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Innate immune responses play important roles in material-induced bone formation and such roles were further explored in the current study with an emphasis on M2 macrophages and osteoclastogenesis. With the presence of M-CSF and RANKL, M0 macrophages from FVB mouse bone marrow-derived monocytes (BMMs) fused to osteoclasts with both M2 marker and osteoclast marker at day 5, and such osteoclast formation at day 5 was enhanced when the cells were treated with IL-4 at day 3. With IL-4 treatment alone for 24 h, M0 polarized into M2 macrophages. Conditioned medium of M2 macrophages enhanced osteogenic differentiation of MC3T3-E1 (pre-osteoblasts) while osteoclast conditioned medium enhanced osteogenic differentiation of CRL-12424 (osteogenic precursors). TCPs (a typical osteoinductive material) supported M2 macrophage polarization at day 4 and osteoclast formation at day 5, while TCPb (a typical non-osteoinductive material) was less effective. Moreover, osteoclasts formed on TCPs produced osteogenic factors including S1P, Wnt10B and BMP-6, resulting osteogenic differentiation of CRL-12424 cells. Similar to in vitro testing, TCPs favored M2 macrophage polarization followed by the formation of osteoclasts in vivo, as compared to TCPb. The overall data provided evidence of a coupling between M2 macrophages, osteoclasts and material-induced bone formation: osteoclasts formed from M2 macrophages secreting osteogenic cytokines induce osteogenic differentiation of osteogenic precursor cells to finally form bone. The current findings outlined a biological mechanism of material-induced bone formation and further rationalized the use of osteoinductive materials for bone regeneration. STATEMENT OF SIGNIFICANCE: This paper provides evidence for finding out the relationship between M2 macrophages, osteoclasts and osteogenesis in material-induced bone formation. It suggested that osteoinductive materials enhanced macrophage polarized to M2 macrophages which fuses to osteoclasts, osteoclasts subsequently secret osteogenic cytokines to differentiate finally osteogenic precursors to form bone in osteoinductive materials. The data support scientifically the superiority of osteoinductive materials for bone regeneration in clinics.

We performed a systematic review and meta-analysis to evaluate the diagnostic value of fibrinogen (FB) for acute appendicitis and whether it can distinguish between uncomplicated and complicated appendicitis.A search of electronic information sources was conducted to identify all studies reporting FB in patients with clinical suspicion or confirmed diagnosis of acute appendicitis. We considered two comparisons: (1) appendicitis versus no appendicitis and (2) uncomplicated appendicitis versus complicated appendicitis. To assess the diagnostic value of FB, sensitivity, specificity, diagnostic odds ratios, summary receiver operating characteristic curves, area under the curve, and 95% confidence intervals (95% CIs) were estimated.Seven studies (917 confirmed appendicitis and 1026 controls) for overall appendicitis and eight studies (602 complicated appendicitis and 1386 uncomplicated appendicitis) for complicated appendicitis were identified. The pooled sensitivity and specificity of FB for the diagnosis of appendicitis were 0.62 (95% CI: 0.58-0.65) and 0.79 (95% CI: 0.77-0.82), respectively. FB was more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 0.74 (95% CI: 0.69-0.78), specificity of 0.76 (95% CI: 0.73-0.78), and the area under the curve was 0.84.As per this meta-analysis, FB has a potential diagnostic value in overall appendicitis and that it has a higher diagnostic value in the diagnosis of complicated appendicitis. Future well-designed prospective studies are needed to corroborate the findings.

Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine.We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 10Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p0·0001).We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination.National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program.

CGA

Gel polymer electrolytes (GPEs) are one of the promising candidates for high-energy-density quasi-solid-state lithium metal batteries (QSSLMBs), for their high ionic conductivity and excellent interfacial compatibility. The comprehension of dynamic evolution and structure-reactivity correlation at the GPE/Li interface becomes significant. Here, in situ electrochemical atomic force microscopy (EC-AFM) provides insights into the LiNO3-regulated micromechanism of the Li plating/stripping behavior upon cycles in GPE-based LMBs at nanoscale. The additive LiNO3 induces the formation of amorphous nitride SEI film and facilitates the Li+ ion diffusion. It stabilizes a compatible interface and regulates the Li nucleation/growth at steady kinetics. The deposited Li is in the shape of chunks and tightly compact. The Li dissolution shows favorable reversibility, which guarantees the cycling performance of LMBs. In situ AFM monitoring provides a deep understanding into the dynamic evolution of Li deposition/dissolution and the interphasial properties of tunable SEI film, regulating the rational design of electrolyte and interfacial establishment for GPE-based QSSLMBs.

