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BACKGROUND: Neer type II/bilateral distal clavicular fracture is an extremely rare injury combination, with few cases having been reported. CASE PRESENTATION: This paper reports a case of polytrauma in a 16-year-old female following a road traffic accident. The radiographs revealed distal fractures of the bilateral clavicles (Neer type II), and an open reduction and internal fixation procedure was performed. Initially, the distal fracture of the right clavicle was fixed with a six-hole hook plate before the fracture of the left clavicle was fixed using a pre-contoured lateral locking plate following reduction. At the two-year follow-up, the patient had an excellent constant score in terms of the bilateral shoulder joints. CONCLUSION: It is important to achieve stability and to aim for excellence in terms of full shoulder function in this rare combination injury.

Regulating the distance of Fe2O3 nanowires and Au nanoparticles achieves the oriented generation of ˙OH and ˙O2− for efficient degradation of contaminants.

PurposeThis article aims to develop an accurate and efficient meshfree Galerkin method based on the strain smoothing technique for linear elastic continuous and fracture problems.Design/methodology/approachThis paper proposed a generalized linear smoothed meshfree method (LSMM), in which the compatible strain is reconstructed by the linear smoothed strains. Based on the idea of the weighted residual method and employing three linearly independent weight functions, the linear smoothed strains can be created easily in a smoothing domain. Using various types of basic functions, LSMM can solve the linear elastic continuous and fracture problems in a unified way.FindingsOn the one hand, the LSMM inherits the properties of high efficiency and stability from the stabilized conforming nodal integration (SCNI). On the other hand, the LSMM is more accurate than the SCNI, because it can produce continuous strains instead of the piece-wise strains obtained by SCNI. Those excellent performances ensure that the LSMM has the capability to precisely track the crack propagation problems. Several numerical examples are investigated to verify the accurate, convergence rate and robustness of the present LSMM.Originality/valueThis study provides an accurate and efficient meshfree method for simulating crack growth.

Purpose: We present the five-year in-orbit background evolution of Insight-HXMT since the launch, as well as the effects of the background model in data analysis. Methods: The backgrounds of the three main payloads, i.e., Low-Energy Telescope, Medium-Energy Telescope and High-Energy Telescope, are described, respectively. The evolution of the background over time is obtained by simply comparing the background in every year during the in-orbit operation of Insight-HXMT. Results: The major observational characteristics of the Insight-HXMT in-orbit background are presented, including the light curve, spectrum, geographical distribution, and long-term evolution. The systematic error in background estimation is investigated for every year. Conclusion: The observational characteristics of the five-year in-orbit background are consistent with our knowledge of the satellite design and the space environment, and the background model is still valid for the latest observations of Insight-HXMT., 22 pages, 25 figures, accepted for publication in RDTM

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.

Piwi-interacting RNAs (piRNAs) are a class of short chain noncoding RNAs that are constituted by 26-30 nucleotides (nt) and can couple with PIWI protein family. piRNAs were initially described in germline cells and are believed to be critical regulators of the maintenance of reproductive line. Increasing evidence has extended our perspectives on the biological significance of piRNAs and indicated that they could still affect somatic gene expression through DNA methylation, chromatin modification and transposon silencing, etc. Many studies have revealed that the dysregulation of piRNAs might contribute to diverse diseases through epigenetic changes represented by DNA methylation and chromatin modification. In this review, we summarized piRNA/PIWI protein-mediated DNA methylation regulation mechanisms and methylation changes caused by piRNA/PIWI proteins in different diseases, especially cancers. Since DNA methylation and inhibitory chromatin marks represented by histone H3 lysine 9 (H3K9) methylation frequently cooperate to silence genomic regions, we also included methylation in chromatin modification within this discussion. Furthermore, we discussed the potential clinical applications of piRNAs as a new type promising biomarkers for cancer diagnosis, as well as the significance of piRNA/PIWI protein-associated methylation changes in treatment, providing disparate insights into the potential applications of them.

Introduction: Disorders of sex development (DSDs) are congenital abnormalities in which chromosomal, gonadal, and anatomical sex development are atypical. One of these disorders, 46, XY DSD, is particularly difficult to diagnose and manage because its etiology and clinical phenotypes are highly heterogeneous. Methods: We used a gene panel containing 141 genes implicated in DSDs to perform targeted next-generation sequencing (NGS) in 50 patients with 46, XY DSD. Results: Gene variants were detected in 23 patients (46%). Among them, thirteen patients had previously reported pathogenic or likely pathogenic variants, nine patients had novel variants, and one patient had a previously reported variant of uncertain significance. Three of the patients with novel variants were pathogenic and the remaining are variants of uncertain significance; therefore, 16 patients had pathogenic or likely pathogenic variants according to ACMG guidelines, and the overall diagnostic rate of 46, XY DSD was 32%. The most common gene variants were SRD5A2 variants, followed by the AR variant. In addition, we analyzed the association between gene variants and clinical phenotypes. Most patients presented with multiple DSD phenotypes (i.e., two or more DSD phenotypes were observed, such as micropenis, hypospadias, and cryptorchidism), but the phenotype with the highest diagnostic rate was micropenis. Conclusion: Our results indicate that targeted NGS can effectively detect pathogenic gene variants in patients with 46, XY DSD.

