technologies are conducive to the intelligence of PD-L1 as a predictive biomarker. In this review, we will provide an overview of the recent progress in this rapidly growing area and discuss the clinical and technical challenges.

As a unique coherent diffraction imaging method, X-ray ptychography has an ultrahigh resolution of several nanometers for extended samples. However, ptychography is often degraded by various noises that are mixed with diffracted signals on the detector. Some of the noises can transform into periodic artifacts (PAs) in reconstructed images, which is a basic problem in raster-scan ptychography. Herein, we propose a novel periodic-artifact suppressing algorithm (PASA) and present a new understanding of PAs or raster-grid pathology generation mechanisms, which include static intensity (SI) as an important cause of PAs. The PASA employs a gradient descent scheme to iteratively separate the SI pattern from original datasets and a probe support constraint applied in the object update. Both simulative and experimental data reconstructions demonstrated the effectiveness of the new algorithm in suppressing PAs and improving ptychography resolution and indicated a better performance of the PASA method in PA removal compared to other mainstream algorithms. In the meantime, we provided a complete description of SI conception and its key role in PA generation. The present work enhances the feasibility of raster-scan ptychography and could inspire new thoughts for dealing with various noises in ptychography.

An online automatic feedback system has been successfully installed and commissioned at the BL08U1A Soft X-ray Spectromicroscopy Beamline of Shanghai Synchrotron Radiation Facility, which can monitor the incident X-ray beam in real time by measuring the blade-edge signals of the exit slit and automatically adjust the elliptical cylindrical mirror parameters to achieve beam calibration and maintain the optimal X-ray flux of the sample. This work provides a comprehensive description of the hardware composition, system implementation, feedback logic, function and software design, system optimization and commission, as well as the online experimental results supported by the system. The experimental results demonstrated that the online automatic feedback system is capable of effectively maintaining the optimal X-ray beam flux for X-ray absorption spectroscopy experiments. Its success can provide valuable technique assistance for the design, construction and optimization of similar systems at various beamlines in synchrotron sources in the future.

The “five-aquifer” occurrence conditions of Zhuxianzhuang Coal Mine are complex, and there are some water disaster characteristics such as large static reserves, strong dynamic supply and high water pressure, which seriously threatens the mine safety production. The water damage governance method of “curtain closure and drainage mining” is adopted, and the ground grouting drilling technology is the basis for this method implementation. Combined the technical parameters of geological conditions, drilling technology and grouting technology, the drilling equipment, construction technology, casing solid completion technology and trajectory control technology of ground grouting well are systematically studied, and a set of drilling equipment and key technologies for the ground grouting well of Zhuxianzhuang Coal Mine are formed. The field application shows that the drilling equipment and technology are safe and reliable, energy-saving and environmentally-friendly, the grouting effect is good.

A growing body of evidence associated particulate matter (PM) exposure with lipid metabolism disorders, yet, the underlying mechanism remains to be elucidated. Among the major lipid metabolism modulators, peroxisome proliferator-activated receptor (PPAR) alpha plays an important role. In the current study, an individually ventilated cage (IVC) system was used to expose C57/B6 mice to real-ambient PM for six weeks, with or without co-treatment of PPAR alpha agonist WY14,643. The general parameters, liver and adipose tissue pathology, serum lipids, metal deposition and lipid profile of liver were assessed. The results indicated that six weeks of real-ambient PM exposure induced dyslipidemia, including increased serum triglycerides (TG) and decreased high density lipoprotein cholesterol (HDL-C) level, along with steatosis in liver, increased size of adipocytes in white adipose tissue (WAT) and whitening of brown adipose tissue (BAT). ICP-MS results indicated increased Cr and As deposition in liver. Lipidomics analysis revealed that glycerophospholipids and cytochrome P450 pathway were most significantly affected by PM exposure. Several lipid metabolism-related genes, including CYP4A14 in liver and UCP1 in BAT were downregulated following PM exposure. WY14,643 treatment alleviated PM-induced dyslipidemia, liver steatosis and whitening of BAT, while enhancing CD36, SLC27A1, CYP4A14 and UCP1 expression. In conclusion, PPAR alpha pathway participates in PM-induced lipid metabolism disorder, PPAR alpha agonist WY14,643 treatment exerted protective effects on PM-induced dyslipidemia, liver steatosis and whitening of BAT, but not on increased adipocyte size of WAT.

