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Key Message: Embryo abortion at the heart-shaped stage is the main reason for the failure of interspecific hybridization of hydrangea, and salicylic acid plays a key role during embryo abortion. Difficulties in obtaining seeds from interspecific hybridization between Hydrangea macrophylla and H. arborescens had severely restricted the process of breeding new hydrangea varieties. To clarify the cause of reproductive barriers, an interspecific hybridization was made between H. macrophylla 'Endless Summer' (female parent) and H. arborescens 'Annabelle' (male parent). The results showed that both parents' floral organs developed normally, 'Annabelle' had high pollen viability (84.83% at 8 h after incubation), and the pollen tube could enter into the ovule of 'Endless Summer' at 72 h after pollination. Therefore, the pre-fertilization barrier was not the main reason for the failure of interspecific hybridization. However, observation of the embryo development by paraffin sections showed that the embryo was aborted at the heart-shaped stage. In addition, salicylic acid (SA) content was significantly higher (fourfold, P < 0.01) at 21 days after pollination (DAP) as compared to that of 17 DAP, which means SA may be closely correlated with embryo development. A total of 957 metabolites were detected, among which 78 were significantly different. During the embryo abortion, phenylpropanoids and polyketides were significantly down-regulated, while organic oxygen compounds were significantly up-regulated. Further analysis indicated that the metabolic pathway was enriched in the shikimic acid biosynthesis pathway, which suggests that more SA was synthesized. Taken together, it can be reasonably speculated that SA plays a key role leading to embryo abortion underlying the interspecific hybridization between Hydrangea macrophylla and H. arborescens. The result is helpful to direct the breeding of hydrangea through distant hybridization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Little is known about the links of disturbed lipid metabolism with hyperuricemia (HUA). We aimed to investigate the associations of lipidomic profiles with uric acid (UA)/HUA and their modifying factors in middle-aged and elderly Chinese. A total of 350 lipids were quantified in 2247 community-based Chinese aged 50-70 years by high-coverage targeted lipidomics. HUA was defined by plasma UA > 420 μmol/L in men or > 360 μmol/L in women. The prevalence of HUA in this population was 10.4%. After multivariable adjustment including BMI and lifestyle, 123 lipids were significantly associated with UA, predominantly glycerolipids (GLs) and glycerophospholipids (GPs). Specifically, diacylglycerol [DAG (16:0/22:5), DAG (16:0/22:6), DAG (18:1/20:5), DAG (18:1/22:6)], phosphatidylcholine [PC (16:0/20:5)), and triacylglycerol (TAG (53:0)] were the most significant lipid signatures positively associated with HUA risk, while lysophosphatidylcholine (LPC (20:2)) was inversely associated with HUA risk ( p  < 0.05). Network analysis also showed a positive association between TAGs/PCs/DAGs contained module and HUA risk ( p  < 0.01). Notably, HUA-related lipids were associated with de novo lipogenesis fatty acids, especially 16:1n-7 (Spearman correlation coefficients = 0.32-0.41, p  < 0.001). Reduced rank regression showed that increased aquatic products intake was correlated to elevated HUA risk and HUA-associated lipids; while high dairy consumption was correlated with low level of HUA-associated lipids (|factor loadings| ≥ 0.2). Moreover, mediation analyses suggested that the lipid-HUA associations were partially mediated by retinol-binding protein 4 (RBP4, mediation proportion 5-14%), an adipokine linked with dyslipidemia and insulin resistance. In conclusion, disturbed specific metabolisms of GLs and GPs were associated with high prevalent HUA, partially mediated by RBP4 and/or influenced by certain dietary factors., Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-024-00157-x., Competing Interests: Conflict of InterestOn behalf of all authors, the corresponding authors state that there is no conflict of interest., (© The Author(s) 2024.)

Background: At present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population., Methods: A cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland-Altman plots were employed to verify the validity of eGFR., Results: The participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m 2 , all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland-Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37., Conclusions: This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered., (© 2024. The Author(s).)

Purpose: The purpose of this study was to describe the effectiveness and evaluation of open surgical treatment of basilar artery aneurysms in the context of interventional therapy era, including surgical clipping and blood reconstruction, by retrospectively analyzing the clinical data of basilar artery aneurysms in our center., Methods: Patients with basilar artery aneurysms who were treated at our center were retrospectively included according to the inclusion and exclusion criteria. The basic clinical data, surgical approach, clinical follow-up and prognosis of the enrolled patients were analyzed in detail. In this study, the mRS score was applied to assess the neurological prognosis of the patients, and the relevant data were statistically analyzed using SPSS., Results: A total of 104 eligible patients treated at our center from January 2010 to August 2023 were included in this study, of which 67 were treated by open surgery and 37 by bypass. For the 67 patients with open surgical clipping, the mean age was 60.0 (52.0, 65.0) years. The maximum diameter of the aneurysms ranged from 2.0 mm to 54.0 mm, with a mean of 13.9 (10.0, 19.0) mm. The mean follow-up time was 38 (20, 58) months. At the last follow-up, 61 (91.0%) completely obliterated aneurysms and 6 (9.0%) incompletely obliterated aneurysms were found. The prognosis was good in 59 (88.1%) patients and poor in 8 (11.9%). After surgical clipping, the difference between complete and incomplete postoperative aneurysm elimination was statistically significant between the favorable and poor prognosis groups (P < 0.001). For the 37 bypass group patients, the mean age was 52.0 (45.5, 59.0) years. The maximum diameter of the aneurysm ranged from 10.5 mm to 55.0 mm, with a mean of 28.55 ± 12.08 mm. Bypass combined with proximal occlusion was performed in 18 (48.6%) patients, and bypass only was performed in 19 (51.4%) patients. Clinical follow-up was 19.0 (10.5, 43.0) months. There were 19 (51.4%) patients with complete elimination of the aneurysm, 13 (35.1%) with incomplete elimination of the aneurysm, and 5 (13.5%) with aneurysm stabilization. The prognosis was good in 32 (86.5%) patients and poor in 5 (13.5%) patients., Conclusion: Treatment of basilar artery aneurysms is challenging. In the context of the rapidly evolving interventional therapy era, open surgery including surgical clipping and bypass is an ideal option for complex basilar artery aneurysms not amenable to intervention., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The influence of harsh Arctic environmental factors has caused ship-ice collision accidents to become the main threat faced by navigating ships. It is necessary to quantify the causation of ship accidents and perform effective risk management and control measures to ensure ship navigation safety. This study proposes a Bayesian network (BN) model-based risk analysis method for ship-ice collision accidents, which is used to quantitatively analyze the key risk factors and primary risk causation paths of ship accidents. First, the fault tree analysis (FTA) method is proposed to constructing the BN structure model, and the BN parameter solution method is further established. Consequently, a triangular fuzzy and defuzzification method is developed to quantify uncertain expert knowledge. Then, the BN inference method is used to analyze the collision risk causation where the North Atlantic and Arctic waters meet. The results indicate that the main risk factors in Arctic waters come from the environment. There are four primary risk causation paths; the proposed management and control measures of the risk causation paths (A), (B), (C), and (D) can effectively reduce the navigation risk by 29.95%, 9.98%, 25.05%, and 3.99%, respectively; the combination of these four measures can reduce the navigation risk by 54.63%.The proposed method has positive guiding significance for ensuring the safety of ship navigation in Arctic waters., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study analyzed and compared the biomechanical properties of maxillary sinus floor mucosa with implants at three different maxillary sinus angles during a modified internal sinus floor elevation procedure., Methods: 3D reconstruction of the implant, maxillary sinus bone, and membrane were performed. The maxillary sinus model was set at three different angles. Two internal maxillary sinus elevation models were established, and finite element analysis was used to simulate the modified maxillary sinus elevation process. The implant was elevated to 10 mm at three maxillary sinus angles when the maxillary sinus floor membrane was separated by 0 and 4 mm. The stress of the maxillary sinus floor membrane was analyzed and compared., Results: When the maxillary sinus floor membrane was separated by 0 mm and elevated to 10 mm, the peak stress values of the implant on the maxillary sinus floor membrane at three different angles were as follows: maxillary sinus I: 5.14-78.32 MPa; maxillary sinus II: 2.81-73.89 MPa; and maxillary sinus III: 2.82-51.87 MPa. When the maxillary sinus floor membrane was separated by 4 mm and elevated to 10 mm, the corresponding values were as follows: maxillary sinus I: 0.50-7.25 MPa; maxillary sinus II: 0.81-16.55 MPa; and maxillary sinus III: 0.49-22.74 MPa., Conclusion: The risk of sinus floor membrane rupture is greatly reduced after adequate dissection of the maxillary sinus floor membrane when performing modified internal sinus elevation in a narrow maxillary sinus. In a wide maxillary sinus, the risk of rupture or perforation of the wider maxillary sinus floor is reduced, regardless of whether traditional or modified internal sinus elevation is performed at the same height., (© 2024. The Author(s).)

