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Abstract Since the Qin terracotta warriors were unearthed, polyamide 650 cross-linked E-44 epoxy resin binder has been employed to bond and restore them. In this paper, the chemical aging of the binders service in indoor natural environment during the past 30 years in the terracotta warriors was studied by means of infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis. The results indicated that the binders did not emerge the characteristic peak of carbonyl stretching vibration at 1700 cm−1 in the IR spectra of all determined binders, and their thermal decomposition curves did not emerge any abnormal changes, and the thermal decomposition mainly occurred above 300 °C. There are evident ceramic grains attached to the surface of the binders being peeled off for sampling. These results that the binders service in the Qin terracotta warriors did not exhibit an observable chemical aging and still has strong adhesion. Generally, discrepancies were observed between natural aging and accelerated artificial aging due to the ineffectiveness of the latter to reproduce the effects of complex weather conditions. Compared to artificially accelerated aging, the evaluation results in a long-term natural aging of the binder which is used for restoration of the life-size Qin terracotta warriors, providing in the present investigation, are more reliable in terms of predicting the safety of restored terracotta warriors.

Abstract Background β-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the β-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation. Results In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of β-catenin. Our analysis showed that a truncated β-catenin lacking both N- and C-terminal domains (ΔN148C) could robustly rescue the DE formation, whereas hyperactive β-catenin mutants with S33Y mutation or N-terminal deletion (ΔN90) had limited ability to induce DE lineage. Notably, the ΔN148C mutant exhibited significant nuclear translocation that was positively correlated with successful DE rescue. Transcriptomic analysis further uncovered that two weak β-catenin mutants lacking the C-terminal transactivation domain (CTD) activated primitive streak (PS) genes, whereas the hyperactive β-catenin mutants activated mesoderm genes. Conclusion Our study uncovered an unconventional regulatory function of β-catenin through weak transactivation, indicating that the levels of β-catenin activity determine the lineage bifurcation from mesendoderm into endoderm and mesoderm.

ObjectiveThis study utilized lung ultrasound to investigate whether lung protective ventilation reduces pulmonary atelectasis and improves intraoperative oxygenation in infants undergoing laparoscopic surgery.MethodsEighty young infants (aged 1–6 months) who received general anesthesia for more than 2 h during laparoscopic surgery were randomized into the lung protective ventilation group (LPV group) and the conventional ventilation group (control group). The LPV group received mechanical ventilation starting at 6 mL/kg tidal volume, 5 cmH2O PEEP, 60% inspired oxygen fraction, and half-hourly alveolar recruitment maneuvers. Control group ventilation began with 8–10 mL/kg tidal volume, 0 cmH2O PEEP, and 60% inspired oxygen fraction. Lung ultrasound was conducted five times—T1 (5 min post-intubation), T2 (5 min post-pneumoperitoneum), T3 (at the end of surgery), T4 (post-extubation), and T5 (prior to discharge from the PACU)—for each infant. Simultaneous arterial blood gas analysis was performed at T1, T2, T3, and T4.ResultsStatistically significant differences were observed in pulmonary atelectasis incidence, lung ultrasound scores, and the PaO2, PaCO2, PaO2/FiO2 ratios at T2, T3, and T4. However, at T5, no statistically significant differences were noted in terms of lung ultrasound scores (4.30 ± 1.87 vs. 5.00 ± 2.43, 95% CI: −1.67 to 0.27, p = 0.153) or the incidence of pulmonary atelectasis (32.5% vs. 47.5%, p = 0.171).ConclusionIn infants aged 1–6 months, lung protective ventilation during laparoscopy under general anesthesia significantly reduced the incidence of pulmonary atelectasis and enhanced intraoperative oxygenation and dynamic lung compliance compared to conventional ventilation. However, these benefits did not persist; no differences were observed in lung ultrasound scores or the incidence of pulmonary atelectasis at PACU discharge.Clinical trial registrationhttp://www.chictr.org.cn/, identifier: ChiCTR2200058653.

