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As a promising antitumor strategy, combination oncotherapy can achieve better therapeutic efficacy. However, given the different properties of drugs, carriers need to meet requirements for efficient encapsulation and controllable release of multi-drugs. Herein, we propose a graphene oxide (GO)-templated biomineralization nanosystem to optimize oncotherapy. For preparation, GO is conjugated with polyethylene glycol (PEG) to improve biostability, and glyeyrrhetinic acid (GA) is further grafted onto PEG chains for site-specific targeting. The generated nanosheet structure and large specific surface area support high doxorubicin (DOX) encapsulation and mineralized deposition of siRNA via π-π stacking and calcium phosphate co-precipitation, respectively. Followed by highly efficient penetration into tumor cells, GO-templated nanosystem performs swift drug release in response to tumor acidic microenvironment through dissolution of calcium phosphate and disruption of molecular interactions. After administration, the GO-templated nanosystem performs superior pharmacy properties and significant antitumor efficacy via the synergy of chemotherapy and RNA interference therapy. Collectively, a GO-templated biomineralization nanosystem provides an innovative delivery system for multi-drug administration in combinative tumor therapy. [ABSTRACT FROM AUTHOR]

The tetrel-bonded complexes formed between the selected boron-substituted carbenes and TH3F (T = C, Si, Ge, Sn, Pb) have been explored by using the high-level quantum chemical method. The binding sites of TH3F in the complexes are generally consistent with the positions of VS,min points of the carbenes, and the -Eint values of the complexes exhibit a general increasing tendency with the increase of the -VS,min values of the carbenes for a given TH3F. The complexes can be divided into the type-I and type-II groups. The type-I complexes are characterized by the 3c(B-C-B)→BD*(T-F) and BD(B-C)→BD*(T-F) orbital interactions, and the type-II complexes are characterized by the LP(C)→BD*(T-F) orbital interactions. The type-II complexes have more negative Eint values than the type-I complexes. The -Eint values of the type-I complexes exhibit a roughly increasing tendency with the increase of the T atomic number, and the -Eint values go in the order SnH3F > PbH3F > GeH3F > SiH3F > CH3F for most type-I complexes, which is consistent with the order of VS,max values of TH3F. Unlike type-I complexes, the -Eint values of the type-II complexes exhibit a zigzag tendency with the increase of the T atomic number, and the -Eint values go in the order SiH3F > SnH3F > GeH3F > PbH3F > CH3F for type-II complexes. The AIM and SAPT analysis has been employed to explore the nature of the intermolecular interactions in these complexes. [ABSTRACT FROM AUTHOR]

Aspect-Based Sentiment Classification (ABSA), predicting the sentimental tendency towards given aspects, is an important branch in natural language understanding. However, in the existing deep learning models for ABSA, there is a contradiction between the fine sentiment analysis and the small amount of corpus. To solve this contradiction, we propose a BERT-based Multi-Semantic Learning (BERT-MSL) model with aspect-aware enhancement for aspect polarity classification, which follows the Transformer structure in BERT and uses lightweight multi-head self-attentions for encoding. First, we make full use of the extensive pre-training and post-training of the BERT model to obtain the initialization parameters with rich knowledge for our BERT-MSL model, so that our model can be quickly adapted to the ABSA task only by fine-tuning on a small corpus. Second, to achieve the fine sentiment analysis centered on aspect target, we propose a BERT-based multi-semantic learning model composed of the left-side local semantic, right-side local semantic, aspect target semantic and global semantic learning modules, and propose an aspect-aware enhancement method based on BERT and multi-head attention. Third, we propose two alternative semantic merging methods to generate the final expressive-powerful sentiment semantics for ABSA. Furthermore, to expand the application scope of our model, we design an advanced structure for our model by introducing a CNN-based semantic refinement layer. Experimental results on five SemEval and Twitter datasets demonstrate that our model improves the stability and robustness of ABSA and significantly outperforms some of the state-of-the-art models under the BERT Post-Training (BERT-PT) environment. [ABSTRACT FROM AUTHOR]