This paper proposed a new friction mechanical model based on the Coulomb friction law to describe the nonlinear stiffness degradation of bolted joints. Several different contact pressure distributions are analyzed, and the results show that the fourth polynomial distribution has a better effect on characterizing the contact pressure distribution of the bolted interface. Then, a new density function of friction shear stress is obtained through mathematical deduction. There is an interesting discovery that the new density function curve is similar to the truncated power-law spectrum curve. In addition, a method of parameter identification is proposed, and multiple sets of parameters are identified for the subsequent model verification. Finally, the correlation between the theoretical value and the experimental data under different pre-tightening forces is analyzed. The results show the accuracy improvement of the new model compared with the existing model. The new model has better mechanism rationality and can be applied to stiffness degradation analysis.

The mechanical properties of silicone foam will degrade when exposed to environmental loads such as temperature and pressure for a long time. In recent years, the variation law of the stress–strain response of silicone foam during the aging process has received more and more attention, but there are few works that quantitatively analyze the variation of the stress–strain response. In this work, we quantitatively analyzed the variation law of the stress–strain response of silicone foam during aging by the constitutive model. Firstly, the accelerated aging test of silicone rubber foam under long-term compressive strain was carried out, and its compression set, stress relaxation and strain stress curves of different aging degrees were obtained. Further, degenerate trajectory equations for the compression set and stress–relaxation were obtained. In addition, the hyper-foam constitutive model was obtained by fitting stress–strain curves, and the changes in the model parameters after aging were studied. The results show that the compressed set and stress–relaxation are exponential functions of time, while different to existing research findings, we found that the stress–strain curves do not change monotonically with increasing time, which first softens, then hardens, and finally softens. Additionally, to better understand the changing trend of the stress–strain response, the correlation between the stress–strain curve and the compression set and stress–relaxation was discussed qualitatively. Finally, in the stage of monotonic change of the stress–strain curve, the exponential function of the model parameters with the increase of aging time was obtained.

The prevalence of pulmonary fibrosis is increasing with an aging population and its burden is likely to increase following COVID-19, with large financial and medical implications. As approved therapies in pulmonary fibrosis only slow disease progression, there is a significant unmet medical need. Hyperbaric oxygen (HBO) is the inhaling of pure oxygen, under the pressure of greater than one atmosphere absolute, and it has been reported to improve pulmonary function in patients with pulmonary fibrosis. Our recent study suggested that repetitive HBO exposure may affect biological processes in mice lungs such as response to wounding and extracellular matrix. To extend these findings, a bleomycin-induced pulmonary fibrosis mouse model was used to evaluate the effect of repetitive HBO exposure on pulmonary fibrosis. Building on our previous findings, we provide evidence that HBO exposure attenuates bleomycin-induced pulmonary fibrosis in mice. In vitro, HBO exposure could reverse, at least partially, transforming growth factor (TGF)-β–induced fibroblast activation, and this effect may be mediated by downregulating TGF-β–induced expression of hypoxia inducible factor (HIF)-1α. These findings support HBO as a potentially life-changing therapy for patients with pulmonary fibrosis, although further research is needed to fully evaluate this.

We prove that every family of (not necessarily distinct) even cycles D1,...D⌊1.2(n-1)⌋+1 on some fixed n-vertex set has a rainbow even cycle (that is, a set of edges from distinct Di's, forming an even cycle). This resolves an open problem of Aharoni, Briggs, Holzman and Jiang. Moreover, the result is best possible for every positive integer n. [ABSTRACT FROM AUTHOR]

Basic leucine zipper (bZIP) transcription factors of the ABA-responsive element binding factor/ABA-responsive element binding proteins (ABF/AREB) subfamily have been implicated in abscisic acid (ABA) and abiotic stress responses in plants. However, the specific function of ABF/AREB transcription factors under saline–alkaline stress is unclear. Here, we identified four ABF/AREB transcription factors in tomato and found that SlAREB1 strongly responded to both ABA and saline–alkaline stress. To further explore the function of SlAREB1 under saline–alkaline stress, SlAREB1-overexpressing lines were constructed. Compared with wild-type plants, SlAREB1-overexpressing transgenic tomato plants showed reduced malondialdehyde content, increased the relative water content, and alleviated the degradation of chlorophyll under saline–alkaline stress. Importantly, SlAREB1 directly physically interacted with SlMn-SOD, which improved the activity of antioxidant enzymes and increased the scavenging of excess reactive oxygen species. Overall, the overexpression of SlAREB1 increased the antioxidant capacity of the transgenic tomato under saline–alkaline stress.