The geographic range of Zika virus (ZIKV) has expanded from Asia to the Americas, leading to the 2015-2016 pandemic with enhanced neurovirulence. At present, ZIKV is continuously circulating in many Southeast Asian countries. Unfortunately, the persistent evolution of ZIKV in Southeast Asia and its influence on the biological characteristics of the virus remain incompletely understood. In this study, the in vitro and in vivo properties of a new ZIKV isolate obtained from Cambodia in 2019 (CAM/2019) were characterized and compared with those of the Cambodian strain (CAM/2010). Compared with CAM/2010, the CAM/2019 virus showed similar plaque morphology and growth curves in cell cultures and induced comparable viremia and organ viral loads profiles in both BALB/c and A129 (IFNAR1

We study the lepton pair photoproduction in peripheral heavy-ion collisions based on the formalism in our previous work [Phys. Rev. D 104, 056011 (2021)]. We present the numerical results for the distributions of the transverse momentum, azimuthal angle and invariant mass for $e^{+}e^{-}$ and $\mu^{+}\mu^{-}$ pairs as functions of the impact parameter and other kinematic variables in Au+Au collisions. Our calculation incorporates the information on the transverse momentum and polarization of photons which is essential to describe the experimental data. We observe a broadening effect in the transverse momentum for lepton pairs with and without smear effects. We also observe a significant enhancement in the distribution of $\cos(2\varphi)$ for $\mu^{+}\mu^{-}$ pairs. Our results provide a baseline for future studies of other higher order corrections beyond Born approximation and medium effects in the lepton pair production., Comment: 19 pages, 10 figures

Thyroid cancer (TC) is one of the most common malignant tumors, with high morbidity and mortality rates worldwide. The incidence of TC, especially that of papillary thyroid carcinoma (PTC); has increased rapidly in recent decades. Autoimmune thyroid disease (AITD) is closely related to TC and has an estimated prevalence of 5%. Thus, it is becoming increasingly important to identify potential diagnostic biomarkers and therapeutic targets for TC and AITD. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently bonded circular structures that lack 5'-3' polarity and polyadenylated tails. Several circRNAs play crucial roles in the development of various diseases, including TC and AITD, and could be important new biomarkers and/or targets for the diagnosis and therapy of such disorders. Although there are four subtypes of TC, research on circRNA has largely focused on its connection to PTC. Therefore, this review mainly summarizes the relationships between circRNAs and PTC and AITD, including the molecular mechanisms underlying these relationships. In particular, the functions of "miRNA sponges" and their interactions with proteins and RNA are discussed. The possible targeting of circRNAs for the prevention, diagnosis, and treatment of TC and AITD is also described. CircRNAs could be potential biomarkers of TC and AITD, although validation will be required before they can be implemented in clinical practice.

Accurate background estimation is essential for spectral and temporal analysis in astrophysics. In this work, we construct the in-orbit background model for the High-Energy Telescope (HE) of the Hard X-ray Modulation Telescope (dubbed as Insight-HXMT). Based on the two-year blank sky observations of Insight-HXMT/HE, we first investigate the basic properties of the background and find that both the background spectral shape and intensity have long-term evolution at different geographical sites. The entire earth globe is then divided into small grids, each with a typical area of 5x5 square degrees in geographical coordinate system. For each grid, an empirical function is used to describe the long-term evolution of each channel of the background spectrum; the intensity of the background can be variable and a modification factor is introduced to account for this variability by measuring the contemporary flux of the blind detector. For a given pointing observation, the background model is accomplished by integrating over the grids that are passed by the track of the satellite in each orbit. Such a background model is tested with both the blank sky observations and campaigns for observations of a series of celestial sources. The results show an average systematic error of 1.5% for the background energy spectrum (26-100 keV) under a typical exposure of 8 ks, and, 27 pages, 16 figures, accepted by Journal of High Energy Astrophysics

