Heterogeneous integration of spin-photon interfaces with a CMOS platform.

Colour centres in diamond have emerged as a leading solid-state platform for advancing quantum technologies, satisfying the DiVincenzo criteria1 and recently achieving quantum advantage in secret key distribution2. Blueprint studies3-5 indicate that general-purpose quantum computing using local quantum communication networks will require millions of physical qubits to encode thousands of logical qubits, presenting an open scalability challenge. Here we introduce a modular quantum system-on-chip (QSoC) architecture that integrates thousands of individually addressable tin-vacancy spin qubits in two-dimensional arrays of quantum microchiplets into an application-specific integrated circuit designed for cryogenic control. We demonstrate crucial fabrication steps and architectural subcomponents, including QSoC transfer by means of a 'lock-and-release' method for large-scale heterogeneous integration, high-throughput spin-qubit calibration and spectral tuning, and efficient spin state preparation and measurement. This QSoC architecture supports full connectivity for quantum memory arrays by spectral tuning across spin-photon frequency channels. Design studies building on these measurements indicate further scaling potential by means of increased qubit density, larger QSoC active regions and optical networking across QSoC modules.

Application of stem cells in engineered vascular graft and vascularized organs.

Recent studies report that stem cell therapies have been applied successfully to patients, This has increased anticipations that this regeneration strategy could be a potential method to treat a wide range of intractable diseases some day. Stem cells offer new prospects for the treatment of incurable diseases and for tissue regeneration and repairation because of their unique biological properties. Angiogenesis a key process in tissue regeneration and repairation. Vascularization of organs is one of the main challenges hindering the clinical application of engineered tissues. Efficient production of engineered vascular grafts and vascularized organs is of critical importance for regenerative medicine. In this review, we focus on the types of stem cells that are widely used in tissue engineering and regeneration, as well as their application of these stem cells in the construction of tissue-engineered vascular grafts and vascularization of tissue-engineered organs.

Arid1a regulates cell cycle exit of transit-amplifying cells by inhibiting the Aurka-Cdk1 axis in mouse incisor.

Stem cells self-renew or give rise to transit-amplifying cells (TACs) that differentiate into specific functional cell types. The fate determination of stem cells to TACs and their transition to fully differentiated progeny is precisely regulated to maintain tissue homeostasis. Arid1a, a core component of the switch/sucrose nonfermentable complex, performs epigenetic regulation of stage- and tissue-specific genes that is indispensable for stem cell homeostasis and differentiation. However, the functional mechanism of Arid1a in the fate commitment of mesenchymal stem cells (MSCs) and their progeny is not clear. Using the continuously growing adult mouse incisor model, we show that Arid1a maintains tissue homeostasis through limiting proliferation, promoting cell cycle exit and differentiation of TACs by inhibiting the Aurka-Cdk1 axis. Loss of Arid1a overactivates the Aurka-Cdk1 axis, leading to expansion of the mitotic TAC population but compromising their differentiation ability. Furthermore, the defective homeostasis after loss of Arid1a ultimately leads to reduction of the MSC population. These findings reveal the functional significance of Arid1a in regulating the fate of TACs and their interaction with MSCs to maintain tissue homeostasis.

Direct Synthesis of α-Ketoamides via Copper-Catalyzed Reductive Amidation of Nitroarenes with α-Oxocarboxylic Acids.

Nitroarenes are known for their stability, low toxicity, easy availability, and cost-effectiveness, making them one of the most fundamental chemical feedstocks. The direct utilization of nitroarenes as nitrogen sources in amidation reactions offers significant advantages over using arylamines. Herein, we disclose a streamlined method for constructing α-ketoamides through the direct coupling of nitroarenes with α-oxocarboxylic acids. This transformation obviates the need for preparing, isolating, and purifying arylamines, leading to improved efficiency, cost-effectiveness, and time savings.

Ganonorsterone A, a norsteroid from the medicinal fungus Ganoderma lingzhi.

