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A cast-free approach is described to fabricate an implant-supported interim restoration by using the postoperative cone beam computed tomography (CBCT) scan to locate the placed implant. A postoperative intraoral scan was aligned to the postoperative CBCT scan through a dental implant planning software program. An attached interim abutment and implant analog complex was then scanned and superimposed on the placed implant in the postoperative CBCT scan. Once the best alignment was achieved, a virtual cast was generated, and an interim restoration with bilateral positioning wings was fabricated on the interim abutment and inserted during the second-stage surgery. This technique offers a cast-free approach to inserting an implant-supported interim restoration immediately after the second-stage surgery to guide the healing of the soft tissue that can minimize chairside time and optimize the clinical workflow.

Metastasis, in which cancer cells detach from the original site and colonise other organs, is the primary cause of death induced by bladder cancer (BCa). Epithelial Membrane Protein 1 (EMP1) is dysregulated in many human cancers, and its clinical significance and biological function in diseases, including BCa, are largely unclear. Here, we demonstrated that EMP1 was downregulated in BCa cells. The deficiency of EMP1 promotes migration and confers resistance to ferroptosis/oxidative stress in BCa cells, favouring tumour cell metastasis. Mechanistically, we demonstrated that EMP1 deficiency enhanced tumour metastasis by increasing PPARG expression and promoting its activation, leading to upregulation of pFAK(Y397) and SLC7A11, which promoted cell migration and anti-ferroptotic cell death respectively. Moreover, we found EMP1-deficient sensitized cells to PPARG's ligand, which effect are metastatic phenotype promoted and could be mitigated by FABP4 knockdown. In conclusion, our study, for the first time, reveals that EMP1 deficiency promotes BCa cell migration and confers resistance to ferroptosis/oxidative stress, thus promoting metastasis of BCa via PPARG. These results revealed a novel role of EMP1-mediated PPARG in bladder cancer metastasis.

Two oxidative degradation impurities of sugammadex sodium have been successfully synthesized under stress conditions and isolated by preparative high performance liquid chromatography, which would be extremely difficult to prepare stochiometrically by conventional methods due to their structural complexity. Characteristic fragmentation pattern observed by mass spectrometry for sugammadex series compounds helped distinguish the two regioisomeric di-sulfoxide impurities. Confirmed by nuclear magnetic resonance analysis, Impurity I was identified as ortho-disulfoxide sugammadex and Impurity II as meta-disulfoxide sugammadex. It is the first time detailed structures of these two impurities are reported. Additionally, HPLC analysis also indicated the observance of these two impurities in long-term stored sugammadex sodium finished pharmaceutical product but absence in three pilot batches of sugammadex sodium drug substance which met ICH requirements. The compounded analysis technique has proven to be successful and reliable, and we hope that it could be well applied to structure identification for other sugammadex impurities and will be beneficial for other researchers focusing on this field.

Owing to their anti-fouling properties, zwitterionic polypeptides demonstrate great advantage on protecting protein drugs. When conjugated to glucagon-like peptide-1 (GLP-1), a drug for type-II diabetes, zwitterionic polypeptides confer better pharmacokinetics than uncharged counterparts. However, its microscopic mechanism is still unclear due to the complicated conformational space. To address this challenge, this work explored the interaction modes of GLP-1 with the unconnected repeat units, instead of the full-length polypeptides. The three repeat units are two zwitterionic pentapeptides VPKEG and VPREG, and one uncharged control VPGAG. Our molecular simulations revealed that the helical conformation of GLP-1 was stabilized by adding 40 polypeptides. Both VPGAG and VPREG formed dense packing shells around GLP-1, but the driving forces were hydrophobic and electrostatic interactions, respectively. In contrast, the packing shell composed of VPKEG was most loose, while could still stabilize GLP-1. The moderate electrostatic interactions endowed VPKEG an anti-fouling property, thereby avoiding non-specific interaction with other amino acids. The strong electrostatic interactions exerted by arginine promoted atomic contacts between VPREG and other residues, making it as "hydrophobic" as VPGAG. In summary, the combination of hydrophobic and moderate electrostatic interactions in VPKEG brings about a subtle balance between stabilizing GLP-1 and avoiding non-specific interaction.