The tissue equivalent proportional counter (TEPC) is often used in the measurement of ionizing radiation. However, there are many factors that can cause the micro-dose spectrum’s distortion and affect the accuracy of the measurement. In the TEPC design process, several factors can be analyzed through simulation methods. The simulation capabilities of the TEPC physical process are established and verified in this paper. The wall material, tissue equivalent gas, and electrode are selected as the main objects, and the corresponding design choices are given. The wall material has a great impact on the spectrum, and y¯F and y¯D show that A-150 plastic is closer to the human tissue in the TEPC physical process simulation. Both the two tissue equivalent gases have good simulation accuracy. After further analysis, propane-based equivalent gas is the better choice. Among the three electrode sizes, the size of 0.006 35 cm is the most suitable one for TEPC. The analysis results and analysis methods can provide references for the important elements design of TEPC.

In this paper we present a generative, high resolution face representation which extends the wellknown active appearance model (AAM)[5], [6], [7] with two additional layers. (i) One layer refines the global AAM (PCA) model with a dictionary of learned face components to account for the shape and intensity variabilities of eyes, eyebrows, nose and mouth. (ii) The other layer divides the face skin into 9 zones with a learned dictionary of sketch primitives to represent skin marks and wrinkles. This model is no longer of fixed dimensions and is flexible for it can select the diverse representations in the dictionaries of face components and skin features depending on the complexity of the face. The selection is modulated by the grammatical rules through hidden "switch" variables. Our comparison experiments demonstrate that this model can achieve nearly lossless coding of face at high resolution (256 x 256 pixels) with low bits. We also show that the generative model can easily generate cartoon sketches by changing the rendering dictionary. Our face model is aimed at a number of applications including cartoon sketch in non-photorealistic rendering, super-resolution in image processing, and low bit face communication in wireless platforms.

In this paper, we propose a framework for modelling human faces over scales. As a person walks towards the camera, more details of the face will be revealed and thus more random variables and parameters have to be introduced. Accordingly, a series of existing generative models are organized as five regimes, which form nested probabilistic families. The generative model in higher regime is augmented by (1) adding more latent variables, features extractors, and (2) enlarging the dictionary of description, e.g. PCA bases, local parts or sketch patches. The minimum description length (MDL) is used as a criterion for the model selection and transition. As observed in our experiment, the optimal model switches among the different regimes when the scale changes. A sequence of tasks, such as face detection, recognition, sketching and super-resolution etc. can be accomplished based on the models in the different regimes.

The crystal oscillator is a widely used electronic component in a circuit, whose accuracy is strongly affected by the external mechanical environment. To depict the failure mechanism of the crystal oscillator, the damage boundary of this component under the shock environment is studied experimentally in this paper. Through subjecting “step-up” loads on different groups of crystal oscillators, two failure modes (frequency jumping and structural fracture) are monitored and validated. Experimental results prove that “frequency jumping” failure mode is governed by the value of the acceleration shock response spectrum (ASRS) in a certain frequency range, while the failure mode “structural fracture” is governed by the peak value of the ASRS. Through analyzing the shock response spectrum, damage boundaries are given for these two failure modes, which can provide a reference for component design and failure assessment.

Merkel cells are mechanoreceptors located in the epidermis whose developmental origin is unclear. Here the authors show that Merkel cells originate from SOX9 positive cells inside hair follicles and that FGFR2-mediated epithelial signalling is required for their specification.

Parkinson’s disease (PD) is a neurodegenerative condition that results in dyskinesia, with oxidative stress playing a pivotal role in its progression. Antioxidant peptides may thus present therapeutic potential for PD. In this study, a novel cathelicidin peptide (Cath-KP; GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV) was identified from the skin of the Asiatic painted frog (Kaloula pulchra). Structural analysis using circular dichroism and homology modeling revealed a unique αββ conformation for Cath-KP. In vitro experiments, including free radical scavenging and ferric-reducing antioxidant analyses, confirmed its antioxidant properties. Using the 1-methyl-4- phenylpyridinium ion (MPP+)-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- induced PD mice, Cath-KP was found to penetrate cells and reach deep brain tissues, resulting in improved MPP+- induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1 (Sirt1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Both focal adhesion kinase (FAK) and p38 were also identified as regulatory elements. In the MPTP-induced PD mice, Cath-KP administration increased the number of tyrosine hydroxylase (TH)-positive neurons, restored TH content, and ameliorated dyskinesia. To the best of our knowledge, this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress. These findings expand the known functions of cathelicidins, and hold promise for the development of therapeutic agents for PD. [ABSTRACT FROM AUTHOR]