Water-soluble organic compounds (WSOCs) have received extensive attention due to their indistinct chemical components, complex sources, negative environmental impact, and potential health effects. To the best of our knowledge, until now, there has been no comprehensive review focused on the research progress of WSOCs. This paper reviewed the studies on chemical constituent and characterization, distribution condition, sources, environmental impact, as well as the potential health effects of WSOCs in the past 13 years. Moreover, the main existing challenges and directions for the future research on WSOCs were discussed from several aspects. Because of the complex composition of WSOCs and many unknown individual components that have not been detected, there is still a need for the identification and quantification of WSOCs. As modern people spend more time in indoor environments, it is meaningful to fill the gaps in the component characteristics and sources of indoor WSOCs. In addition, although in vitro cell experiments have shown that WSOCs could induce cellular oxidative stress and trigger the inflammatory response, the corresponding mechanisms of action need to be further explored. The current population epidemiology research of WSOCs is missing. Prospectively, we propose to conduct a comprehensive and simultaneous analysis strategy for concentration screening, source apportionment, potential health effects, and action mechanisms of WSOCs based on high throughput omics coupled with machine learning simulation and prediction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pseudomonas aeruginosa is one of the top-listed pathogens in nosocomial infection. It is notorious for its complicated virulence system and rapid adaptability to drugs or antimicrobials. In this study, we aimed to evaluate the prevalence of sixteen virulence genes in four groups including type III secretion system, biofilm formation, extracellular toxin biosynthesis and enzymes amongst 209 clinical Pseudomonas aeruginosa strains. We investigated the different distribution patterns of virulence genotypes based on carbapenem-resistant phenotype or the carriage of carbapenemase genes. The detection rate of each virulence gene varied greatly. phzM and plcN were detected in all collected strains, while pilB and exoU were only carried by a small portion of isolates (6.7% and 16.3%). Additionally, the number of genotypes observed in each group of examined virulence genes ranged from 4 to 8. Only the distribution of genotypes of type III secretion system showed statistical difference between carbapenem-mediated or carbapenem-resistant and carbapenem-sensitive strains. The virulence genotype of Pseudomonas aeruginosa was possibly interrelated to its resistance mechanism. Further research suggested that one particular TTSS genotype exhibited higher ratio in carbapenemase-producing strains and exoS was less frequently detected in CRPA strains carrying carbapenemase gene. Generally, the significant genetic diversity of virulence genes amongst Pseudomonas aeruginosa strains was highlighted in this study. Specific TTSS genotypes were associated with carbapenem-resistance. In particular, certain incompatibility might exist between exoS and carbapenemase genes, which provided valuable information for further understanding the relationship between carbapenem resistance and virulence., (© 2023. The Author(s).)

The emerging worldwide distributed porcine circovirus type 3 (PCV3) infection poses a serious threat to swine herds. An important means of preventing and controlling PCV3 infection is the development of the vaccine, while, the inability to cultivate in vitro has become the biggest obstacle. Orf virus (ORFV), the prototypic member of the Parapoxviridae, has been proven to be a novel valid vaccine vector for preparing various candidate vaccines. Here, recombinant ORFV expressing capsid protein (Cap) of PCV3 was obtained and proved its favorable immunogenicity inducing antibody against Cap in BALB/c mice. Based on the enhanced green fluorescent protein (EGFP) as a selectable marker, the recombinant rORFVΔ132-PCV3Cap-EGFP was generated. Then, recombinant ORFV expressing Cap only, rORFVΔ132-PCV3Cap, was obtained based on rORFVΔ132-PCV3Cap-EGFP using a double homologous recombination method by screening single non-fluorescent virus plaque. Results of the western blot showed that the Cap can be detected in rORFVΔ132-PCV3Cap infected OFTu cells. The results of immune experiments in BALB/c mice indicated that a specific antibody against Cap of PCV3 in serum was induced by rORFVΔ132-PCV3Cap infection. The results presented here provide a candidate vaccine against PCV3 and a feasible technical platform for vaccine development based on ORFV., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Liver cirrhosis is a confirmed risk factor for poor prognosis of stroke; however, the contribution of clinically inapparent liver fibrosis to cardioembolic stroke (CES) and its outcomes are poorly understood. This study aimed to investigate the associations between liver fibrosis-measured by the Fibrosis-4 (FIB-4) score-and stroke severity and short-term clinical outcomes of patients with acute CES due to nonvalvular atrial fibrillation (NVAF). A total of 522 patients were followed for a median of 90 days. We calculated the FIB-4 score and defined liver fibrosis as follows: likely advanced fibrosis (FIB-4 > 3.25), indeterminate advanced fibrosis (FIB-4, 1.45-3.25), and unlikely advanced fibrosis (FIB-4 < 1.45). Logistic regression analysis and Cox regression analysis were used to investigate the relations between the FIB-4 score and stroke severity, major disability at discharge, and all-cause mortality. Among these 522 acute CES patients with NVAF, the mean FIB-4 score (2.28) on admission reflected intermediate fibrosis, whereas liver enzymes were largely normal. In multivariate regression analysis, patients with advanced liver fibrosis were more likely to have a higher risk of severe stroke (OR = 2.21, 95% CI 1.04-3.54), major disability at discharge (OR = 4.59, 95% CI 1.88-11.18), and all-cause mortality (HR = 1.25, 95% CI 1.10-1.56) than their counterparts. Regarding sex, these associations were stronger in males but not significant in females. In patients with acute CES due to NVAF, advanced liver fibrosis is associated with severe stroke, major disability, and all-cause death. Our findings indicate that early screening and management of liver fibrosis may decrease stroke severity and risk of death in patients with NVAF, especially for male patients. Consequently, FIB-4 > 3.25 of male patients should receive ultrasound elastography to further determine the degree of liver fibrosis., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Green credit encompasses financial instruments and services utilized to mitigate greenhouse gas emissions and facilitate adaptation to global climate change. Establishing a long-term stable green credit institution is crucial to promoting carbon abatement goals. This study uses the difference-in-difference (DID) model to discuss the impact of green credit policy (GCP) on environmental performance based on the China industrial enterprise data. Our results show that GCP inhibits the pollution emissions and improve firm environmental performance. This improvement effect is attributed to a reduction in production scale, and financing constraints. Moreover, GCP increases the firms' exit risk from market and promotes the technological innovation of incumbent firms. Economic growth target constraints trigger a positive moderation role in the implementation of GCP. Heterogeneity results show that such improvement effect is more pronounced in state-owned firm, large-scale firms, and high R&D intensity firms. Importantly, our findings also suggest the environmental monitoring effect of green credit is dependent on the institutional quality. Only in a sound market environment can GCP effectively improve firm environmental performance. Finally, we propose to build a systematic incentives and constraints mechanism to achieve the sustainable development. The conclusions of this paper provide empirical evidence and policy implications for the implementation of GCP., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