Sediments are the long-term sinks of microplastics (MPs) and nutrients in freshwater ecosystems. Therefore, understanding the effect of MPs on sediment nutrients is crucial. However, few studies have discussed the effects of MPs on nitrogen and phosphorus cycles in freshwater sediments. Herein, 0.5% (w/w) polyvinyl chloride (PVC), polylactic acid (PLA), and polypropylene (PP) MPs were added to freshwater sediments to evaluate their effects on microbial communities and nitrogen and phosphorus release. The potential biochemical functions of the bacterial communities in the sediments were predicted and assessed via 16S rRNA gene sequencing. The results showed that MPs significantly affected the microbial community composition and nutrient cycling in the sediments. PVC and PP MPs can promote microbial nitrification and nitrite oxidation, while PP can significantly promote alkaline phosphatase (ALP) activity and the abundance of the phosphorus-regulation (phoR) gene. PLA MPs had the potential to promote the abundance of microbial phosphorus transporter (ugpB), nitrogen fixation (nifD, nifH, and nifX), and denitrification (nirS, napA, and norB) genes and inhibit nitrification, resulting in massive accumulation and release of ammonia nitrogen. Although PLA MPs inhibited the activity of ALP and the abundance of the organophosphorus mineralization (phoD) gene, it could enhance dissimilatory iron and sulfite reduction, which may promote the release of sedimentary phosphorus. Our findings may help understand the mechanisms of nitrogen and phosphorus cycles and microbial communities driven by MPs in sediments and provide a basis for future assessments of the environmental behavior of MPs in freshwater ecosystems.

Mental stress-induced myocardial ischemia (MSIMI) has attracted increasing attention in the last 30 y. Positron emission tomography/computed tomography (PET/CT) is among the most accurate methods for evaluating myocardial perfusion. Even so, echocardiography seems to be a more harmless option when the radiation exposure and high expense of PET/CT are considered. To date, no previous studies have compared the consistency between echocardiography and PET/CT in the diagnosis of MSIMI. The primary aim of this research was to compare the consistency of myocardial contrast echocardiography and PET/CT in diagnosing MSIMI in women with angina symptom/ischemia but no obstructive coronary artery disease (INOCA). Fifty adult female patients with INOCA were recruited for a 12-min-long mental stress test. Each patient underwent both echocardiography and PET/CT at baseline and during mental stress testing; the interval between the two examinations was 1–3 d and the sequence was assigned naturally. MSIMI is defined by a summed difference score (SDS) ≥3 on PET-CT during mental stress testing. It is also defined by new abnormal wall motion, ejection fraction reduction ≥5%, and/or development of ischemic ST change on the electrocardiogram during mental stress testing. This study examined the consistency of PET/CT and myocardial contrast echocardiography in diagnosing MSIMI.

Reinforcement Learning (RL) technologies are powerful to learn how to interact with environments and have been successfully applied to various important applications. Q-learning is one of the most popular methods in RL, which leverages the Bellman equation to update the Q-function. Considering that data collection in RL is both time and cost consuming and Q-learning converges slowly, different kinds of transfer RL algorithms are designed to improve the sample complexity of the new tasks 1 . However, most of the previous transfer RL algorithms are similar to the transfer learning methods in deep learning and are heuristic with no theoretical guarantee of the convergence rate. Therefore, it is important for us to clearly understand how and when will transfer learning help RL method and provide the theoretical guarantee for the improvement of the sample complexity. In this paper, we rethink the transfer Rl problems in the RL perspective and propose to transfer the Q-function learned in the old task to the target Q-function in the Q-learning of the new task. We call this new transfer Q-learning method target transfer Q-Learning (abbrev. TTQL). The transfer process is controlled by the error condition which can help to avoid the harm to the new tasks brought by the transferred target. We design the error condition in TTQL as whether the Bellman error of the transferred target Q-function is less than the current Q-function. We show that TTQL with the error condition will achieve a faster convergence rate than Q-learning. Our experiments are consistent with our theoretical results and verify the effectiveness of our proposed target transfer Q-learning method.

Recently, the Transformer architecture has achieved state-of-the-art performance in many natural language processing tasks. One key component in the Transformer architecture is the attention layer, which captures the relation between tokens. In this paper, we show that the weight of the attention layer has scale-invariant property, i.e. the output is invariant to a rescaling of weights. However, optimization algorithms in the vector space of weight such as SGD are not scaling invariant. This mismatch will potentially hurt the optimization process. To solve the mismatch, we seek a new parameter space for attention layer that is both scale-invariant and can sufficiently represent the output of attention, so that we can employ optimization algorithms in the scale-invariant parameter space. To achieve this goal, we first show that the output of the attention layer can be represented using scale-invariant variables, which is called paths. Then, we define basis paths which are an independent subset of all paths and are sufficient to represent all other paths. We prove that the Scale-Invariant (SI) space for the attention layer is composed of the basis path. Finally, we design an Attention Basis Path Identification(ABPI) Method to identify the basis paths and propose optimizing the attention layer directly in its SI space. Several experiments on benchmark datasets show that we can obtain more effective neural networks with the attention layer by optimizing the attention layer directly in its SI space.