Background: The early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) is particularly important due to poor prognosis and the lack of effective therapies. This study aims to systematically describe the cellular atlas of human intramucosal ESCC.Methods: Five paired samples of intramucosal ESCC, para-ESCC esophageal tissue from endoscopically resected specimen, and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. A computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells.Results: A total of 164,715 cells were profiled. The abundance of CD8+ TEXs , Tregs and PD1+CD4+T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells such as CXCL13 and CXCR5 in PD1+CD4+ T cells and PADI4 in Mono2 cells were identified as new biomarkers for poor prognosis. Epithelial cells exhibited high intra-tumor heterogeneity and two evolutional trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normal differentiated epithelial cells or malignant cells, respectively. Intercellular interaction analysis based on ligand-receptor pairs revealed malignant cells interacting with CAFs via the MDK-NCL pathway, which is an important hallmark in the change of tumor microenvironment, and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumor invasion, and therefore suggesting a potential early biomarker of ESCC progression.Conclusions: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, providing unique insights into the development of novel biomarkers and potential intervention strategies.

Pregnane X receptor (PXR) is highly expressed in the liver and plays a pivotal role in xenobiotic and endobiotic metabolism. We previously reported that PXR activation by its specific mouse agonist pregnenolone 16α-carbonitrile (PCN) significantly induces liver enlargement and lipid accumulation. However, the effect of long-term PCN treatment on PXR and mouse liver is still unknown. This study aimed to explore the influence of long-term administration of PCN on mouse liver and hepatic lipid homeostasis. Male C57BL/6 mice were injected intraperitoneally with PCN (100 mg/kg once a week) for 42 weeks. Serum and liver samples were collected for biochemical and histological analysis. PXR activation was investigated by Western blot. Ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS)-based lipidomics analysis was performed to explore the change in different lipid categories. The results showed that long-term treatment with PCN significantly promoted hepatomegaly without hepatocyte proliferation and enlargement. Long-term treatment with PCN did not upregulate PXR target proteins in mice, and there was no significant upregulation of CYP3A11, CYP2B10, UGT1A1, MRP2, or MRP4. Lipidomics analysis showed obvious hepatic lipid accumulation in the PCN-treated mice, and the most significant change was found in triglycerides (TGs). Additionally, long-term treatment with PCN had no risk for carcinogenesis. These findings demonstrated that long-term PCN treatment induces hepatomegaly and lipid accumulation without hepatocyte proliferation or enlargement.

Background Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). Methods This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Findings Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p

Electromagnetically induced transparency (EIT) and absorption (EIA) are two phenomena that can be observed in whispering-gallery-mode (WGM) optical microresonators. Transition from EIT to EIA has potential applications in optical switching, filtering and sensing. In this paper an observation of the transition from EIT to EIA in a single WGM microresonator is presented. A fiber taper is used to couple light into and out of a sausage-like microresonator (SLM) that contains two coupled optical modes with significantly different quality factors. By stretching the SLM axially the resonance frequencies of the two coupled modes are tuned to the same, a transition from EIT to EIA is then observed in the transmission spectra when the fiber taper is moved closer to the SLM. It is the special spatial distribution of the optical modes of the SLM that provide a theoretical basis for the observation.

A heterojunction photoanode of Fe2O3 loaded on a WO3 film on a fluorine-doped tin oxide substrate (FTO-WO3/Fe2O3) was prepared via a simple hydrothermal and chemical vapor deposition (CVD) growth method. The photoanode showed higher photoelectrochemical (PEC) water-splitting activity than that of the pristine FTO-WO3 under simulated sunlight because of the synergistic effect of Fe2O3 and WO3. The as-synthesized material was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The photocurrent density was estimated by linear sweep voltammetry and further confirmed using intensity-modulated photocurrent spectra. Experiments demonstrated that the coated Fe2O3 enhanced the separation and migration efficiencies of the photoinduced electrons and holes, improving the PEC water-splitting properties. The FTO-WO3/Fe2O3 photoanode showed a 1.25 times enhancement in photocurrent density compared with FTO-WO3. This result suggests that facile chemical vapor deposition growth is an effective way to fabricate heterojunctions and improve the properties of WO3 photoanodes for PEC water-splitting applications.

In this study, solitary waves passing over a submerged breakwater are investigated both experimentally and numerically. A total of 9 experimental conditions are carried out, including different incident wave heights and water depths. Numerical simulations are performed using a high-order finite-difference model solving Navier-Stokes (N-S) equations. The predicted water wave elevation, velocity and pressure show good agreement with experimental data, verifying the accuracy and capacity of the numerical model. Furthermore, parametric studies are conducted by numerical modelling to examine the effects of the geometrical features of submerged dike on hydrodynamic characteristics around the breakwater.