During the growth of Pinellia ternata (Thunb.) Breit. (P. ternata), the violet-red skin was occasionally produced spontaneously under natural cultivation. However, the specific mechanism leading to the color change is still unclear. This study performed transcriptomes in violet-red and pale-yellow skin and their peeled tubers of P. ternata, and the total flavonoids and anthocyanin contents were also determined. The results showed that the majority of genes involved in anthocyanin production were considerably increased in the violet-red skin of P. ternata tuber compared to the pale-yellow skin. Especially, phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) showed a remarkable increase in gene expression levels. Notably, shikimate O-hydroxycinnamoyltransferase (HCT), naringenin 3-dioxygenase (F3H), flavanone 4-reductase (DFR), and anthocyanidin synthase (ANS) were explicitly expressed in violet-red skin of P. ternata tuber, while undetectable in pale-yellow skin. The upregulation of these genes may explain the accumulation of anthocyanins, which forms the violet-red skin of P. ternata tuber. The transcription factors, including C2H2, bZIP, ERF, GATA, bHLH, C3H, NAC, MYB-related, and MYB families, might trigger the skin color change in P. ternata. The entire anthocyanin content in the violet-red skin of P. ternata tuber was 71.10 μg/g, and pale-yellow skin was 7.74 μg/g. According to phenotypic and transcriptome results, the elevated expression levels of genes linked to the synthesis of anthocyanins considerably contributed to the violet-red skin alterations in P. ternata tuber. This study provides a new understanding of the formation of the violet-red skin, lays a theoretical foundation for the cultivation of unique varieties of P. ternata, and provides transcriptome data for further study of the differences between different colors of P. ternata., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Plectin, as the cytolinker and scaffolding protein, are widely expressed and abundant in many tissues, and has involved in various cellular activities contributing to tumorigenesis, such as cell adhesion, migration, and signal transduction. Due to the specific expression and differential localization of plectin in cancer, most researchers focus on the role of plectin in cancer, and it has emerged as a potent driver of malignant hallmarks in many human cancers, which provides the possibility for plectin to be widely used as a biomarker and therapeutic target in the early diagnosis and targeted drug delivery of the disease. However, there is still a lack of systematic review on the interaction molecules and mechanism of plectin. Herein, we summarized the structure, expression and function of plectin, and mainly focused on recent studies on the functional and physical interactions between plectin and its interacting molecules, shedding light on the potential of targeting plectin for cancer therapy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Key Message: DcWRKY5 increases the antioxidant enzyme activity and proline accumulation, oppositely, reduces the accumulation of ROS and MDA, through directly activating the genes expression, finally enhances the salt and drought tolerance. Drought and salinity are two main environmental factors that limit the large-scale cultivation of the medicinal plant Dioscorea composita (D. composita). WRKY transcription factors (TFs) play vital roles in regulating drought and salt tolerance in plants. Nevertheless, the molecular mechanism of WRKY TF mediates drought and salt resistance of D. composita remains largely unknown. Here, we isolated and characterized a WRKY TF from D. composita, namely DcWRKY5, which was localized to the nucleus and bound to the W-box cis-acting elements. Expression pattern analysis showed that it was highly expressed in root and significantly up-regulated in the presence of salt, polyethylene glycol-6000 (PEG-6000) and abscisic acid (ABA). Heterologous expression of DcWRKY5 increased salt and drought tolerance in Arabidopsis, but was insensitive to ABA. In addition, compared with the wild type, the DcWRKY5 overexpressing transgenic lines had more proline, higher antioxidant enzyme (POD, SOD, and CAT) activities, less reactive oxygen species (ROS) and malondialdehyde (MDA). Correspondingly, the overexpression of DcWRKY5 modulated the expression of genes related to salt and drought stresses, such as AtSS1, AtP5CS1, AtCAT, AtSOD1, AtRD22, and AtABF2. Dual luciferase assay and Y1H were further confirmed that DcWRKY5 activate the promoter of AtSOD1 and AtABF2 through directly binding to the enrichment region of the W-box cis-acting elements. These results suggest that DcWRKY5 is a positive regulator of the drought and salt tolerance in D. composita and has potential applications in transgenic breeding., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

SETβ is the predominant isoform of oncoprotein SE translocation (SET) in various breast cancer cell lines. Interactome-transcriptome analysis has shown that SETβ is intimately associated with cellular stress response. Among various exogenous stimuli, formaldehyde (FA) causes distinct biological effects in a dose-dependent manner. In response to FA at different concentrations, SET dynamically shuttles between the nucleus and cytoplasm, performing diverse biofunctions to restore homeostasis. At a low concentration, FA acts as an epidermal growth factor (EGF) and activates the HER2 receptor and downstream signaling pathways in HER2 + breast cancer cells, resulting in enhanced cell proliferation. Nucleocytoplasmic transport of SETβ is controlled by the PI3K/PKCα/CK2α axis and depletion or blockade of the transport of SETβ suppresses EGF-induced activation of AKT and ERK. SETβ also inhibits not only stress-induced activation of p38 MAPK signaling pathway, but also assembly of stress granules by hindering formation of the G3BP1-RNA complex. Our findings suggest that SET functions as an important regulator which modulates cellular stress signaling pathways dynamically., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Mitochondria are crucial for the regulation of intracellular energy metabolism, biosynthesis, and cell survival. And studies have demonstrated the role of mitochondria in oxidative stress-induced autophagy in plants. Previous studies found that waterlogging stress can induce the opening of mitochondrial permeability transition pore (mPTP) and the release of cytochrome c in endosperm cells, which proved that mPTP plays an important role in the programmed cell death of endosperm cells under waterlogging stress. This study investigated the effects of the opening of mPTP and the inhibition of ETC on mitophagy in wheat roots under waterlogging stress. The results showed that autophagy related genes in the mitochondria of wheat root cells could respond to waterlogging stress; waterlogging stress led to the degradation of the characteristic proteins cytochrome c and COXII in the mitochondria of root cells. With the prolongation of waterlogging time, the protein degradation degree and the occurrence of mitophagy gradually increased. Under waterlogging stress, exogenous mPTP opening inhibitor CsA inhibited mitophagy in root cells and alleviated mitophagy induced by flooding stress, while exogenous mPTP opening inducer CCCP induced mitophagy in root cells; exogenous mPTP opening inducer CCCP induced mitophagy in root cells. The electron transfer chain inhibitor antimycin A induces mitophagy in wheat root cells and exacerbates mitochondrial degradation. In conclusion, waterlogging stress led to the degradation of mitochondrial characteristic proteins and the occurrence of mitophagy in wheat root cells, and the opening of mPTP and the inhibition of ETC induced the occurrence of mitophagy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