IntroductionEarthen sites are essential cultural relic resources, and site museums are a fundamental component of China’s cultural heritage protection. The mausoleum of the Qin Shi Huang Emperor is one of the largest, most peculiar, and richest imperial tombs in the world. The exhibition hall of the burial pit No. 1 of the Terra Cotta Warriors is the earliest exhibition hall built and opened to the public. However, after years of excavation and open exhibitions, the earthen site of the Emperor Qinshihuang’s Mausoleum Site Museum has deteriorated to varying degrees due to changes in the modern environment. There is an urgent need to control microbial diseases and protect the earthen site.MethodsWe analyzed the physical and chemical properties and bioindicators of the collected soil samples. We also established a metagenomic library and conducted a correlation analysis between microbial community composition and environmental factors. Cultivable fungi obtained from air and soil samples were identified, and allicin volatile gas fungistasis test was conducted.ResultResearch has found that four different areas of the exhibition hall have different types of microbial diseases owing to their different environments. The main pathogenic fungi in earthen site may lead to potential microbial diseases that affect important cultural relics such as the Terra Cotta Warriors. Penicillium, Aspergillus and Talaromyces showed relatively specific growth in relation to environmental factors and showed a better raw growth advantage.Allicin gas had a inhibitory effect on 12 types of fungi, therefore allicin gas had a potent inhibitory effect on the growth of the most culturable fungal hyphae.DiscussionThis study provides basic data for the study of microbial diversity in the exhibition hall of Pit No. 1 at the Terracotta Warriors Museum in Emperor Qinshihuang’s Mausoleum Site Museum. It provides a reference for future protection work, which is of great significance.

Abstract The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype–phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10–3), and higher white blood cell count (p-value for heterogeneity = 8.5 × 10–131). These data suggest a more salutary effect of IL6R blockade for T2D among individuals of AFR vs EUR ancestry and provide data to inform ongoing clinical trials targeting IL6 for an expanding number of conditions. Moreover, the method to test for heterogeneity of associations can be applied broadly to other large-scale genotype–phenotype screens in diverse populations.

Background: Diabetic foot is a major complication of diabetes. The bone transverse transport method could be applied in clinics for treatment, which could improve the metabolism of the tissues via lasting distraction forces. However, the process’ specific regulating mechanism is still unknown. Methods: Based on the notion that the healing of bones involves the recruitment of calcium ions, in this study, we established the model of tibial cortex transverse transport (TTT) on rats and then used tissue immunologic detection, such as the double fluorescent staining to explore the expression of the calcium channels’ calcium release-activated calcium modulator 1 (Orai1)/stromal interaction molecule 1 (STIM1), which belong to the store-operated calcium entry (SOCE) signaling pathways on the tissues around the bone transport area. By using the laser capture microdissection (LCM) tool, we acquired samples of tissues around the bone and endeavored to identify pivotal protein molecules. Subsequently, we validated the functions of key protein molecules through in vitro and in vivo experiments. Results: After protein profile analysis, we found the differentially expressed key protein osteopontin (OPN). The in vitro experiments verified that, being stimulated by OPN, the migration, proliferation, and angiogenesis of human umbilical vein endothelial cells (HUVEC) were observed to be enhanced. The activation of Orai1/STIM1 might increase the activity of endothelial nitric oxide synthase (eNOS) and its effect on releasing nitric oxide (NO). Subsequently, the migration and proliferation of the HUVECs are improved, which ultimately accelerates wound healing. These signaling pathway was also observed in the OPN-stimulated healing process of the skin wound surface of diabetic mice. Conclusion: This study identifies the molecular biological mechanism of OPN-benefited the migration and proliferation of the HUVECs and provides ideas for searching for new therapeutic targets for drugs that repair diabetes-induced wounds to replace invasive treatment methods. The translational potential of this article: The OPN is highly expressed in the tissues surrounding the TTT bone transfer area, which may possibly stimulate the activation of eNOS to increase NO release through the SOCE pathway mediated by Orai1/STIM1. This mechanism may play a significant role in the angiogenesis of diabetic foot's wounds promoted by TTT, providing new therapeutic strategies for the non-surgical treatment for this disease.

Background: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored. Methods: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE−/− mice, while EC-specific knockdown of Nrf2 was generated in Cdh5CreCas9floxed-stopApoE−/− mice. Results: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE−/− mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5CreCas9floxed-stopApoE−/− mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis. Conclusions: Upon HCD feeding in ApoE−/− mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis.

IntroductionChronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more).MethodsThirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network.ResultsThe differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia.DiscussionIn our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Abstract Semi-exposed relics within an air–soil system often have earthworks partially buried, leading to moisture migration and substantial salt accumulation. Salt accumulation threatens relic preservation, but destructive sampling is hindered by conservation concerns. We conducted a case study on salt enrichment at K9901 Armour Pit of Emperor Qinshihuang 's Mausoleum Site Museum. Environmental factors and soil salt characteristics were assessed through sampling and monitoring. A relic-soil coupling system was established with a soil column device containing burned bricks. Using 5-TE sensors, water and salinity movement was tracked, and X-ray diffraction analyzed relic salt crystals. The soil column experiment effectively simulated water-salt migration in relics. Salts, like Cl−, NO3 −, SO4 2−, Na+, and Mg2+, concentrated on the soil surface during evaporation. Simulation linked specific salt species to relic ailments. Salt solution from soil migrated to bricks, forming CaSO4 crystals. Results highlight coupling's role in salt-related deterioration and the need to protect it for optimal relic preservation. Findings impact semi-exposed relic conservation, revealing salt accumulation processes and their impact on historical artifacts.

[Objective] Soil phosphorus fractions determine the migration and availability of phosphorus during soil evolution. The spatial distribution characteristics of soil phosphorus fractions in alpine meadows under different desertification levels were studied in order to provide a scientific reference for vegetation restoration in sandy meadows. [Methods] The modified Hedley phosphorus classification method was used to determine changes in phosphorus fraction in alpine meadow soils under different degrees of desertification (non-desertification; and light, medium and heavy desertification) using desertifed Zoige alpine meadow soils on the Qinghai-Tibet Plateau. [Results] ① Soil organic carbon, total nitrogen, total phosphorus, active phosphorus, and water content decreased significantly (p

E-wallet, also referred to as digital wallet, is a software application designed to replace physical wallets, with the primary purpose of facilitating online transactions when users wish to make virtual payments. Nowadays, E-wallets are not limited to mobile applications, but they have also been extended to wearable devices, such as smartwatches, enabling users to make payments via their watches. This research study focuses on three main E-wallet service providers in Malaysia, namely TouchNGo E-wallet, Boost, and Grab pay, as they are the top three E-wallets in the country. The aim of this paper is to explore the real-world implementation of E-wallets among mobile phone users in Malaysia, employing the Technology Adoption Model as the theoretical framework. Six independent variables were identified to study the implementation of E-wallets, and a total of 500 respondents shared their opinions on retaining the usage of E-wallet in Malaysia. The data collected were analysed using SPSS for Pearson Correlation Analysis and Multiple Linear Regression. Out of the six variables, five independent variables were accepted, and one independent variable was rejected due to the greater significant level. The highest correlation coefficient falls under Business Resources with 0.704. The study delves into the implications and constraints, providing insights for the future advancement of E-wallets within the Malaysian context.

BackgroundRenal fibrosis is the final common pathway of chronic kidney disease (CKD), which is clinically irreversible and without effective therapy. Renal tubules are vulnerable to various insults, and tubular injury is involving in the initiation and evolution of renal inflammation and fibrosis. Neurokinin-1 receptor (NK-1R) functions by interacting with proinflammatory neuropeptide substance P (SP), exerting crucial roles in various neurological and non-neurological diseases. However, its roles in renal inflammation and fibrosis are still unknown.MethodsWe collected renal biopsy specimens and serum samples of individuals with or without CKD. Additionally, knockout mice lacking NK-1R expression, SP addition and NK-1R pharmacological antagonist treatment in the unilateral ureteral obstruction (UUO) model, and NK-1R-overexpressed HK-2 cells were employed.ResultsRenal SP/NK-1R and serum SP were increased in patients with CKD and mice experiencing UUO and correlated with renal fibrosis and function. SP addition enhanced UUO-induced progressive inflammatory responses and renal fibrosis, whereas genetically or pharmacologically targeting NK-1R attenuated these effects. Mechanistically, TFAP4 promoted NK-1R transcription by binding to its promoter, which was abolished by mutation of the binding site between TFAP4 and NK-1R promoter. Furthermore, SP acted through the NK-1R to activate the JNK/p38 pathways to modulate cell fate of tubular epithelial cells including growth arrest, apoptosis, and expression of profibrogenic genes.ConclusionOur data reveals that SP/NK-1R signaling promotes renal inflammatory responses and fibrosis, suggesting NK-1R could be a potential therapeutic target for the patients with CKD.