Methods: The intermolecular interactions between the heavy-atom analogues of acetylene T2H2 (T = Si, Ge, Sn, Pb) and HCN have been investigated by theoretical calculations at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVDZ level. Results: The global energy minimum of T2H2 is the butterfly structure A, and another energy minimum is the planar structure B. Both structures A and B exhibit the dual behavior when binding with HCN. The various hydrogen bond (HB), dihydrogen bond (DB) and tetrel bond (TB) complexes can be found according to the MEP maps of T2H2. One TB and three HB complexes formed between structure A and HCN can be located for Si2H2 and Ge2H2. One TB, two HB and one DB complexes formed between structure A and HCN can be located for Sn2H2 and Pb2H2. Four TB and one HB complexes formed between structure B and HCN can be located for all the T2H2. The geometries and binding strengths of the complexes are compared and analyzed. Conclusions: The interactions in these complexes are generally weak, and the interaction energies of these complexes range from −0.53 to −8.23 kcal/mol. The interaction energies of the TB complexes are larger than those of the corresponding HB and DB complexes for structure A···HCN systems. The relative binding strength of the four TB complexes exhibits different order for different structure B···HCN systems, which is consistent with the MEP maps of the isolated monomers. [ABSTRACT FROM AUTHOR]

Critical-sized bone defects often lead to non-union and full-thickness defects of the calvarium specifically still present reconstructive challenges. In this study, we show that neurotrophic supplements induce robust in vitro expansion of mesenchymal stromal cells, and in situ transplantation of neurotrophic supplements-incorporated 3D-printed hydrogel grafts promote full-thickness regeneration of critical-sized bone defects. Single-cell RNA sequencing analysis reveals that a unique atlas of in situ stem/progenitor cells is generated during the calvarial bone healing in vivo. Notably, we find a local expansion of resident Msx1+ skeletal stem cells after transplantation of the in situ cell culture system. Moreover, the enhanced calvarial bone regeneration is accompanied by an increased endochondral ossification that closely correlates to the Msx1+ skeletal stem cells. Our findings illustrate the time-saving and regenerative efficacy of in situ cell culture systems targeting major cell subpopulations in vivo for rapid bone tissue regeneration. Critical-sized bone defects still present clinical challenges. Here the authors show that transplantation of neurotrophic supplement-incorporated hydrogel grafts promote full-thickness regeneration of the calvarium and perform scRNA-seq to reveal contributing stem/progenitor cells, notably a resident Msx1+ skeletal stem cell population. [ABSTRACT FROM AUTHOR]

With the development of IoT, the concept of intelligent services has gradually come to the fore. Intelligent services usually involve a large number of computation intensive tasks with data dependencies that are often modelled as directed acyclic graphs (DAGs), and the offloading of DAG tasks is complex and has proven to be an NP hard challenge. As a key research issue, the task offloading process migrates the computation intensive tasks from resource-constrained IoT devices to nearby edge servers, and pursuing a lower delay and energy consumption. However, data dependencies among tasks are complex, and it is challenging to coordinate the computation intensive tasks among multiple edge servers. In this paper, a flexible and generic DAG task model is built to support the associative task offloading process with complex data dependencies in IoT edge computing environments. Additionally, a priority-based DAG task offloading algorithm and a secondary resource allocation algorithm are proposed to minimize the response delay and improve the resource utilization of edge servers. Experimental results demonstrate that the proposed method can well support the DAG task offloading process with the shortest response delay, while outperforming all the benchmark policies, which is suitable for IoT edge computing environments. [ABSTRACT FROM AUTHOR]