This article examines the innovation in the green sector frequently facing a financial conundrum. Production of renewable energy is the eighth sustainable development, based on the data from the 30 Chinese provinces (2000-2017). This study presents an analysis of the effects of green digital finance on green innovation on protection of environment using influence mechanism analysis. Digital finance, which has become a major driver of green innovations in China, may first increase the number and quality of green technical innovation. The results show that the promotion effect of digital finance on the efficiency of renewable energy markets is greater than the inhibitory effect, making the total effect less obviously favorable. In other results, the elasticity of lnGFDI is significant at the 5% level and is 0.1545% and 0.1880% in the present and 1-year delayed periods, respectively. Further, the average total effect of FDI on the effectiveness of green innovation is 0.008, with an average encouraging effect of 0.0051 and an average inhibiting effect of 0.0039. We conclude that diverse behavior for that policy support increases the impact of green digital finance, promote green innovation, and generate emission free environment for sustainable energy markets., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aimed to investigate the feasibility of early oral feeding (EOF) after neoadjuvant chemotherapy (nCT) combined with "non-tube no fasting"-enhanced recovery after minimally invasive esophagectomy (MIE)., Methods: This retrospective study investigated patients who underwent nCT combined with non-tube no fasting-enhanced recovery after MIE in the Department of Thoracic Surgery, Ward I, of the authors' hospital from January 2014 to August 2017. These patients were divided into an early oral feeding (EOF) group (n = 112) and a late oral feeding (LOF) group (n = 69). The postoperative complications were compared between the two groups., Results: The study enrolled 181 patients (112 patients in the EOF group and 69 patients in the LOF group). No significant differences were found between the two groups in the incidence rates of complications such as anastomotic leakage (P = 0.961), pneumonia (P = 0.450), respiratory failure (P = 0.944), heart failure (P = 1.000), acute respiratory distress syndrome (ARDS) (P = 0.856), and unplanned reoperation (P = 0.440), whereas the time to the first postoperative flatus/bowel movement (P < 0.001) and the postoperative length of stay (P < 0.001) were significantly better in the EOF group than in the LOF group.., Conclusions: In this study, EOF after nCT combined with non-tube no fasting-enhanced recovery after MIE did not significantly increase complications, but significantly shortened the time to the first postoperative flatus/bowel movement and the postoperative length of stay., (© 2022. Society of Surgical Oncology.)

Background: The order of significance of clinicopathologic characteristics for the prognosis of patients with regional metastases from head and neck cutaneous squamous cell carcinoma (HNcSCC) is not well characterized. This study aimed to understand the impact of the known characteristics, including the presence of immunosuppression, number of deposits, largest deposit size, location and laterality of deposits, and presence of extranodal extension (ENE) on overall survival (OS) and disease-specific survival (DSS)., Methods: A retrospective study of 366 patients treated with curative intent for HNcSCC with regional metastatic disease was undertaken using recursive partitioning analysis (RPA)., Results: Using RPA modeling, the study determined that number of metastatic deposits carried the highest impact for both OS and DSS, followed by largest deposit size. The presence of ENE and immunosuppression was less significant., Conclusions: The results from this study provide new evidence for identifying and stratifying high-risk patients with metastatic HNcSCC. This information will be valuable in determining future HNcSCC staging systems., (© 2022. Crown.)

The COVID-19 issue deteriorated South Africa's already dire economic situation, exacerbated by years of considerable debt increase. The COVID-19 pandemic has disrupted trade to such an extent that some enterprises are barely working at a quarter of their potential. Furthermore, economic agents delay economic decisions while waiting to see how the crisis develops. According to some economists, increased government expenditure will raise GDP enough to keep the country's debt-to-GDP ratio steady and restore fiscal sustainability. We use a panel data model to estimate a fiscal reaction function, which we then apply to historical data to assess the government's prior efforts to maintain or restore budgetary sustainability. We calculate the impact fiscal balance, government expenditure, interest rate, and revenue changes that the government will have to make to restore the country's fiscal stability due to the financial impact of the COVID-19 issue.The findings show that fiscal balance and tax revinue have a significant impact on the economics growth, while government expenditure and corruption reduce the growth of the country., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