Abstract In this paper, X-ray diffraction spectroscopy (XRD), Raman spectroscopy (RS), firing temperature analysis, pore size distribution analysis, Fourier infrared spectroscopy (FTIR), scanning electron microscopy-energy dispersive spectroscopy (SEM–EDS), and transmission electron microscopy (TEM) were utilized to analyze the unearthed vulnerable terracotta figures of Emperor Qin Shihuang's Terracotta Army, as well as the unknown precipitated white crystals and black substances. The results show that the firing temperature of the vulnerable terracotta figure is much lower than those of similar terracotta figures and red terracotta figures with good texture. The pore size of this kind of vulnerable pottery is smaller and the specific surface area is larger. In the pores, there is an alkaline solution containing Ca2+ that accounted for approximately 4.3% of the total mass of the sample. Along with the fracture of the delicate pottery matrix, the solution in the pores migrated to the fracture surface and chemically reacted with CO2 in the air, generating a layer of white calcium carbonate crust. The black matter on the fracture surface of the vulnerable terracotta figure is mainly composed of amorphous carbon and graphitized carbon, which shows high activity under the catalysis of Fe and Ti elements and alkaline soil. The discovery and analysis of amorphous carbon, graphitized carbon, and white calcium carbonate crystals on the fracture surface of the Qin Shihuang’s Terracotta Army provide a theoretical foundation for in-depth analysis of the terracotta warriors and horses' composition and structure, as well as scientific protection and restoration, and the stability of the original site display.

ObjectiveTo detect the effects of exercise preconditioning on autophagy protein and apoptosis factor of cardiomyocytes in aged rats with myocardial ischemia reperfusion injury.MethodsA total of 60 aged male SD rats were randomly divided into the control group (Con group), the ischemia/reperfusion group (IR group), the exercise preconditioning+ischemic preconditioning group (EP+IPC group), the exercise preconditioning+ischemic preconditioning+normal saline group (EP+IPC+saline group), the exercise preconditioning+ischemic preconditioning+autophagy inhibitor group (EP+IPC+3-MA group), with 12 cases in each group. The Con group and the IR group did not receive special exercise intervention, the EP+IPC group, the EP+IPC+saline group and the EP+IPC+3-MA group received exercise preconditioning intervention (gradient exercise training was performed on an electric animal experimental treadmill, one time a day, five days a week, continuous training for six weeks). In addition, the EP+IPC+saline group and the EP+IPC+3-MA group were given normal saline and 3-methyladenine inhibitor (3-MA) during reperfusion respectively. The isolated rat myocardial ischemia/reperfusion model was established using the Langendorff in vitro perfusion system. Cardiomyocyte autophagosomes were observed by transmission electron microscope (TEM); cardiomyocyte apoptosis was detected by TUNEL staining; Beclin-1, LC3-Ⅱ, Bax, Caspase-9, Bcl-2, Bcl-XL protein expression levels were detected by Western blot method.Results① TEM observation results: a small amount of autolysosomes were observed in the Con group; more autolysosomes and autophagy vesicles were observed in the IR group; a small amount of autolysosomes were observed in the EP+IPC group; a small number of autophagic vesicles were observed in the EP+IPC+saline group; there wasn't typical autophagic vesicles and lysosomes were observed in the EP+IPC+3-MA group. ② TUNEL positive cell ratio results: only a few TUNEL positive cells were found in the Con group. Compared with the Con group, the ratio of TUNEL positive cells in the IR group increased significantly (PPPPPP

This paper presents the design of a high-intensity 10 mA deuteron RFQ accelerator that generates a 2.1 MeV beam in a continuous wave (CW) mode. The operation frequency is 162.5 MHz. The results of beam dynamics simulations demonstrate excellent output beam quality, achieving a transmission efficiency of 98.63%. The beam tracking results indicate that the RFQ is capable of managing errors within reasonable tolerances. In addition, the RF electromagnetic design and optimization are based on an RFQ model. Multiphysics simulations are then performed for the CW mode. Vacuum calculations suggest that the RFQ requires four 1200 L/s vacuum pumps and one 440 L/s ion pump to attain a vacuum pressure of 10−6 Pa.

C23H18FeO, orthorhombic, Pna21 (no. 33), a = 28.3217(11) Å, b = 5.7477(2) Å, c = 10.3071(3) Å, β = 90°, V = 1677.84(10) Å3, Z = 4, Rgt(F) = 0.0372, wRref(F2) = 0.0713, T = 150 K.