Phytochemical investigation on the fruiting bodies of the medicinal fungus Ganoderma lingzhi led to the isolation of a new norsteroid, namely ganonorsterone A (1), together with one known steroid, cyathisterol (2). The structure and absolute configuration of compound 1 were assigned by extensive analysis of MS, NMR data, and quantum-chemical calculations including electronic circular dichroism (ECD) and calculated 13C NMR-DP4+ analysis. Bioassay results showed that compound 1 displayed moderate inhibition on NO production in RAW 264.7 macrophages.

Mutation spectrum of FLT3 and significance of non-canonical FLT3 mutations in haematological malignancy.

Fms-like tyrosine kinase 3 (FLT3) is frequently mutated in haematological malignancies. Although canonical FLT3 mutations including internal tandem duplications (ITDs) and tyrosine kinase domains (TKDs) have been extensively studied, little is known about the clinical significance of non-canonical FLT3 mutations. Here, we first profiled the spectrum of FLT3 mutations in 869 consecutively newly diagnosed acute myeloid leukaemia (AML), myelodysplastic syndrome and acute lymphoblastic leukaemia patients. Our results showed four types of non-canonical FLT3 mutations depending on the affected protein structure: namely non-canonical point mutations (NCPMs) (19.2%), deletion (0.7%), frameshift (0.8%) and ITD outside the juxtamembrane domain (JMD) and TKD1 regions (0.5%). Furthermore, we found that the survival of patients with high-frequency (>1%) FLT3-NCPM in AML was comparable to those with canonical TKD. In vitro studies using seven representative FLT3-deletion or frameshift mutant constructs showed that the deletion mutants of TKD1 and the FLT3-ITD mutant of TKD2 had significantly higher kinase activity than wild-type FLT3, whereas the deletion mutants of JMD had phosphorylation levels comparable with wild-type FLT3. All tested deletion mutations and ITD were sensitive to AC220 and sorafenib. Collectively, these data enrich our understanding of FLT3 non-canonical mutations in haematological malignancies. Our results may also facilitate prognostic stratification and targeted therapy of AML with FLT3 non-canonical mutations.

Structure and ecological function of the soil microbiome associated with 'Sanghuang' mushrooms suffering from fungal diseases.

BACKGROUND: The most serious challenges in medicinal 'Sanghuang' mushroom production are the fungal diseases caused by various molds. Application of biological agents has been regarded as a potential crop disease management strategy. Here, the soil microbiome associated with 'Sanghuang' mushroom affected by fungal diseases grown under field cultivation (FC) and hanging cultivation (HC) was characterized using culture-dependent and culture-independent methods. RESULTS: A total of 12,525 operational taxonomic units (OTUs) and 168 pure cultures were obtained using high-throughput sequencing and a culture-dependent method, respectively. From high-throughput sequencing, we found that HC samples had more OTUs, higher α-diversity, and greater microbial community complexity than FC samples. Analysis of ß-diversity divided the soil microbes into two groups according to cultivation mode. Basidiomycota (48.6%) and Ascomycota (46.5%) were the two dominant fungal phyla in FC samples, with the representative genera Trichoderma (56.3%), Coprinellus (29.4%) and Discosia (4.8%), while only the phylum Ascomycota (84.5%) was predominant in HC samples, with the representative genera Discosia (34.0%), Trichoderma (30.2%), Penicillium (14.9%), and Aspergillus (7.8%). Notably, Trichoderma was predominant in both the culture-independent and culture-dependent analyses, with Trichoderma sp. FZ0005 showing high host pathogenicity. Among the 87 culturable bacteria, 15 exhibited varying extents of antifungal activity against Trichoderma sp. FZ0005, with three strains of Bacillus spp. (HX0037, HX0016, and HX0039) showing outstanding antifungal capacity. CONCLUSIONS: Overall, our results suggest that Trichoderma is the major causal agent of 'Sanghuang' fungal diseases and that Bacillus strains may be used as biocontrol agents in 'Sanghuang' cultivation.

High FAAP24 expression reveals poor prognosis and an immunosuppressive microenvironment shaping in AML.