Two new compounds Talaromycin A (1) and Talaromycin B (2) were isolated from a liquid culture of Talaromyces aurantiacus. The structures of 1 and 2 were elucidated by IR, MS, 1D and 2D NMR spectra and comparison of the experimental and calculated electronic circular dichroism spectra. Additional known compounds (3–6) were also isolated. These compounds were tested for monoamine oxidase, acetylcholinesterase and PI3K inhibitory activity, but showed only weak activity.

Objective: Graphene oxide (GO) has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to investigate the effects of cell penetrating peptide (CPP) modified and polyethylene-glycol- (PEG-) grafted GO (pGO) loaded with photosensitive agent 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH) and Epirubicin (EPI) (HPPH/EPI/CPP-pGO) on tumor growth in osteosarcoma.Methods: The HPPH/EPI/CPP-pGO were prepared, and then in vitro drug release assay was conducted. The detection of singlet oxygen (1O2) and cellular uptake of HPPH was performed as well. Next, the effects of control (saline solution), CPP-pGO, EPI, HPPH, HPPH/CPP-pGO, EPI/CPP-pGO, HPPH/EPI/pGO, and HPPH/EPI/CPP-pGO were evaluated by MTT assay, colony-forming assay, and cell apoptosis assay in MG-63 cells. Furthermore, the antitumor effects of HPPH/EPI/CPP-pGO on osteosarcoma xenograft mice were unraveled.Results: The 1O2 generation and cellular uptake of HPPH were significantly increased after CPP and pGO modification compared with free HPPH. In addition, compared with control cells, CPP-pGO treatment had low cytotoxicity in MG-63 cells. Compared with free HPPH or EPI, HPPH/CPP-pGO or EPI/CPP-pGO treatment significantly inhibited cell viability and colony forming number, as well as inducing cell apoptosis. HPPH/EPI-pGO treatment showed stronger inhibition effects on MG-63 cells than HPPH/CPP-pGO or EPI/CPP-pGO, and HPPH/EPI/CPP-pGO was the most effective one. Similarly, in vivo experiments revealed that, compared with control group, the tumor size and weight of osteosarcoma xenograft mice were obviously decreased after free HPPH or EPI treatment, which were further reduced in other groups, especially in HPPH/EPI/CPP-pGO group.Conclusion: HPPH/EPI/CPP-pGO had superior tumor-inhibiting effects in vitro and in vivo on osteosarcoma.

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase‐activating protein (GAP) and modulate integrin‐mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling.

The principal focus of this work is to analysis water flooding characteristics of carbonate fracture reservoir, summarize main contradiction of water flooding development of different types of development strata, and further put forward some corresponding measures on injection-production system optimization. Taking an oil field in Pre-Caspian Basin for example, based on the geological features and development performance of different development strata by waterflooding, summarized waterflooding characteristics and the main contradiction in water injection development. According to the production performance of well pattern under different water injection contradictions, the optimization methods of injection-production system are proposed. Results show that in the case of water injection development of carbonate oil reservoirs, waterflooding characteristics are closely related to reservoir conditions. The contradiction of flooding is shown either as horizontal with a unimodal tracer curve for single-layer reservoirs or as vertical with a multimodal tracer curve for multilayered reservoirs. For the single-layer development strata with horizontal contradiction, cyclic water injection and asynchronous injection-production are proposed. For the multilayered development strata with vertical contradiction, separate-layer cyclic water injection technology is recommended. For the multilayered strata with both horizontal and vertical contradictions, separate-layer injection-production coupling technology is the best choice. This work proposes corresponding optimization measures of injection-production system according to different types of development strata with different waterflooding characteristics in carbonate fracture reservoirs development, which is of great significance for the efficient development of these reservoirs by water flooding.

The effect of finance business partnering (FBP) implementation on the firm performance remains largely unexplored. The main aims of this study are to investigate whether there is a significant effect between FBP and firm performance and to identify the mediating effect of non-financial performance between FBP and firm performance. A questionnaire-based survey was conducted among 117 Chinese manufacturing firms in the year 2018, and research hypotheses were tested by partial least squares structural equation modelling (PLS-SEM). The findings showed that 1) FBP does not exert a significant and direct effect on the firms’ financial performance, 2) when non-financial measures (employees performance, internal process performance, and market performance) are used as mediating variables, the effect of all the three mediating variables on the relationship between FBP and non-financial variables are positive and significant. However, when the relationship between non-financial measures and firm’s performance is considered, the mediating effect of the non- financial variables is positive and significant only for the market performance. This study provides, for the first time, empirical evidence that non-financial performance, such as employee skills, internal processes, and market performance, can be enhanced by considering FBP. It also provides practical implications suggesting that manufacturing firms should motivate finance staff to be involved in various decision-making processes.