Hyperglycemia is a crucial risk factor for cardiovascular diseases. Chronic inflammation is a central characteristic of obesity, leading to many of its complications. Recent studies have shown that high glucose activates Yes-associated protein 1 (YAP) by suppressing AMPK activity in breast cancer cells. Metformin is a commonly prescribed anti-diabetic drug best known for its AMPK-activating effect. However, the role of YAP in the vasoprotective effect of metformin in diabetic endothelial cell dysfunction is still unknown. The present study aimed to investigate whether YAP activation plays a role in obesity-associated endothelial dysfunction and inflammation and examine whether the vasoprotective effect of metformin is related to YAP inhibition. Reanalysis of the clinical sequencing data revealed YAP signaling, and the YAP target genes CTGF and CYR61 were upregulated in aortic endothelial cells and retinal fibrovascular membranes from diabetic patients. YAP overexpression impaired endothelium-dependent relaxations (EDRs) in isolated mouse aortas and increased the expression of YAP target genes and inflammatory markers in human umbilical vein endothelial cells (HUVECs). High glucose-activated YAP in HUVECs and aortas was accompanied by increased production of oxygen-reactive species. AMPK inhibition was found to induce YAP activation, resulting in increased JNK activity. Metformin activated AMPK and promoted YAP phosphorylation, ultimately improving EDRs and suppressing the JNK activity. Targeting the AMPK–YAP–JNK axis could become a therapeutic strategy for alleviating vascular dysfunction in obesity and diabetes.

PDCD10, also known as CCM3, is a gene found to be associated with the human disease cerebral cavernous malformations (CCMs). PDCD10 forms a complex with GCKIII kinases including STK24, STK25, and MST4. Studies in C. elegans and Drosophila have shown a pivotal role of the PDCD10-GCKIII complex in maintaining epithelial integrity. Here, we found that mice deficient of Pdcd10 or Stk24/25 in the kidney tubules developed polyuria and displayed increased water consumption. Although the expression levels of aquaporin genes were not decreased, the levels of total and phosphorylated aquaporin 2 (Aqp2) protein in the apical membrane of tubular epithelial cells were decreased in Pdcd10- and Stk24/25-deficient mice. This loss of Aqp2 was associated with increased expression and membrane targeting of Ezrin and phosphorylated Ezrin, Radixin, Moesin (p-ERM) proteins and impaired intracellular vesicle trafficking. Treatment with Erlotinib, a tyrosine kinase inhibitor promoting exocytosis and inhibiting endocytosis, normalized the expression level and membrane abundance of Aqp2 protein, and partially rescued the water reabsorption defect observed in the Pdcd10-deficient mice. Our current study identified the PDCD10-STK-ERM signaling pathway as a potentially novel pathway required for water balance control by regulating vesicle trafficking and protein abundance of AQP2 in the kidneys.

Abstract Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain areas. The detailed pathogenic mechanisms underlying the selective loss of dopaminergic neurons in PD are unclear, and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in PD. However, the formation of α-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD, possibly stemming from the consequence of protein misfolding and dysfunctional proteostasis. Proteostasis is the mechanism for maintaining protein homeostasis via modulation of protein translation, enhancement of chaperone capacity and the prompt clearance of misfolded protein by the ubiquitin proteasome system and autophagy. Deregulated protein translation and impaired capacities of chaperone or protein degradation can disturb proteostasis processes, leading to pathological protein aggregation and neurodegeneration in PD. In recent years, multiple molecular targets in the modulation of protein translation vital to proteostasis and dopaminergic neuron degeneration have been identified. The potential pathophysiological and therapeutic significance of these molecular targets to neurodegeneration in PD is highlighted.

Abstract At the heart of bureaucratic practice during Warring States and early Imperial China were regular, small acts of accountancy in which objects and people were marked so that their movements could be kept track of, their quality checked and their numbers marshalled. In the mausoleum complex of the Qin Shihuang (259-210 bc, the First Emperor of the Qin Dynasty), the longer texts and shorter inscribed marks found on the bronze weapons of the Terracotta Army are reasonably well known, and such information helps us to understand aspects of Qin craft organisation and logistics at this crucial period of Chinese state formation. This paper’s modest starting point is a study of two further, less well-known ink inscriptions found on crossbow triggers from Terracotta Army Pit 1. Using multispectral photography, digital microscopy and Raman analysis, we uncover evidence of further marks on the same two triggers that suggest a similar pattern of ‘matching’ marks as suggested by the incised evidence. We also identify the black substance used to make the marks as a soot-based ink. Spatial analysis of both the inked and incised trigger marks then provides wider context for how such marking practices amongst Qin bronze-workers may have operated.