BACKGROUND: As a core member of the FA complex, in the Fanconi anemia pathway, FAAP24 plays an important role in DNA damage repair. However, the association between FAAP24 and patient prognosis in AML and immune infiltration remains unclear. The purpose of this study was to explore its expression characteristics, immune infiltration pattern, prognostic value and biological function using TCGA-AML and to verify it in the Beat AML cohort. METHODS: In this study, we examined the expression and prognostic value of FAAP24 across cancers using data from TCGA, TARGET, GTEx, and GEPIA2. To further investigate the prognosis in AML, development and validation of a nomogram containing FAAP24 were performed. GO/KEGG, ssGSEA, GSVA and xCell were utilized to explore the functional enrichment and immunological features of FAAP24 in AML. Drug sensitivity analysis used data from the CellMiner website, and the results were confirmed in vitro. RESULTS: Integrated analysis of the TCGA, TARGET and GTEx databases showed that FAAP24 is upregulated in AML; meanwhile, high FAAP24 expression was associated with poor prognosis according to GEPIA2. Gene set enrichment analysis revealed that FAAP24 is implicated in pathways involved in DNA damage repair, the cell cycle and cancer. Components of the immune microenvironment using xCell indicate that FAAP24 shapes an immunosuppressive tumor microenvironment (TME) in AML, which helps to promote AML progression. Drug sensitivity analysis showed a significant correlation between high FAAP24 expression and chelerythrine resistance. In conclusion, FAAP24 could serve as a novel prognostic biomarker and play an immunomodulatory role in AML. CONCLUSIONS: In summary, FAAP24 is a promising prognostic biomarker in AML that requires further exploration and confirmation.

Remote Effect from Boron Cluster: Tunable Photophysical Properties of o-Carborane-Based Luminogens.

We proposed a new molecular design strategy that the o-carboranyl group is attached as "an innocent unit" to the remote side of luminogens to tune photophysical properties. To verify this strategy, two o-carborane-based compounds with asymmetric molecular geometry were designed and synthesized. Photophysical properties of o-carborane-based luminogens were investigated on the basis of UV-Vis spectra, photoluminescence spectra, crystal structure analysis and theoretical calculations. The results indicate that the o-carboranyl group has a slight effect on the energy gap between the ground state (S0 ) and the first excited state (S1 ) in the solution state but a significant effect on the energy gap between S0 and S1 in the solid state. Besides, the radiative and non-radiative transition processes are modulated by the o-carboranyl unit. This leads to emission quenching in the solution state but an enhanced luminous efficiency in the aggregate state with a typical aggregation-induced emission (AIE) property.

Building quantum mechanics quality force fields of proteins with the generalized energy-based fragmentation approach and machine learning.

We combined our generalized energy-based fragmentation (GEBF) approach and machine learning (ML) technique to construct quantum mechanics (QM) quality force fields for proteins. In our scheme, the training sets for a protein are only constructed from its small subsystems, which capture all short-range interactions in the target system. The energy of a given protein is expressed as the summation of atomic contributions from QM calculations of various subsystems, corrected by long-range Coulomb and van der Waals interactions. With the Gaussian approximation potential (GAP) method, our protocol can automatically generate training sets with high efficiency. To facilitate the construction of training sets for proteins, we store all trained subsystem data in a library. If subsystems in the library are detected in a new protein, corresponding datasets can be directly reused as a part of the training set on this new protein. With two polypeptides, 4ZNN and 1XQ8 segment, as examples, the energies and forces predicted by GEBF-GAP are in good agreement with those from conventional QM calculations, and dihedral angle distributions from GEBF-GAP molecular dynamics (MD) simulations can also well reproduce those from ab initio MD simulations. In addition, with the training set generated from GEBF-GAP, we also demonstrate that GEBF-ML force fields constructed by neural network (NN) methods can also show QM quality. Therefore, the present work provides an efficient and systematic way to build QM quality force fields for biological systems.

Transition orbital projection approach for excited state tracking.