Articular cartilage damage is a universal health problem. Despite recent progress, chondrocyte dedifferentiation has severely compromised the clinical outcomes of cell-based cartilage regeneration. Loss-of-function changes are frequently observed in chondrocyte expansion and other pathological conditions, but the characteristics and intermediate molecular mechanisms remain unclear. In this study, we demonstrate a time-lapse atlas of chondrocyte dedifferentiation to provide molecular details and informative biomarkers associated with clinical chondrocyte evaluation. We performed various assays, such as single-cell RNA sequencing (scRNA-seq), live-cell metabolic assays, and assays for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), to develop a biphasic dedifferentiation model consisting of early and late dedifferentiation stages. Early-stage chondrocytes exhibited a glycolytic phenotype with increased expression of genes involved in metabolism and antioxidation, whereas late-stage chondrocytes exhibited ultrastructural changes involving mitochondrial damage and stress-associated chromatin remodeling. Using the chemical inhibitor BTB06584, we revealed that early and late dedifferentiated chondrocytes possessed distinct recovery potentials from functional phenotype loss. Notably, this two-stage transition was also validated in human chondrocytes. An image-based approach was established for clinical use to efficiently predict chondrocyte plasticity using stage-specific biomarkers. Overall, this study lays a foundation to improve the quality of chondrocytes in clinical use and provides deep insights into chondrocyte dedifferentiation. [ABSTRACT FROM AUTHOR]

Tendon heterotopic ossification (HO) is characterized by bone formation inside tendon tissue, which severely debilitates people in their daily life. Current therapies fail to promote functional tissue repair largely due to our limited understanding of HO pathogenesis. Here, we investigate the pathological mechanism and propose a potential treatment method for HO. Immunofluorescence assays showed that the Mohawk (MKX) expression level was decreased in human tendon HO tissue, coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx−/− mice. Single-cell RNA sequencing analyses of wild-type and Mkx−/− tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx−/− tendon cells. Single-cell analysis revealed that the gene expression program of angiogenesis, which is strongly associated with bone formation, was activated in all cell types during HO. Moreover, inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of HO. These findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO. [ABSTRACT FROM AUTHOR]

Articular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and application, and, when used in combination, act as powerful tools for manipulating cellular fate. In this review, we present current achievements in the development of small molecular drugs for cartilage regeneration, particularly in the fields of chondrocyte generation and reversion of chondrocyte degenerative phenotypes. Several clinically or preclinically available small molecules, which have been shown to facilitate chondrogenesis, chondrocyte dedifferentiation, and cellular reprogramming, and subsequently ameliorate cartilage degeneration by targeting inflammation, matrix degradation, metabolism, and epigenetics, are summarized. Notably, this review introduces essential parameters for high-throughput screening strategies, including models of different chondrogenic cell sources, phenotype readout methodologies, and transferable advanced systems from other fields. Overall, this review provides new insights into future pharmaceutical therapies for cartilage regeneration. [ABSTRACT FROM AUTHOR]

The intermolecular interactions between the heavy alkenes H2Si = TH2 (T = C, Si, Ge, Sn, Pb) and C2H2 have been calculated at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVDZ level, and the nature of these complexes has been investigated by natural bond orbital. The four types (type-A, type-B, type-C and type-D) of complexes can be located for H2Si = TH2···C2H2 system. The complexes involving H2Si = TH2···C2F2 and H2Si = TH2···C2(CN)2 have also been examined to explore the substituent effects. Some complexes which are stable for H2Si = TH2···C2H2 system become unstable for H2Si = TH2···C2F2 or H2Si = TH2···C2(CN)2 system, while other complexes which are unstable for H2Si = TH2···C2H2 system become stable for H2Si = TH2···C2F2 or H2Si = TH2···C2(CN)2 system. [ABSTRACT FROM AUTHOR]

Purpose: Sediment is a good substrate for microorganism colonization in aqueous environments. The secretion of metabolic products by microorganism induces biofilm growth on sediment surfaces, which further affects their interaction with pollutants and exerts important impacts on aqueous ecosystems. In this study, the effects of biofilm on the phosphorus (P) adsorption of sediment were quantified. Methods: A specially designed cylinder was used for biofilm cultivation with different original sediment sizes (0.02–0.05, 0.05–0.1, and 0.1–0.2 mm) and under different hydrodynamic conditions (flow velocities of 0.1, 0.15, and 0.2 m s−1), and their kinetic and equilibrium P adsorption characteristics were experimentally explored. Then, an expression of P adsorption by bio-sediment was derived through incorporating the amount of biomass into the modified Langmuir isotherm. Results: The adsorption kinetic process of bio-sediment was best described by the pseudo-second-order model. The P adsorption capacity increased with the increasing biofilm cultivation period (i.e., an approximate increase of an order of magnitude), which increased quickly in the first few weeks due to the rapid biofilm growth and then tended to be stable due to the gradually stabilization of biofilm growth. More biomass accumulated on the surface of finer sediment after biofilm growth leading to a greater P adsorption capacity, while the difference in P adsorption was not so obvious for bio-sediment formed under different flow velocities. Conclusion: The P adsorption of sediment was significantly enhanced after biofilm growth, and the derived model could reasonably predict the adsorption characteristics of bio-sediment, verifying the possibility to consider the biomass into adsorption isotherms. Further studies considering the structure and components of biofilm need to be conducted in the future. [ABSTRACT FROM AUTHOR]