With the large-scale construction of suburban railway viaducts, the noise problem along the viaducts is becoming more and more prominent. Conventional vertical noise barriers have been widely used to alleviate the noise problem along the suburban railway viaducts. However, conventional vertical noise barriers often have an adverse effect on the urban landscape and also block the view of train drivers and passengers. A type of near-rail low-height noise barrier was planned to install on the viaducts of Wenzhou Rail Transit Line S1 to reduce the impact of noise on residents along the railway lines. To assess the acoustic performance of the near-rail low-height noise barrier, a numerical procedure for railway viaduct comprehensive noise considering wheel-rail noise and structure-borne noise of the bridge and noise barriers was proposed and then verified by a field test. On this basis, numerical models were established to compare the acoustic performances of the near-rail low-height noise barrier and conventional vertical noise barrier. The influences of the height and top shape of the near-rail low-height noise barrier on the acoustic performance were discussed. Based on the numerical analysis results, it is found that both the near-rail low-height noise barrier and conventional vertical noise barrier have good acoustic performances. The noise reduction effect of the near-rail low-height noise barrier is slightly better than that of the conventional vertical noise barrier. The acoustic performance of the near-rail low-height noise barrier gradually improves, but the improvement rate gradually slows down as the height of the noise barrier increases. The noise reduction effects of both the inverted L-shaped and Y-shaped near-rail low-height noise barrier are obviously better than that of the vertical one, while the noise reduction effects of the inverted L-shaped near-rail low-height noise barrier are slightly better than the Y-shaped one., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This paper investigates volatility spillovers between the global crude oil market and the stock markets of the global oil stock markets (Russian, Canada, China, Kuwait, and the USA) pre and after the COVID-19 pandemic. We use wavelet Granger causality methods to study the volatility spillovers between global oil stock markets, mainly from January 1, 2019, to March 31, 2021. Our Results (1) shows that WTI and Brent oil prices had a negative mean return before COVID-19 but a positive mean return during the pandemic spread. Other Results (2) find the positive, significantly lowest, and highest frequency during the COVID-19 outbreak for all selected countries. The results also show that the link between oil WTI & Brent prices and stock markets return in the lowest (33-66 days) and highest frequency range (4-16) before the Covid-19 epidemic, especially in the first quarter of 2020. Before the COVID-19 period, the Russian oil stock market is seriously prejudiced with oil prices on a modest scale, but not after the pandemic's start. This study also perceives direction opposite between the COVID-19 period. The Canadian and United States America oil and stock markets influence the lowest scale in the previous COVID-19 sample for the U.S. market. Moreover, this paper exposed that oil marketing highest oil futures in their portfolios than stock shares for all times. We found that oil price shocks had a more significant impact on the stock markets of the United States and Canada than on the stock markets of other countries., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Green development is a strategy for China's sustainable economic growth, and improving green total factor energy efficiency (GTFEE) is the key to achieving the dual goals of energy conservation, emission reduction, and economic development. This paper takes panel data of 267 prefecture-level cities in China from 2004 to 2019 as samples to explore how heterogeneous environmental regulation can have the effects of FDI on GTFEE. The results show that, first, except for environmental regulation and FDI independently affecting GTFEE, there is a synergistic effect between environmental regulation and FDI, and their interaction can also significantly affect GTFEE. Secondly, FDI has no significant impact on GTFEE when environmental regulation is low, but FDI can significantly improve GTFEE when environmental regulation is high. Thirdly, market-based environmental regulations (MER) have a better improvement effect on GTFEE than command-based environmental regulations (CER). Therefore, it is necessary to pay attention to the benign interaction between FDI and environmental regulation, especially giving full play to the role of market-based environmental regulation and further improving the design of command-based environmental regulation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Porcine circovirus type 3 (PCV3) is a highly contagious virus belonging to the family Circoviridae that causes the severe dermatitis and nephropathy syndrome. To date, PCV3 has a worldwide distribution and bring huge economic losses to swine industry. Replicase (Rep) and capsid (Cap) are two major coded proteins of PCV3. Considering the large number of new PCV3 isolates were reported in the past few years and the research for the codon usage pattern of Rep and Cap genes was still a gap, phylogenetic and codon usage analysis of these two genes was performed. Phylogenetic analyses showed that Rep genes in PCV3a were dispersed with no clear clusters while corresponding sequences in PCV3b clustered into two groups and Cap genes clustered into distinct clades according to different genotypes. Relative synonymous codon usage (RSCU) analysis revealed that the codon usage bias existed and effective number of codon (ENC) analysis showed that the bias was slight low. ENC-GC3s plot indicated that mutational pressure and other factors both played a role in PCV3 codon usage and neutrality plot analysis showed that natural selection was the main force influencing the codon usage pattern. The results presented here provided the important basic data on codon usage pattern of Rep and Cap genes, and a better understanding of the evolution and potential origin of PCV3., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Developing a biomechanical model which connected with the actual anatomy of the human body is helpful to understand the human response to vibration. A finite element model of the seated human body with 175 cm in stature and 68.6 kg in weight, which consists of seven segments, six joints and soft tissue, was established to reflect apparent mass based on the Hybrid III dummy model. By comparing the body segment mass percentages with previous data, the rationality of mass distribution in this model was verified. The biomechanical parameters play a crucial role in biodynamic modeling, while the joint and soft tissue parameters are difficult to choose due to the wide range of anthropometric parameters. In this study, the root-mean-square error between the calculated and the measured apparent mass was taken as objective function, and the effect of fifteen human parameters on the objective function was analyzed through sensitivity analysis. Then seven parameters with a considerable influence on the objective function were selected as design variables, and four approximate models were established for parameter optimization. Soft tissues and joint parameters of the model were determined by parameter identification, and the finite element model that can reflect vertical in-line and fore-and-aft cross-axis apparent mass of the human body without backrest was developed. The seated human model presented in this paper can also reflect the transmissibility from seat to the first thoracic spine and the main modes of the human body below 10 Hz, which is conducive to express the human response to vibration., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accurate tissue segmentation of large-scale pediatric brain MR images from multiple sites is essential to characterize early brain development. Due to imaging motion/Gibbs artifacts and multi-site issue (or domain shift issue), it remains a challenge to accurately segment brain tissues from multi-site pediatric MR images. In this paper, we present a multi-scale self-supervised learning (M-SSL) framework to accurately segment tissues for multi-site pediatric brain MR images with artifacts. Specifically, we first work on the downsampled images to estimate coarse tissue probabilities and build a global anatomic guidance. We then train another segmentation model based on the original images to estimate fine tissue probabilities, which are further integrated with the global anatomic guidance to refine the segmentation results. In the testing stage, to alleviate the multi-site issue, we propose an iterative self-supervised learning strategy to train a site-specific segmentation model based on a set of reliable training samples automatically generated for a to-be-segmented site. The experimental results on pediatric brain MR images with real artifacts and multi-site subjects from the iSeg2019 challenge demonstrate that our M-SSL method achieves better performance compared with several state-of-the-art methods.

Background/aims: Inflammation is well known to play a pivotal role in renal injury. Rhein is a major component of the medicinal Rhubarb. The aim of this study was to investigate whether Rhein protects against renal injury and explore its underlying mechanism., Methods: 5/6 nephrectomization (5/6 Nx) was operated on Sprague-Dawley rats. Human kidney tubular epithelial (HK-2) cells were treated with lipopolysaccharide (LPS). The level of blood urea nitrogen (BUN) and serum creatinine (SCr) was examined. Kidney tissues were stained with hematoxylin and eosin to check the morphology. The cell viability was examined. The levels of cytokines and chemokines were measured by ELISA kit. The protein expression was determined by western blot., Results: Rhein significantly decreased SCr and BUN levels in 5/6 Nx rat. The morphologic findings indicated noteworthy amelioration of the damaged renal tissue in Rhein-treated rats. Rhein significantly protects HK-2 cells from LPS-mediated apoptosis. The productions of inflammatory signaling molecules (TNF-α, IL-6 and MCP-1) were inhibited by Rhein. LPS-induced NF-κB activation was also attenuated by Rhein via blocking its nuclear translocation by inhibiting phosphorylation of IκBα., Conclusion: These findings provide evidence that Rhein protect against renal injury, and NF-κB signaling pathway is involved in this protective effect.

Background: In patients with biliary colic, high-quality prospective data supporting the precise timing of cholecystectomy are lacking. The purpose of this study was to determine the effectiveness of early laparoscopic cholecystectomy in children with biliary colic., Methods: A multicenter, parallel-group, randomized study was conducted in patients with biliary colic at 5 hospitals in China. Pediatric patients with biliary colic were prospectively randomized to either the early cholecystectomy or conservative management strategy. The clinical outcomes within 6 months, including the number of biliary colic-free patients and gallstone-related complications, were compared (register number ChiCTR1900021830)., Results: During the first 2 months of follow-up, 71 patients (59.2%, 71/120) receiving conservative management and 124 patients (97.6%, 124/127) in the early cholecystectomy group (p < 0.001) reported being entirely colic-free. The GIQLI measures were higher in the early cholecystectomy group than in the conservative management group (p = 0.032). Acute readmissions occurred in 7 (5.5%) of 127 patients in the early cholecystectomy group, compared with 23 (19.2%) of 120 patients in the conservative management group (risk ratio [RR] 0.25; 95% CI [0.10-0.60], p = 0.001) in the 6-month period., Conclusions: Early cholecystectomy is effective in providing beneficial outcomes in terms of both short-term and long-term improvement of symptoms.