Quantitively comparing the features between different electronic excited states (ESs) is a crucial task in both potential energy surface (PES) studies and excited-state fragmentation approaches. However, it is still a challenging problem in regard to the comparison of complex and highly degenerate systems. Herein, we present a transition orbital projection (TOP) method to calculate the similarity of different ESs based on the configuration vectors of two types of transition densities. It fully considers four significant problems, including phase, hole-particle bijectivity, orbital permutation, and sign of configuration coefficients. TOP state-tracking-based excited-state optimization shows high robustness in several high-symmetric systems, which are difficult to describe with traditional state-tracking approaches. The TOP state-tracking method is expected to be widely applied to the PES of photochemical reactions, ES molecular dynamics to track the diabatic states, and fragmentation approaches for local excitation of large systems.

Cryptoanalysis and enhancement of a binary image encryption system based on interference.

In this paper, cryptoanalysis on a binary image encryption system based on interference is conducted. In the cryptosystem under study, the binary plaintext image modulated by a random phase mask (RPM) is separated directly into two phase-only masks (POMs) as private keys. Phase wrapping operation is applied to modulate two separated POMs further for silhouette removal. The plaintext image can be reconstructed by compositing two phase-wrapped POMs. However, since the RPM used in the encryption process is irrelative to the plaintexts, it is possible to retrieve the RPM by a known-plaintext attack (KPA). And then with the help of the retrieved RPM, the information encoded in the arbitrarily given ciphertext can be reconstructed by a ciphertext-only attack (COA). Based on our analysis, a hybrid attack including a KPA and a COA with different constraints is proposed in this study. Besides, the cryptosystem under study can only be used to encode binary plaintexts, which would limit the application of this scheme in the information security. Consequently, an improved cryptosystem in which both binary and gray-scale plaintext images can be encoded is proposed. In addition, the RPM to generate two private keys in the enhanced system is dependent on the plaintexts, which makes the proposed encryption scheme immune to the proposed hybrid attack. The feasibility and effectiveness of the security-enhanced cryptosystem have been validated by numerical simulations.

A novel positive feedback loop of linc02042 and c-Myc mediated by YBX1 promotes tumorigenesis and metastasis in esophageal squamous cell carcinoma.

BACKGROUND: Long non-coding RNA (lncRNA) is a class of endogenous RNA with a length of more than 200 nucleotides, which is emerging as a pivotal player in cancer development and progression. However, the functional roles of many members in this class remain largely uncharacterized. In the present study, we explored the biological relevance of linc02042 in esophageal squamous cell carcinoma (ESCC). METHODS: qRT-PCR was used to detect the levels of linc02042 and c-Myc. Western blot was used to assess protein expression level. CCK-8 and Transwell assays were employed to test ESCC cell proliferation and invasion, respectively. The mice study including xenograft tumor and lung metastasis models was used to determine the role of linc02042 in vivo. RNA pull-down, ChIP and luciferase reporter assays were employed to test the relationship between linc02042, YBX1 and c-Myc. RESULTS: Linc02042 was found to be markedly upregulated in ESCC cell lines, tissues and plasma, and was closely correlated with malignant clinical features. Knockdown of linc02042 significantly inhibited ESCC cell viability and invasion in vitro as well as tumor growth and lung metastasis in vivo, whereas overexpression of linc02042 resulted in the opposite results. Mechanistically, linc02042 acted as a scaffold for YBX-1 binding to the 3'-UTR of c-Myc mRNA, leading to enhanced c-Myc mRNA stability, thereby facilitating ESCC growth and metastasis. Moreover, in turn, c-Myc was able to transcriptionally elevate linc02042 by directly binding to the E-box motif proximal to the transcription start site (TSS) of linc02042 promoter. Clinically, linc02042 was identified as an effective diagnostic and prognostic biomarker for ESCC patients, and its expression was strongly positively correlated with c-Myc expression in ESCC tissues. CONCLUSION: Our data suggest that linc02042 plays an important tumor-promoting role in ESCC, which lays a foundation for considering it as a potential target for ESCC patients.