Abstract Background Cultured human cells are pivotal models to study human gene functions, but introducing complete loss of function in diploid or aneuploid cells has been a challenge. The recently developed CRISPR/Cas9-mediated homology-independent knock-in approach permits targeted insertion of large DNA at high efficiency, providing a tool for insertional disruption of a selected gene. Pioneer studies have showed promising results, but the current methodology is still suboptimal and functional outcomes have not been well examined. Taking advantage of the promoterless fluorescence reporter systems established in our previous study, here, we further investigated potentials of this new insertional gene disruption approach and examined its functional outcomes. Results Exemplified by using hyperploid LO2 cells, we demonstrated that simultaneous knock-in of dual fluorescence reporters through CRISPR/Cas9-induced homology-independent DNA repair permitted one-step generation of cells carrying complete disruption of target genes at multiple alleles. Through knocking-in at coding exons, we generated stable single-cell clones carrying complete disruption of ULK1 gene at all four alleles, lacking intact FAT10 in all three alleles, or devoid of intact CtIP at both alleles. We have confirmed the depletion of ULK1 and FAT10 transcripts as well as corresponding proteins in the obtained cell clones. Moreover, consistent with previous reports, we observed impaired mitophagy in ULK1−/− cells and attenuated cytokine-induced cell death in FAT10−/− clones. However, our analysis showed that single-cell clones carrying complete disruption of CtIP gene at both alleles preserved in-frame aberrant CtIP transcripts and produced proteins. Strikingly, the CtIP-disrupted clones raised through another two distinct targeting strategies also produced varied but in-frame aberrant CtIP transcripts. Sequencing analysis suggested that diverse DNA processing and alternative RNA splicing were involved in generating these in-frame aberrant CtIP transcripts, and some infrequent events were biasedly enriched among the CtIP-disrupted cell clones. Conclusion Multiallelic gene disruption could be readily introduced through CRISPR/Cas9-induced homology-independent knock-in of dual fluorescence reporters followed by direct tracing and cell isolation. Robust cellular mechanisms exist to spare essential genes from loss-of-function modifications, by generating partially functional transcripts through diverse DNA and RNA processing mechanisms.

Imbalance of gut microbiota can induce or aggravate intestinal inflammation. To enhance our understanding of the molecular mechanisms of gut microbiota and inflammatory bowel disease (IBD), we studied the role of repulsive guidance molecule b (RGMb) in gut microbiota and colitis in mice. We generated Rgmb knockout mice and inducible Rgmb knockout mice and induced colitis using dextran sulfate sodium (DSS) in these mice. 16S ribosomal RNA (rRNA) high-throughput sequencing was performed to acquire the gut microbiota composition and abundance. We found that Rgmb deficiency significantly altered the diversity of gut microbiota and also induced dysbiosis. In sharp contrast to the balanced distribution of various bacteria in control mice, Prevotellaceae was almost exhausted in Rgmb-deficient mice under both basal and inflammatory conditions. Correlation analysis indicated that Prevotellaceae was negatively associated with inflammation in Rgmb-deficient mice with colitis. Similar results were obtained at the early inflammatory stage of colitis associated colon cancer (CAC). Taken together, our results reveal that Rgmb deficiency leads to dysbiosis of predominant gut microbiota under basal and inflammatory conditions. Rgmb-deficiency-mediated Prevotellaceae loss may render mice more susceptible to intestinal inflammation. Therefore, RGMb may be a novel potential target for reconstruction of the gut microbiota for the treatment of IBD.

In order to figure out the migration and deposition of impurities on the first wall of HL-2A/2M tokamak, Peking University and Southwestern Institute of Physics are co-developing a deuteron RFQ as part of the in situ ion-beam diagnostic for the material. The RFQ, which operates at 162.5 MHz, is designed to accelerate a 10-mA deuteron beam from 40 keV up to 1.5 MeV. Key design considerations and the final design parameters are presented. The RFQ has been conditioned at a 1% duty factor for 80 h at RF cavity power of 55 kW. The specific shunt impedance of the cavity is 221 kΩ·m by measuring the bremsstrahlung spectrum. The intrinsic Q-value after the high-power tests measured by the Ring-Down method is 13,780. Beam commissioning has been taken place during the first half of 2021, and the beam measurements include beam current and energy of 2H+ ion. A 10 mA 2H+ beam was successfully accelerated through the RFQ.