Transvaginal ultrasound (TVUS) and MRI are currently two mainstream imaging techniques used to diagnose deep endometriosis (DE) with comparable accuracy, but there is still ample room for improvement. As endometriotic lesions progress to fibrosis concomitant with the increase in tissue stiffness, transvaginal elastosonography (TVESG) is well-suited for diagnosing DE. To test the hypothesis that lesional stiffness as measured by TVESG correlates with the extent of lesional fibrosis, the markers of progression, hormonal receptor expression, and vascularity, we recruited 30 patients suspected to have DE who went through pelvic examination, TVUS and/or MRI, and TVESG and were ultimately diagnosed by histology. Their lesional tissue samples were subjected to immunohistochemistry analysis of markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), estrogen and progesterone receptors (ERβ and PR), microvessel density (MVD), and vascularity, as well as quantification of lesional fibrosis. We found that pelvic examination, TVUS, and MRI detected 83.3%, 66.7%, and 83.3% of all DE cases, respectively, while TVESG detected them all. The lesions missed by pelvic exam, TVUS and MRI were significantly smaller than those detected but nonetheless had higher lesional stiffness. Lesional stiffness correlated closely and positively with the extent of lesional fibrosis, negatively with the markers of EMT, MVD, vascularity, and PR expression, but positively with the marker for FMT and ERβ. Thus, through the additional use of information on differential stiffness between DE lesions and their surrounding tissues, TVESG improves diagnostic accuracy, provides a ballpark estimate on the developmental stage of the lesions, and may help clinicians choose the best treatment modality. [ABSTRACT FROM AUTHOR]

In the information age, the amount of data is huge which shows an exponential growth. In addition, most services of application need to be interdependent with data, cause that they can be executed under the driven data. In fact, such a data-intensive service deployment requires a good coordination among different edge servers. It is not easy to handle such issues while data transmission and load balancing conditions change constantly between edge servers and data-intensive services. Based on the above description, this paper proposes a Data-intensive Service Edge deployment scheme based on Genetic Algorithm (DSEGA). Firstly, a data-intensive edge service composition and an edge server model will be generated based on a graph theory algorithm, then five algorithms of Genetic Algorithm (GA), Simulated Annealing Algorithm (SA), Ant Colony Algorithm (ACO), Optimized Ant Colony Algorithm (ACO_v) and Hill Climbing will be respectively used to obtain an optimal deployment scheme, so that the response time of the data-intensive edge service deployment reaches a minimum under storage constraints and load balancing conditions. The experimental results show that the DSEGA algorithm can get the shortest response time among the service, data components and edge servers. [ABSTRACT FROM AUTHOR]

The binary and ternary complexes composed of GeH3F, AsH2F and ring compounds (benzene, borazine and cyclopentadienyl anion) have been studied by theoretical calculations to understand the interplay between the tetrel bond and pnicogen bond interactions. The bonding strength of intermolecular interactions in these complexes is analyzed by means of atoms in molecules (AIM), natural bond orbital (NBO) and noncovalent interaction (NCI) index methods. The binary tetrel-bonded and pnicogen-bonded complexes can be classified as an n-type or π-type complex according to the orbital interactions involved in the complexes. Three binding modes can be distinguished according to the interplay between interactions for the ternary complexes. The binding mode A is characterized by the interplay between π-type tetrel bond and n-type pnicogen bond; binding mode B is characterized by the interplay between π-type pnicogen bond and n-type tetrel bond, and binding mode C is characterized by the interplay between π-type tetrel bond and π-type pnicogen bond. The binding modes A and B exhibit the synergistic interplay effect, while the antagonistic effect is reflected in mode C. The synergistic effect in binding modes A and B is stronger than antagonistic effect in mode C, and the synergistic effect in binding mode B is stronger than that in mode A. [ABSTRACT FROM AUTHOR]