The antitumor effect of hinesol, extract from Atractylodes lancea (Thunb.) DC. by proliferation, inhibition, and apoptosis induction via MEK/ERK and NF-κB pathway in non-small cell lung cancer cell lines A549 and NCI-H1299.

Lung cancer (especially, non-small cell lung cancer [NSCLC]) is one of the most malignant cancers in the world. Hinesol is the major component of the essential oil of Atractylodes lancea (Thunb.) DC and possesses the most promising anticancer function. However, the effects and molecular mechanism of hinesol on antiproliferation in NSCLC cells has not been well understood. In this study, we found that hinesol effectively inhibited the A549 and NCI-H1299 cells in a dose- and time-dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. In addition, hinesol induced cell cycle arrest at G0/G1 phase and apoptosis assessed by flow cytometry in A549 cells. Furthermore, Western blot analysis showed that hinesol decreased phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, IκBα, and p65 inhibited the expressions of Bcl-2, cyclin D1 and upregulated the expression of Bax. Based on these results, hinesol might be a potential drug candidate of anti-NSCLC for therapy.

The novel circular RNA circ-CAMK2A enhances lung adenocarcinoma metastasis by regulating the miR-615-5p/fibronectin 1 pathway.

BACKGROUND: Circular RNA (circRNA) has recently been considered as a key regulator in carcinogenesis. In this study, we investigated the functional significance and regulatory role of circ-CAMK2A (hsa_circ_0128332) in lung adenocarcinoma (LUAD). METHODS: GSE101586 was employed to screen differentially expressed circRNAs. = Relative expression levels of circ-CAMK2A, miR-615-5p, fibronectin 1 (FN1), MMP2, and MMP9 were tested by quantitative reverse transcription PCR (qRT-PCR) or western blotting. Functional experiments were performed by CCK-8, wound healing, and transwell assays. Luciferase reporter and biotin-labeled RNA pull-down assays were carried out to evaluate the interaction between circ-CAMK2A, miR-615-5p, and fibronectin 1. In addition, a lung metastasis model was constructed to determine the metastasis-promoting role of circ-CAMK2A in vivo. RESULTS: Circ-CAMK2A overexpression was observed in LUAD and was closely associated with lymph node metastasis, distant metastasis, advanced clinical stage, and poor prognosis. Circ-CAMK2A silencing evidently inhibited LUAD cell migration and invasion, whereas circ-CAMK2A overexpression had an opposite effect. Importantly, overexpression of circ-CAMK2A also enhanced LUAD metastasis in vivo. Mechanistically, miR-615-5p was identified as a direct target of circ-CAMK2A. Circ-CAMK2A up-regulates the expression level of fibronectin 1 by sponging miR-615-5p, thereby increasing MMP2 and MMP9 expression to promote the metastasis of LUAD. CONCLUSION: Circ-CAMK2A plays a crucial role in the metastasis of LUAD, at least partially, by regulating the miR-615-5p/fibronectin 1 axis.

[Assessment of congenital vascular rings with MDCT on children].