Metastasis is the primary cause of treatment failure in nasopharyngeal carcinoma (NPC); however, the current tumour-node-metastasis staging system has limitations in predicting distant metastasis and guiding induction chemotherapy (IC) application. Here, we established a transcriptomics-based gene signature to assess the risk of distant metastasis and guide IC in locoregionally advanced NPC.Transcriptome sequencing was performed on NPC biopsy samples from 12 pairs of patients with different metastasis risks. Bioinformatics and qPCR were used to identify differentially expressed genes (DEGs), while univariate and multivariate analyses were used to select prognostic indicators for the gene signature. A signature-based nomogram was established in a training cohort (n = 191) and validated in an external cohort (n = 263).Eleven DEGs were identified between metastatic and non-metastatic NPC. Four of these (AK4, CPAMD8, DDAH1 and CRTR1) were used to create a gene signature that effectively categorised patients into low- and high-risk metastasis groups (training: 91.1 versus 70.4%, p 0.0001, C-index = 0.752; validation: 88.4 versus 73.9%, p = 0.00057, C-index = 0.741). IC with concurrent chemoradiotherapy (CCRT) improved distant metastasis-free survival in low-risk patients (94.4 versus 85.0%, p = 0.043), whereas patients in the high-risk group did not benefit from IC (72.6 versus 74.9%, p = 0.946).Our transcriptomics-based gene signature was able to reliably predict metastasis in locoregionally advanced NPC and could be used to identify candidates that could benefit from IC + CCRT.

Records of the thermal-age path of orogenic rocks are crucial in understanding subduction and collisional processes between a continent and an arc. Tectonic events and thermochronological data of the Taiwan Orogen have been extensively investigated. We use the zircon U Pb youngest ages as the (initial) subduction age, the Raman Spectroscopy of Carbonaceous Material, 40Ar/39Ar age of mica porphyroblasts, whole-rock Lu Hf isochron age and thermal results as prograde peak metamorphic condition during subduction and basal accretion, and the apatite fission-track data for cooling age of the Taiwan Orogen to illuminate the subduction and collisional processes between the Eurasian Plate and the Luzon Arc. The Hsuehshan Range Nappe in the west of the Taiwan Orogen, whose subduction was initiated at 12 Ma, reached peak metamorphism with a temperature of ~250 °C to 490 °C at a depth of 8 km during the interval 6–2.5 Ma, mainly by basal superimposed accretion. The isothermal dwelling during peak metamorphism condition of the Hsuehshan Range suggests that tectonic underplating through basal superimposed accretion contribute significantly to the formation of the Taiwan Orogen, and led to a sudden increase of subduction and decollement depths, and slow downward thickening of the orogenic wedge and mountain root growth. Located in the east of the Taiwan Orogen, the Yuli Beltsubduction was initiated at 15.4–16 Ma, and attained peak metamorphism at a depth of 40 km, with a temperature of 550–560 °C and a pressure of 10.5–13 kbar during the interval 12.2–4.4 Ma due to basal superimposed accretion. The exhumation of the Hsuehshan Range commenced at ~2.5 Ma, which is later than that of the Yuli Belt at ~3.4 Ma. Such distinct and different thermal-age paths of the Hsuehshan Range and the Tananao Complex indicate that different tectonic wedges in the Taiwan Orogen are formed through different subduction and accretional processes.