Virus-induced gene silencing (VIGS) is a technology for rapid gene functional analysis that depends on the degradation of viral RNA and is part of the natural defense mechanism in plants. Senecio cruentus is an important Compositae ornamental species that is plentiful and available in a variety of colors and has a typical blue variety that is rare in Compositae. These advantages make it a good material for studying the anthocyanin biosynthesis and blue flower formation mechanism. With the development of gene sequencing technology, the functions of many candidate genes that may be involved in anthocyanin biosynthesis in S. cruentus need to be identified. However, a stable and rapid genetic transformation system of S. cruentus is still lacking. Here, we screened two cultivars, ‘Venezia’ and ‘Jseter’, selected ScPDS and ScANS as test genes, and investigated the effect of developmental periods, bacterial cell concentrations and infection methods on gene silencing efficiency. The results showed that the silencing efficiency of S. cruentus leaves was low (13%), and it was less affected by the parameters. However, the transcription factor gene ScbHLH17 was still silenced by VIGS, which resulted in the loss of anthocyanin accumulation in leaves, and the expression levels of anthocyanin biosynthesis pathway (ABP) structural genes, including ScCHI, ScDFR3 and ScANS, were decreased significantly. The result proved that ScbHLH17 was an important transcription factor that regulated flower color formation in S. cruentus. In addition, ScANS-silencing phenotypes were observed in S. cruentus capitulum by vacuum-infiltrating S1 stage buds for 10 min after scape injection. In general, the present study provided an important technical support for the study of anthocyanin metabolism pathways in S. cruentus.

A novel efficient method for synthesizing ferrocene-based schiff bases and their metal (II) complexes was developed. The compounds were characterized by XRD and various spectroscopic techniques. In addition, their physicochemical studies were carried out using TGA-DTA analysis. The biological activities of ligands and their metal (II) complexes have been screened for in vitro antibacterial (such as S. aureus, B. cereus and E. coli), antifungal properties (such as A. niger and A. fumigatus). The results of these studies have revealed that Zn (II) complexes B11 was the most active against all bacterial strains, and antifungal activity was overall enhanced after complexation of the ligands.

The study aimed to investigate bone marrow mesenchymal stem cells (BMSCs) and extracellular signal-regulated kinase (ERK) gene-modified BMSCs (ERK-BMSCs) transplantation in ameliorating cognitive deficits in Parkinson's disease (PD). The PD rat model was built by 6-hydroxydopamine (6-OHDA) injection into the right striatum for 8 weeks, then successful PD rats were randomly divided into three groups and respectively transplanted in the same position of striatum as modeling with PBS, BMSCs and ERK-BMSCs for another 8 weeks. The 6-OHDA-induced PD rat model was successfully established, as demonstrated by reduced active avoidance response (AAR) times, percentage of time exploring in the light area (Ltime%) and platform quadrant time (PQT), as well as p-ERK expression. Compared with PBS rats, both BMSCs and ERK-BMSCs transplantation significantly reduced the left turn number, while increased AAR, Ltime%, PQT and p-ERK expression, suggesting improved cognitive abilities through restoring p-ERK expression. In addition, ERK-BMSCs injection exhibited higher therapeutic efficacy against cognitive deficits compared with BMSCs injection. These results demonstrated that BMSCs transplantation ameliorated cognitive deficits, and ERK-BMSCs exerted synergistic effects, which may prove beneficial against cognitive impairments in PD.

Objectives Methicillin-resistant coagulase-negative staphylococci (CoNS) have emerged as one of the major nosocomial pathogens, and antimicrobial resistance has aggravated the problem. Sixteen million public shared bicycles (PSBs) were launched in China, and 106 million users were recorded. However, no standard clean strategy has been applied to PSBs in China, and no formal surveillance has been carried out. The objective of this study was to understand the diversity and antimicrobial resistance of staphylococcal species from PSBs. Methods Seventy-nine specimens and 128 isolates were collected from 79 PSBs in Tianjin city, China. Antimicrobial susceptibility and molecular testing were performed to understand the species, antimicrobial resistance, carriage of mecA gene, and clonal lineage. Results Thirty-five staphylococcal isolates were identified, and 80% of staphylococci were resistant to at least one antibiotic. Seventeen (49%) staphylococci were mecA-positive. SCCmec type V (n = 5), SCCmec type 1A (n = 5), SCCmec type I (n = 3), SCCmec type III (n = 2), 1 SCCmec type II (n = 1), and SCCmec type IV (n = 1) were determined. In addition, Staphylococcus epidermidis ST5, ST35, ST234 and ST419 were determined, and a new ST (ST831) was also found. Conclusions The Staphylococcus epidermidis group was prevalent among PSBs, and multiple resistant staphylococci were determined in this study. The diversity of SCCmec elements was observed, and PSBs may act as the reservoir for antimicrobial pathogenic bacteria. Moreover, additional studies are necessary to systematically understand the prevalence and molecular epidemiology of methicillin-resistant staphylococci in PSBs.