Based on a spin-dependent Boltzmann-Uehling-Uhlenbeck transport model with spin-dependent potentials incorporated using the lattice Hamiltonian method, we have studied the global spin polarization perpendicular to the reaction plane as well as the local spin polarization in the longitudinal direction in non-central intermediate-energy heavy-ion collisions, as an extension of similar studies in relativistic heavy-ion collisions. Both the global and the local spin polarizations are found to be mostly dominated by the time-odd component of the nuclear spin-orbit potential. Impacts of various theoretical uncertainties on the nucleon spin polarization as well as its dependence on the beam energy and impact parameter are discussed. Our study serves as a baseline for understanding the spin polarization mechanism of strongly interacting matter produced in heavy-ion collisions dominated by nucleon degree of freedom.

Understanding moisture transport is an important step in the study of the durability of cement-based materials. A neutron imaging detection method for water transport in cement-based materials, based on a compact neutron source is provided. We visualize the moisture transport and obtain the capillarity coefficients for different cement-based materials using PKUNIFTY.

Summary: Though genetic data suggest that Polycomb group proteins (PcGs) are central chromatin modifiers and repressors that have been implicated in control of embryonic stem cell (ESC) pluripotency, the precise mechanism of PcG complex recruitment remains elusive, especially in mammals. We now report that the first and second MBT repeats of L3mbtl2 are important structural and functional features that are necessary and sufficient for L3mbtl2-mediated recruitment of PRC1.6 complex to target promoters. Interestingly, this region of L3mbtl2 harbors the evolutionarily conserved Pho-binding pocket also present in Drosophila Sfmbt, and mutation of the critical residues within this pocket completely abolishes its interaction with target promoters. Additionally, decreased PRC1.6 chromatin occupancy was observed following loss of individual components (L3mbtl2, Pcgf6, and Max) of the complex. Our findings suggest that the recruitment of noncanonical PRC1.6 complex in ESCs might be the result of L3mbtl2’s interaction with multiple components of the complex. : Yikai et al. report that Polycomb group protein L3mbtl2 assembles a complex whose composition is conserved with the Drosophila PhoRC. L3mbtl2-mediated chromatin recruitment of a variant PRC1 requires cooperation among complex components. Keywords: Polycomb, PRC1, PRC1.6, L3mbtl2, Pcgf6, Max, Mga, PhoRC, Sfmbt, Ring1b

A consistent derivation of the equations of motion (EOMs) of test particles for solving the spin-dependent Boltzmann–Vlasov equation is presented. The resulting EOMs in phase space are similar to the canonical equations in Hamiltonian dynamics, and the EOM of spin is the same as that in the Heisenburg picture of quantum mechanics. Considering further the quantum nature of spin and choosing the direction of total angular momentum in heavy-ion reactions as a reference of measuring nucleon spin, the EOMs of spin-up and spin-down nucleons are given separately. The key elements affecting the spin dynamics in heavy-ion collisions are identified. The resulting EOMs provide a solid foundation for using the test-particle approach in studying spin dynamics in heavy-ion collisions at intermediate energies. Future comparisons of model simulations with experimental data will help to constrain the poorly known in-medium nucleon spin–orbit coupling relevant for understanding properties of rare isotopes and their astrophysical impacts.

Both extrinsic and intrinsic tissues contribute to tendon repair, but the origin and molecular functions of extrinsic tissues in tendon repair are not fully understood. Here we show that tendon sheath cells harbor stem/progenitor cell properties and contribute to tendon repair by activating Hedgehog signaling. We found that Osteocalcin (Bglap) can be used as an adult tendon-sheath-specific marker in mice. Lineage tracing experiments show that Bglap-expressing cells in adult sheath tissues possess clonogenic and multipotent properties comparable to those of stem/progenitor cells isolated from tendon fibers. Transplantation of sheath tissues improves tendon repair. Mechanistically, Hh signaling in sheath tissues is necessary and sufficient to promote the proliferation of Mkx-expressing cells in sheath tissues, and its action is mediated through TGFβ/Smad3 signaling. Furthermore, co-localization of GLI1+ and MKX+ cells is also found in human tendinopathy specimens. Our work reveals the molecular function of Hh signaling in extrinsic sheath tissues for tendon repair.