To determine prognostic factors for postoperative velopharyngeal function following the primary cleft palate repair at the age of five and above. This study reviewed patients with cleft palate who had undergone Furlow palatoplasty at age 5 or older from 2009 to 2014. We obtained intraoperative measurements, including velar length, pharyngeal depth, cleft width, maxillary width, cleft palate index (cleft width/maxillary width) and palatopharyngeal ratio (velar length/pharyngeal depth), as well as speech evaluation results at least 1 year after surgery. Logistic regression and retrospective analyses were performed to determine factors associated with speech performance after the primary cleft palate repair. Among the six intraoperative measurements of velopharyngeal morphology, only pharyngeal depth was incorporated into the regression model, and was found to have an inverse association with postoperative velopharyngeal function, Exp (B) 0.883 (95% CI 0.798-0.976). Moreover, a pharyngeal depth greater than 16 mm was significantly associated with a higher risk of postoperative velopharyngeal insufficiency (P Pharyngeal depth is potentially a prognostic indicator for the primary management of cleft palate in older patients. Pharyngoplasty may need to be considered when the pharyngeal depth is large and the patient’s access to surgery is limited.

Drawing on the dynamic managerial capabilities perspective, we examine the effects of the global mindset of subsidiary managers on headquarters–subsidiary relationships and the moderating effects of their cognitive flexibility, overseas study experience, and exchanges with headquarters managers on the relationship. The analysis of dyadic survey data collected from managers at the headquarters and subsidiaries of 312 Chinese multinational enterprises reveals that the subsidiary managers’ global mindset is positively associated with the quality of headquarters–subsidiary relationships. This association is stronger when the subsidiary managers exhibit higher cognitive personality flexibility and more overseas study experience but weaker when exchanges with the headquarters managers become more frequent.

The vibrant subject of blood banking and blood distribution is addressed where lateral resupply of blood products is allowed. In this paper, we studied a blood supply chain network design consisting of four conventional levels each of which corresponding to one entity in the real world: donors, blood collection facilities, blood centers, and hospitals. The blood supply chain network considered two important properties: ABO-Rh factors and shelf lives of blood products. Moreover, an integrated inventory system for sharing hospitals’ inventory levels is considered to investigate the two performance indicators of the network in terms of cross-matching and outdated units. This type of inventory system is known as “Lateral Resupply” permitting a hospital to satisfy its demand by the other hospitals’ inventories in the absence of the required product at the blood center and its excess in any hospital. The proposed mixed-integer mathematical programming model entails three objectives referring to the three underlying concepts of sustainability, additionally, to cope with uncertainties and multi objectiveness, a scenario-based optimization approach and revised multi-choice goal programming technique were employed, respectively. Finally, the results confirmed that the lateral resupply virtue improved the performance indicators.

Plant resistance against insects mainly depends on nutrient restriction and toxic metabolites, but the relative importance of nutrition and toxins remains elusive. We examined performance, nutrition ingestion, and transcriptome response of the English grain aphid, Sitobion avenae, feeding on resistant Xiaoyan 22 (XY22) and susceptible Xinong 979 (XN979) wheat cultivars. Aphids had lower body weight and fecundity when feeding on XY22 than on XN979, although the phloem sap of XY22 had a higher nutritive quality (in terms of amino acid:sucrose ratio). Aphids feeding on XY22 also had a lower honeydew excretion rate than those on XN979, suggesting that aphids ingested less phloem sap from XY22. The transcriptome data showed 600 differentially expressed genes (DEGs), and 11 of the top 20 KEGG pathways significantly enriched in DEGs were involved in nutrient metabolism. We found 81 DEGs associated with the metabolism of sugars, lipids, and amino acids, 59 of which were significantly downregulated in aphids feeding on XY22. In contrast, there were 18 DEGs related to detoxifying metabolism, namely eight UDP-glucuronosyltransferases, six cytochromes P450 monooxygenases, one glutathione S-transferase, two ATP-binding cassette transporters, and one major facilitator superfamily transporter; 12 of these were upregulated in the aphids feeding on XY22. Our results indicated that both the quantity and quality of phloem nutrition available to aphids are critical for the growth and development of aphids, and the higher resistance of XY22 is mainly due to the reduction in phloem sap ingested by aphids, rather than toxic metabolites.