Biofilm growth on cohesive sediment deposits plays a crucial role in the inherent properties of aqueous environment, such as the biostabilization of sediment deposits, sediment-associated contaminant transport, and habitat change. Here, a specially designed cylinder was used for biofilm cultivation under static water (with sediment sizes of 0.02-0.05, 0.05-0.1, and 0.1-0.2 mm) and dynamic water flow conditions. A biomass dynamics model, including the accrual term and detachment term (velocity-dependent and/or autogenic), was proposed to study the effects of sediment size and hydrodynamic condition on biofilm growth. The results showed that more biofilm formed on fine sediment than coarse sediment due to the greater surface area for bacterial attachment and nutrients accumulation. Increased flow velocity inhibited biofilm accumulation and a greater velocity caused more velocity-dependent chronic detachment, resulting in less biofilm growth on sediment particles. Under static water condition, there was more biomass compared with dynamic water flow condition. The proposed model can reasonably reflect the evolution of biofilm growth, as well as the effects of sediment size and hydrodynamic condition, which might be applied for the management of natural aqueous systems. [ABSTRACT FROM AUTHOR]

The binding behavior of coinage metal anions with some electron-deficient arenes has been investigated by MP2 calculations, and the character of interactions in these complexes has been examined by NBO analysis. The results indicate that coinage metal anions can interact with electron-deficient arenes to form anion-π, strong σ-type and hydrogen-bonding complexes. The σ-type structure is the global minimum for triazine, trifluorotriazine, hexafluorobenzene and tricyanobenzene, and the hydrogen-bonding structure is the global minimum for trifluorobenzene. There exist some differences in the stability of anion-π complexes for coinage metal anions: the anion-π complexes of Au are minima expect for triazine complex; the anion-π complexes of Ag are minima expect for tricyanobenzene complex; and the anion-π complexes of Cu are not minima expect for trifluorobenzene complex. The binding strength of anion-π and hydrogen-bonding complexes for Au is larger than that for Ag and Cu, but the binding strength of σ complex displays a different sequence: Cu > Au > Ag. The binding behavior of coinage metal anions is more similar to that of F than that of Cl and Br. The relaxed potential energy surface scans for some selected systems have been performed to help understand the interactions between coinage metal anions with electron-deficient arenes. [ABSTRACT FROM AUTHOR]

The figure in the pdf version is correct. These authors contributed equally: Yishan Chen, Yeke Yu, Ya Wen Correction to: I Bone Research i https://doi.org/10.1038/s41413-022-00209-w, published online 27 April 2022 Following the publication of the original article [1], it was noted that due to a typesetting error some elements in Fig. [Extracted from the article]

The ternary complexes X · 1 · YF ( 1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH and AsH) have been investigated by MP2 calculations to understand the noncovalently electron-withdrawing effects on anion-arene interactions. The results indicate that in binary complexes ( 1 · X), both weak σ-type and anion-π complexes can be formed for Cl and Br, but only anion-π complex can be formed for I. Moreover, the hydrogen-bonding complex is the global minimum for all three halides in binary complexes. However, in ternary complexes, anion-π complex become unstable and only σ complex can retain in many cases for Cl and Br. Anion-π complex keeps stable only when YF = HF. In contrast with binary complexes, σ complex become the global minimum for Cl and Br in ternary complexes. These changes in binding mode and strength are consistent with the results of covalently electron-withdrawing effects. However, in contrast with the covalently electron-withdrawing substituents, Cl and Br can attack the aromatic carbon atom to form a strong σ complex when the noncovalently electron-withdrawing effect is induced by halogen bonding. The binding behavior for I is different from that for Cl and Br in two aspects. First, the anion-π complex for I can also keep stable when the noncovalent interaction is halogen bonding. Second, the anion-π complex for I is the global minimum when it can retain as a stable structure. [ABSTRACT FROM AUTHOR]