Three previously undescribed cytochalasins, named xylariasins A‒C (1‒3), together with six known ones (4‒9) were isolated from Xylaria sp. CFL5, an endophytic fungus of Cephalotaxus fortunei. The chemical structures of all new compounds were elucidated on the basis of extensive spectroscopic data analyses and electronic circular dichroism calculation, as well as optical rotation calculation. Biological activities of compounds 1, 4‒9 were evaluated, including cytotoxic, LAG3/MHC II binding inhibition and LAG3/FGL1 binding inhibition activities. Compounds 6 and 9 possessed cytotoxicity against AGS cells at 5 μM, with inhibition rates of 94% and 64%, respectively. In addition, all tested isolates, except compound 6, exhibited obvious inhibitory activity against the interaction of both LAG3/MHC II and LAG3/FGL1. Compounds 1, 5, 7, and 8 inhibited LAG3/MHC II with IC 50 values ranging from 2.37 to 4.74 μM. Meanwhile, the IC 50 values of compounds 1, 7, and 8 against LAG3/FGL1 were 11.78, 4.39, and 7.45 μM, respectively.

To characterize early cerebellum development, accurate segmentation of the cerebellum into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) tissues is one of the most pivotal steps. However, due to the weak tissue contrast, extremely folded tiny structures, and severe partial volume effect, infant cerebellum tissue segmentation is especially challenging, and the manual labels are hard to obtain and correct for learning-based methods. To the best of our knowledge, there is no work on the cerebellum segmentation for infant subjects less than 24 months of age. In this work, we develop a semi-supervised transfer learning framework guided by a confidence map for tissue segmentation of cerebellum MR images from 24-month-old to 6-month-old infants. Note that only 24-month-old subjects have reliable manual labels for training, due to their high tissue contrast. Through the proposed semi-supervised transfer learning, the labels from 24-month-old subjects are gradually propagated to the 18-, 12-, and 6-month-old subjects, which have a low tissue contrast. Comparison with the state-of-the-art methods demonstrates the superior performance of the proposed method, especially for 6-month-old subjects.

Autism, or autism spectrum disorder (ASD), is a complex developmental disability, and usually diagnosed with observations at around 3-4 years old based on behaviors. Studies have indicated that the early treatment, especially during early brain development in the first two years of life, can significantly improve the symptoms, therefore, it is important to identify ASD as early as possible. Most previous works employed imaging-based biomarkers for the early diagnosis of ASD. However, they only focused on extracting features from the intensity images, ignoring the more informative guidance from segmentation and parcellation maps. Moreover, since the number of autistic subjects is always much smaller than that of normal subjects, this class-imbalance issue makes the ASD diagnosis more challenging. In this work, we propose an end-to-end informative feature-guided Siamese network for the early ASD diagnosis. Specifically, besides T1w and T2w images, the discriminative features from segmentation and parcellation maps are also employed to train the model. To alleviate the class-imbalance issue, the Siamese network is utilized to effectively learn what makes the pair of inputs belong to the same class or different classes. Furthermore, the subject-specific attention module is incorporated to identify the ASD-related regions in an end-to-end fully automatic learning manner. Both ablation study and comparisons demonstrate the effectiveness of the proposed method, achieving an overall accuracy of 85.4%, sensitivity of 80.8%, and specificity of 86.7%.

Surface texturing is one of the most important techniques for improving the performance of photovoltaic (PV) device. As an appealing front texture, inverted pyramid (IP) has attracted lots of research interests due to its superior antireflection effect and structural characteristics. In this paper, we prepare high-uniform silicon (Si) IPs structures on a commercial monocrystalline silicon wafer with a standard size of 156 × 156 mm 2 employing the metal-assisted chemical etching (MACE) and alkali anisotropic etching technique. Combining the front IPs textures with the rear surface passivation of Al 2 O 3 /SiN x , we fabricate a novel Si IP-based passivated emitter and rear cell (PERC). Benefiting from the optical superiority of the optimized IPs and the improvement of electrical performance of the device, we achieve a high efficiency of 21.4% of the Si IP-based PERC, which is comparable with the average efficiency of the commercial PERC solar cells. The optimizing morphology of IP textures is the key to the improvement of the short circuit current I sc from 9.51 A to 9.63 A; meanwhile, simultaneous stack SiO 2 /SiN x passivation for the Si IP-based n + emitter and stack Al 2 O 3 /SiN x passivation for rear surface guarantees a high open-circuit voltage V oc of 0.677 V. The achievement of this high-performance PV device demonstrates a competitive texturing technique and a promising prospect for the mass production of the Si IP-based PERC.

The rapidly developmental RNA-guided CRISPR/Cas system is a powerful tool for RNA and DNA editing in a variety of cells from different species and makes a great contribution to gene function research, disease model generation and gene therapy development in the past few years. The ease of use, low cost and high efficiency of CRISPR/Cas make it commonly used in various conditions. In this review, we introduce the CRISPR/Cas system and its diverse applications in nervous system briefly, which provides a better understanding for its potential application values.

Background: Soft tissue metastases (STMs) are reported to predict worse prognosis than extra-nodal extension (ENE) in metastatic head and neck cutaneous squamous cell carcinoma. This study aimed to update the authors' previous analysis of STM in a larger series., Methods: The study analyzed 535 cases of consecutive cSCC metastatic to the parotid and/or neck treated by primary surgical resection between 1987 and 2007. A Cox proportional hazard model was used to determine the effect of STM, with adjustment for other relevant prognostic factors. Overall survival (OS) and disease-specific survival (DSS) were the primary end points., Results: Of the 535 patients, 275 (51.4%) had STM. After adjustment for the effects of age, tumor location, number of metastatic deposits, and adjuvant radiotherapy, both STM (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.08-2.22; p = 0.018) and ENE (HR, 1.56; 95% CI 1.10-2.22; p = 0.013) were shown to be independent predictors of reduced OS, with similar size of effect., Conclusion: In metastatic cSCC of the head and neck, STM is an independent predictor of reduced survival and has an impact on survival similar to that of ENE.