Recent expansions in the roles of women in combat have prompted increased interest in the psychological toll combat exposure may have on female service members as compared to males. This study examined the interactive effects of gender and combat exposure on transitions in posttraumatic stress disorder (PTSD) diagnostic status (presence or absence of PTSD diagnosis). We used administrative data of 20,000 U.S. Army soldiers whose combat exposure was assessed after return from deployment between January 1, 2008 and June 30, 2014; soldiers' PTSD diagnostic status was determined using International Classification of Diseases-9 diagnoses at four time points separated by 12 months. We used a mixed-effects logit transition model to examine the effects of combat and gender on incidence, persistence, and prevalence of PTSD diagnosis. Incidence and prevalence of PTSD diagnosis were higher among women, but persistence of PTSD diagnosis was higher in men. Higher rates of new PTSD diagnosis among women were not dependent on combat exposure, suggesting that other types of trauma may be responsible for increased rates among women. Gender differences in prevalence and persistence of PTSD diagnosis were greater among combat-exposed soldiers than among those not exposed to combat. Men maintained a PTSD diagnosis over longer periods of time than women suggesting greater PTSD persistence, and this pattern was particularly pronounced among soldiers exposed to combat. These results have implications for the recent policy changes and gender-based prevention strategies, and suggest that women in combat roles may be no more vulnerable to PTSD than are their male counterparts. Though the gender differences were small, they are indicative of healthcare utilization patterns that may be important for prevention and that warrant further exploration.

The study on Lower Cambrian dolostones in Tarim Basin can improve our understanding of ancient and deeply buried carbonate reservoirs. In this research, diagenetic fluid characteristics and their control on porosity evolution have been revealed by studying the petrography and in situ geochemistry of different dolomites. Three types of diagenetic fluids were identified: (1) Replacive dolomites were deviated from shallow burial dolomitizing fluids, which might probably be concentrated ancient seawater at early stage. (2) Fine-to-medium crystalline, planar-e diamond pore-filling dolomites (Fd1) were likely slowly and sufficiently crystallized from deep-circulating crustal hydrothermal fluids during Devonian. (3) Coarse crystalline, non-planar-a saddle pore-filling dolomites (Fd2) might rapidly and insufficiently crystallize from magmatic hydrothermal fluids during Permian. Early dolomitizing fluids did not increase the porosity, but transformed the primary pores to dissolution pores through dolomitization. Deep-circulating crustal hydrothermal fluids significantly increased porosity in the early stages by dissolving and then slightly decreased the porosity in the late stage due to Fd1 precipitation. Magmatic hydrothermal fluids only precipitated the Fd2 dolomites and slightly decreased the porosity. In summary, Devonian deep-circulating crustal hydrothermal fluids dominated the porosity evolution of the Lower Cambrian dolostone reservoir in the Tarim Basin.

The oriental armyworm, Mythimna separata (Lepidoptera: Noctuidae) is a harmful pest which causes heavy loss in agricultural crops. Sex identification of M. separata is very important for understanding the biology and management of this pest. Development of fast and convenient methods to identify M. separata female and male is the necessary prerequisite for conducting gender-related studies. In this study, new methods to differentiate sex of M. separata at pupal and adult stages were investigated. Our results showed that posterior abdominal segments containing genital organs which are morphological traits to differentiate female and male. Genital openings are important characters for the female and male pupae differentiation. For female pupa, it locates on the ventral side of eighth and ninth abdominal segments and appears as a visible longitudinal suture; for male pupa, it locates on the ventral side of the ninth abdominal segment and appears as a short slit surrounded by a pair of visible semicircular lumps. Bristle numbers are another indicator for sex differentiation of adults. Each female has three-bristled frenulum and each male has one bristled-frenulum near the base of hind wing of each side of moth body. We confirmed the two sex differentiation methods manually by dissecting genitalia of adults and found their genger was as same as what we examined the sex of pupae and adults using the morphological methods.