Objective. COQ2 mutations have been reported in Japanese multiple system atrophy (MSA) patients. We examined the role of COQ2 in patients with dementia and essential tremor (ET), two common neurodegenerative conditions. Materials & Methods. A total of 2064 subjects, including 560 patients with dementia, 466 patients with ET, and 1038 healthy controls, were included. Genotyping for the COQ2 V393A (T>C) was carried out. Odds ratio (OR) adjusted by age and gender, together with 95% confidence interval (CI), was reported by means of logistic regression. Results. The frequency of the polymorphic variant V393A heterozygous (T/C) was 2.7% in dementia, 1.1% in ET, and 2.5% in controls (OR = 0.70, 95% confidence interval is 0.29–1.72 for dementia, and OR = 0.47, 95% confidence interval is 0.17–1.31, p=0.1217 for ET). There was no significant association between V393A variant with dementia and ET. Conclusion. There was no significant association between V393A variant with dementia and ET. COQ2 gene is unlikely to play a significant role in patients with dementia or ET in our population.

Cardiomyocytes are quite resistant to gene transfer using standard techniques. We developed an expression vector carrying an attenuated but infectious and replicative coxsackievirus B3 (CVB3) genome, and unique ClaI-StuI cloning sites for an exogenous gene, whose product can be released from the nascent viral polyprotein by 2A(pro) cleavage. This vector was tested as an expression vehicle for green fluorescent protein (GFP). The vector transiently expressed GFP in cell cultures for at least ten passages and delivered functional GFP to the infected cardiomyocytes for at least 6 days. Moreover, the recombinant viruses showed virulence attenuation in vitro and in vivo. The findings suggest that the recombinant CVB3 vector could be a useful tool for viral tracking study and delivering exogenous proteins to cardiomyocytes.

From 2007 to 2008, many bronze wares of Qin Dynasty were excavated from tombs at Xinfeng town. Being an important finding, these bronze wares attracted people’s attention, especially for their conservation. Therefore, the corrosive products were explored by using Scanning Electron Microscope with Energy Dispersive X-ray Detector (SEM/EDS), X-Ray diffraction (XRD), and Raman spectroscopy (RM), which provided much valuable information on the conservation of these bronze wares. According to tested results, the corrosive products of bronzes were found to be comprised of cuprite (Cu2O), covellite (CuS), lead carbonate (PbCO3), and malachite (CuCO3·Cu(OH)2). Meantime, the multilayer corrosive structure was found in some samples due to the cracks in Cu2O layer which had formed many microchannels to promote the material migration.

Hepcidin is an antimicrobial peptide, which also negatively regulates iron in circulation by controlling iron absorption from dietary sources and iron release from macrophages. Hepcidin is synthesized mainly in the liver, where hepcidin is regulated by iron loading, inflammation and hypoxia. Recently, we have demonstrated that bone morphogenetic protein (BMP)-hemojuvelin (HJV)-SMAD signaling is central for hepcidin regulation in hepatocytes. Hepcidin is also expressed by macrophages. Studies have shown that hepcidin expression by macrophages increases following bacterial infection, and that hepcidin decreases iron release from macrophages in an autocrine and/or paracrine manner. Although previous studies have shown that lipopolysaccharide (LPS) can induce hepcidin expression in macrophages, whether hepcidin is also regulated by BMPs in macrophages is still unknown. Therefore, we examined the effects of BMP signaling on hepcidin expression in RAW 264.7 and J774 macrophage cell lines, and in primary peritoneal macrophages. We found that BMP4 or BMP6 alone did not have any effect on hepcidin expression in macrophages although they stimulated Smad1/5/8 phosphorylation and Id1 expression. In the presence of LPS, however, BMP4 and BMP6 were able to stimulate hepcidin expression in macrophages, and this stimulation was abolished by the NF-κB inhibitor Ro1069920. These results suggest that hepcidin expression is regulated differently in macrophages than in hepatocytes, and that BMPs regulate hepcidin expression in macrophages in a LPS-NF-κB dependent manner.