We present the performances of our mathematical deep learning (MathDL) models for D3R Grand Challenge 4 (GC4). This challenge involves pose prediction, affinity ranking, and free energy estimation for beta secretase 1 (BACE) as well as affinity ranking and free energy estimation for Cathepsin S (CatS). We have developed advanced mathematics, namely differential geometry, algebraic graph, and/or algebraic topology, to accurately and efficiently encode high dimensional physical/chemical interactions into scalable low-dimensional rotational and translational invariant representations. These representations are integrated with deep learning models, such as generative adversarial networks (GAN) and convolutional neural networks (CNN) for pose prediction and energy evaluation, respectively. Overall, our MathDL models achieved the top place in pose prediction for BACE ligands in Stage 1a. Moreover, our submissions obtained the highest Spearman correlation coefficient on the affinity ranking of 460 CatS compounds, and the smallest centered root mean square error on the free energy set of 39 CatS molecules. It is worthy to mention that our method on docking pose predictions has significantly improved from our previous ones.

Differential scanning fluorimetry (DSF) is an accessible, rapid, and economical biophysical technique that has seen many applications over the years, ranging from protein folding state detection to the identification of ligands that bind to the target protein. In this review, we discuss the theory, applications, and limitations of DSF, including the latest applications of DSF by ourselves and other researchers. We show that DSF is a powerful high-throughput tool in early drug discovery efforts. We place DSF in the context of other biophysical methods frequently used in drug discovery and highlight their benefits and downsides. We illustrate the uses of DSF in protein buffer optimization for stability, refolding, and crystallization purposes and provide several examples of each. We also show the use of DSF in a more downstream application, where it is used as an in vivo validation tool of ligand-target interaction in cell assays. Although DSF is a potent tool in buffer optimization and large chemical library screens when it comes to ligand-binding validation and optimization, orthogonal techniques are recommended as DSF is prone to false positives and negatives.

Background: Regional nodal metastases from cutaneous squamous cell carcinoma (cSCC) is strongly associated with a poor prognosis, but these metastases are difficult to predict clinically. Sentinel node biopsy (SNB) has been used for a wide range of malignancies to assess for regional nodal metastasis, but is not widely used for cSCC., Methods: Patients presenting with high-risk cSCC of the head and neck with clinically N0 necks were offered SNB at the time of primary cSCC excision or secondary wide local excision. Patients with positive sentinel nodes were offered completion lymph node dissection, and all the patients were followed up at regular intervals for up to 5 years., Results: In this study, 105 lesions underwent SNB, and 10 sentinel nodes (9.5%) were positive. In an additional five patients, regional recurrence developed after a negative sentinel node, with a total subclinical nodal metastasis rate of 14.3%. Nodal metastases were significantly associated with reduced disease-specific survival. The significant predictors of metastasis were four or more high-risk features or tumors with a concurrent invasion deeper than 5 mm and PNI., Conclusion: For high-risk cSCC, SNB is a safe and feasible staging technique. The total number of high risk features and certain combinations of high-risk features predicted metastasis better than individual high-risk features.

Cell size has implications for the package effect in photon absorption as well as for metabolic scaling of metabolism. In this study, we have avoided species-related differences by using isolates of the marine planktonic diatom Coscinodiscus granii with cells of different sizes and grown at different light intensities to investigate their energy allocation strategies. To make full use of incident light, several fold variations in cellular chlorophyll a content were employed across cell size. This modulation of pigment-related light absorbance was deemed effective as similar light absorbing capacities were found in all treatments. Unexpected low values of O 2 evolution rate at the highest irradiance level of 450 μmol photons m -2  s -1 were found in medium and large cells, regardless of more photons being absorbed under these conditions, suggesting the operation of alternative electron flows acting as electron sinks. The growth rate was generally larger at higher irradiance levels except for the large cells, in which growth slowed at 450 μmol photons m -2  s -1 , suggesting that larger cells achieved a balance between growth and photoprotection by sacrificing growth rate when exposed to high light. Although the ratio of carbon demand to rates of uncatalysed CO 2 diffusion to the cell surface reached around 20 in large cells grown under higher irradiance, the carbon fixation rate was not lowered, due to the presence of a highly effective carbon dioxide concentrating mechanism.

Exogenous growth factors could accelerate the process of wound healing. However, the underlying mechanisms have not been clearly clarified. The aim of the present study was to investigate the effect of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on the expression of type I collagen (cola1), type III collagen (cola3), and Elastin in fibroblasts, which are widely expressed in fibroblasts and promote the function of fibroblasts. We measured the levels of cola1 and cola3 in human fibroblast cells cultured in medium containing EGF or bFGF at concentrations ranging from 0.1 to 1000 μg/L by Western blotting and RT-PCR assays, and found that EGF or bFGF enhanced the expression of cola1 and cola3 in a concentration-dependent manner. We further discovered that after stimulation with EGF or bFGF in human fibroblast cells, mitogen-activated protein kinases (MAPK) family members were generally activated, whose expression trend was consistent with that of cola1, cola3, and Elastin. In summary, in this study, we uncovered that exogenous growth factors enhance the expression of cola1, cola3, and Elastin, which is probably regulated via activating MAPK signaling pathway.

Epilepsy is one of the most common complex neurological diseases. It is frequently associated with intellectual and developmental disabilities (ID/DD). In recent years, copy number variation (CNV), especially microdeletion, was proven to be a potential key factor of genetic epilepsy. In this paper, the authors tested the hypothesis that the large de novo rare CNV is an important cause of epilepsy with ID/DD. We performed a custom array comparative genomic hybridization (aCGH) to detect the CNVs of 96 Chinese epileptic patients with ID/DD. The aCGH was designed with a higher density probe coverage of 320 genes known to be involved in epilepsy and ID/DD with lower density whole-genome backbone coverage. We detected 9 large de novo rare microdeletions from 8 patients. These CNVs are located on 2q24.1, 2q33.1-q34, 5q13.2 (2 similar CNVs), 5q33.1-q34, 17p13.2, 22q11.21-q11.22 (2 identical CNVs) and Xp22.31. We also found that only a few genes in the CNVs are known epilepsy related genes. By analysis with systems biology, we found most of the genes are interacting genes known to be epilepsy related genes. We also found a gene motif "BGNADP", constructed by BTD, GALNT10, NMUR2, AUTS2, DLG2 and PTPRD, would be a key motif in epilepsy and ID/DD. These findings strongly indicate that some large de novo rare microdeletion is an important pathological cause of epilepsy with ID/DD. Our study also found a gene motif "BGNADP" should be a key small network in epilepsy with ID/DD.

Zero-valent iron/activated carbon (Fe/C) particles can degrade persistent organic pollutants via micro-electrolysis and therefore, they may be used to develop materials for permeable reactive barriers (PRBs). In this study, surfactant-enhanced electrokinetics (EK) was coupled with a Fe/C-PRB to treat phenanthrene (PHE) and 2,4,6-trichlorophenol (TCP) co-contaminated clay soil. An environment-friendly biosurfactant, rhamnolipid, was selected as the solubility-enhancing agent. Five bench-scale tests were conducted to investigate the performance of EK-PRB on PHE and TCP removal from soil as well as the impact of pH and rhamnolipid concentration. The results show that both PHE and TCP, driven by electro-osmotic flow (EOF), moved toward the cathode and reacted with the Fe/C-PRB. Catholyte acidification and rhamnolipid concentration increase improved the removal efficiencies of PHE and TCP. The highest removal efficiency of PHE in soil column was five times the efficiency of the control group on which only EK was applied (49.89 versus 9.40%). The highest removal efficiency of TCP in soil column was 4.5 times the efficiency of the control group (64.60 versus 14.30%). Desorption and mobility of PHE and TCP improved with the increase of rhamnolipid concentration when this exceeded the critical micelle concentration. This study indicates that the combination of EK and a Fe/C-PRB is efficient and promising for removing persistent organic pollutants (POPs) from contaminated soil with the enhancement of rhamnolipid.