The heterogeneity and complex composition of crop straw are some of the main obstacles to its scientific and efficient industrial utilization. To thoroughly reveal and identify the composition of different crop straw types and their latent attributes, in this study, 784 straw samples of rice, wheat, corn, rape and cotton were collected. Based on the large sample size, 18 composition characteristics, including chemical composition, proximate composition, ultimate composition, and heating values, were adopted to determine the profiles of the crop straw composition characteristics. Correlation analysis and 7 different types of multivariate analysis were applied and compared. The results indicated that among the 18 characteristics, hemicellulose, water-soluble carbohydrates, crude proteins, phosphorus, fixed carbon, hydrogen, nitrogen, and sulfur had non-normal distributions. Spearman method was a more suitable correlation analysis approach for the crop straw characteristics than Pearson method. The results of the different multivariate analysis methods were reflected in the different classification attributes of water-soluble carbohydrates, phosphorus, hydrogen and sulfur. Non-parametric principal component analysis and non-parametric exploratory factor analysis provided consistent results. The characteristics could be divided into 4 categories of intrinsic associated attributes, namely, (1) lignin, volatile matter, fixed carbon, carbon, hydrogen, higher heating value, and lower heating value; (2) potassium, ash, and sulfur; (3) cellulose, hemicellulose, moisture, and oxygen; and (4) water-soluble carbohydrates, crude proteins, phosphorus, and nitrogen, which exhibited combustion positive, combustion negative, biochemical conversion, and nutritional property, respectively. The study results provide data and methodology support for the development of crop straw utilization strategies.

Renpenning syndrome belongs to a group of X-linked intellectual disability disorders. The Renpenning syndrome–associated protein PQBP1 (polyglutamine-binding protein 1) is intrinsically disordered, associates with several splicing factors, and is involved in pre-mRNA splicing. PQBP1 uses its C-terminal YxxPxxVL motif for binding to the splicing factor TXNL4A (thioredoxin like 4A), but the biological function of this interaction has yet to be elucidated. In this study, using recombinant protein expression, in vitro binding assays, and immunofluorescence microscopy in HeLa cells, we found that a recently reported X-linked intellectual disability–associated missense mutation, resulting in the PQBP1-P244L variant, disrupts the interaction with TXNL4A. We further show that this interaction is critical for the subcellular location of TXNL4A. In combination with other PQBP1 variants lacking a functional nuclear localization signal required for recognition by the nuclear import receptor karyopherin β2, we demonstrate that PQBP1 facilitates the nuclear import of TXNL4A via a piggyback mechanism. These findings expand our understanding of the molecular basis of the PQBP1–TXNL4A interaction and of the etiology and pathogenesis of Renpenning syndrome and related disorders.

The aim of this study was two-fold: (1) to develop and externally validate a multiparameter MR-based machine learning model to predict the pathological complete response (pCR) in locally advanced rectal cancer (LARC) patients after neoadjuvant chemoradiotherapy (nCRT), and (2) to compare different classifiers' discriminative performance for pCR prediction.This retrospective study includes 151 LARC patients divided into internal (centre A, n = 100) and external validation set (centre B, n = 51). The clinical and MR radiomics features were derived to construct clinical, radiomics, and clinical-radiomics model. Random forest (RF), support vector machine (SVM), logistic regression (LR), K-nearest neighbor (KNN), naive Bayes (NB), and extreme gradient boosting (XGBoost) were used as classifiers. The predictive performance was assessed using the receiver operating characteristic (ROC) curve.Eleven radiomics and four clinical features were chosen as pCR-related signatures. In the radiomics model, the RF algorithm achieved 74.0% accuracy (an AUC of 0.863) and 84.4% (an AUC of 0.829) in the internal and external validation sets. In the clinical-radiomics model, RF algorithm exhibited high and stable predictive performance in the internal and external validation datasets with an AUC of 0.906 (87.3% sensitivity, 73.7% specificity, 76.0% accuracy) and 0.872 (77.3% sensitivity, 88.2% specificity, 86.3% accuracy), respectively. RF showed a better predictive performance than the other classifiers in the external validation datasets of three models.The multiparametric clinical-radiomics model combined with RF algorithm is optimal for predicting pCR in the internal and external sets, and might help improve clinical stratifying management of LARC patients.• A two-centre study showed that radiomics analysis of pre- and post-nCRT multiparameter MR images could predict pCR in patients with LARC. • The combined model was superior to the clinical and radiomics model in predicting pCR in locally advanced rectal cancer. • The RF classifier performed best in the current study.