OBJECTIVE: To evaluate the value of MDCT on diagnosis of congenital vascular rings on children. METHODS: Retrospective analysis on 43 cases of congenital vascular rings, which underwent MDCT during Oct 2008 to Dec 2014 in Beijing Anzhen hospital affiliated to capital medical university. 21 males, 22 females; age from 29 days to 8 years, mean age 1.46 years, 33 cases are not beyond 1 year. All the results were compared with that of the echocardiogram or record of the surgery. The CT data were read and reconstructed with multiplanar reconstruction (MPR), maximum intensity projection (MPR), minimum intensity projection (MinIP), volume rendering (VR). The image quality was evaluated and the diagnostic value and the standard diagnostic program were discussed. RESULTS: Of 43 cases of vascular rings:there were 6 cases of pulmonary artery sling (13.95%), 9 cases of right aortic arch /aberrant left subclavian artery(20.93%), 18 cases of left aortic arch/aberrant right subclavian artery (41.86%), 10 cases of double aortic arch (23.26%). Forty cases (93.02%) were combined with other cardiovascular or pulmonary malformations. Every malformation was revealed clearly and proved by echocardiogram. Of 3 cases (6.98%) without any other malformation, 2 cases were combined tracheal stenosis. A pulmonary artery sling was proved by surgery; the other 2 cases were double aortic arch. All the images of 43 cases could be reconstructed well. MPR and VR showed the origin, shape, and whole course of vascular rings directly; MinIP and VR could display the shape, width and development of trachea, revealed the relationship between vascular rings, trachea and esophagus. It was important to show and measure the component vascular of the ring. Attention should be paid to the whole course of trachea and esophagus, especially those segments which were close to the ring vascular. The tracheal stenosis as well as intra-cardio anatomy malformations should be measured on MPR images if existed. According to the segmental analysis method, comes the overall final diagnosis. A standard diagnostic program on vascular ring was proposed. CONCLUSION: MDCT axis images with various 3D post processing methods could reveal the compose of vascular rings and the relationship between vascular rings, trachea and esophagus.

Quantifying the Level of 8-oxo-dG Using ELISA Assay to Evaluate Oxidative DNA Damage in MCF-7 Cells.

8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) base is the predominant form of commonly observed DNA oxidative damage. DNA impairment profoundly impacts gene expression and serves as a pivotal factor in stimulating neurodegenerative disorders, cancer, and aging. Therefore, precise quantification of 8-oxoG has clinical significance in the investigation of DNA damage detection methodologies. However, at present, the existing approaches for 8-oxoG detection pose challenges in terms of convenience, expediency, affordability, and heightened sensitivity. We employed the sandwich enzyme-linked immunosorbent assay (ELISA) technique, a highly efficient and swift colorimetric method, to detect variations in 8-oxo-dG content in MCF-7 cell samples stimulated with different concentrations of hydrogen peroxide (H2O2). We determined the concentration of H2O2 that induced oxidative damage in MCF-7 cells by detecting its IC50 value in MCF-7 cells. Subsequently, we treated MCF-7 cells with 0, 0.25, and 0.75 mM H2O2 for 12 h and extracted 8-oxo-dG from the cells. Finally, the samples were subjected to ELISA. Following a series of steps, including plate spreading, washing, incubation, color development, termination of the reaction, and data collection, we successfully detected changes in the 8-oxo-dG content in MCF-7 cells induced by H2O2. Through such endeavors, we aim to establish a method to evaluate the degree of DNA oxidative damage within cell samples and, in doing so, advance the development of more expedient and convenient approaches for DNA damage detection. This endeavor is poised to make a meaningful contribution to the exploration of associative analyses between DNA oxidative damage and various domains, including clinical research on diseases and the detection of toxic substances.

High performance poly(L-lactic acid)-based film by one-step synthesis of poly (L-lactic acid-co-butylene itaconate-co-glycolic acid) for efficient preservation of yogurt storage.

Biodegradable poly(L-lactic acid) (PLLA) has seldom used for dairy packaging due to medium permeability and brittleness. Novel PLLA copolymers, poly (L-lactic acid-co-butylene itaconate-co-glycolic acid) (PLBIGA), were developed by integrating glycolic acid (GA) and poly(butylene itaconate) (PBI) into PLLA's structure using low molecular weight PLLA as a key initiator. Then, packaging materials with better barrier and mechanical properties were obtained by blended PLBIGA with PLLA. Both PLLA/PLBIGA films and polyethylene nylon composite film (PE/NY) were used for stirred yogurt packaging and storage at 4 °C for 25 days. Results revealed that yogurt packed by PLLA/PLBIGA films maintained stabler water-holding capacity, color, and viscosity over the storage period. Moreover, the integrity of the gel structure and the total viable count of lactic acid bacteria in yogurt packaged in PLLA/40-PLBIGA8 were also found to be superior to those in PE/NY packages, highlighting its eco-friendly advantages in dairy packaging.