Although aminoglycoside antibiotics such as kanamycin are widely used clinically to treat life-threatening bacterial infections, ototoxicity remains a significant dose-limiting side effect. The prevailing view is that the hair cells are the primary ototoxic target of aminoglycosides and that spiral ganglion neurons begin to degenerate weeks or months after the hair cells have died due to lack of neurotrophic support. To test the early developmental aspects of this issue, we compared kanamycin-induced hair cell and spiral ganglion pathology in rat postnatal day 3 cochlear organotypic cultures with adult whole cochlear explants. In both adult and postnatal day 3 cultures, hair cell damage began at the base of the cochleae and progressed toward the apex in a dose-dependent manner. In postnatal day 3 cultures, spiral ganglion neurons were rapidly destroyed by kanamycin prior to hair cell loss. In contrast, adult spiral ganglion neurons were resistant to kanamycin damage even at the highest concentration, consistent with in vivo models of delayed SGN degeneration. In postnatal day 3 cultures, kanamycin preferentially damaged type I spiral ganglion neurons, whereas type II neurons were resistant. Spiral ganglion degeneration of postnatal day 3 neurons was associated with upregulation of the superoxide radical and caspase-3-mediated cell death. These results show for the first time that kanamycin is toxic to postnatal day 3 spiral ganglion neurons, but not adult neurons.

Background: Mutations in genes encoding tumor necrosis factor (TNF)-α and interleukin (IL)-6 were previously shown to affect mortality. Single nucleotide polymorphisms (SNPs) in the functional promoter regions of TNF-α (G308A) and IL-6 (G174C) are among the most widely studied., Objectives: To determine whether TNF-α G308A and IL-6 G174C SNPs confer susceptibility to longevity, we performed a meta-analysis to comprehensively estimate the association between these SNPs and longevity in long-lived individuals (LLI, aged ≥ 80 years)., Materials and Methods: Studies addressing the role of TNF-α and IL-6 SNPs in longevity were identified from the PubMed database. Pooled ORs with 95 % confidence intervals (CIs) were used to assess the association between SNPs and longevity., Results: The meta-analysis was based on four studies of TNF-α G308A and nine of IL-6 G174C, covering a total of 2945 LLI individuals and 2992 controls. Overall, no significantly increased risks were observed for G308A [A vs. G (additive model): OR = 0.98, 95 % CI = 0.79-1.22, p = 0.852; AA + AG vs. GG (dominant model): OR = 0.97, 95 % CI = 0.75-1.24, p = 0.791] or for G174C [C vs. G (additive model): OR = 1.07, 95 % CI = 0.94-1.22, p = 0.293; CC + CG vs. GG (dominant model): OR = 1.09, 95 % CI = 0.93-1.28, p = 0.299]. There was no change in the significance when a cutoff age of ≥ 90 years was introduced., Conclusions: We found no evidence that the TNF-α G308A and IL-6 G174C SNPs affected the probability of reaching an advanced age in Caucasians, and that they have little effect on delaying the onset and progression of age-related diseases, but this does not rule out the possibility of population-specific effects caused by different genes and/or environmental factors and their interactions.

Four Astragalus polysaccharides (APS1-APS4) were isolated from the water extract of Radix Astragali and purified through ethanol precipitation with 20 %, 40 %, 60 % and 80 % ethanol, respectively. The total sugar content was measured by sulfuric acid-phenol method. Their molecular weight was determined using high performance gel permeation chromatography (HPGPC) and their monosaccharide composition was analyzed by reversed-phase high performance liquid chromatography (HPLC) after pre-column derivatization. Then the immunobiologic activity of APS was evaluated by the experiment of spleen lymphocytes proliferation in vitro. The data suggested that precipitation by different concentration of ethanol will obtain different molecular weight APS, the higher concentration of ethanol the smaller molecular weight for APS. The molecular weights of four APS were 257.7 kDa, 40.1 kDa, 15.3 kDa and 3.2 kDa. Monosaccharide composition analysis indicated that APS1 consisted of glucose only, and APS2 all consisted of arabinose. APS3 consisted of rhamnose, glucose, galactose and arabinose and APS4 consisted of galactose and arabinose, in a molar ratio of 1:10.76:6.55:12 and 3.02:1. The result of immunobiologic activity assay showed that both APS2 and APS3 can effectively stimulate normal spleen lymphocyte proliferation in vitro. Apart from this, the effect of APS2 also showed dose dependent tendency from 6.25 μg/mL to 800 μg/mL. The result of this research indicated that Astragalus polysaccharides, which consist of arabinose and their molecular weight between 15.2 kDa to 40.1 kDa, neither too high nor too low, had significant immune activity.

Rap2B, a member of the Ras family of small GTP-binding proteins, reportedly presents a high level of expression in various human tumors and plays a significant role in the development of tumor. However, the function of Rap2B in prostate cancer (PCa) remains unclear. We elucidated the stimulative role of Rap2B in PCa cell proliferation, migration and invasion by means of the CCK-8 cell proliferation assay, cell cycle analysis and transwell migration assay. Western blot analysis uncovered that elevated Rap2B leads to increased phosphorylation levels of FAK, suggesting that FAK-dependent pathway might be responsible for the effect of Rap2B on PCa cells migration and invasion. Inversely, FAK-specific inhibitor (PF-573228) can abort Rap2B-induced FAK phosphorylation. In vivo experiment confirmed that Rap2B positively regulated PCa growth and metastasis, as well as the expression of phosphorylated FAK. Collectively, these findings shed light on Rap2B as a potential therapeutic target for PCa.

The diazotrophic cyanobacterium Trichodesmium is a major contributor to marine nitrogen fixation. We analyzed how light acclimation influences the photophysiological performance of Trichodesmium IMS101 during exponential growth in semi-continuous nitrogen fixing cultures under light levels of 70, 150, 250, and 400 μmol photons m(-2) s(-1), across diel cycles. There were close correlations between growth rate, trichome length, particulate organic carbon and nitrogen assimilation, and cellular absorbance, which all peaked at 150 μmol photons m(-2) s(-1). Growth rate was light saturated by about 100 μmol photons m(-2) s(-1) and was photoinhibited above 150 μmol photons m(-2) s(-1). In contrast, the light level (I k) to saturate PSII electron transport (e (-) PSII(-1) s(-1)) was much higher, in the range of 450-550 μmol photons m(-2) s(-1), and increased with growth light. Growth rate correlates with the absorption cross section as well as with absorbed photons per cell, but not to electron transport per PSII; this disparity suggests that numbers of PSII in a cell, along with the energy allocation between two photosystems and the state transition mechanism underlie the changes in growth rates. The rate of state transitions after a transfer to darkness increased with growth light, indicating faster respiratory input into the intersystem electron transport chain.